Identification and Verification of Novel Biomarkers Involving Rheumatoid Arthritis with Multimachine Learning Algorithms: An In Silicon and In Vivo Study.

Background: Rheumatoid arthritis (RA) remains one of the most prevalent chronic joint diseases. However, due to the heterogeneity among RA patients, there are still no robust diagnostic and therapeutic biomarkers for the diagnosis and treatment of RA. Methods: We retrieved RA-related and pan-cancer information datasets from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. Six gene expression profiles and corresponding clinical information of GSE12021, GSE29746, GSE55235, GSE55457, GSE77298, and GSE89408 were adopted to perform differential expression gene analysis, enrichment, and immune component difference analyses of RA. Four machine learning algorithms, including LASSO, RF, XGBoost, and SVM, were used to identify RA-related biomarkers. Unsupervised cluster analysis was also used to decipher the heterogeneity of RA. A four-signature-based nomogram was constructed and verified to specifically diagnose RA and osteoarthritis (OA) from normal tissues. Consequently, RA-HFLS cell was utilized to investigate the biological role of CRTAM in RA. In addition, comparisons of diagnostic efficacy and biological roles among CRTAM and other classic biomarkers of RA were also performed. Results: Immune and stromal components were highly enriched in RA. Chemokine- and Th cell-related signatures were significantly activated in RA tissues. Four promising and novel biomarkers, including CRTAM, PTTG1IP, ITGB2, and MMP13, were identified and verified, which could be treated as novel treatment and diagnostic targets for RA. Nomograms based on the four signatures might aid in distinguishing and diagnosing RA, which reached a satisfactory performance in both training (AUC = 0.894) and testing (AUC = 0.843) cohorts. Two distinct subtypes of RA patients were identified, which further verified that these four signatures might be involved in the immune infiltration process. Furthermore, knockdown of CRTAM could significantly suppress the proliferation and invasion ability of RA cell line and thus could be treated as a novel therapeutic target. CRTAM owned a great diagnostic performance for RA than previous biomarkers including MMP3, S100A8, S100A9, IL6, COMP, LAG3, and ENTPD1. Mechanically, CRTAM could also be involved in the progression through immune dysfunction, fatty acid metabolism, and genomic instability across several cancer subtypes. Conclusion: CRTAM, PTTG1IP, ITGB2, and MMP13 were highly expressed in RA tissues and might function as pivotal diagnostic and treatment targets by deteriorating the immune dysfunction state. In addition, CRTAM might fuel cancer progression through immune signals, especially among RA patients.

The Association between Dietary Habits and Rapid Postoperative Recovery of Rotator Cuff Repair.

Some nutritional factors have been suggested to improve postoperative outcomes in rotator cuff (RC) repair, but dietary effects on the recovery speed after the surgery remain undefined. To investigate the potential roles of dietary habits in this context, we analyzed the 12-month follow-up data of 55 patients with RC repair and found that these patients could be categorized into a rapid recovery group (n = 35) and slow recovery group (n = 20) according to their postoperative recovery patterns. Group-based logistic analysis revealed that habitual intakes of meat (OR = 1.84, 95%CI, 1.22-2.76, p = 0.003), fruits (OR = 2.33, 95%CI, 1.26-5.67, p = 0.01), and wheat-flour foods (OR = 1.62, 95%CI, 1.2-2.25, p = 0.002) were significantly associated with rapid recovery. Moreover, among all intakes of wheat-flour foods, intakes of steamed and boiled flour products were also associated with rapid recovery. Further mediation analysis showed that eosinophilic granulocytes (EOs) significantly mediated the association between rapid RC recovery and the habitual intakes of meat (mediation proportion = 17.5%, P-mediation < 0.0001), fruits (17.9%, p < 0.0001), and wheat-flour foods (11.4%, p < 0.0001). Thus, our study suggests that certain dietary habits play beneficial roles in the context of postoperative recovery for RC repair.

A Sternoclavicular Joint-Specific Plate for the Displaced Medial-End Clavicle Fracture.

