Association between driving pressure-guided ventilation and postoperative pulmonary complications in surgical patients: a meta-analysis with trial sequential analysis.

BACKGROUND: Prior studies have reported inconsistent results regarding the association between driving pressure-guided ventilation and postoperative pulmonary complications (PPCs). We aimed to investigate whether driving pressure-guided ventilation is associated with a lower risk of PPCs. METHODS: We systematically searched electronic databases for RCTs comparing driving pressure-guided ventilation with conventional protective ventilation in adult surgical patients. The primary outcome was a composite of PPCs. Secondary outcomes were pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS). Meta-analysis and subgroup analysis were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CI). Trial sequential analysis (TSA) was used to assess the conclusiveness of evidence. RESULTS: Thirteen RCTs with 3401 subjects were included. Driving pressure-guided ventilation was associated with a lower risk of PPCs (RR 0.70, 95% CI 0.56-0.87, P=0.001), as indicated by TSA. Subgroup analysis (P for interaction=0.04) found that the association was observed in non-cardiothoracic surgery (nine RCTs, 1038 subjects, RR 0.61, 95% CI 0.48-0.77, P< 0.0001), with TSA suggesting sufficient evidence and conclusive result; however, it did not reach significance in cardiothoracic surgery (four RCTs, 2363 subjects, RR 0.86, 95% CI 0.67-1.10, P=0.23), with TSA indicating insufficient evidence and inconclusive result. Similarly, a lower risk of pneumonia was found in non-cardiothoracic surgery but not in cardiothoracic surgery (P for interaction=0.046). No significant differences were found in atelectasis and ARDS between the two ventilation strategies. CONCLUSIONS: Driving pressure-guided ventilation was associated with a lower risk of postoperative pulmonary complications in non-cardiothoracic surgery but not in cardiothoracic surgery. SYSTEMATIC REVIEW PROTOCOL: INPLASY 202410068.

Decreased Synovial Fluid Biomarkers Levels Are Associated with Rehabilitation of Function and Pain in Rotator Cuff Tear Patients Following Electroacupuncture Therapy.

BACKGROUND The aim of this study was to assess inflammatory cytokines levels in synovial fluid (SF) before and after electroacupuncture (EA) treatment and to explore whether these biomarkers are associated with function of rotator cuff tear (RCT) patients. MATERIAL AND METHODS We recruited 54 patients with RCT and separated them into an EA group and a control group. The SF biomarker levels were detected at baseline and at 6-week and 6-month follow-up. The symptomatic severity was evaluated by visual analog scale (VAS), Constant-Murley score, and American Shoulder and Elbow Surgeons score (ASES). We also investigated the correlation between symptomatic severity and biomarker levels in SF of the shoulder joint. RESULTS The reductions in VAS and improved functional score (ASES and Constant-Murley score) were significantly different between the 2 groups, and SF biomarker concentrations were significantly lower in the EA group. IL-1ß levels were significantly negatively correlated with Constant-Murley score (r=-0.73, P=0.04) and ASES score (r=-0.59, P<0.001) and positively correlated with VAS scores (r=0.81, P=0.004). IL-6 levels were significantly negatively correlated with Constant-Murley score (r=-0.67, P=0.03) and positively correlated with VAS score (r=0.7, P=0.01). MMP-1 levels were significantly negatively correlated with ASES score (r=-0.57, P<0.001). CONCLUSIONS The biomarkers in SF were directly associated with shoulder pain and shoulder function in rotator cuff tear. EA, as a safe and effective conservative therapy, obviously decreased the level of inflammatory cytokines in RCT patients, accompanied by a reduction in shoulder pain and improved function.

Relationship between serum and synovial fluid CCL20 concentrations with disease severity in primary knee osteoarthritis.

