Determining prognostic factors and optimal surgical intervention for early-onset triple-negative breast cancer.

Background: Few studies have focused specifically on prognostic factors and optimal surgical intervention for early-onset triple-negative breast cancer (eTNBC), which is characterized by high malignancy and poor prognosis. Methods: We performed a cohort study with a median follow-up of 31 months using Surveillance, Epidemiology, and End Results (SEER) data of patients diagnosed with stages I-III eTNBC between 2010 and 2016. In addition, we collected cases between 2006 and 2016 from our center as an external validation set. Clinical features, pathologic characteristics and oncologic outcomes were analyzed. Prognostic factors for overall survival (OS) and breast cancer-specific survival (BCSS) were determined by Cox proportional hazards analyses and were incorporated into the prognostic nomogram. Subgroup analysis based on propensity score matching method was conducted to explore the subset of patients that would benefit from breast-conserving therapy (BCT). Results: Based on SEER dataset, patients with eTNBC were more likely to undergo mastectomy than BCT. On multivariable analysis, patients with better survival outcomes were those not married, uninsured, had higher T and N stage, and had histological type of mixed invasive ductal and lobular carcinoma. The prognostic nomogram based on these variables successfully predicted the 3- and 5-year BCSS (C-index in training cohort, 0.774; in validation cohort from SEER, 0.768; in validation cohort from our center, 0.723). Subgroup analysis illustrated that patients with T1N0M0 or T2-4N+M0 tumors who underwent BCT achieved longer overall survival than those who underwent mastectomy (for T1N0M0, P = 0.022; for T2-4N+M0, P = 0.003); however, the type of surgery did not influence OS among patients with T1N+M0 or T2-4N0M0 tumors (for T1N+M0, P = 0.305; for T2-4N0M0, P = 0.317). Conclusions: The prognosis of patients with eTNBC is mainly affected by marital status, insurance status, T stage, N stage and histological type. The prognostic nomogram based on these factors is quite reliable. Subgroup analysis suggested that BCT may be a superior option for patients with eTNBC, especially those with T1N0M0 and T2-4N+M0 tumors.

Prognostic Factors and a Nomogram Predicting Survival in Patients with Breast Ductal Carcinoma in situ with Microinvasion: A Population-Based Study.

PURPOSE: Ductal carcinoma in situ with microinvasion (DCISM) can be challenging to balance the risks of overtreatment versus undertreatment. We aim to identify prognostic factors in patients with DCISM and construct a nomogram to predict breast cancer-specific survival (BCSS). MATERIALS AND METHODS: A retrospective cohort study of women diagnosed with DCISM from 1988 to 2015 who were identified in the Surveillance, Epidemiology and End Results database. Clinical variables and tumor characteristics were evaluated, and Cox proportional-hazards regression was performed. A nomogram was constructed from the multivariate logistic regression to combine all the prognostic factors to predict the prognosis of DCISM patients at 5 years, 10 years, and 15 years. RESULTS: We identified 5438 total eligible breast cancer patients with a median and max survival time of 78 and 227 months, respectively. Here, patients with poorer survival outcomes were those diagnosed between 1988 and 2001, African-American race, under 40 years of age, higher tumor N stage, progesterone receptor-negative tumor, and received no surgery. The nomogram was constructed by the seven variables and passed the calibration and validation steps. The area under the receiver operating characteristic (ROC) curve (AUC) of both the training set and the validating set (5-year AUC: 0.77 and 0.88, 10-year AUC: 0.75 and 0.73, 15-year AUC: 0.72 and 0.65). Receiving chemotherapy was associated with a better BCSS (hazard ratio, HR=0.45, 95% confidence interval, 95% CI = 0.23-0.89), especially in patients with estrogen receptor (ER) negative, progesterone receptor (PR) negative (HR = 0.35, 95% CI = 0.13-0.97) and ER+PR-/ER-PR+ DCISM (HR = 0.07, 95% CI = 0.01-0.59). CONCLUSION: Our current study is the first to construct nomograms of patients with DCISM which could help physicians identify breast cancer patients that more likely to benefit from more intensive treatment and follow-up. Chemotherapy might benefit patients with ER-PR- and ER+PR-/ER-PR+ DCISM.

[Clinical outcomes of hip arthroscopic treatment for femoroacetabular impingement:a comparative study between Inside-out and Outside-in approach].