Objectives: This study aimed to introduce a sternoclavicular joint (SCJ)-specific plate for the treatment of medial-end clavicle fracture and evaluate the clinical and radiological results of this method. Methods: From January 2006 to December 2020, 31 patients with displaced medial-end clavicle fractures were included in this study, with 8 patients with accompanying SCJ dislocation. Abduction and forward elevation of the shoulder, the Visual Analogue Scale (VAS), and the American Shoulder and Elbow Surgeons Score (ASES) were used for evaluation before index surgery and at the latest follow-up. Results: After an average of 98.5 (range, 13 to 171) months, the mean VAS significantly decreased from 6.8 ± 1.0 preoperatively to 0.9 ± 0.8 at the latest follow-up (P < 0.001). The mean ASES score significantly increased from 34.3 ± 7.8 preoperatively to 90.2 ± 4.9 at the latest follow-up (P < 0.001). The mean abduction of the shoulder significantly increased from 72.1 ± 6.6 preoperatively to 169.5 ± 8.5 at the latest follow-up (P < 0.001). The mean forward elevation of the shoulder significantly increased from 97.1 ± 11.0 preoperatively to 163.1 ± 11.5 at the latest follow-up (P < 0.001). The union of all fractures was achieved, and all implants were removed. No loose or breakage of implants was observed. No vascular or nerve damage occurred during the operation. Conclusions: This SCJ-specific plate provided excellent long-term results for the treatment of displaced medial-end clavicle fractures and was an alternative implant for medial-end clavicle fractures with or without small or comminuted medial fragments, especially those associated with SCJ dislocation.

Neohesperidin Ameliorates Steroid-Induced Osteonecrosis of the Femoral Head by Inhibiting the Histone Modification of lncRNA HOTAIR.

BACKGROUND: Neohesperidin (NH) and lncRNA HOTAIR (HOTAIR) could regulate osteoclastic and osteogenic differentiation. This study aimed to explore whether HOTAIR-mediated osteogenic differentiation was regulated by NH. METHODS: Steroid-induced osteonecrosis of the femoral head (SONFH) mice model was established. Histopathological changes in mouse osteonecrosis tissues were detected by hematoxylin-eosin staining. Bone marrow stromal cells (BMSCs) were isolated from healthy mice bone marrow samples by Ficoll density gradient and identified by flow cytometry. After treating the BMSCs with NH and dexamethasone or transfecting with HOTAIR overexpression plasmids and siHOTAIR, histone modification of HOTAIR, the cell viability, osteogenic differentiation, and adipogenic differentiation were detected by chromatin immunoprecipitation, MTT, Alizarin Red and Oil Red O staining, respectively. The expressions of HOTAIR and differentiation-related factors in the BMSCs were detected by RT-qPCR and Western blot. RESULTS: HOTAIR was highly expressed in SONFH model mice. NH ameliorated histopathological changes in the model mice, but the effect was reversed by overexpressed HOTAIR. NH increased viability of BMSCs and the H3K27me3 occupancy of HOTAIR, but decreased the expression and the H3K4me3 occupancy of HOTAIR. HOTAIR expression was down-regulated in BMSCs after osteogenic differentiation but was up-regulated after adipogenic differentiation. HOTAIR overexpression inhibited osteogenic differentiation and the expressions of RUNX2, OCN, and ALP, but increased adipogenic differentiation and the expressions of LPL and PPARr in BMSCs; moreover, the opposite results were observed in siHOTAIR. CONCLUSION: NH ameliorated SONFH by inhibiting the histone modifications of HOTAIR.

Changes of hemoglobin and hematocrit in elderly patients receiving lower joint arthroplasty without allogeneic blood transfusion.

