Arthroscopic Lateral Meniscus Root Repair With Reverse Suture Anchor Technique.

The stability of the knee joint is crucially dependent on the integrity of the lateral meniscus posterior root, which is often accompanied by anterior cruciate ligament injury. Anchor suture repair for lateral meniscus posterior root injury not only achieves better biomechanical effects but also ensures favorable prognosis. However, the placement of anchors often requires the establishment of a posterior approach, and the insertion of an anchor is a technical challenge. In light of this, we have applied the technique of reverse anchor fixation for repairing the lateral meniscus posterior root, which not only simplifies the procedure but also effectively reduces the "bungee effect."

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.

Machine learning identification and immune infiltration of disulfidptosis-related Alzheimer's disease molecular subtypes.

BACKGROUND: Alzheimer's disease (AD) is a common neurodegenerative disorder. Disulfidptosis is a newly discovered form of programmed cell death that holds promise as a therapeutic strategy for various disorders. However, the functional roles of disulfidptosis-related genes (DRGs) in AD remain unknown. METHODS: Microarray data and clinical information from patients with AD and healthy controls were downloaded from the Gene Expression Omnibus database. A thorough examination of DRG expression and immune characteristics in both groups was performed. Based on the identified DRGs, we performed an unsupervised clustering analysis to categorize the AD samples into various disulfidptosis-related molecular clusters. Weighted gene co-expression network analysis was performed to select hub genes specific to disulfidptosis-related AD clusters. The performances of various machine learning models were compared to determine the optimal predictive model. The predictive ability of the optimal model was assessed using nomogram analysis and five external datasets. RESULTS: Eight DRGs showed differential expression between the AD and control samples. Two different molecular clusters were identified. The immune cell infiltration analysis revealed distinct differences in the immune microenvironment of the two clusters. The support vector machine model showed the highest performance, and a panel of five signature genes was identified, which showed excellent performance on the external validation datasets. The nomogram analysis also showed high accuracy in predicting AD. CONCLUSION: We identified disulfidptosis-related molecular clusters in AD and established a novel risk model to assess the likelihood of developing AD. These findings revealed a complex association between disulfidptosis and AD, which may aid in identifying potential therapeutic targets for this debilitating disorder.

Role of Mutations of Mitochondrial Aminoacyl-tRNA Synthetases Genes on Epileptogenesis.

Mitochondria are the structures in cells that are responsible for producing energy. They contain a specific translation unit for synthesizing mitochondria-encoded respiratory chain components: the mitochondrial DNA (mt DNA). Recently, a growing number of syndromes associated with the dysfunction of mt DNA translation have been reported. However, the functions of these diseases still need to be precise and thus attract much attention. Mitochondrial tRNAs (mt tRNAs) are encoded by mt DNA; they are the primary cause of mitochondrial dysfunction and are associated with a wide range of pathologies. Previous research has shown the role of mt tRNAs in the epileptic mechanism. This review will focus on the function of mt tRNA and the role of mitochondrial aminoacyl-tRNA synthetase (mt aaRS) in order to summarize some common relevant mutant genes of mt aaRS that cause epilepsy and the specific symptoms of the disease they cause.

Yeast UPS1 deficiency leads to UVC radiation sensitivity and shortened lifespan.

UPS1/YLR193C of Saccharomyces cerevisiae (S. cerevisiae) encodes a mitochondrial intermembrane space protein. A previous study found that Ups1p is needed for normal mitochondrial morphology and that UPS1 deficiency disrupts the intramitochondrial transport of phosphatidic acid in yeast cells and leads to an altered unfolded protein response and mTORC1 signaling activation. In this paper, we first provide evidence showing that the UPS1 gene is involved in the UVC-induced DNA damage response and aging. We show that UPS1 deficiency leads to sensitivity to ultraviolet C (UVC) radiation and that this effect is accompanied by elevated DNA damage, increased intracellular ROS levels, abnormal mitochondrial respiratory function, an increased early apoptosis rate, and shortened replicative lifespan and chronological lifespan. Moreover, we show that overexpression of the DNA damage-induced checkpoint gene RAD9 effectively eliminates the senescence-related defects observed in the UPS1-deficient strain. Collectively, these results suggest a novel role for UPS1 in the UVC-induced DNA damage response and aging.

Repair of rotator cuff tears in patients aged 75 years and older: Does it make sense? A systematic review.

