Icariin-Curcumol promotes docetaxel sensitivity in prostate cancer through modulation of the PI3K-Akt signaling pathway and the Warburg effect.

BACKGROUND: Docetaxel (DTX) resistance reduces therapeutic efficacy in prostate cancer (PCa). Accumulating reports support the role of phytochemicals in the reversal of DTX resistance. This study aimed to determine whether Epimedium brevicornu and Curcuma zedoaria extracts (ECe), specially icariin-curcumol, attenuates DTX resistance and explore their potential mechanisms. METHODS: Regulatory pathways were predicted between ECe active ingredients and PCa using network pharmacology. DTX-resistant cell LNCaP/R were established based on DTX-sensitive LNCaP, and xenograft models were further established. Active ingredients in ECe by HLPC-MS were identified. The binding of icariin and curcumol to the target was analyzed by molecular docking. Biochemical experiments were applied to determine the possible mechanisms by which Icariin-Curcumol regulates DTX sensitivity. RESULTS: Akt1 and the PI3K-Akt signaling pathway were predicted as the primary functional target between drug and PCa. ECe and DTX inhibited xenograft tumor growth, inflammation, cell viability and promoted apoptosis. Icariin and curcumol were detected in ECe, and icariin and curcumol docked with Akt1. ECe, Icariin-Curcumol and DTX downregulated AR, PSA, PI3K, Akt1, mTOR, and HIF-1ɑ. Moreover, ECe, Icariin-Curcumol and DTX increased glucose and PDH, decreased lactic acid, ATP and LDH, and downregulated c-Myc, hnRNPs, VEGF, PFK1, and PKM2. Notably, the anti-PCa effect of DTX was attenuated compared to ECe or Icariin-Curcumol in the LNCaP/R model. The combined effect of Icariin-Curcumol and DTX was superior to that of DTX. CONCLUSION: Our data support that Icariin-Curcumol reverses DTX resistance by inhibiting the PI3K-Akt signaling and the Warburg effect, providing new ideas for improving therapeutic measures for PCa.

ACL stump and ACL femoral landmarks are equally reliable in ACL reconstruction for assisting ACL femoral tunnel positioning.

PURPOSE: This study aimed to comparatively evaluate the accuracy of femoral tunnel positioning after anatomic single-bundle anterior cruciate ligament (ACL) reconstruction performed with the remnant preservation (RP) technique versus the non-remnant preservation (NRP) technique. METHODS: A retrospective review of 145 patients who underwent ACL reconstruction from May 2020 to May 2022 were performed in this single-surgeon study. A total of 120 patients met the inclusion criteria and were allocated into two groups according to the surgical technique (i.e. RP group and NRP group). The relative location of the femoral tunnel in the lateral condyle was evaluated as a percentage using a standardized grid system on the three-dimensional computed tomography (3D-CT) image. The accuracy and precision of the RP group were assessed based on published anatomical data in direct comparison with the NRP group. RESULTS: According to the surgical procedure, 57 of the 120 patients included were allocated into the RP group, and 63 into the NRP group. Significant differences were observed between the two groups in terms of tunnel position (posterior-to-distal (PD): 28.4 ± 5.4% (RP) vs. 31.8 ± 5.3% (NRP); P = 0.01), (anterior-to-posterior (AP): 32.6 ± 7.7% (RP) vs. 38.8 ± 7.7% (NRP); P = 0.00), while no significant differences were found in terms of the accuracy (8.6% (RP) vs. 8.9% (NRP); n.s) and precision (4.4% (RP) vs. 5.6% (NRP); n.s) of femoral tunnel positioning between the two groups. CONCLUSIONS: From this single-surgeon study, it was concluded that there were no differences in the creation of ACL femoral tunnel between the RP technique and the non-remnant preserving technique. Meanwhile, the RP technique would not sacrifice the ideal position of the femoral tunnel and is able to retain the possible benefits of the ACL stump. LEVEL OF EVIDENCE: Level III.