BACKGROUND: It has rarely been reported about the changes of hemoglobin (Hb) and hematocrit (Hct) in elderly patients receiving total knee arthroplasty (TKA) or total hip arthroplasty (THA). This study aimed to evaluate the changes of Hb and Hct after TKA or THA in elderly patients, and analyze its relationship with sex and type of arthroplasty. METHODS: This is a prospective cohort study, including 107 patients receiving TKA or THA without allogeneic blood transfusion. There were 54 males and 53 females, with a mean age of 69.42 years. Levels of Hb and Hct were examined preoperatively and during the 6 months follow-up after operation. RESULTS: Levels of Hb and Hct decreased postoperatively and reached their minimum points on postoperative day 4. Thereafter, Hb and Hct recovered to their preoperative levels within 6-12 weeks. No significant differences in the levels of Hb and Hct were noticed between different sexes. THA patients showed significantly greater drop in Hb and Hct than TKA patients in the first 4 days postoperatively (P < 0.05). CONCLUSIONS: Levels of Hb and Hct decreased during the first 4 days after arthroplasty and gradually returned to their normal levels within 6-12 weeks postoperatively. THA may be associated with higher postoperative blood loss than TKA.

Effect of perioperative parecoxib on postoperative pain and local inflammation factors PGE2 and IL-6 for total knee arthroplasty: a randomized, double-blind, placebo-controlled study.

To assess the efficacy of postoperative pain management and the concentration change of PGE-2 and IL-6 of joint fluid with parecoxib after postoperative total knee arthroplasty. In the study, 100 patients experiencing primary TKA were randomly divided into study group, receiving parecoxib sodium (40 mg) intravenously (IV) at the completion of surgery and once every 12 h for totally 6 times postoperatively, and placebo group, receiving normal saline 2 mL IV at the same time points. Efficacy was assessed by total amount of morphine consumed, pain intensity, range of motion (ROM), the concentration change of PGE-2 and IL-6 of joint fluid, and postoperative nausea and vomiting (PONV) postoperatively. Patients in study group consumed significantly less morphine, experienced significant less pain scores, and obtained significantly more ROM (P < 0.01) compared with that in placebo group during 3 days postoperatively. The concentration of PGE-2 and IL-6 of joint fluid in study group are significantly lower than that in placebo group (P < 0.01) during 24 h postoperatively. The overall incidence of PONV was low and was not significantly different between the two groups. The present study demonstrated that the perioperative administration of parecoxib after primary TKA resulted in significantly improved postoperative analgesic management as defined by reduction in opioid requirement, lower pain scores and ROM, and significantly lowered local inflammation factors PGE2 and IL-6.

Patella rings for treatment of patellar fracture.

To evaluate a new fixation technique for patellar fracture using patella rings. A total of 75 patients (average age of 51.3 years) with comminuted or transverse patellar fractures were treated by fixation with patella rings. The Böstman scores at the time of bone union and at 12 months postoperatively were recorded, as was the degree of pain on a visual analogue scale (VAS), the range of motion of the knee at 12 months postoperatively, and any signs of postoperative complications. The average Böstman scores for patients in the transverse fracture group were 25.2 and 29.4 at 3 and 12 months postoperatively, respectively, while the scores for patients in the comminuted fracture group were 27.6 and 28.7, at the same time points. Böstman scores were graded as excellent and good in more than 90 % for patients with either a transverse or comminuted fracture. At the time of 12 months after surgery, the VAS score for patients with comminuted fractures was 0.38, whereas the score for patients in the transverse fracture group was 0.35. No statistically significant difference was found in the range of motion between the affected and uninjured knee at 12 months after surgery for patients in both groups (P > 0.05). This new fixation technique using a patella ring resulted in good outcomes for both transverse fracture and comminuted fracture and is beneficial for patients wishing to commence early functional activity.

Patellar reshaping versus resurfacing in total knee arthroplasty - Results of a randomized prospective trial at a minimum of 7 years' follow-up.