Background: Rotator cuff injuries are common, and morbidity increases with age. The asymptomatic full-thickness tear rate is 40% in the over 75-year-old population. Purpose: This study aimed to systematically review the literature on the outcomes of rotator cuff repair among >75 years old patients. Study design: Systematic review. Methods: A systematic review of the literature was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A literature search was performed in the electronic databases of PubMed, Medline, Embase, and The Cochrane Library. Studies in English evaluating repair of full-thickness rotator cuff tears in patients aged >75 years were included. Results: Six studies were reviewed, including 311 patients (313 shoulders) treated with arthroscopic and/or open rotator cuff repair. Sixty-one patients were lost to follow-up, leaving 252 shoulders with outcome data. Patients in this age group demonstrated a significant improvement in the clinical and functional scores after rotator cuff repair, with a high satisfaction rate. The mean American Shoulder and Elbow Surgeons scores improved from 43.8 (range, 42.0-45.5) preoperatively to 85.3 (range, 84.0 to 86.5) postoperatively, and the mean Constant scores improved from 45.4 (range, 34.7-55.5) to 78.6 (range, 67.0-91.6). Pain, evaluated in all studies by the visual analog scale for pain, showed a significant improvement at the last follow-up compared with the mean preoperative score. Furthermore, range of motion and return to daily activities and sports gained marked improvements. Conclusion: Rotator cuff repair in patients aged >75 years could achieve high clinical success rates with good outcomes and pain relief. Although patients in this age group are at a high risk of retear, rotator cuff repair may offer a good option with significant functional and clinical improvement.

Yeast YPK9 deficiency results in shortened replicative lifespan and sensitivity to hydrogen peroxide.

YPK9/YOR291W of Saccharomyces cerevisiae encodes a vacuolar membrane protein. Previous research has suggested that Ypk9p is similar to the yeast P5-type ATPase Spf1p and that it plays a role in the sequestration of heavy metals. In addition, bioinformatics analysis has suggested that Ypk9p is a homolog of human ATP13A2, which encodes a protein of the subfamily of P5 ATPases. However, no specific function of Ypk9p has been described to date. In this study, we found, for the first time, that YPK9 is involved in the oxidative stress response and modulation of the replicative lifespan (RLS). We found that YPK9 deficiency confers sensitivity to the oxidative stress inducer hydrogen peroxide accompanied by increased intracellular ROS levels, decreased mitochondrial membrane potential, abnormal mitochondrial function, and increased incidence of early apoptosis in budding yeast. More importantly, YPK9 deficiency can lead to a shortened RLS. In addition, we found that overexpression of the catalase-encoding gene CTA1 can reverse the phenotypic abnormalities of the ypk9Δ yeast strain. Collectively, these findings highlight the involvement of Ypk9p in the oxidative stress response and modulation of RLS.

Is implantation of autologous chondrocytes superior to microfracture for articular-cartilage defects of the knee? A systematic review of 5-year follow-up data.

BACKGROUND: Autologous chondrocyte implantation (ACI) and microfracture are two of the main surgical treatment options for articular cartilage lesions of the knee. Consensus regarding the best clinical options to repair knee cartilage lesions is lacking. We undertook a systematic review to clarify the clinical efficacy of ACI and microfracture at minimum mean 5-year follow-up. METHODS: A literature search was conducted using the MEDLINE, Embase and Cochrane Library databases up to August 2018. Only comparative clinical studies of ACI and microfracture for the treatment of articular cartilage lesions of the knee with level I/Ⅱ evidence were included. Clinical outcomes and the prevalence of treatment failure from each study were extracted and compared. The methodological quality of the included studies was analyzed by means of the PEDro scale. RESULTS: Five comparative studies (three randomized controlled trials and two prospective cohort studies) met our eligibility criteria. ACI and microfracture elicited significant improvement in clinical outcomes after 5 years. However, better clinical results with significant differences were found with modified versions of ACI (ACI with a modified collagen membrane [ACI-C] or matrix-applied chondrocyte implantation [MACI]) than with microfracture as determined by the Knee Injury and Osteoarthritis Outcome Score, activities of daily living assessment, Tegner Activity Scale score, and the International Knee Documentation Committee objective and subjective scores. No significant difference was observed in the treatment failure rate between these two methods within a particular study. CONCLUSIONS: Currently, the best-available evidence suggests that some clinical outcomes of articular cartilage lesions of the knee treated with modified versions of ACI (ACI-C or MACI) can significantly improve patient outcomes at the mid-term follow-up of 5 years compared with those obtained using microfracture.