[Effect of Polygonati Rhizoma in improving pyroptosis injury of diabetic macroangiopathy via NLRP3/caspase-1/GSDMD pathway].

This study aims to explore the influence of Polygonati Rhizoma on the pyroptosis in the rat model of diabetic macroangiopathy via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/gasdermin D(GSDMD) pathway. The rat model of diabetes was established by intraperitoneal injection of streptozotocin(STZ) combined with a high-fat, high-sugar diet. The blood glucose meter, fully automated biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, and Western blot were employed to measure blood glucose levels, lipid levels, vascular thickness, inflammatory cytokine levels, and expression levels of pyroptosis-related proteins. The mechanism of pharmacological interventions against the injury in the context of diabetes was thus explored. The results demonstrated the successful establishment of the model of diabetes. Compared with the control group, the model group showed elevated levels of fasting blood glucose, total cholesterol(TC), triglycerides(TG) and low-density lipoprotein cholesterol(LDL-c), lowered level of high-density lipoprotein cholesterol(HDL-c), thickened vascular intima, and elevated serum and aorta levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß) and interleukin-18(IL-18). Moreover, the model group showed increased NLRP3 inflammasomes and up-regulated levels of caspase-1 and GSDMD in aortic vascular cells. Polygonati Rhizoma intervention reduced blood glucose and lipid levels, inhibited vascular thickening, lowered the levels of TNF-α, IL-1ß, IL-18 in the serum and aorta, attenuated NLRP3 inflammasome expression, and down-regulated the expression levels of caspase-1 and GSDMD, compared with the model group. In summary, Polygonati Rhizoma can slow down the progression of diabetic macroangiopathy by inhibiting pyroptosis and alleviating local vascular inflammation.

Clinical results of arthroscopic tight fibrous band release for adult moderate-to-severe gluteal fibrosis using anterior and posterior portals: a retrospective analysis of 118 consecutive cases.

BACKGROUND: To evaluate the clinical outcomes of arthroscopic tight fibrous band release in the treatment of adult moderate-to-severe gluteal fibrosis using anterior and posterior portals during mid-term follow-up. METHODS: The data of 138 patients (58 males, 80 females) aged between 18 and 42 years (mean, 28.6 years), presenting with bilateral moderate-to-severe gluteal fibrosis (GF) from October 2013 to August 2019, was retrospectively analyzed. All patients underwent arthroscopic tight fibrous band release using anterior and posterior portals with radiofrequency energy. Under arthroscopic guidance through the posterior portal, we debrided the fatty tissue overlying the contracted band of the gluteal muscle and excised the contracted bands using a radiofrequency device introduced through the anterior portal. The pre- and post-operative gluteal muscle contracture disability (GD) scale and the patient satisfaction rate were compared to evaluate the curative effect of the operation. RESULTS: The average operation time was 18 min (range, 10-30 min) and the average blood loss was 4 ml (range, 2-10 ml) for unilateral arthroscopic release. Two cases of post-operative minimal hematomas, 2 cases of bruising and 2 cases of local subcutaneous edema were observed as early complications and were cured by conservative treatment. After surgery, all incisions healed in stage I, and no other complications such as wound infection, nerve and blood vessel injury were detected. One hundred eighteen patients were followed up for 6 to 72 months (mean, 36 months). No lateral instability of the hip was observed and all patients returned to normal gait. The degree of adduction of the hip joint in all these 118 patients was significantly improved relative to their pre-operative conditions. One hundred fifteen patients (97.5%) were able to crouch with knees close to each other after surgery. One hundred fourteen patients (96.6%) were able to cross the affected leg completely without any support. The GD scale was improved from 55.5 ± 10.6 before operation to 90.1 ± 5.2 at the last follow-up (p < 0.05). The patient satisfaction rate was 95.8%. CONCLUSION: Arthroscopic tight fibrous band release using anterior and posterior portals is minimally invasive for adult moderate-to-severe gluteal fibrosis, with a high success rate, quick recovery after surgery and reliable medium-term effect.