OBJECTIVES: The current study was performed to examine serum and synovial fluid (SF) CCL20 levels and their correlations with disease severity in primary knee osteoarthritis patients. METHODS: A total of 99 patients diagnosed with primary knee OA were enrolled in the study, and 95 healthy individuals receiving regular medical examination were recruited as controls. Serum and SF CCL20 concentrations were determined using an enzyme-linked immunosorbent assay. The radiographic severity of OA was assessed by the Kellgren-Lawrence (K-L) classification system. The Lequesne algofunctional index and a visual analogue scale (VAS) were used to evaluate the clinical severity of knee OA in patients. RESULTS: The serum CCL20 levels were not significantly different between patients with knee OA and controls. Patients with a K-L grade of 4 had significantly higher SF CCL20 levels than those with K-L grades of 2 and 3. Knee OA patients with a K-L grade of 3 showed significantly higher levels of CCL20 in SF than those with a K-L grade of 2. In addition, SF CCL20 levels were significantly related to the Lequesne algofunctional index and VAS score. CONCLUSIONS: These findings suggest that local CCL20 levels may reflect the disease severity of knee OA.

[Chromatin architectural protein CTCF regulates gene expression of the UGT1 cluster].

UDP-glucuronosyltransferases (UGTs) are an important family of phase 2 drug-metabolizing enzymes that catalyze the glucuronidation of numerous endogenous or exogenous small compounds. The aberrant expression of UGT isoforms causes many diseases, such as hyperbilirubinemia and affect drug efficacy or toxicity. Understanding mechanisms of UGT gene regulation will provide scientific foundations for disease prevention and personalized or precision medicine. Vertebrate UGT family genes can be divided into UGT1 and UGT2 subfamilies. Similar to the protocadherin, immunoglobulin, and T-cell receptor gene clusters and different from the UGT2 gene cluster, the UGT1 gene cluster is organized into variable and constant regions. The UGT1 variable region contains a tandem array of variable exons, each of which can be alternatively spliced to a single set of 4 downstream constant exons, generating at least nine UGT1 mRNAs that could be translated into different UGT1 glucuronyltransferase isoforms. Our previous work reveals that the relative orientations and locations of CTCF binding sites play a key role in the three-dimensional organization of the mammalian genomes in cell nuclei. Thus in order to study the transcriptional mechanisms of UGT1 gene cluster, the distributions and orientations of CTCF binding sites (CBSs) are analyzed and compared between human and mouse UGT1 gene clusters. We find that the CBSs in the UGT1 gene cluster are not conserved between human and mouse species. We show that CTCF and cohesin regulate the transcription of the UGT1 gene cluster by knocking down the CTCF or the cohesin subunit SMC3 in the human A549 cell line. By using CRISPR DNA-fragment editing, we deleted and inverted hCBS1. By RNA-seq experiments, we find that hCBS1 deletion results in a significant decrease of levels of the UGT1A6, UGT1A7, and UGT1A9 gene expression and that hCBS1 inversion results in a significant decrease of levels of the UGT1A7 gene expression. Our data suggest that the CTCF binding site hCBS1 plays an important regulatory role in the regulation of UGT1 gene expression, providing an experimental basis for further mechanistic studies of the 3D genome regulation of the UGT1 gene cluster.

Involvement of aberrant miR-139/Jun feedback loop in human gastric cancer.

Accumulating evidence indicates that some miRNAs could form feedback loops with their targets to fine-tune tissue homeostasis, while disruption of these loops constitutes an essential step towards human tumorigenesis. In this study, we report the identification of a novel negative feedback loop formed between miR-139 and its oncogenic target Jun. In this loop, miR-139 could inhibit Jun expression by targeting a conserved site on its 3'-UTR, whereas Jun could induce miR-139 expression in a dose dependent manner through a distant upstream regulatory element. Interestingly, aberration in this loop was found in human gastric cancer, where miR-139 was down-regulated and inversely correlated with Jun expression. Further functional analysis showed that restored expression of miR-139 in gastric cancer cells significantly induces apoptosis, and inhibits cell migration and proliferation as well as tumour growth through targeting Jun. Thus, our data strongly suggests a role of aberrant miR-139/Jun negative feedback loop in the development of human gastric cancer and miR-139 as a potential therapeutic target for gastric cancer. Given that miR-139 and Jun are deregulated in many cancers, our findings here might have broader implication in other types of human cancers.