OBJECTIVE: To compare the results of primary total knee arthroplasty with patellar reshaping or resurfacing. METHODS: One hundred thirty-three patients were randomized into patellar reshaping group and patellar resurfacing group. Patellar reshaping includes resecting the partial lateral facet of the patella and the osteophytes surrounding the patella, trimming the patella to match the trochlea of the femoral component. The minimum follow-up time was 7 years. The outcome was measured by anterior knee pain rate, Knee Society clinical score, and radiographs. RESULTS: Eight patients in the reshaping group (12.5%) and 10 patients in the resurfacing group (14.7%) complained of anterior knee pain (P=0.712). Meanwhile, there were no significant differences between the two groups in terms of total Knee Society score, Knee Society pain score, Knee Society function score, as well as anterior knee pain rate. CONCLUSIONS: With the numbers available, there was no significant difference between the groups treated with patellar reshaping or patellar resurfacing with regard to the KSS, anterior knee pain rate and radiographs. We prefer reshaping the patella to resurfacing the patella because the former preserves sufficient patellar bone stock and can easily be converted to patellar replacement if patients complain of recurrent anterior knee pain.

[Effectiveness comparison of two arthroscopic different fixations for anterior cruciate ligament tibial eminence avulsion fractures].

OBJECTIVE: To compare the effectiveness of arthroscopic screw and suture fixations in treatment of anterior cruciate ligament tibial eminence avulsion fractures. METHODS: Between January 2002 and January 2009, 43 patients with fresh anterior cruciate ligament tibial eminence avulsion fracture were treated, which were rated as types II and III according to Meyers-McKeever-Zaricznyj classification. Fractures were fixed with either screw (screw group, n = 21) or nonabsorbable suture (suture group, n = 22). There was no significant difference in sex, age, disease duration, and fracture type between 2 groups (P > 0.05). The range of motion (ROM) and Lysholm score were compared between 2 groups, and the knee stability was evaluated based on the Lachman test and KT-2000 measurement. RESULTS: The operation time was 48-60 minutes (mean, 51.6 minutes) in the screw group, and 55-68 minutes (mean, 63.2 minutes) in the suture group, showing significant difference (t = 4.645, P = 0.032). Incisions healed by first intention and no complication occurred in 2 groups. All patients were followed up (5.7 +/- 0.6) years in the screw group and (5.3 +/- 0.5) years in the suture group. The fracture healed completely in both groups; the healing time was (3.3 +/- 0.6) months in the screw group and (3.2 +/- 0.4) months in the suture group, showing significant difference (t = 3.723, P = 0.019). Between the screw group and the suture group, no significant difference was found in ROM [(128.6 +/- 10.1)degrees vs. (130.2 +/- 14.1) degrees, P > 0.05] and Lysholm score (94.6 +/- 14.5 vs. 95.1 +/- 17.2, P > 0.05). The stabilities based on KT-2000 measurement were also similar between 2 groups at last follow-up [(0.9 +/- 0.3) mm vs. (1.0 +/- 0.4) mm, P > 0.05]. Lachman test of 2 groups were negative. CONCLUSION: Both the screw and nonabsorbable suture fixation techniques for anterior cruciate ligament tibial eminence avulsion fracture (type II or III) have good results in terms of functional outcome and stability. However, some patients show flexion contractures of 5 degrees or 10 degrees.

Co and Cr accumulation in hair after metal-on-metal hip resurfacing arthroplasty.

BACKGROUND: Currently, it is unclear whether Co and Cr levels are persistently elevated in the body after hip resurfacing arthroplasty (HRA). This study aimed to evaluate Co and Cr levels in the body after HRA using hair as samples. METHODS: Among 22 patients who had metal-on-metal HRA(m-o-m group) using the DePuy ASR system, scalp hair of 1.5 cm in length and 2 g in weight was collected before and at 6 and 12 months after surgery. Inductively coupled plasma-mass spectrometry (ICP-MS) was used to detect Co and Cr levels in the scalp hair. Another 22 patients with total hip replacements were randomly selected from a similar age range as controls (m-o-p group). Metal levels in hair were detected with multiple measurements and analysed by repeated measures analysis of variance. RESULTS: Both Co and Cr levels were significantly increased in the m-o-m group after surgery compared with those in the m-o-p group (P < 0.01). Co levels at 6 months post-operatively were 12-fold those before surgery, and Co levels 12 months postoperatively were lower than those at 6 months, but this difference was not significant (P = 0.0805) between the two time points in the m-o-m group. Cr levels were persistently elevated after surgery and were increased by 10-fold compared with those at baseline in the m-o-m group. CONCLUSIONS: Co and Cr levels in scalp hair are ideal indicators for metal levels in the body after HRA. Co and Cr levels in the body were greatly increased after metal-on-metal HRA. Long-term accumulation of these metals needs to be further investigated