Clinical outcome of arthroscopic internal drainage of popliteal cysts with or without cyst wall resection.

BACKGROUND: This study aimed to compare the arthroscopic internal drainage of popliteal cysts alone or in combination with cyst wall resection in terms of clinical outcomes. METHODS: Forty-two consecutive patients with symptomatic popliteal cysts received arthroscopic treatment. Specifically, 20 of them received arthroscopic internal drainage (AI group) alone and 22 received arthroscopic internal drainage combined with cyst wall resection (AICR group) through double posteromedial portals. Magnetic resonance imaging (MRI) was performed to identify recurrence of popliteal cysts. The Lysholm score and Rauschning-Lindgren grade were used to assess the clinical outcomes. The median of the follow-up period was 24 months (12-48 months). RESULTS: The two groups (AI group and AICR group) were similar in age, gender, cyst diameter, associated joint disorder, preoperative Lysholm score, preoperative Rauschning-Lindgren grade and follow-up period (P > 0.05). Relative to the AI group, the AICR group had a significantly prolonged operation time (P < 0.05) and a higher incidence of complications (P < 0.05). In both groups, the Rauschning-Lindgren grade at the last follow-up significantly differed from the preoperative grade (P < 0.05) and the Lysholm knee score remarkably increased compared to the preoperative score (P < 0.05); however, there were no differences between the two groups at the last follow-up (P > 0.05). According to the MRI results, the cyst disappeared in 11 (55%), shrank in size in 6 (30%) and existed in 3 (15%) patients in the AI group, and was absent in 18 (81.8%) and shrank in size in 4 (18.2%) patients in the AICR group, suggesting a significant difference between the two (P < 0.05). CONCLUSION: Additional resection of cyst wall can result in a lower recurrence rate of cysts but extend the operation time and increase the incidence of perioperative complications compared with arthroscopic internal drainage of popliteal cysts alone.

Polygonatum sibiricum polysaccharides protect against knee osteoarthritis by inhibiting the TLR2/NF-κB signaling pathway in vivo and in vitro.

Polygonatum sibiricum polysaccharides (PSP), the primary constituent of Polygonatum sibiricum, have been shown to exhibit a wide range of pharmacological effects, but their impact on osteoarthritis (OA) remains unclear. The objective of this study was to investigate the protective effects of PSP against OA and to elucidate its underlying molecular mechanism. In our in vitro experiments, PSP not only inhibited the IL-1ß-induced inflammatory responses and the nuclear factor kappa-B (NF-κB) signaling pathway in chondrocytes but also regulated the cartilage matrix metabolism. In addition, we detected 394 significantly differentially expressed genes through RNA-seq analysis on PSP-intervened chondrocytes, and the toll-like receptor 2 (TLR2) was identified as the most important feature by functional network analysis and qRT-PCR. It was also revealed that PSP treatment significantly reversed the IL-1-induced up-regulation of TLR2 expression in chondrocytes, while TLR2 overexpression partially inhibited the regulatory effects of PSP on inflammation, NF-κB signaling pathway and matrix metabolism. In our in vivo experiments, PSP treatment alleviated the development of destabilization of medial meniscus (DMM)-induced OA in mouse knee joints, inhibited the DMM-induced activation of the TLR2/NF-κB signaling pathway in mouse knee joint cartilage, and reduced the serum levels of inflammatory cytokines. In conclusion, PSP exerts its anti-inflammatory, matrix synthesis-promoting and matrix catabolism-suppressing effects in knee OA by inhibiting the TLR2/NF-κB signaling pathway, suggesting that PSP may be potentially targeted as a novel all-natural, low-toxicity drug for OA prevention and treatment.

Pyroptosis-related crosstalk in osteoarthritis: Macrophages, fibroblast-like synoviocytes and chondrocytes.