[Evaluation of intellectual development level of 300 children with language disorder].

OBJECTIVE: To investigate the features of intellectual development in children with language disorder. METHODS: The developmental quotients (DQs) of motor, object, language and social abilities were evaluated in 300 children with language disorder by Gesell Developmental Schedules. RESULTS: All the 300 children had normal mean DQs of motor ability and lower mean DQs of object, language, and social abilities. Of all children, 31.0% had abnormal motor ability, 49.0% had abnormal object ability, and 52.7% had abnormal social ability. The DQ of language ability was significantly positively correlated with the DQs of the other three abilities (r=0.506, 0.644, and 0.711 respectively, P<0.01). CONCLUSIONS: Children with language disorder may have abnormal motor ability, adaptive behavior, and personal-social behavior. Diagnostic intellectual development evaluation and comprehensive intervention for other developmental abnormalities should be performed for these children.

[Ubiquitous Ribonucleic Acid:miRNA is the Ubiquitin of RNA].

Small RNAs, especially microRNAs (miRNAs),widely exist in eukaryotic cells, with their main functions being regulating gene expression and function of target molecules through the degradation of cellular target RNAs by the ribonuclease-based system. Ubiquitins and ubiquitin-like proteins are polypeptides that exist in most eukaryotic cells, and their main function is almost to regulate protein level through the degradation of cellular proteins by ubiquitin proteasome system. Small RNAs, including miRNAs,and ubiquitins or ubiquitin-like proteins have similarities in many aspects although small RNAs and ubiquitin or ubiquitin-like proteins interact different substrates respectively. Therefore, miRNAs can be defined as ubiquitra (ubiquitous ribonucleic acid, ubiquitra or uRNA), and the other small RNAs can be defined as ubiquitra-like RNA or uRNA-like RNA. The concept of ubiquitra may be applied for explaining the biological essence of small RNAs diversity.

Functional screening for miRNAs targeting Smad4 identified miR-199a as a negative regulator of TGF-ß signalling pathway.

The transforming growth factor-ß (TGF-ß) signalling pathway participates in various biological processes. Dysregulation of Smad4, a central cellular transducer of TGF-ß signalling, is implicated in a wide range of human diseases and developmental disorders. However, the mechanisms underlying Smad4 dysregulation are not fully understood. Using a functional screening approach based on luciferase reporter assays, we identified 39 microRNAs (miRNAs) as potential regulators of Smad4 from an expression library of 388 human miRNAs. The screening was supported by bioinformatic analysis, as 24 of 39 identified miRNAs were also predicted to target Smad4. MiR-199a, one of the identified miRNAs, was inversely correlated with Smad4 expression in various human cancer cell lines and gastric cancer tissues, and repressed Smad4 expression and blocked canonical TGF-ß transcriptional responses in cell lines. These effects were dependent on the presence of a conserved, but not perfect seed paired, miR-199a-binding site in the Smad4 3'-untranslated region (UTR). Overexpression of miR-199a significantly inhibited the ability of TGF-ß to induce gastric cancer cell growth arrest and apoptosis in vitro, and promoted anchorage-independent growth in soft agar, suggesting that miR-199a plays an oncogenic role in human gastric tumourigenesis. In conclusion, our functional screening uncovers multiple miRNAs that regulate the cellular responsiveness to TGF-ß signalling and reveals important roles of miR-199a in gastric cancer by directly targeting Smad4.

Mechanistic insights into the effects of diuron exposure on Alexandrium pacificum.