Is platelet-rich plasma an ideal biomaterial for arthroscopic rotator cuff repair? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Recently, many authors have reported the effects of platelet-rich plasma (PRP) on rotator cuff repair. Whether PRP treatment during arthroscopic rotator cuff repair improves tendon healing rates or restores full function remains unknown. The purpose of this meta-analysis was to evaluate the clinical improvement and radiological outcomes of PRP treatment in patients undergoing arthroscopic rotator cuff repair. METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched. The study included only level 1 or 2 randomized controlled trials (RCTs) that compared the injection of platelet-rich plasma or platelet-rich fibrin matrix. The methodological quality of the trials was assessed using the Cochrane Handbook for Systematic Reviews of Interventions, 5.3. Continuous variables were analysed using the weighted mean difference, and categorical variables were assessed using relative risks. P < 0.05 was considered statistically significant. RESULTS: The meta-analysis revealed a lower retear rate following PRP treatment than that following the control method (mean difference, 1.10; 95% CI, 1.03 to 1.18; P = 0.004). Constant shoulder scores improved with PRP (mean difference, 2.31; 95% CI, 1.02 to 3.61; P = 0.0005). PRP treatment also resulted in higher UCLA scores (mean difference, 0.98; 95% CI, 0.27 to 1.69; P = 0.007), and simple shoulder test scores were improved (mean difference, 0.43; 95% CI, 0.11 to 0.75; P = 0.008). Finally, lower visual analogue scale scores were observed with PRP augmentation (mean difference, - 0.35; 95% CI, - 0.57 to - 0.13; P = 0.002). CONCLUSIONS: The current systematic review and meta-analysis reveals that PRP treatment with arthroscopic repair of rotator cuff tears decreases the retear rate and improves the clinical outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016048416.

Comparison of lateral entry with crossed entry pinning for pediatric supracondylar humeral fractures: a meta-analysis.

BACKGROUND: The standard treatment for severe displaced pediatric supracondylar humeral fracture (SCHF) is closed reduction and percutaneous pin fixation. However, controversy persists concerning the optimal pin fixation technique. The purpose of this study was to compare the safety and efficacy on the configuration of lateral entry only with crossed entry pin fixation for SCHF, including Gartland type II and type III fractures in children. METHODS: Published literatures, including retrospective studies, prospective studies, and randomized controlled trials, presenting the probability of poor functional consequence of elbow and/or loss of reduction and/or iatrogenic ulnar nerve injury and/or superficial infection and/or cubitus varus were included. Statistical analysis was performed with the Review Manager 5.3 software. RESULTS: Twenty-four studies were included in the present meta-analysis involving 1163 patients with lateral entry pins and 1059 patients with crossed entry pins. An excellent score of Flynn criteria occurred more commonly in patients who treated with crossed pins than in patients with lateral pins only (RR = 0.93; 95% CI 0.87-0.99; P = 0.03). In accordance with previous systematic review, the incidence of iatrogenic ulnar nerve injury in crossed entry group was significantly more than in lateral entry group with statistical difference (RR = 0.26; 95% CI 0.14-0.47; P < 0.0001). And, results of subgroup analysis on iatrogenic ulnar nerve injury based on experimental design of retrospective study (RR = 0.23; 95% CI 0.10-0.52; P < 0.0004) and randomized control trial (RR = 0.29; 95% CI 0.10-0.79; P < 0.02) were similar. CONCLUSIONS: In consideration of the contradictoriness of lateral entry with two pins only (possible risk of poor functional consequence of elbow) and crossed entry pins (risk of iatrogenic ulnar nerve injury), the recommended strategy for the treatment of SCHF is the lateral entry technique with introducing divergent three pins which can provide a stable configuration and avoid the injury of the ulnar nerve. And additional protective measures for the ulnar nerve should be taken by surgeons that wish for the more stable structure with the crossed entry technique.

IL1R1 polymorphisms are associated with ankylosing spondylitis in the Han Chinese population: a case-control study.

Several studies have demonstrated that polymorphisms within the IL-1 gene cluster are associated with the risk of ankylosing spondylitis (AS) in different populations. In this study, we desired to know whether IL1R1, a gene located in the IL-1 gene cluster, is a susceptible gene for AS in a Northwest Chinese Han population. The Sequenom MassARRAY assay technique was used to determine the genotype of 267 AS patients and 297 controls from Northwest China. Genotype and allele distributions of the investigated IL1R1 variants (rs10490571, rs12712127, rs956730, rs3917225, and rs3917318) were compared among the cases and controls using Chi-square/Fisher's exact tests. In addition, the associations of these polymorphisms with AS risk were also assessed under dominant, recessive, and additive genetic models using PLINK software. We found the minor G allele of rs3917225 was associated with an increased risk of AS (OR=1.39, 95% CI: 1.09-1.77, P=0.007). Significant association was also detected for rs956730 under the dominant model (OR=0.54, 95% CI: 0.30-0.96, P=0.032) and the additive model (OR=0.55, 95% CI: 0.34-0.90, P=0.016), adjusting for age and gender. This study is the first to demonstrate the significant association between IL1R1 polymorphisms and AS susceptibility in a Northwest Chinese Han population.