The pathogenesis of osteoarthritis (OA) involves a multifaceted interplay of inflammatory processes. The initiation of pyroptosis involves the secretion of pro-inflammatory cytokines and has been identified as a critical factor in regulating the development of OA. Upon initiation of pyroptosis, a multitude of inflammatory mediators are released and can be disseminated throughout the synovial fluid within the joint cavity, thereby facilitating intercellular communication across the entire joint. The main cellular components of joints include chondrocytes (CC), fibroblast-like synoviocytes (FLS) and macrophages (MC). Investigating their interplay can enhance our understanding of OA pathogenesis. Therefore, we comprehensively examine the mechanisms underlying pyroptosis and specifically investigate the intercellular interactions associated with pyroptosis among these three cell types, thereby elucidating their collective contribution to the progression of OA. We propose the concept of ' CC-FLS-MC pyroptosis-related crosstalk', describe the various pathways of pyroptotic interactions among these three cell types, and focus on recent advances in intervening pyroptosis in these three cell types for treating OA. We hope this will provide a possible direction for diversification of treatment for OA. The Translational potential of this article. The present study introduces the concept of 'MC-FLS-CC pyroptosis-related crosstalk' and provides an overview of the mechanisms underlying pyroptosis, as well as the pathways through which it affects MC, FLS, and CC. In addition, the role of regulation of these three types of cellular pyroptosis in OA has also been concerned. This review offers novel insights into the interplay between these cell types, with the aim of providing a promising avenue for diversified management of OA.

Guhan Yangsheng Jing mitigates hippocampal neuronal pyroptotic injury and manifies learning and memory capabilities in sleep deprived mice via the NLRP3/Caspase1/GSDMD signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Guhan Yangsheng Jing (GHYSJ) is a traditional Chinese patent medicine, that has the function of nourishing the kidney and replenishing the essence, invigorating the brain and calming the mind. It is often used to treat dizziness, memory loss, sleep disorders, fatigue, and weakness, etc. However, its mechanism for improving sleep has not yet been determined. AIM OF THE STUDY: This study aims to explore the effects of GHYSJ on Sleep Deprivation (SD)-induced hippocampal neuronal pyroptotic injury, learning and cognitive abilities, and sleep quality in mice. METHODS: In this study, a PCPA-induced SD mouse model was established. We assessed the influence of GHYSJ on sleep quality and mood by using the pentobarbital-induced sleep test (PIST) and sucrose preference test (SPT). The pharmacological effects of GHYSJ on learning and memory impairment were evaluated by the Morris Water Maze (MWM) and Open Field Test (OFT). Pathological changes in the hippocampal tissue of the SD rats were observed via HE staining and Nissl staining. The severity of neuronal damage was evaluated by detecting the expression of the neuronal marker Microtubule-associated protein 2 (MAP2), via immunohistochemistry and immunofluorescence. Furthermore, the levels of neurotransmitter 5-hydroxytryptophan (5-HTP), 5-hydroxy tryptamine (5-HT), γ-aminobutyric acid (GABA), and Glutamic acid (Glu) in hippocampal tissues, as well as the expression of inflammatory factors Interleukin-1ß (IL-1ß) and Interleukin-18 (IL-18) in serum, were determined by ELISA. The expressions of mRNA and protein NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Cysteinyl aspartate specific proteinase1 (Caspase1), High mobility group box-1 protein (HMGB1) and Apoptosis-associated speck-like protein containing CARD (ASC) related to the cellular ferroptosis pathway were tested and analyzed by RT-PCR and WB respectively. RESULTS: PCPA significantly diminishes the sleep span of experimental animals by expediting the expenditure of 5-HT, consequently establishing an essentially direct SD model. The intervention of GHYSJ displays remarkable efficacy in mitigating insomnia symptoms, encompassing difficulties in initiating sleep and insufficient sleep duration. Likewise, it ameliorates memory function impairments induced by sleep deprivation, along with symptoms such as fatigue and depletion of vitality. GHYSJ exerts a protective influence on hippocampal neurons facilitated by inhibiting the down regulation of MAP2 and maintaining the equilibrium of neurotransmitters (5-HTP, 5-HT, GABA, and Glu). It diminishes the expression of intracellular pyroptosis-associated inflammatory factors (IL-1ß and IL-18) and curbs the activation of the NLRP3/Caspase1/GSDMD pyroptosis-related signaling pathways, thereby alleviating the damage caused by hippocampal neuronal pyroptosis.

Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer.

BACKGROUND: Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa. METHODS: A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development. RESULTS: After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3+CD8+IFN-γ, CD3+CD8+Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2. CONCLUSIONS: ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.

A review focusing on the role of pyroptosis in prostate cancer.

As one of the types of programmed cell death, pyroptosis has become a focus of research in recent years. Numerous studies have shown that pyroptosis plays a regulatory role in tumor cell invasiveness, differentiation, proliferation, and metastasis. It has been demonstrated that pyroptosis is involved in the regulation of signaling pathways implicated in the pathogenesis of prostate cancer (PCa). Furthermore, the loss of expression of pyroptosis-related genes in PCa has been reported, and pyroptosis-related genes have demonstrated a considerable ability in predicting the prognosis of PCa. Therefore, the potential role of pyroptosis in regulating the development of PCa warrants further investigation and attention. In this review, we summarize the basics of the role of pyroptosis and also discuss research into the mechanisms of action associated with pyroptosis in PCa. It is hoped that by exploring the potential of the pyroptosis pathway in intervening in PCa, it will provide a viable direction for the diversification of PCa treatment.

A review focusing on the benefits of plant-derived polysaccharides for osteoarthritis.

Osteoarthritis (OA) is a chronic joint disease characterized by progressive cartilage degeneration, which imposes a heavy physical and financial burden on the middle-aged and elderly population. As the pathogenesis of OA has not been fully elucidated, it is of great importance to develop targeted therapeutic or preventive medications. Traditional therapeutic drugs, such as non-steroidal anti-inflammatory drugs, steroids and opioids, have significant side effects, making the exploration for safe and effective alternative therapeutic drugs urgent. In recent years, many studies have reported the role of plant-derived polysaccharides in anti-inflammation, anti-oxidation, regulation of chondrocyte metabolism and proliferation, and cartilage protection, and have demonstrated their great potential in the treatment of OA. Therefore, by focusing on studies related to the intervention of plant-derived polysaccharides in OA, including in vivo and in vitro experiments, this review aimed to classify and summarize the existing research findings according to different mechanisms of action. In addition, reports on plant-derived polysaccharides as nanoparticles were also explored. Then, candidate monomers and theoretical bases were provided for the further development and application of novel drugs in the treatment of OA.

Reliability of the Tibial Spine Versus ACL Stump in Assisting Tibial Tunnel Positioning During ACL Reconstruction: Analysis Based on 3-Dimensional Computed Tomography Modeling.