Diuron (N-(3,4-dichlorophenyl)-N,N­dimethylurea, DCMU), a ureic herbicide, is extensively used in agriculture to boost crop productivity; however, its extensive application culminates in notable environmental pollution, especially in aquatic habitats. Therefore, the present study investigated the effect of diuron on the dinoflagellate Alexandrium pacificum, which is known to induce harmful algal blooms (HAB), and its potential to biodegrade DCMU. Following a four-day DCMU exposure, our results revealed that A. pacificum proficiently assimilated DCMU at concentrations of 0.05 mg/L and 0.1 mg/L in seawater, attaining a complete reduction (100 % efficiency) after 96 h for both concentrations. Moreover, evaluations of paralytic shellfish toxins content indicated that cells subjected to higher DCMU concentrations (0.1 mg/L) exhibited reductions of 73.4 %, 86.7 %, and 75 % in GTX1, GTX4, and NEO, respectively. Exposure to DCMU led to a notable decrease in A. pacificum's photosynthetic efficacy, accompanied by increased levels of reactive oxygen species (ROS) and suppressed cell growth, with a growth inhibition rate of 41.1 % at 72 h. Proteomic investigations pinpointed the diminished expression levels of specific proteins like SxtV and SxtW, linked to paralytic shellfish toxins (PSTs) synthesis, as well as key proteins associated with Photosystem II, namely PsbA, PsbD, PsbO, and PsbU. Conversely, proteins central to the cysteine biosynthesis pathways exhibited enhanced expression. In summary, our results preliminarily resolved the molecular mechanisms underlying the response of A. pacificum to DCMU and revealed that DCMU affected the synthesis of PSTs. Meanwhile, our data suggested that A. pacificum has great potential in scavenging DCMU.

Utilization of lipidic food waste as low-cost nutrients for enhancing the potentiality of biofuel production from engineered diatom under temperature variations.

The scarcity of natural fossil fuels presents a promising opportunity for the development of renewable microalgae-based biofuels. However, the current microalgae cultivation is unable to effectively address the high costs of the production of biofuels. To tackle this challenge, this study focused on recruiting engineered Phaeodactylum tricornutum (FabG-OE) to enhance biomass accumulation and lipid production by employing food waste hydrolysate under temperature variations. The biomass and lipid accumulations of FabG-OE were improved effectively in mixed culture medium and food waste hydrolysate at a volume ratio (v/v) of 80:20 at 30 °C. It was found that oxidative stress might contribute to the overexpression of lipogenic genes, thereby leading to lipogenesis at 30 °C. Upscaling cultivation of FabG-OE at 30 °C using a semi-continuous strategy and batch strategy was conducted to achieve 0.73 and 0.77 g/L/d of biomass containing 0.35 and 0.38 g/L/d of lipid, respectively. In summary, these findings provide valuable insights for advancing microalgae-based biofuel production.

Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases.

BACKGROUND: Tertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated the prognostic value and relevant mechanisms of TLSs in colorectal cancer liver metastases (CRCLM). METHODS: 603 patients with CRCLM treated by surgical resection from three cancer centers were included. The TLSs were categorized according to their anatomic subregions and quantified, and a TLS scoring system was established for intratumor region (T score) and peritumor region (P score). Differences in relapse-free survival (RFS) and overall survival (OS) between groups were determined. Multiplex immunohistochemical staining (mIHC) was used to determine the cellular composition of TLSs in 40 CRCLM patients. RESULTS: T score positively correlated with superior prognosis, while P score negatively associated with poor survival (all p<0.05). Meanwhile, T score was positively associated with specific mutation subtype of KRAS. Furthermore, TLSs enrichment gene expression was significantly associated with survival and transcriptomic subtypes of CRCLM. Subsequently, mIHC showed that the densities of Treg cells, M2 macrophages and Tfh cells were significantly higher in intratumor TLSs than in peritumor TLSs (p=0.029, p=0.047 and p=0.041, respectively), and the frequencies of Treg cells and M2 macrophages were positively correlated with P score, while the frequencies of Tfh cells were positively associated with T scores in intratumor TLSs (all p<0.05). Next, based on the distribution and abundance of TLSs, an Immune Score combining T score and P score was established which categorized CRCLM patients into four immune classes with different prognosis (all p<0.05). Among them, patients with higher immune class have more favorable prognoses. The C-index of Immune Class for RFS and OS was higher than Clinical Risk Score statistically. These results were also confirmed by the other two validation cohorts. CONCLUSIONS: The distribution and abundance of TLSs is significantly associated with RFS and OS of CRCLM patients, and a novel immune class was proposed for predicting the prognosis of CRCLM patients.