OBJECTIVE: To compare the clinical outcomes and complications of hip arthroscopic treatment for femoroacetabular impingement (FAI) performed with either Inside-out or Outside-in approach. METHODS: The clinical date of 48 patients with FAI treated by hip arthroscopy surgery and follow-up from June 2016 to June 2019 were retrospectively analyzed. According to the different operative methods, the patients were divided into two groups. Inside-out group, from central compartment to peripheral compartment;Outside-in group, from peripheral compartment to central compartment. There were 14 males and 10 females in Inside-out group with an averageage of (39.8±7.6)years old, 13 males and 11 females in Inside-out group with an average age of (39.5±9.1)years old in Outside-in group. There was no significant difference in age, gender, body mass index, side, impingement type, medical history and follow-up time between the two groups. The complication occurrence rate, modified Harris hip score (mHHS)and nonarthritic hip score (NAHS) were compared between these two groups. RESULTS: The mHHs and NAHS scores of the two groups were significantly higher than those before operation, but there was no significant difference between the two groups (P>0.05). In the Inside-out group, there were 4 cases of nerve traction injury and 3 cases of iatrogenic injury, while only 1 case of nerve traction injury occurred in the Outside-in group. The incidence of complications in the inside out group was higher than that in the outside in group (16.7% vs 4.2%, χ2=5.400, P=0.020). CONCLUSION: Both hip arthroscopic surgery methods can obtain satisfactory clinical efficacy in the treatment of FAI, but the incidence of postoperative complications of Outside-in surgical method is lower. The out-side in method can be preferentially selected for the patients with the indications of operation.

Association between hip and knee osteoarthritis with falls: A systematic review and meta-analysis.

OBJECTIVE: To examine the association between hip and knee osteoarthritis (OA) and falls. Potentially relevant articles that examine the association between hip, knee, radiological, and self-reported OA and falls were retrieved from PubMed, EMBASE, Scopus, and Web of Science up until March of 2020. METHODS: The pooled risk ratios (RRs) as well as their related 95% confidence intervals (CIs) were calculated. Statistic and subgroup analyses were performed. A total of 21 studies involving 146 965 participants were included. RESULTS: No association was found between hip OA and falls. The pooled RRs value suggested a higher prevalence of falls in knee OA patients (RR = 1.35, 95% CI: 1.20 to 1.51, P < .00001) and self-reported OA (RR = 1.33, 95% CI: 1.23 to 1.45, P < .00001) than in non-OA subjects. The pooled RR value suggested no difference between prevalence of falls in radiological OA patients compared to non-OA subjects (RR = 1.82, 95% CI: 0.89 to 3.73, P = .10). Both radiological and self-reported knee OA seem to be positively associated with falls, while no obvious association was found between hip OA and falls. CONCLUSIONS: Therefore, knee OA is a risk factor for falls which should be closely monitored.

The therapeutic effects of earthworm extract on deep second-degree burn wound healing.

BACKGROUND: To investigated the effect of earthworm extract (EE) on deep second-degree burn wound healing process. METHODS: A burn wound model was created on the mice's skin and was subject to different treatments: the control group received no treatment; the Jingwanhong (JWH: a well-established, widely used external ointment for treating burn wounds) group was treated with 0.1 g of JWH cream and spray it on the wound surface; the EE group was treated with 0.1 mL of EE solution. All the mice were sacrificed at 3, 7, 11, and 15 days after injury (n=6/group/time point). Macroscopic observation, wound healing rate (WHR), wound healing time (WHT), water content (WC), hydroxyproline (Hyp) content, histological, and hematological analyses were performed at the burn wound sites. RESULTS: Better, faster burn wound healing in the JWH and EE groups than the control group at 15 days after injury were detected at the wound sites. Compared to the control group, the EE group had higher WHR, shorter WHT, lower WC, higher Hyp content, more fibroblasts, fibrocytes, and capillary endothelial cells; in addition, they showed greater capillary endothelial cell grouping at the wound sites during the healing process. This group also showed more platelets, white blood cells (WBCs), and neutrophilic granulocytes in serum at the early stages after burn injury. CONCLUSIONS: EE could effectively promote skin wound healing by decreasing edema, suppressing fibrosis, activating angiogenesis and epithelial regeneration, inhibiting scar formation, and reducing the risk of infection. Thus, it could be made into a promising healing agent for burn wound.

The ß-catenin/TCF-4 pathway regulates the expression of OPN in human osteoarthritic chondrocytes.