Background: Several techniques have been used by surgeons for anatomic tibial tunnel placement in anterior cruciate ligament (ACL) reconstruction, including the ACL stump positioning (ASP) technique and the tibial spine positioning (TSP) technique. Purpose/Hypothesis: The purpose of this study was to evaluate whether bony landmarks (medial and lateral tibial spine [MLTS]) can be a reliable reference for improving the accuracy of tibial tunnel placement in anatomic single-bundle ACL reconstruction compared with the ACL stump. It was hypothesized that the MLTS would not be a reliable bony landmark for tibial tunnel placement. Study Design: Cohort study; Level of evidence, 3. Methods: The 3-dimensional computed tomography images of 111 patients who underwent ACL reconstruction between 2020 and 2021 were included in this study. For tibial tunnel placement, the ASP technique was used in 49 patients, and the TSP technique was used in 62 patients. The 3-dimensional computed tomography images were reconstructed to enable measurements of the locations of the MLTS and tunnel center based on a grid method. Statistical analysis was conducted to compare the MLTS location and tibial tunnel position as well as the accuracy (mean distance of each actual location from the anatomic center) and precision (standard deviation of the accuracy, indicating the reproducibility of the tunnel position) of the tunnel position between the ASP and TSP groups. Results: Significant differences were observed between the ASP and TSP groups in terms of the tibial tunnel position on the mediolateral axis (46.7% ± 2.0% vs 45.9% ± 2.2%, respectively; P = .034), while no significant differences were found in terms of the accuracy (4.1% vs 4.6%, respectively; P = .259) or precision (2.1% vs 2.1%, respectively; P = .259) of tibial tunnel positioning between the 2 groups. Conclusion: In anatomic single-bundle ACL reconstruction, the use of the MLTS for tibial tunnel placement achieved comparable accuracy and precision compared with the use of ACL remnants, supporting its role as a reliable bony landmark in tibial tunnel positioning.

The Evaluation of the Efficacy and Safety of Oral Colchicine in the Treatment of Knee Osteoarthritis: A Meta-Analysis of Randomized Controlled Trails.

OBJECTIVE: To evaluate the efficacy and safety of oral colchicine in the treatment for knee OA. DESIGN: Meta-analysis. Data Sources. Embase, PubMed (MEDLINE), the Cochrane Library, and Web of Science from inception to December 12, 2021. Study Selection. RCTs comparing colchicine with placebo for knee OA were included. No language or date restrictions were applied. Two authors abstracted data and determined quality. Outcomes of interest included VAS-pain, WOMAC total index, and patient-reported adverse events. RESULTS: A total of five RCTs including 400 adult patients with OA met the inclusion criteria. The mean age of patients included was 56.05 years (range 21 to 79), and 80.87% were female. There was no difference in VAS-pain (MD -1.49; 95% CI -3.15, 0.17; p = 0.08) when compared colchicine group with placebo group. And there was no statistically difference in WOMAC total index (std. MD -0.13; 95% CI -0.64, 0.38; p = 0.61) and patient report adverse events (RR 1.23; 95% CI 0.72, 2.11; p = 0.46). CONCLUSION: Colchicine is not currently recommended as a treatment for knee OA but might have insignificant effect. The conclusion is limited due to the variation in assessment indicator among available data. Further RCTs with larger sample size and longer follow-up are needed to confirm the findings.

Arthroscopic Intra-Articular Repair of the Torn Subscapularis Tendon with Single Anterior Portal, Single Suture Anchor, and X-Shaped Fixation Technique.

Subscapular tendon plays an important role in shoulder joint function. With the advance of magnetic resonance imaging technology and the popularization of arthroscopic shoulder surgery, subscapularis tears have been increasingly detected. However, reduction and fixation of subscapular tendon tears appears to be technically challenging. This study aims to describe an arthroscopic intra-articular X-shaped fixation technique: a procedure of subscapularis tendon repair performed with the aid of a suture passer using only a single anterior portal and a single suture anchor. By incorporating the advantages of a single anterior working portal for anchor placement and tear repair, this technique provides an easier way to use suture lasso and make knots in a limited working space, and the whole procedure is minimally invasive with a short learning curve. This technique has been applied in patients with subscapularis tears involving no intraoperative or postoperative complications. Our technology offers a valuable new treatment option for subscapularis tears.

OPN Deficiency Increases the Severity of Osteoarthritis Associated with Aberrant Chondrocyte Senescence and Apoptosis and Upregulates the Expression of Osteoarthritis-Associated Genes.