Cellular microRNA let-7c inhibits M1 protein expression of the H1N1 influenza A virus in infected human lung epithelial cells.

The influenza virus (IV) triggers a series of signalling events inside host cells and induces complex cellular responses. Studies have suggested that host factors play an essential role in IV replication. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that target mRNAs, triggering either translation repression or RNA degradation. Emerging research suggests that host-derived cellular miRNAs are involved in mediating the host-IV interaction. Using miRNA microarrays, we identified several miRNAs aberrantly expressed in IV-infected human lung epithelial cells (A549). Specifically, miR-let-7c was highly up-regulated in IV-infected A549 cells. PITA and miRanda database screening indicated that the let-7c seed sequence is a perfect complementary sequence match to the 3' untranslated region (UTR) of viral gene M1 (+) cRNA, but not to PB2 and PA. As detected by a luciferase reporter system, let-7c directly targeted the 3'-UTR of M1 (+) cRNA, but not PB2 and PA. To experimentally identify the function of cellular let-7c, precursor let-7c was transfected into A549 cells. Let-7c down-regulated IV M1 expression at both the (+) cRNA and protein levels. Furthermore, transfection with a let-7c inhibitor enhanced the expression of M1. Therefore, let-7c may reduce IV replication by degrading M1 (+) cRNA. This is the first report indicating that cellular miRNA regulates IV replication through the degradation of viral gene (+) cRNA by matching the 3'-UTR of the viral cRNA. These findings suggest that let-7c plays a role in protecting host cells from the virus in addition to its known cellular functions.

Occurrence and biodegradation of nonylphenol in the environment.

Nonylphenol (NP) is an ultimate degradation product of nonylphenol polyethoxylates (NPE) that is primarily used in cleaning and industrial processes. Its widespread use has led to the wide existence of NP in various environmental matrices, such as water, sediment, air and soil. NP can be decreased by biodegradation through the action of microorganisms under aerobic or anaerobic conditions. Half-lives of biodegradation ranged from a few days to almost one hundred days. The degradation rate for NP was influenced by temperature, pH and additions of yeast extracts, surfactants, aluminum sulfate, acetate, pyruvate, lactate, manganese dioxide, ferric chloride, sodium chloride, hydrogen peroxide, heavy metals, and phthalic acid esters. Although NP is present at low concentrations in the environment, as an endocrine disruptor the risks of long-term exposure to low concentrations remain largely unknown. This paper reviews the occurrence of NP in the environment and its aerobic and anaerobic biodegradation in natural environments and sewage treatment plants, which is essential for assessing the potential risk associated with low level exposure to NP and other endocrine disruptors.

Effect of Diabetes Mellitus on Implant Osseointegration of Titanium Screws: An Animal Experimental Study.

