Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

OBJECTIVE: To investigate the effectiveness of preemptive analgesia with imrecoxib on analgesia after anterior cruciate ligament (ACL) reconstruction. METHODS: A total of 160 patients with ACL injuries who met the selection criteria and were admitted between November 2020 and August 2021 were selected and divided into 4 groups according to the random number table method (n=40). Group A began to take imrecoxib 3 days before operation (100 mg/time, 2 times/day); group B began to take imrecoxib 1 day before operation (100 mg/time, 2 times/day); group C took 200 mg of imrecoxib 2 hours before operation (5 mL of water); and group D did not take any analgesic drugs before operation. There was no significant difference in gender, age, body mass index, constituent ratio of meniscal injuries with preoperative MRI grade 3, constituent ratio of cartilage injury Outerbridge grade 3, and visual analogue scale (VAS) score at the time of injury and at rest among 4 groups (P>0.05). The operation time, hospitalization stay, constituent ratio of perioperative American Society of Anesthesiologists (ASA) grade 1, postoperative opioid dosage, and complications were recorded. The VAS scores were used to evaluate the degree of knee joint pain, including resting VAS scores before operation and at 6, 24, 48 hours, and 1, 3, 6, and 12 months after operation, and walking, knee flexion, and night VAS scores at 1, 3, 6, and 12 months after operation. The knee injury and osteoarthritis score (KOOS) was used to evaluate postoperative quality of life and knee-related symptoms of patients, mainly including pain, symptoms, daily activities, sports and entertainment functions, knee-related quality of life (QOL); and the Lysholm score was used to evaluate knee joint function. RESULTS: All patients were followed up 1 year. There was no significant difference in operation time, hospitalization time, or constituent ratio of perioperative ASA grade 1 among 4 groups (P>0.05); the dosage of opioids in groups A-C was significantly less than that in group D (P<0.05). Except for 1 case of postoperative fever in group B, no complications such as joint infection, deep vein thrombosis of the lower extremities, or knee joint instability occurred in each group. The resting VAS scores of groups A-C at 6 and 24 hours after operation were lower than those of group D, and the score of group A at 6 hours after operation was lower than those of group C, and the differences were significant (P<0.05). At 1 month after operation, the knee flexion VAS scores of groups A-C were lower than those of group D, the walking VAS scores of groups A and B were lower than those of groups C and D, the differences were significant (P<0.05). At 1 month after operation, the KOOS pain scores in groups A-C were higher than those in group D, there was significant difference between groups A, B and group D (P<0.05); the KOOS QOL scores in groups A-C were higher than that in group D, all showing significant differences (P<0.05), but there was no significant difference between groups A-C (P>0.05). There was no significant difference in VAS scores and KOOS scores between the groups at other time points (P>0.05). And there was no significant difference in Lysholm scores between the groups at 1, 3, 6, and 12 months after operation (P>0.05). CONCLUSION Compared with the traditional analgesic scheme, applying the concept of preemptive analgesia with imrecoxib to manage the perioperative pain of ACL reconstruction can effectively reduce the early postoperative pain, reduce the dosage of opioids, and promote the early recovery of limb function.
Humans ; Quality of Life ; Analgesics, Opioid ; Analgesia ; Osteoarthritis, Knee ; Pain, Postoperative/prevention & control* ; Anterior Cruciate Ligament Reconstruction ; Knee Injuries