BACKGROUND: Cartilage destruction is the main characteristic of osteoarthritis (OA), and osteopontin (OPN) is elevated in OA articular cartilage; however, the reason for the increased OPN level is not determined. In addition, Wnt/ß-catenin signaling participates in the progression of OA. The aim of the present study was to evaluate whether canonical Wnt signaling could regulate the expression of OPN in human chondrocytes in vitro. METHODS: Human chondrocytes were cultured in vitro, and we first assayed the mRNA levels of OPN and ß-catenin in chondrocytes. Next, we performed transient transfection of TCF 4 shRNA into chondrocytes to inhibit TCF 4 expression and explore changes in the OPN level. Then, the Wnt/ß-catenin signaling inhibitor Dickkopf-1 (Dkk-1) was incubated with chondrocytes, and we assayed the changes in ß-catenin and OPN. RESULTS: Our results showed that the expression of both ß-catenin and OPN was increased in OA chondrocytes, but there were no correlations between ß-catenin and OPN expression. TCF4 shRNA downregulated the expression of TCF 4 and OPN in chondrocytes, while after treatment with rDKK-1 at a concentration of 400 ng/ml for 24 h, the mRNA and protein expression of both ß-catenin and OPN was significantly decreased in chondrocytes. CONCLUSIONS: Elevated OPN expression might be regulated by the ß-catenin/TCF-4 pathway, and the Wnt/ß-catenin inhibitor DKK1 could inhibit the expression of ß-catenin and OPN in OA chondrocytes.

The effect of earthworm extract on promoting skin wound healing.

Chronic nonhealing wounds pose a significant challenge to healthcare system because of its tremendous utilization of resources and time to heal. It has a well-deserved reputation for reducing the quality of life for those affected and represent a substantial economic burden to the healthcare system overall. Earthworms are used as a traditional Chinese medicine, and have been applied pharmacologically and clinically since a long time in China. However, there is paucity in data regarding its wound healing effects. Therefore, we investigated the effect of earthworm extract (EE) on skin wound healing process. The obtained data showed that EE has healing effects on local wound of mice. It decreased the wound healing time and reduced the ill-effects of inflammation as determined by macroscopic, histopathologic, hematologic, and immunohistochemistry parameters. The potential mechanism could be accelerated hydroxyproline and transforming growth factor-ß secretion-thus increasing the synthesis of collagen, promoting blood capillary, and fibroblast proliferation. It could accelerate the removal of necrotic tissue and foreign bodies by speeding up the generation of interleukin-6, white blood cells, and platelets. It thus enhances immunity, reduces the risk of infection, and promotes wound healing. All in all, the obtained data demonstrated that EE improves quality of healing and could be used as a propitious wound healing agent.

Study of analgesic effect of earthworm extract.

Pain represents a major clinical problem and one which has exercised generations of healthcare professionals. Earthworms are used as a traditional Chinese medicine, and have been applied pharmacologically and clinically since a long time in China. However, the analgesic effects of earthworm extract (EE) are seldom studied. Hence, we evaluated the analgesic effects of EE in mice. The obtained data showed that EE increased pain threshold and exhibited peripheral but not central analgesic effects in mice; evidenced by increased inhibition ratio in acetic acid writhing test and formalin test, whereas only slight increase in inhibition ratio in hot plate test and tail immersion test. In addition, EE decreased serum norepinephrine (NE), 5-hydroxytryptamine (5-HT), and nitric oxide (NO) synthase (NOS) concentration, similar to other analgesic drugs like morphine and aspirin. In a nutshell, the obtained data have demonstrated that EE has peripheral analgesic properties and could be used as a promising analgesic drug.

Effects of the acetabular fracture index and other factors of posterior wall acetabular fracture on functional outcome.