OBJECTIVE: To explore the effect of diabetes mellitus (DM) on implant osseointegration of titanium screws. METHODS: Sixty rats were randomly divided into a DM group and a control group (each group, n = 30). DM group rats were injected with 1% Streptozotocin solution at 65 mg/kg to establish a DM model. Titanium screws were implanted into the rats' distal femurs in both groups. The rats were sacrificed for micro-CT scanning, micro-indentation, biomechanical detection, confocal Raman microspectroscopy, and histological and histomorphometric analysis at 4, 8, and 12 weeks post-implantation, respectively. Messenger RNA (mRNA) expression and protein expression of the related growth factors around the implant were analyzed using real-time polymerase chain reaction and Western blots. RESULTS: At 4, 8 and 12 weeks, micro-CT scanning, hematoxylin-eosin (HE) staining, Gieson's acid-magenta staining, and fluorescent labeled staining showed disorder in the bone tissue arrangement, a lack of new bone tissue, poor maturity and continuity, and poor trabecular bone parameters around the implant in the DM group. At 4, 8, and 12 weeks, the interfacial bone binding rate in the DM group was significantly lower (16.2% ± 4.8%, 25.7% ± 5.7%, 42.5% ± 5.8%, respectively) than that in the control group (23.6% ± 5.2%, 40.8% ± 6.3%, 64.2% ± 7.3%, respectively; P < 0.05). At 8 and 12 weeks, the elastic modulus (17.0 ± 1.8 and 15.1 ± 1.5 GPa, respectively) and trabecular bone hardness (571 ± 39 and 401 ± 37 MPa, respectively) in the DM group were significantly lower than the elastic modulus (23.4 ± 2.3 and 23.8 ± 1.8 GPa, respectively) and trabecular bone hardness (711 ± 45 and 719 ± 46 MPa, respectively) in the control group (P < 0.05). The maximum load required for the prosthesis pull-out experiment in the DM group at 4, 8, and 12 weeks (55.14 ± 6.74 N, 73.34 ± 8.43 N, and 83.45 ± 8.32 N, respectively) was significantly lower than that in the control group (77.45 ± 7.48 N, 93.28 ± 8.29 N, and 123.62 ± 9.43 N, respectively, P < 0.05). At 8 and 12 weeks, the mineral-to-collagen ratio in the DM group (6.56 % ± 1.35% and 4.45%± 1.25%, respectively) was significantly higher than that in the control group (5.31% ± 1.42% and 3.62% ± 1.33%, respectively, P < 0.05). At 12 weeks, mRNA and protein expression levels of bone morphogenetic protein 2, transforming growth factor-ß1, vascular endothelial growth factor, osteopontin, osteocalcin, and runt-related transcription factor 2 in the DM group were significantly lower than that in the control group. CONCLUSIONS: DM can negatively affect bone osseointegration, manifesting as disorder in bone tissue arrangement around the implant, a lack of new bone tissue, poor maturity and continuity, poor trabecular bone parameters and lower expression of the related growth factors.

The efficacy of ankle arthroplasty on motor function recovery in patients with orthopedic ankle injury: a systematic review and meta-analysis.

BACKGROUND: This study analyzed the effects of ankle arthroplasty on the recovery of motor function in patients with orthopedic ankle injury. METHODS: English databases including PubMed, Web of Science, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) examining the effects of ankle arthroplasty, ankle replacement, and joint prosthesis on motor function recovery in patients with orthopedic ankle injury. The outcome indicators included the American Orthopedic Foot and Ankle Society (AOFAS) score, the 36-item short form survey (SF-36) score, the Foot and Ankle Ability Measures (FAAM) score, and the visual analog scale (VAS) score. The quality of the included literature was evaluated using the Jadad tool, and meta-analysis of the experimental data was performed using the Review Manager 5.3 software. RESULTS: A total of 7 articles, including 443 patients, were analyzed. The meta-analysis showed significant improvement in AOFAS scores among patients in the experiment group (who underwent ankle replacement) compared with those in the control group (who did not undergo ankle replacement) [mean difference (MD) =-41.89, 95% confidence interval (CI): -51.29 to 32.49, Z=8.73, P<0.00001], VAS scores (MD =5.59, 95% CI: 4.84 to 6.34, Z=14.56, P<0.00001), SF-36 scores (MD =-13.89, 95% CI: -26.74 to 1.04, Z=2.12, P=0.03), and FAAM scores (MD =-25.78, 95% CI: -31.27 to 20.29, Z=9.20, P<0.00001) compared to patients in the control group. DISCUSSION: Ankle arthroplasty had a positive effect on the quality of life, daily activities, and motor function recovery of patients with orthopedic ankle injuries. While ankle arthroplasty has potential for clinical application, future high-quality, long-term studies with larger samples and more outcome indicators are warranted to verify these results.

Long noncoding RNA H19 accelerates tenogenic differentiation by modulating miR-140-5p/VEGFA signaling.