Objective:To investigate the effect of flap combined with 3D printed microporous titanium(tantalum)prosthesis in the treatment of lower extremity soft tissue defect with large bone defect.Methods:From January 2019 to December 2020, 2 patients with large soft tissue defects on dorsal foot together with large metatarsal bone defect and 4 patients with soft tissue defects of calf with large tibial bone defect were treated. The areas of soft tissue defect were 5.0 cm×8.0 cm-15.0 cm×10.0 cm. The length of the bone defect were 3.8 cm to 7.0 cm, 5.75 cm in average. In the first stage, metatarsal bone defect or tibial bone defect was filled with vancomycin blended bone cement, meanwhile, soft tissue defect was repaired with anterolateral femoral flap(ALTF) with vascular anastomosis in 2 cases of feet, and local fascia flap was trans-positioned in 4 cases of lower extremity defects. The sizes of repairing flap were 6.0 cm×8.5 cm-16.0 cm×11.0 cm. Two to 7 months after the initial surgery, the customer designed microporous titanium prostheses were used(5 cases with microporous titanium and 1 with microporous tantalum) to repair the bone defects. The wound healing, the integration of metatarsal and tibial fractures with 3D printed microporous titanium(tantalum) prostheses, and the walking condition were observed after surgery. The follow-up lasted from 6 to 25 months, with an average of 12.7 months.Results:The wound healing in 5 patients was good. The patients stood on the foot in 2 months after surgery, started to walk with the assistance of crutch in 3 months after surgery, and took walk without assistance in 5-6 months after surgery. Good osseous integration were achieved. One diabetic patient had infection of foot wound 3 months after surgery. After removal of microporous titanium prosthesis and replacement of vancomycin blended interstitial substance of bone cement, the wound healed and the patient resumed walking.Conclusion:It is an effective method to encourage the patients to take early ambulation after the surgery for lower extremity soft tissue defect with large bone defect that was repaired by a flap and 3D printed microporous titanium(tantalum)prosthesis. Further observations are required to investigate the long-term efficacy, and the reduction of prosthesis infection rate requires further exploration.

Objective:To study the correlation between non-contact anterior cruciate ligament (ACL) injury and functional ankle instability (FAI) in young patients.Methods:A retrospective analysis was conducted of the 102 patients with non-contact ACL injury[61 males and 41 females, with an age of (31.9±6.1) years and a Tegner activity score of (6.1±1.9) points] who had been treated at Department of Orthopedics, Sun Yat-sen Memorial Hospital from January 2017 to March 2020 (injury group). Another 102 citizens without ACL injury from Guangzhou [56 males and 46 females, with an age of (30.3±7.2) years and a Tegner activity score of (6.0±2.1) points] were recruited as a control group. The Cumberland ankle instability tool (CAIT) and the Ankle Joint Functional Assessment Tool (AJFAT) were used to assess whether the subjects had self-conscious FAI or not. A correlation analysis was conducted using the data collected.Results:The 2 groups were comparable because there were no significant differences between them in general data ( P>0.05). By the CAIT score, the incidence of FAI in the injury group [52.9% (54/102)] was significantly higher than that in the control group [32.4% (33/102)] ( P<0.05); by the AJFAT score, the incidence of FAI in the injury group [59.8% (61/102) ] was significantly higher than that in the control group [39.2% (40/102)] ( P<0.05). Pearson correlation analysis showed that diagnoses of FAI by CAIT and by AJFAT were respectively correlated with ACL injury ( r=-0.159, P=0.023; r=-0.215, P=0.002). Conclusions:The incidence of FAI may be high in patients with ACL injury and there is a correlation between FAI and ACL injury.