Objective To analyze the effects of the acetabular fracture index (AFI) and other factors on the functional outcome of patients with acetabular fractures involving the posterior wall. Methods Forty-eight patients who underwent surgery in our department were reviewed. According to the AFI, which indicates the percentage of remaining intact posterior acetabular arc, the patients were divided into Group A (AFI ≤ 25%, 11 patients), Group B (25% < AFI ≤ 50%, 23 patients), Group C (50% < AFI ≤ 75%, 7 patients), and Group D (75% < AFI ≤ 100%, 7 patients). The AFI was measured with a computed tomography picture archiving and communication system or calculated with the cosine theorem. A nonparametric test and ordinal regression were used to determine the role of the AFI and other factors on the functional outcome. Perioperative information, including demographic and fracture-related data, reduction quality, physical therapy duration, association with a lower limb fracture and avascular necrosis of the femoral head were prospectively gathered. Results The mean AFIs of A, B, C, and D groups were 14.3%, 35.9%, 59.5%, and 81.2%, respectively. No statistically significant differences were observed among the groups for demographic and fracture-related data. A better reduction quality (OR = 4.21, 95%CI 1.42 ∼ 12.43, χ2 = 6.781, P = 0.009) and a larger value of AFI (OR = 2.56, 95%CI 1.18 ∼ 5.55, χ2 = 5.648, P = 0.017) result in a higher functional score. The functional outcome of a physical therapy duration of more than 12 months (OR = 0.15, 95%CI 0.02 ∼ 0.90, χ2 = 4.324, P = 0.038) was better than that of less than 12 months. Lower limb fracture (OR = 0.13, 95%CI 0.02 ∼ 0.74, χ2 = 5.235, P = 0.022) and avascular necrosis of femoral head (OR = 0.02, 95%CI 0.00 ∼ 0.87, χ2 = 4.127, P = 0.042) were found to correlate with a lower functional score. Conclusion With a greater of AFI, the functional outcome score would be better. Other factors, including reduction quality, physical therapy duration, association with a lower limb fracture, and avascular necrosis of the femoral head, most likely also affect hip functional recovery.

MicroRNA-379 inhibits the proliferation, migration and invasion of human osteosarcoma cells by targetting EIF4G2.

Osteosarcoma (OS) is an aggressive malignant mesenchymal neoplasm amongst adolescents. The aim of the present study was to explore the various modes of action that miR-379 has on the proliferation, migration, and invasion of human OS cells. miR-379 achieves this by targetting eukaryotic initiation factor 4GII (EIF4G2). Human OS cell lines U2OS and MG-63 were selected and assigned into blank, miR-379 mimics, miR-379 mimic negative control (NC), miR-379 inhibitors, miR-379 inhibitor NC, EIF4G2 shRNA, control shRNA, and miR-379 inhibitor + EIF4G2 shRNA group. The miR-379 expression and EIF4G2 mRNA expression were detected utilising quantitative real-time PCR (qRT-PCR) and the EIF4G2 protein expression using Western blotting. MTT assay, scratch test, Transwell assay, and flow cytometry were performed to determine the proliferation, migration, invasion, and cell cycle, respectively. In comparison with the miR-379 mimic NC group, the miR-379 mimics group had decreased EIF4G2 expression; the miR-379 inhibitors group indicated an increased EIF4G2 expression. Compared with the control shRNA group, the EIF4G2 expression was lower in the EIF4G2 shRNA group and the miR-379 expression was dropped in the miR-379 inhibitor + EIF4G2 shRNA group. The proliferation, migration, and invasion abilities of OS cells were reduced in the miR-379 mimics and EIF4G2 shRNA groups. The percentage of OS cells at the G0/G1 stage was increased, and the percentage at the S-stage was decreased in the miR-379 mimics and EIF4G2 shRNA groups. miR-379 may inhibit the proliferation, migration and invasion of OS cells through the down-regulation of EIF4G2.

Single nucleotide polymorphisms in the CD40 gene associate with the disease susceptibility and severity in knee osteoarthritis in the Chinese Han population: a case-control study.

BACKGROUND: This study explored the association between single nucleotide polymorphisms (SNPs) in the CD40 gene, rs4810485 G > T and rs1883832 C > T, as well as disease susceptibility and severity in knee osteoarthritis (KOA) in the Chinese Han population. METHOD: Peripheral venous blood was collected from 133 KOA patients (KOA group) and 143 healthy people (control group) from December 2012 to November 2013. The patients in the KOA group were classified into mild, moderate and severe groups according to disease severity. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to test the genotypes of all subjects. Binary logistic regression analyses were performed to analyze the risk factors for KOA. RESULTS: The KOA group was significantly different from the control group in living environment (P < 0.05). The KOA group had a lower frequency of TT genotype and T allele distribution of rs4810485 G > T compared with the control group, and rs4810485 G > T TT genotype and T allele may associate with low incidence of KOA (all P < 0.05). Besides, T allele and mutant homozygous TT genotype of rs1883832 C > T increased the susceptibility to KOA. Genotype and allele distribution of rs4810485 G > T and rs1883832 C > T were significantly different among the mild, moderate and severe groups (P < 0.05). There were more patients with rs4810485 G > T GG genotype and rs1883832 C > T TT genotype in the severe group than other genotypes of these two SNPs. According to binary logistic regression analysis, rs4810485 G > T TT genotype could alleviate disease severity in KOA, rs1883832 C > T TT genotype increase the severity of KOA and living environment is an important external factor that affects KOA severity. CONCLUSIONS: These data provide evidences that rs4810485 G > T and rs1883832 C > T in the CD40 gene may be associated with disease susceptibility and severity in KOA.