Rotator cuff tear (RCT) is a common tendon injury, but the mechanisms of tendon healing remain incompletely understood. Elucidating the molecular mechanisms of tenogenic differentiation is essential to develop novel therapeutic strategies in clinical treatment of RCT. The long noncoding RNA H19 plays a regulatory role in tenogenic differentiation and tendon healing, but its detailed mechanism of action remains unknown. To elucidate the role of H19 in tenogenic differentiation and tendon healing, tendon-derived stem cells were harvested from the Achilles tendons of Sprague Dawley rats and a rat model of cuff tear was established for the exploration of the function of H19 in promoting tenogenic differentiation. The results showed that H19 overexpression promoted, while H19 silencing suppressed, tenogenic differentiation of tendon-derived stem cells (TDSCs). Furthermore, bioinformatic analyses and a luciferase reporter gene assay showed that H19 directly targeted and inhibited miR-140-5p to promote tenogenic differentiation. Further, inhibiting miR-140-5p directly increased VEGFA expression, revealing a novel regulatory axis between H19, miR-140-5p, and VEGFA in modulating tenogenic differentiation. In rats with RTC, implantation of H19-overexpressing TDSCs at the lesion promoted tendon healing and functional recovery. In general, the data suggest that H19 promotes tenogenic differentiation and tendon-bone healing by targeting miR-140-5p and increasing VEGFA levels. Modulation of the H19/miR-140-5p/VEGFA axis in TDSCs is a new potential strategy for clinical treatment of tendon injury.

Arthroscopic Hip Surgery versus Conservative Therapy on Femoroacetabular Impingement Syndrome: A Meta-Analysis of RCTs.

To determine the outcome and differences between arthroscopic hip surgery and conservative therapy in patients suffering from femoroacetabular impingement syndrome, we searched articles from PubMed, Embase, Cochrane, Web of Science and Clinicaltrials.gov using a Boolean search algorithm. Only randomized controlled trials comparing arthroscopic hip surgery and conservative therapy were included in this meta-analysis of femoroacetabular impingement syndrome management. Two authors determined eligibility, extracted the needed data and assessed the risk of bias of eligible studies independently. Then we meta-analyzed three articles to assess pooled estimate size (ES) and 95% confidence interval for Hip Outcome Score of activities of daily living (HOS ADL subscale), Hip Outcome Score sport (HOS sports subscale) and International Hip Outcome Tool (iHOT-33) analyses were performed by using STATA version 14.0 MP (STATA, College Station, TX, USA) with the principal summary measures are mean between group difference, sample size, and standard deviation. We collected 52 articles in total after removing duplicates and screened by titles and abstracts. A total of three RCTs were included finally. There was definite evidence of additional benefit of arthroscopic hip surgery against conservative therapy in the field of improving quality of life (three trials, 575 participants, ES = 2.109, 95% CI: 1.373 to 2.845, I2  = 42.8%, P = 0.000) and activity of daily living (two trials, 262 participants, ES = 9.220, 95% CI: 5.931 to 12.508, I2  = 16.5%, P = 0.000). However, no significant difference could be seen in sports function improvement (two trials, ES = 7.562, 95% CI: -2.957 to 18.082, I2  = 60.1%, P = 0.159). In conclusion, this meta-analysis suggests that arthroscopic hip surgery provided essential benefit compared with conservative therapy in improving activity of daily living and quality of life.

Diabetes mellitus accelerates the progression of osteoarthritis in streptozotocin-induced diabetic mice by deteriorating bone microarchitecture, bone mineral composition, and bone strength of subchondral bone.