Objective:To study the clinical features of the "migration birds" population in Hainan Province in winter presenting with acute cholecystitis.Methods:Patients who were diagnosed to suffer from acute cholecystitis in the winter months from November to February of the following year of 2017, 2018 and 2019 and admitted in Hainan Hospital of Chinese PLA General Hospital were included in this study. The "migration birds" patients who arrived in Hainan Province in less than 30 days were defined as the short-term group ( n=49), 30-89 days as the mid-term group ( n=24), more than 90 days as the long-term group ( n=48). The general information, associated medical diseases, clinical presentations, interventional strategies and in-hospital outcomes were compared, and further analyze the clinical characteristics of patients with purulent cholecystitis and non-purulent cholecystitis in the short-term group. Results:Of 120 patients, there were 49 patients in the short-term group (29 males and 20 females with an average age of 65.18±15.02 years), 24 patients in the mid-term group (13 males and 11 females with an average age of 66.21±11.93 years), and 48 patients in the long-term group (30 males and 18 females with an average of 60.73±12.54 years). The general information, interventional strategies and in-hospital outcomes were similar among the three groups. When compared with patients in the long-term group, patients in the short-term group had higher incidences of hypertension [20.83% (10/48) vs 48.98% (24/49)] and diabetes [10.42% (5/48) vs 30.61% (15/49)]. The gallbladder wall in the short-term group was significantly thicker than that in the long-term group [0.60(0.40, 0.70) cm vs 0.50(0.30, 0.60) cm, P<0.017]. The proportion of purulent cholecystitis in the short-term group was significantly higher than that in the long-term group [48.15% (13/27) vs 17.24% (5/29) , P<0.017] . In the short-term group, the incidences of silt-like stones of purulent cholecystitis [38.46% (5/13) vs 14.29% (2/14)], gallbladder perforation [30.77% (4/13) vs 0], gallbladder gangrene [53.85% (7/13) vs 7.14% (1/14)], perigallbladder effusion [76.92% (10/13) vs 14.29% (2/14)], abdominal effusion [46.15% (6/13) vs 7.14% (1/14)] were significantly higher than that of patients with non-purulent cholecystitis, (all P<0.05). Conclusion:Patients presenting with acute cholecystitis after arrival in Hainan in the short term had more severe inflammation with complications of suppuration, perforation and gangrene. Patients with hypertension and diabetes were the high risk group of patients presenting with acute cholecystitis after short-term arrival in Hainan.

Objective: To summarize the research progress of killer turn in posterior cruciate ligament (PCL) reconstruction. Methods: The literature related to the killer turn in PCL reconstruction in recent years was searched and summarized. Results: The recent studies show that the killer turn is considered to be the most critical cause of graft relaxation after PCL reconstruction. In clinic, this effect can be reduced by changing the fixation mode of bone tunnel, changing the orientation of bone tunnel, squeezing screw fixation, retaining the remnant, and grinding the bone at the exit of bone tunnel. But there is still a lack of long-term follow-up. Conclusion: There are still a lot of controversies on the improved strategies of the killer turn. More detailed basic researches focusing on biomechanics to further explore the mechanism of the reconstructed graft abrasion are needed.

Objective This study aimed to investigate the relationship between CLPTM1L gene and lung cancer 95-D cells sensitivity to gemcitabine,and to explore its potential mechanism of action. Methods Overexpression of lentivirus against CLPTM1L gene was constructed and infected with lung cancer 95-D cells;Cells were divided into the CLPTM1L overexpression group and con-trol group;The proliferation of cells in the overexpressing and control groups after gemcitabine treatment was detected by CCK-8;The changes of CLPTM1L gene and protein were detected by real-time PCR,Western blot and immunochemiluminescence;The changes of caspase-3/7 and caspase-9 activities were detected by bioluminescence;Western blot was used to detect the changes of p-4E-BP1 protein. Results The expression of CLPTM1L gene( P =0. 036) and its protein ( P <0. 01) was significantly increased after CLPTM1L overexpressed lentivirus-infected 95 -D cells;Compared with the control group,the proliferation of CLPTM1L overex-pressing group after gemcitabine treatment was increased(P <0. 01);The activity of caspase activity showed that the activities of caspase-3/7 and caspase-9 in the CLPTM1L overexpression group were significantly lower than those in the control group(P<0. 01);The phosphorylated level of 4E-BP1 protein in the CLPTM1L overexpression group was significantly higher than that in the control group. Conclusion Overexpression of CLPTM1L can reduce the sensitivity of lung cancer cells to gemcitabine. Its mechanism may be to increase the phosphorylation level of 4E-BP1.