Single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone after arthroscopic knee surgery: a meta-analysis of randomized controlled trials.

PURPOSE: The purpose of this meta-analysis was to compare the efficacy and safety of single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone for pain management following arthroscopic knee surgery. METHOD: A comprehensive literature search was conducted to identify randomized controlled trials that used single-dose intra-articular bupivacaine plus morphine and bupivacaine alone for post-operative pain, using MEDLINE (1966-2014), Cochrane Library and EMBASE databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95 % confidence intervals (CIs) were calculated using RevMan statistical software. RESULT: A total of twenty-nine trials (n = 1167) were included. The post-operative visual analog scale (VAS) pain score of the bupivacaine plus morphine group compared with the bupivacaine alone group was significantly lower (WMD -1.15, 95 % CI -1.67 to -0.63, p < 0.0001). As far as safety, there was no significant difference in side effects between the two groups (RR 1.10, 95 % CI 0.59-2.04, n.s.). Sensitivity analyses suggested that the results of these two primary outcomes were stable and reliable. However, the current evidence did not suggest a superior effect with respect to the time to first analgesic request (WMD 51.33, 95 % CI -110.99 to 213.65, n.s.) and the number of patients requiring supplementary analgesia (RR 1.13, 95 % CI 0.92-1.39, n.s.). CONCLUSIONS: On the basis of the currently available literature, this study is the first to suggest that single-dose intra-articular bupivacaine plus morphine was shown to be significantly better than bupivacaine alone at relieving post-operative pain after arthroscopic knee surgery without increasing the short-term side effects. Routine use of single-dose intra-articular bupivacaine plus morphine is an effective way for pain management after arthroscopic knee surgery. LEVEL OF EVIDENCE: II.

Long noncoding RNAs in osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis that may affect all joint tissues. Unfortunately, the pathogenesis of OA is not fully understood yet and it cannot be cured totally. Long noncoding RNA (lncRNA) is a type of RNA molecule greater than 200 nucleotides, and deregulated expression of lncRNAs plays an important role in many types of inflammation-related diseases. In this review, we have focused on the association of lncRNAs in the development and progression of OA and the possibility of lncRNAs as a therapeutic agent for the treatment of OA. Some lncRNAs are up-regulated in OA cartilage, and plays a critical role in the degradation of chondrocyte extracellular matrix, consequently weakening the integrity of the articular cartilage. Therapeutic targeting of these lncRNAs has shown significant influence on controlling OA progression. More clinical studies are in focus for OA treatment strategy by targeting lncRNAs.

Network Meta-Analysis of Pharmacological Agents for Osteoporosis Treatment and Fracture Prevention.

BACKGROUND AND OBJECTIVE: Osteoporosis afflicts a large number of populations in the world and is featured by systemic impairment of bone mass and strength which may further trigger an increase in the risk of fragile fractures. This network meta-analysis (NMA) is designed to distinguish therapies more preferable than others with respect to efficacy and safety. METHODS: We searched the medical literature for relevant studies systematically. Both direct and indirect evidence were synthesized to compare the efficacy, described by odds ratios (OR) and 95% credible intervals (CrI). Moreover, the surface under cumulative ranking curve was calculated to rank probabilities with respect to clinical outcomes. The new non-vertebral fractures, hip and wrist fractures, and adverse events were evaluated in this NMA. RESULTS: Patients treated by alendronate, denosumab, teriparatide were associated with a reduced risk of new non-vertebral fractures compared to those treated by placebo. Alendronate, denosumab and zoledronic acid had better efficacy in preventing hip fractures. With respect to wrist fractures prevention, no significant difference was observed. Zoledronic acid exhibited significantly increased risk of adverse events than placebo, alendronate, denosumab, and raloxifene. According to SUCRA, teriparatide ranked highest in new non-vertebral fractures prevention, etidronate and denosumab balanced safety and efficacy well. CONCLUSION: In summary, teriparatide appeared to be the most efficacious drug for preventing new non-vertebral fractures, while etidronate and denosumab were preferable for balancing safety and efficacy well.