BACKGROUND: The purpose of this study was to develop an optimal diabetes-osteoarthritis (DM-OA) mouse model to validate that diabetes aggravates osteoarthritis (OA) and to evaluate the microarchitecture, chemical composition, and biomechanical properties of subchondral bone (SB) as a consequence of the DM-OA-induced damage induced. METHODS: Mice were randomly divided into three groups: DM-OA group, OA group, and sham group. Blood glucose levels, body weight, and food intake of all animals were recorded. Serum calcium (Ca) and osteocalcin (OCN) levels were compared in the three groups. The messenger ribonucleic acid (mRNA) and protein expression of key regulators for bone metabolism were detected. A semi-quantitative grading system [Osteoarthritis Research Society International (OARSI)] was used to evaluate cartilage and SB degeneration. Microspectroscopy, microindentations, micro-computed tomography (CT) imaging, and fracture load of compression testing were also used to evaluate trabecular SB properties. RESULTS: Glycemic monitoring and pancreas pathological results indicated stable high blood glucose and massive destruction of pancreas and islet cells in the DM-OA group. Serum levels of bone specific alkaline phosphatase (ALP-B) and tartrate-resistant acid phosphatase 5b (TRACP-5b) in the DM-group were higher than those of the other two groups while levels of serum Ca and OCN were lower. Meanwhile, the protein and mRNA expression of osteoblast-specific biomarkers [osteoprotegerin/receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) ratio, collagen type I (COL-I), Runt-related transcription factor 2 (RUNX-2), OCN] were suppressed, and osteoclast-specific biomarkers [sclerostin (SOST)] was elevated in the DM-OA group. The mineral-to-collagen ratio, microindentation elastic modulus, hardness, micro-architectural parameters, bone mineral density, and fracture load of SB trabecular bone of the DM-OA group joint were lower than those of the other two groups. On the other hand, The OARSI score, trabecular spacing, and structural model index of the DM-OA group joint were higher than those of the other two groups. CONCLUSIONS: The glycemic and pancreatic pathological results indicated that the DM-OA model was a simple and reliable model induced by streptozotocin (STZ) and surgery. The results revealed the mechanisms through which diabetes accelerates OA; that is, by damaging and deteriorating the functions of SB, including its microarchitecture, chemical composition, and biomechanical properties.

[Research progress on mechanism of acupuncture and moxibustion promoting fracture healing].

Acupuncture has a significant effect on promoting fracture healing. It can dredge meridians and collaterals, regulate qi and blood, eliminate swelling and remove stasis. However, its mechanism is still not fully elucidated. With the development of research, it has been found in recent years that the mechanism of acupuncture and moxibustion promoting fracture healing involves regulating the expression level of cell growth factor, activating Wnt/ß-Catenin and other signal pathways, improving local blood circulation, affecting the content of mineral elements in bone, regulating the endocrine system, promoting the differentiation and proliferation of bone cells, promoting the proliferation and activation of osteoblasts and influencing the apoptosis of bone cells And so on. The mechanism of acupuncture and moxibustion promoting fracture healing is very complex, which is still at the level of animal experiments and cells.

LncRNA TUG1 positively regulates osteoclast differentiation by targeting v-maf musculoaponeurotic fibrosarcoma oncogene homolog B.

Osteoclast differentiation-mediates bone resorption is the key biological basis of orthodontic treatment while the specific mechanism of osteoclastogenesis remains unclear. This study aims to explore the underlying mechanism of the osteoclast differentiation from the perspective of long non-coding RNA (LncRNA). In the present study, the osteoclast differentiation of CD14+ peripheral blood mononuclear cells (PBMCs) was induced by recombinant human macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL), and LncRNA TUG1 expression was dramatically elevated during this process. Functionally, the silence of TUG1 in CD14+ PBMCs decreased tartrate-resistant acid phosphatase (TRAP)-positive cell numbers and the protein levels of TRAP, nuclear factor of activated T cell c1 (NFATc1), and osteoclast-associated receptor (OSCAR), whereas increased V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MafB) protein level. The subsequent experiments confirmed that TUG1 lessened the MafB protein level via accelerating its degradation. Then, the interference of MafB reversed the inhibitory effect of si-TUG1 on osteoclastogenesis, including increased the TRAP-positive cell numbers and up-regulated the protein levels of osteoclast markers. Finally, the in vivo experiments displayed that the increased TUG1 levels could promote tooth movement and bone resorption via facilitating osteoclast differentiation in the rat model of orthodontic tooth movement. In summary, TUG1 overexpressed during the process of osteoclast differentiation and positively regulated osteoclast differentiation by targeting MafB.