Are Chinese Correlative Conjunctions Psychologically Real? An Investigation of the Combination Frequency Effect.

The present study used an online grammaticality judgment task to examine whether Chinese discontinuous correlative conjunctions are psychologically real in mental lexicon. High- and low-frequency discontinuous correlative conjunctions were compared with random combinations differing in combination frequencies but matched for constituent word frequency. Forty graduate students participated in the study. Results showed that responses were faster and more accurate for high-frequency correlative conjunctions than low-frequency ones, but the effects were absent for random combinations. The results indicate that Chinese discontinuous correlative conjunctions have psychological reality in mental lexicon in addition to the representation of their constituent words, and that grammatical functions of correlative conjunctions may be a critical factor for the formation of such holistic representations.

The effective mode of growth and differentiation factor-5 in promoting the chondrogenic differentiation of adipose-derived stromal cells.

Our study aimed to find out the most effective mode for chondrogenic differentiation based on time, dose and culture method. ADSCs were cultured and identified by CD44, CD49d, and CD106 immumohistochemical staining method, and their differentiation potential to chondrocyte were detected by Alizarin red staining. ADSCs induced by different concentrations of GDF-5 for chondrogenic differentiation were detected by blue and toluidine blue staining and collagen type II and X immumohistochemical staining. The expression of collagen I, II, X and aggrecan gene in GDF-induced ADSCs cultured in 2- and 3-dimension was identified by real-time PCR. Cell microstructure and proliferation in three-dimensional scaffolds at day 7, 14, 21 and 28 were analyzed by scanning electron microscopy and MTS assay. The ADSCs were successfully identified by CD44 and CD49d, and their differentiation potential was detected by Alizarin red staining. Real-time PCR showed that collagen and aggrecan were expressed at high levels in 100 or 200 ng/mL GDF-5 treated cells. The collagen types (I, II) and aggrecan genes were higher expressed in GDF-5 induced scaffold group than that in monolayer group. MTS showed that the cell counts were not significantly different among different treated time. Both collagen type II and aggrecan gene were highly expressed at day 14, while collagen types I and X gene expressions peaked at day 21 and 28. The 100 ng/mL GDF-5 is effective and cost-effective for chondrogenic differentiation when cultured at day 14 in vitro under three-dimensional culture conditions.

Identification of genes associated with the differentiation potential of adipose-derived stem cells to osteocytes or myocytes.

Adipose-derived stem cells (ADSCs) have been considered as the optimal cells for regenerative medicine because ADSCs have the potential of multi-directional differentiation. To study the mechanisms of ADSCs differentiation, we analyzed microarray of GSE37329. GSE37329 was downloaded from Gene Expression Omnibus including 3 ADSCs, 2 ADSCs-derived osteocytes, and 2 ADSCs-derived myocytes samples. The differentially expressed genes (DEGs) were screened using limma package. Their underlying functions were predicted by gene ontology and pathway enrichment analyses. Besides, the interaction relationships of the proteins encoded by DEGs were obtained from STRING database, and protein-protein interaction (PPI) network was constructed using Cytoscape. Furthermore, modules analysis of PPI network was performed using MCODE in Cytoscape. We screened 662 and 484 DEG separately for the ADSCs-derived osteocytes and myocytes compared with ADSCs. There were 205 common up-regulated and 128 common down-regulated DEGs between the two groups. Function enrichment indicated that these common DEGs, especially, VEGFA, FGF2, and EGR1 may be related to cell differentiation. PPI network for common DEGs also suggested that VEGFA (degree = 29), FGF2 (degree = 17), and EGR1 (degree = 12) might be more important because they had higher connectivity degrees, and they might be involved in cell differentiation by interacting with other genes in module A (e.g., EGR1-NGF and EGR1-LEP), and B (e.g., VEGFA-PDGFD). Additionally, the IGF1 and BTG1 may be, respectively, specific for osteocytes and myocytes differentiation. VEGFA, PDGFD, FGF2, EGR1, NGF, LEP, IGF1, and BTG1 might serve as target genes in regulating ADSCs differentiation.

P200 can be modulated by orthography alone in reading Chinese words.

The present study examined the relation between the event-related potential component P200 and orthographic processing in reading Chinese words. Participants performed a semantic judgment task on pairs of words (prime-target pairs) presented sequentially and the P200 elicited by the second target word was examined and compared across different prime conditions. The critical pairs were single characters similar in orthography but unrelated in phonology or semantics. Results showed that for both integrated and composite characters, visually similar primes led to reduced P200 than control primes and the effect was larger for composite characters than integrated characters. The study presented clear evidence that P200 is sensitive to orthographic similarity and can be modulated by orthography alone in reading Chinese word.