[The use of uncemented extensively porous-coated femoral components in the management of Vancouver type B2 periprosthetic femoral fractures].

OBJECTIVE: To assess the outcome of patients with Vancouver type B2 periprosthetic fractures treated with femoral revision using an uncemented extensively porous-coated implant. METHODS: From October 2002 to May 2007, a retrospective clinical and radiographic assessment of 10 patients with Vancouver type B2 periprosthetic fractures treated with femoral revision was evaluated, among which 4 was cement fixation, 6 was non-cement fixation in the index procedure. RESULTS: The mean follow-up for these patients was 44 months (range, 12 to 67 months). The mean Harris hip score was 87.6 points. All 10 reconstructions showed solid fracture union and a stable prosthesis, 8 was bone ingrowth, 2 was fibrous ingrowth. Complications in 4 patients included thigh pain in 1, stress shield in 3. CONCLUSIONS: Vancouver type B2 periprosthetic fractures treated with uncemented extensively porous-coated femoral stems incorporate distally allowing stable fixation.

Efficacy of intra-articular cocktail analgesic injection in total knee arthroplasty - a randomized controlled trial.

In a randomized, double-blind, placebo, parallel and controlled study, 80 patients with osteoarthritis who underwent unilateral TKA were randomly assigned to two groups: Trial Group, where patients received intra-articular intraoperative injection containing morphine, bupivacaine and betamethasone, and Control Group, where patients received normal saline as control. All patients received patient-controlled analgesia (PCA) for 48 h postoperatively. We found that intra-articular cocktail analgesic injection significantly reduced the morphine consumption during the 0-36 h postoperative period and the total morphine consumption. VAS at rest in Trial Group at postoperative 6, 10, 24 and 36 h was significantly lower than that in Control Group, and VAS during activity in Trial Group at postoperative 24 h and 36 h was significantly lower than that in Control Group. The time of ability to perform an active straight leg raise and to actively reach 90 degrees knee flexion, as well as ROM of the knee at the 15th postoperative day, was better in Trial Group than those in Control Group. There were no significant differences in postoperative wound healing, infection, blood pressure, heart rate, rash, respiratory depression, urine retention and DVT between the two groups. The occurrence of nausea and vomiting in Trial Group was lower than that of Control Group. This study revealed that intra-articular cocktail analgesic injection reduced the need for morphine and offered a better pain control, without apparent risks following TKA.

[Effect of total hip replacement on lumbago in unilateral developmental hip dysplasia].

OBJECTIVE: To assess the effect of total hip replacement on lumbago in patients with unilaterally developmental hip dysplasia. METHODS: From January 2001 to January 2006, 39 adult patients with unilateral developmental hip dysplasia co-exiting lumbago were included. Among them, there were 32 females and 7 males, age from 38 years to 73 years. According to Crowe classification system, there were 4 in type I, 20 in type II,8 in type III and 7 in type IV. They were performed total hip replacement. The Harris Hip Score and the Oswestry Disability Index were used to evaluate hip and spine symptoms in same patient before and 3, 24 months after operation. RESULTS: Thirty-nine patients were evaluated, both hip and spinal pain and function were significant improved. The mean Harris score increased from 44 to 84 (P < 0.01). The mean Oswestry Scores dropped from 36 to 25 (P < 0.01). CONCLUSION: Spinal function and lumbago is improved after total hip replacement in patients with unilateral developmental hip dysplasia at 3 months, which is maintained and enhanced in 2 years.