Associations of cigarette smoking, betel quid chewing and alcohol consumption with high-sensitivity C-reactive protein in early radiographic knee osteoarthritis: a cross-sectional study.

OBJECTIVES: High-sensitivity C-reactive protein (hsCRP) is possibly related to osteoarthritis (OA) progression and a variety of OA-related symptoms. This study aimed to examine associations between cigarette smoking, betel quid chewing and alcohol consumption and hsCRP in early radiographic knee OA. DESIGN: Cross-sectional health examination survey. SETTING: This primary study was conducted in a health examination centre in China. PARTICIPANTS: 936 (656 men and 280 women) patients with early radiographic knee OA were included in this cross-sectional study. PRIMARY AND SECONDARY OUTCOME MEASURES: Smoking status was classified into four levels based on daily smoking habit: 0/day, 1-10/day, 11-20/day and >20/day. Betel quid chewing and alcohol consumption status was divided into 'Yes' or 'No'. Early radiographic knee OA was defined as Kellgren Lawrence (K-L) grade 1 or 2 in at least one leg, and elevated hsCRP was assessed as ≥ 3.0 mg/L. RESULTS: After adjustment for a number of potential confounding factors, a significant positive association between cigarette smoking and hsCRP was observed in the multivariable model. The multivariable-adjusted ORs (95% CI) of elevated hsCRP (≥ 3.0 mg/L) in the second (1-10/day, n=133), third (11-20/day, n=59) and highest (>20/day, n=104) cigarette smoking categories were 1.54 (95% CI 0.91 to 2.61), 1.27 (95% CI 0.57 to 2.79) and 2.09 (95% CI 1.20 to 3.64), respectively, compared with the non-smoker category (n=640). In addition, there was a positive dose-response relationship between cigarette smoking and elevated hsCRP (p for trend=0.01). No significant associations between betel quid chewing and alcohol consumption and hsCRP were observed in the multivariable model. CONCLUSIONS: This study indicated that cigarette smoking was positively associated with serum hsCRP level in patients with early radiographic knee OA. However, in view of the nature of cross-sectional designs, the results need to be confirmed by further prospective studies.

Relation between phalangeal bone mineral density and radiographic knee osteoarthritis: a cross-sectional study.

BACKGROUND: Major reports have suggested that bone mineral density (BMD) is higher in patients with osteoarthritis (OA), while other studies do not agree. Our aim was to examine the cross-sectional association between phalangeal BMD and radiographic knee OA. METHODS: A total of 2855 participants were included in this study. Radiographic knee OA was defined as Kellgren-Lawrence (K-L) Grade ≥ 2 in at least one leg. BMD scans of the middle phalanges of the second, third and fourth digits of the nondominant hand were performed with a compact radiographic absorptiometry system (Alara MetriScan®). A multivariable logistic analysis model was applied to test the relation between phalangeal BMD with radiographic knee OA, the presence of knee osteophytes (OSTs), and knee joint space narrowing (JSN) after adjusting for a number of potential confounding factors. RESULTS: The multivariable-adjusted odds ratios with 95 % confidence intervals [ORs (95 % CI)] of radiographic knee OA across phalangeal BMDs were 1.08 (95 % CI 0.89-1.32) and 0.62 (95 % CI 0.45-0.86), respectively. The P for trend was 0.09. For the female population, the multivariable-adjusted ORs (95 % CI) of radiographic knee OA across phalangeal BMD were 1.01 (95 % CI 0.73-1.37) and 0.58 (95 % CI 0.38 - 0.87), respectively. The P for trend was 0.02. This positive finding, however, did not exist in the male subgroup. There was a significantly lower prevalence of OST in the osteoporosis (OP) group than in the normal group (OR = 0.59, 95 % CI 0.40-0.88; P for trend was 0.01). In contrast, the prevalence of JSN was significantly higher in the osteopenia group (OR = 1.22, 95 % CI 1.00-1.48) and the OP group (OR = 1.35, 95 % CI 1.00-1.84) than in the normal group. The P for trend was 0.02. CONCLUSIONS: This study observed lower odds for the presence of radiographic knee OA and OST in OP patients than in normal subjects. The prevalence of JSN was higher in the osteopenia and OP groups than in normal subjects.