The interaction of arousal and valence in affective priming: behavioral and electrophysiological evidence.

The affective priming paradigm has been studied extensively and applied in many fields during the past two decades. Most research thus far has focused on the valence dimension. Whether emotional arousal influences affective priming remains poorly understood. The present study demonstrates how arousal impacts evaluation of affective words using reaction time and event-related potential (ERP) measures. Eighteen younger subjects evaluated pleasantness of target words after seeing affective pictures as primes. The participants' responses were faster and/or more accurate for valence-congruent trials than for incongruent trials, particularly with high-arousal stimuli. An ERP affective priming effect (N400) also occurred mainly in high-arousing stimulus pairs. In addition, whereas valence congruency influenced both the N400 and the LPP, arousal congruency influenced only the LPP, suggesting that arousal congruency mainly modulates post-semantic processes, but valence congruency effects begin with semantic processes. Overall, our current findings indicate that the arousal level of visual images impacts both behavioral and ERP effects of affective priming.

Effects of load on the guidance of visual attention from working memory.

An active recent line of research on working memory and attention has shown that the visual attention can be top-down guided by working memory contents. The present study examined whether the guidance effect is modulated by memory load, i.e., the amount of information maintained in working memory. In a set of three experiments, participants were asked to perform a visual search task while maintaining several objects in working memory. The memory-driven attentional guidance effect was observed in all experiments when there were spare working memory resources. When memory load was increased from one item to two items, there was no sign that the guidance effect was attenuated. When load was further increased to four items, the guidance effect disappeared completely, indicating a clear impact of memory load on attentional guidance.

Guidance of visual attention from working memory contents depends on stimulus attributes.

Recent work shows that items maintained in working memory could guide the orienting of attention in visual search, demonstrating an interesting interaction between working memory and attention. For such guidance effect, some studies emphasize the importance of search task type: for fixed-target search, task-irrelevant memory items stay inside the attentional focus and guides attention; for varied-target search, these items stay outside attentional focus and do not guide attention. With two experiments, we showed that stimulus attribute of items held in working memory can play an important role in attentional guidance. The first behavioral experiment duplicated a previous fixed-target search paradigm demonstrating robust guidance effect but failed to find such effect when the stimuli was simply changed from colored shapes to complex artificial shapes. The second event-related potential experiment duplicated a previous varied-target search paradigm that used complex shapes but did not observe any guidance effect. A clear guidance effect was found when we changed the stimuli to colored shapes. The results suggest that attentional guidance from working memory depends on stimulus attributes of the items held in working memory. When effective attribute is used, task-irrelevant items that stay outside the attentional focus are still able to guide attention.

Electrophysiological correlates of proactive interference in the 'Recent Probes' verbal working memory task.

Using event-related potentials (ERPs), the present study examined the temporal dynamics of proactive interference in working memory using a recent probes task. Participants memorized and retained a target set of four letters over a short retention interval. They then responded to a recognition probe by judging whether it was from the memory set. ERP waveforms elicited by positive probes compared to those from negative probes showed positive shifts in a fronto-central early N2 component and a parietal late positive component (LPC). The LPC was identified as the electrophysiological signature of proactive interference, as it differentiated between two types of negative probes defined based on whether they were recently encountered. These results indicate that the proactive interference we observed arises from a mismatch between familiarity and contextual information during recognition memory. When considered together with related studies in the literature, the results also suggest that there are different forms of proactive interference associated with different neural correlates.

P200 and phonological processing in Chinese word recognition.

The present study examined the relationship between P200 and phonological processing in Chinese word recognition. Participants did a semantic judgment task on pairs of words. The critical pairs were all semantically unrelated in one of three conditions: homophonic, rhyme, or phonologically unrelated. Noting the possibility that P200 may be affected by phonological similarity and orthographic similarity and that literature studies may not have assessed such effects separately, the present study used visually dissimilar word pairs sharing no phonetic radicals. Relative to the control pairs, both the homophonic and rhyme pairs elicited a significantly larger P200 with a scalp distribution centering at the centro-parietal areas. The results present strong evidence that P200 can be modulated by lexical phonology alone, independent of sub-lexical phonology, or lexical or sub-lexical orthography. P200 effects were comparable in amplitude and topography between the homophonic and the rhyme conditions, suggesting that P200 is sensitive to phonology at both the syllabic and the sub-syllabic levels.