Objectives: A recent work has reported that the elevated osteopontin (OPN) levels in the articular cartilage and synovial fluid are correlated with the progressive osteoarthritis (OA) joint damage, and OPN has a protective effect against OA by suppressing the expressions of OA-associated genes. The present study examined whether the OPN deficiency was susceptible to OA through the regulation of chondrocyte senescence and apoptosis and the expressions of OA-associated genes. Methods: The mRNA levels of COL2A1 and OPN were compared between human OA chondrocytes and normal chondrocytes. The effects of OPN siRNA on the SA-ß-Gal expressions and the percentage of apoptotic chondrocytes were examined by using SA-ß-Gal staining and apoptosis assay, and the effects on the expressions of COL2A1 and OA-associated genes (COL10A1, IL-1ß, TNF-ɑ, MMP-13, and ADAMTS5) were examined by western blot analysis and quantitative real-time RT-PCR. Furthermore, an in vivo OA model was established to examine the effects of OPN siRNA on the senescence and apoptosis of OA chondrocytes and the expressions of OA-associated genes. Results: The mRNA levels of COL2A1 and OPN were decreased in knee OA chondrocytes in comparison with those in normal chondrocytes. The OPN deficiency enhanced the senescence and apoptosis of OA chondrocytes and increased the expressions of COL10A1, IL-1ß, TNF-ɑ, MMP-13, and ADAMTS5 but decreased the expression of COL2A1. Meanwhile, OPN deficiency could result in severe, accelerated OA in vivo, which was also associated with enhanced senescence and apoptosis of chondrocytes and elevated expressions of OA-associated genes. Conclusions: The findings of this study suggest that the OPN deficiency can result in accelerated OA, which is associated with enhanced senescence and apoptosis of OA chondrocytes and the upregulated expressions of OA-associated genes.

Clinical Outcome of Remnant-Preserving and I.D.E.A.L. Femoral Tunnel Technique for Anterior Cruciate Ligament Reconstruction.

OBJECTIVE: To assess the clinical results of the remnant-preserving and I.D.E.A.L. femoral tunnel technique in the arthroscopic treatment of anterior cruciate ligament (ACL) injuries. METHODS: This was a retrospective single-center, single-surgeon study reviewing data from November 2016 to March 2019. Based on our inclusion/exclusion criteria, a total of 31 patients (18 males, 13 females; mean age, 23.6 years) who underwent arthroscopic ACL reconstruction with the remnant preservation and I.D.E.A.L. femoral tunnel technique were recruited and had a minimum follow-up of 12 months. Clinical data and status of knee stability were recorded. The International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity scale were collected both preoperatively and at a minimum of 1-year follow-up. RESULTS: Statistically significant differences were detected between the preoperative and postoperative values for Lachman test and pivot-shift test (P < 0.01). The mean postoperative Lysholm score was 89.6 ± 9.4, whereas the mean preoperative Lysholm score was 47.3 ± 12.8 (P < 0.01). The mean Tegner activity score was significantly higher at postoperative evaluation than at preoperative evaluation (6.5 ± 2.1 vs 2.6 ± 1.8; P < 0.01). The mean IKDC score was significantly improved from 49.5 ± 10.6 preoperatively to 88.2 ± 10.7 postoperatively (P < 0.01). No case of infection was reported. No radiograph showed any joint space narrowing or degenerative change at the last postsurgical follow-up. CONCLUSION: The anatomical remnant-preserving and I.D.E.A.L. femoral tunnel technique achieves a satisfactory clinical outcome and provides an effective option for the treatment of ACL injuries.

"Figure-of-Eight" Suture-Button Technique for Fixation of Displaced Anterior Cruciate Ligament Avulsion Fracture.