Sodium hyaluronate is one of the natural components of articular cartilage and synovial fluid,which plays important roles in maintaining the structure and physiological functions of joints.Abnormal change of the content and physicochemical properties of sodium hyaluronate in the joints is one of the common pathological causes of osteoarthritis.Supplementation of exogenous sodium hyaluronate,which has similar physical and chemical properties as those in normal joints,has been considered as an effective strategy for clinical treatment of osteoarthritis.However,the benefits of intra-articular injection of sodium hyaluronate are still under debates.Moreover,different recommendations for clinical use were developed in several clinical guidelines.Several guidelines suggested that molecular weight of sodium hyaluronate was an important factor influencing the clinical benefits in osteoarthritis.Diverse products of sodium hyaluronate present different physicochemical and biological characteristics,which may lead to differences in clinical efficacy and safety.High-molecular-weight sodium hyaluronate,with highly modified and cross-linked sugar chains,potentially differ from those with low molecular weight in physicochemical properties,rheological characteristics,and physiological activities.In general,high-molecular-weight sodium hyaluronate have higher viscosity and elasticity.The exogenous hyaluronate,of which the molecular weight is similar to those in normal joints,probably have the similar rheological characteristics.A large number of clinical studies demonstrated that sodium hyaluronate products with high-molecular weight significantly relieved joint pain and improved joint functions in patients with osteoarthritis.In contrast,the clinical efficacy of the low-molecular-weight hyaluronate is still controversial,because several studies could not establish the superiority in osteoarthritis when comparing with the placebo.Studies on molecular mechanisms revealed that some physiological functions of sodium hyaluronate were molecular-weight dependent.High-molecular-weight sodium hyaluronate may have more pronounced impacts on the regulation of inflammation and maintaining the homeostasis of extracellular matrix.This review focused on the effects of sodium hyaluronate with different molecular weight in treating osteoarthritis.Evidence based on clinical studies related to the molecular-weight differences of sodium hyaluronate were presented.Furthermore,the optimal use of various products of sodium hyaluronate with different molecular weight was discussed.

Objective: To summarize the research progress of rehabilitation after autologous chondrocyte implantation (ACI). Methods: The literature related to basic science and clinical practice about rehabilitation after ACI in recent years was searched, selected, and analyzed. Results: Based on the included literature, the progress of the graft maturation consists of proliferation phase (0-6 weeks), transition phase (6-12 weeks), remodeling phase (12-26 weeks), and maturation phase (26 weeks-2 years). To achieve early protection, stimulate the maturation, and promote the graft-bone integrity, rehabilitation protocol ought to be based on the biomechanical properties at different phases. Weight-bearing program, range of motion (ROM), and options or facilities of exercise are importance when considering a rehabilitation program. Conclusion: It has been proved that the patients need a program with an increasingly progressive weight-bearing and ROM in principles of rehabilitation after ACI. Specific facilities can be taken at a certain phase. Evidences extracted in the present work are rather low and the high-quality and controlled trials still need to improve the rehabilitation protocol.

The Wnt signaling pathway and its key component β-catenin have critical roles in the development of diseases such as tumors in mammals. However, little has been reported about involvement of the Wnt/β-catenin signaling pathway in canine mammary tumors (CMTs). The present study detected expression of 30 Wnt signaling pathway-related genes in CMTs; the results are potentially useful for molecular-based diagnosis of CMTs and the development of new targeted therapies. Significant upregulations of dickkopf-1 protein, secreted frizzled-related sequence protein 1 (SFRP1), frizzled 3, β-catenin, and lymphoid enhancer-binding factor 1 (LEF1) were detected in highly malignant CMTs compared to levels in normal mammary gland tissues; moreover, highly significant upregulation of WNT5A was observed in low malignancy CMTs. Downregulation was only detected for SFRP4 in malignant CMT samples. The subcellular location of β-catenin and cyclin D1 in 100 CMT samples was investigated via immunohistochemical analysis, and significantly increased expressions of β-catenin in cytoplasm and cyclin D1 in nuclei were revealed. Western blotting analysis revealed that the expression of β-catenin and LEF1 increased in in the majority of CMT samples. Taken together, the results provide important evidence of the activation status of the Wnt pathway in CMTs and valuable clues to identifying biomarkers for molecular-based diagnosis of CMT.
beta Catenin ; Biomarkers ; Blotting, Western ; Cyclin D1 ; Cytoplasm ; Diagnosis ; Down-Regulation ; Immunochemistry* ; Lymphoid Enhancer-Binding Factor 1 ; Mammals ; Mammary Glands, Human ; Polymerase Chain Reaction* ; Up-Regulation ; Wnt Signaling Pathway