Topical diclofenac therapy for osteoarthritis: a meta-analysis of randomized controlled trials.

The objective of this study was to evaluate the efficacy and safety of topical diclofenac therapy for osteoarthritis (OA). A meta-analysis of randomized controlled trials was conducted. A comprehensive literature search, covering the databases of Medline, the Cochrane Central Register of Controlled Trials, and EMBASE, was conducted in September 2014 to identify the randomized controlled trials which adopted the topical diclofenac therapy for OA. A total of nine papers were included in this meta-analysis. Topical diclofenac appears to be effective in both pain relief (standard mean differences (SMD) = 0.40; 95 % confidence interval (CI) 0.19 to 0.62; P = 0.0003) and function improvement (SMD = 0.23; 95 % CI 0.03 to 0.43; P = 0.03) when compared with the control group. The sensitivity analysis and subgroup analysis showed that the result of pain intensity was stable and reliable, while the result of physical function improvement was vague. With respect to safety, topical diclofenac demonstrated a higher incidence of adverse events such as dry skin, rash, dermatitis, neck pain, and withdrawal. Topical diclofenac is effective in pain relief as a treatment of OA. It may also have a potential effect in function improvement, which needs further studies to be explored. Although, some adverse effects were observed in the application of topical diclofenac, none of them was serious.

JNK pathway in osteosarcoma: pathogenesis and therapeutics.

CONTEXT: The c-Jun NH2-terminal kinase (JNK) is a member of the mitogen-activated protein kinase super family. JNK can phosphorylate a number of activator protein-1 components, activating several transcription factors, and thus, JNK signaling pathway is being involved in several carcinogenic mechanisms. OBJECTIVE: In this study, we have reviewed the recent updates of the association of JNK pathway with osteosarcoma (OS), which is one of the most common and aggressive bone malignancies. METHODS: In this review, we have explored the databases like PubMed, Google Scholar, MEDLINE, etc., and collected the most relevant papers of JNK signaling pathway involved in the pathogenesis and therapeutics of OS. RESULTS: Evidence showed that JNK is a master protein kinase that plays an important role in osteoblast proliferation, differentiation and apoptosis. Interesting reports showed that chemical JNK inhibitors reduce OS cell proliferation and metastasis. Many of the components of this pathway have now been identified and the application of JNK inhibitors has been proven to work in vivo in human and in animal models; however, JNK pathway has not been translated into clinical use. CONCLUSION: Therapeutic interventions of potent and selective inhibitors of JNK might provide promising therapeutic approaches for the treatment of OS, and could improve the survival rate and quality of life of OS patients.

Is posterior tibial slope associated with noncontact anterior cruciate ligament injury?

PURPOSE: This study aimed to: (1) examine whether the association between posterior tibial slope and noncontact ACL injury exists in Chinese population; (2) compare the reliability and consistency of the three methods (longitudinal axis, posterior and anterior tibial cortex axis) in lateral radiograph. METHODS: Case-control study contained 146 patients in total (73 noncontact ACL injuries and 73 meniscus injuries, matched for age and gender), which were verified by arthroscopy, MRI and physical examination. RESULTS: For the total population and the male subgroup, the mean posterior tibial slope of the ACL-injured group was significantly higher than that of the control group (P < 0.001). In addition, the longitudinal axis method exhibited the highest inter-rater (0.898) and intrarater reliability (0.928), whereas the anterior tibial cortex was the most variable (inter-rater reliability, 0.805; intrarater reliability, 0.824). The anterior tibial cortex method produced largest posterior tibial slope measurements (13.8 ± 3.3 for injury group; 11.6 ± 2.7 for control group), while the posterior tibial cortex method was the smallest (9.1 ± 3.1 for injury group; 7.2 ± 2.6 for control group). All three methods were not affected by age, sex, height, weight and BMI (n.s.). CONCLUSIONS: The results of this study suggested that an increased posterior tibial slope was associated with the risk of noncontact ACL injury in Chinese population. Meanwhile, the longitudinal axis method is recommended for measuring posterior tibial slope in lateral radiograph in future studies. Posterior tibial slope measured by longitudinal axis method may be used as predictor of ACL injury. LEVEL OF EVIDENCE: Case-control study, Level III.