OBJECTIVE: To assess the clinical results of the "figure-of-eight" suture-button technique in the arthroscopic treatment of anterior cruciate ligament (ACL) tibial avulsion fractures. METHODS: This was a retrospective study reviewing data from September 2013 to June 2019. A total of 27 patients (13 males and 14 females) who underwent arthroscopic "figure-of-eight" suture-button fixation for displaced ACL avulsion fractures were analyzed. The mean age of the patients in the sample was 15.8 years (10-29 years), with a mean follow-up of 24 months (6-48 months). According to Meyers-McKeever classification, 11 patients were classified as type III and 16 as type IV. All patients were evaluated following the guidelines of the radiological union, the Lysholm knee scoring scale, and the International Knee Documentation Committee (IKDC). RESULTS: Fractures were united within 3 months after surgery in all 27 cases. During the last follow-up, all the anterior drawer and Lachman tests were negative, except in 1 patient whose anterior drawer test was 1° positive. The range of motion was improved from 72.22° ± 27.92° before surgery to 137.78° ± 7.38° at the last follow-up (P < 0.05); the Lysholm score was improved from 45.81 ± 10.94 before surgery to 93.04 ± 5.66 at the last follow-up (P < 0.05); and the IKDC score was increased from 43.89 ± 11.16 before surgery to 90.26 ± 5.86 at the last follow-up (P < 0.05). In 1 patient, an inflammatory reaction was observed at the medial incision of the tibial tubercle; the symptoms disappeared with administration of antibiotics for 1 week. All patients returned to their preinjury physical activities at the last follow-up. CONCLUSION: The "figure-of-eight" suture-button technique achieves a satisfactory clinical outcome and provides an effective method for the treatment of displaced ACL avulsion fractures.

Arthroscopic Treatment of Femoral Avulsion Fracture of the Posterior Cruciate Ligament in Association with Meniscus Tear.

BACKGROUND: Femoral avulsion fracture of the posterior cruciate ligament (PCL) in association with meniscus tear is extremely rare in children, and similar cases are not available in the existing literature. CASE PRESENTATION: In this paper, we present a case of a 9-year-old boy treated by an arthroscopic repair technique using two transfemoral tunnels sparing the epiphyseal plate for 8-shaped suture fixation of femoral avulsion fracture of the PCL and using the Fastfix repair system for a meniscus tear. At 3-month postoperative, the boy showed satisfactory recovery with a full range of motion of the right knee and normal muscular strength, and no complications were observed after operation. The patient had been followed up for 24 months and his final assessment demonstrated stable painless knee with excellent functional outcome. In view of this, we suggest that the "figure-of-eight" suture technique using two transfemoral tunnels sparing the epiphyseal plate can be considered a new choice for the treatment of the PCL femoral attachment avulsion, especially in skeletally immature patients. In addition, six similar cases were found in a comprehensive literature review targeting femoral avulsion fracture of the PCL. According to the relevant findings and cases studies, we proposed a new classification named "Xiangya" which might facilitate future clinical decision making.

Remnant-Preserving Posterior Cruciate Ligament Reconstruction Over Remnant Fibers Using a Figure-of-Four Position and a Posterior Trans-Septal Portal.

Anatomic tunnel formation and remnant preservation are the recent trends in posterior cruciate ligament (PCL) reconstruction. However, it is difficult to observe the anatomical PCL footprint and perform the operation in the process of remnant-preserving PCL reconstruction. This study describes a single-bundle, transtibial PCL reconstruction technique with anatomic graft passage over the remnant PCL fibers. A femoral tunnel of PCL is created at 2 mm medial to the roof of the intercondylar notch and 3 mm proximal to the margin of the articular cartilage. The tibial insertion of PCL is observed using a figure-of-four position through a posterior trans-septal portal. A tibial bone tunnel is made below the distal center portion of the tibial insertion of residual PCL fibers. The graft is passed over the PCL through the tibial bone tunnel, the space between the anterior cruciate ligament (ACL) and the residual PCL fibers, to the femoral socket and is fixed by the EndoButton and screw. This technique is able to ensure a reasonable intra-articular length and optimal isometry. It has been applied in patients with PCL rupture and posterior instability of the knee joint, and no intraoperative or postoperative complications occurred. Our technology provides a valuable new treatment option for PCL rupture. Future comparative studies are needed to further clarify its beneficial effect.