[Patella reshaping versus resurfacing in total knee arthroplasty: a prospective randomized study].

OBJECTIVE: To investigate the differences in the clinical outcome of total knee arthroplasty according to patellar reshaping or resurfacing. METHODS: From January 2002 to December 2002, 60 patients (60 knees) undergoing primary total knee arthroplasty for the treatment of osteoarthritis were enrolled in a prospective, randomized study. All patients received the same posterior-cruciate-substituting total knee prosthetic components. Patients were randomized to the treatment with reshaping or resurfacing of the patella, and the results were followed up for a mean of 54 months (40-60 months). Evaluations consisted of the determination of a Knee Society Score, range of motion for knees, patient satisfaction, and radiographs. RESULTS: With the numbers available for study, no significant difference was found between the knees that had patellar resurfacing and those that had patellar reshaping with regard to the overall score (P=0.12), the subscore for pain (P=0.90), and patient satisfaction (P=0.22). The results showed that the same prevalence of any anterior knee pain in two groups was 10%, and it did not represent a significant difference. The two groups showed statistical difference with regard to the total function score and range of motion. CONCLUSIONS: It has shown that total knee arthroplasty with patella reshaping or resurfacing dramatically relieves pain and improves the function. It seems that postoperative anterior knee pain is related either to the component design or to the details of the surgical technique, rather than to whether or not the patella is resurfaced.

[The use of a closed-suction drain in total knee arthroplasty: a prospective, randomized study].

OBJECTIVE: To determine the value of using a closed-suction drain in cemented knee arthroplasty. METHODS: One hundred patients were prospectively randomized into two groups, one group underwent cemented total knee replacement with a single deep closed-suction drain, and the other group (n = 50) no drain. RESULTS: The total blood loss was significantly greater in those with a drain although those without lost more blood into the dressings. There was no statistical difference in the postoperative swelling or pain score, ecchymosis, deep vein thromboses (DVT), time at which flexion was regained or the incidence of infection at a minimum of two years after surgery in the two groups. CONCLUSION: There is no evidence to support the use of a closed-suction drain in cemented knee arthroplasty.

[The effect of rotational alignment of the femoral components on the patellofemoral biomechanics in total knee arthroplasty].

OBJECTIVE: To study the effect of rotational alignment of the femoral components on the patellofemoral biomechanics in total knee arthroplasty (TKA) demonstrated on autopsy specimens, as the guide for surgeons to choose the correct reference axis for rotational alignment of the femoral components and to reduce the patellofemoral joint complications. METHODS: Select 9 frozen fresh human cadaver knees without gross deformities or instabilities and mount specimens on a patellofemoral joint testing jig connected to a Model 8501 Instron machine (Instron Corporation, Canton, MA). The study simulated the action of squatting from the standing position with the foot firmly planted. Standard TKA was performed in each specimen by the same senior surgeon using Nexgen LPS total knee system (Zimmer Corporation, Warsaw Indiana). Alter rotational alignment of the femoral components referenced to the transepicondylar axis and the Whiteside's line respectively. Measure biomechanics of the patellofemoral joints using Fuji prescale film at 30 degrees , 60 degrees , 90 degrees , 120 degrees of knee flexion respectively. The digital values were obtained by the handheld pressure measurement systems (FPD-305E, FPD-306E) and Autocad software. RESULTS: The rotational alignment of the femoral components paralleled to the transepicondylar axis had the best results of the peak value of the patellofemoral contact pressure (P < 0.05). There were no statistically significant differences in patellofemoral contact area (P > 0.05). But the patellofemoral contact area had the close correlations to the angles of the knee flexion and the specimens. CONCLUSIONS: Rotational alignment of the femoral components has a great influence on the patellofemoral contact pressure in total knee arthroplasty. It is reliable for surgeons to choose the transepicondylar axis as the reference axis to rotate femoral components.