Crosslinking chitosan with glucose via the modified Maillard reaction promotes the osteoinduction of mouse MC3T3-E1 pre-osteoblasts.

Bone defects are a common clinical issue, but therapeutic efficiency can be challenging in cases of more considerable traumas or elderly patients with degenerated physiological metabolism. To address this issue, a more suitable cell-biomaterial construct promoting bone regeneration has been extensively investigated, with the chitosan scaffold being considered a potential candidate. In this study, chitosan was crosslinked with different doses of glucose (CTS-10~50%Glc) using a modified Maillard reaction condition to develop a more appropriate cell-biomaterial construct. Mouse MC3T3-E1 pre-osteoblasts were seeded onto the scaffolds to examine their osteoinductive capability. The results showed that CTS-Glc scaffolds with higher glucose contents effectively improved the adhesion and survival of mouse MC3T3-E1 pre-osteoblasts and promoted their differentiation and mineralization. It was further demonstrated that the membrane integrin α5 subunit of pre-osteoblasts is the primary adhesion molecule that communicates with CTS-Glc scaffolds. After that, Akt signaling was activated, and then bone morphogenetic protein 4 was secreted to initiate the osteoinduction of pre-osteoblasts. The prepared CTS-Glc scaffold, with enhanced osteoinduction capability and detailed mechanism elucidations, offers a promising candidate material for advancing bone tissue engineering and clinical regenerative medicine. As a result, this study presents a potential tool for future clinical treatment of bone defects.

The role of postoperative piriformis fossa and greater trochanter tubercle distance to predict cutout failure after cephalomedullary nail fixation.

BACKGROUND: This study investigated the association between postoperative piriformis fossa and greater trochanter tubercle distance (distance from the deepest point of piriformis fossa to the most lateral greater trochanter tubercle [PG]) and cutout failure after cephalomedullary nail (CMN) osteosynthesis for intertrochanter fracture (ITF). A rotating femur model was designed to analyze PG variation during femur rotation. METHODS: From 2005 to 2010, 311 patients diagnosed of ITF (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association [AO/OTA] 31-A2 and A3) underwent CMN fixation at our institute were reviewed. Of these, 281 (90.3%) patients achieved union without complication, 21 (6.8%) had cutout failure, six (1.9%) had femoral head osteonecrosis, and three (1%) had nonunion during postoperative 2-year follow-up. The side difference of postoperative PG compared to contralateral uninjured hip (dPG) was analyzed between patients who had cutout failure and those who did not. In the rotating femur model, the PG was measured for every 2.5° increments of internal and external rotation from 0° to 50°. RESULTS: The dPG was significantly higher in the failure group (10.2 ± 4.2 vs 6.6 ± 3.5 mm, p <0.001). The odds ratio for lag screw cutout was 6.35 (95% CI, 1.10-11.6, p =0.003) for every 1 mm dPG increment. dPG exhibited high diagnostic performance in predicting cutout failure according to receiver operating characteristic curve analysis. The area under the curve was 0.774 (95% CI, 0.711-0.837). dPG yielded the greatest sensitivity (78.4%) and specificity (78.4%) to predict lag screw cutout when cutoff value being 8.65 mm. In rotating femur model, PG change from baseline demonstrated significant ( p <0.001) positive and negative correlation with increased external and internal rotation, respectively. CONCLUSION: Increased dPG is a risk factor of cutout failure for ITF osteosynthesis with CMN. In conjunction with tip-apex distance, fracture displacement, and reduction quality; dPG can help surgeons interpret postoperative radiograph and predict failure. However, it should be noticed that a proper and standard patient positioning is critical for accurate dPG measurement.

The dynamics of red Noctiluca scintillans in the coastal aquaculture areas of Southeast China.

Noctiluca scintillans (NS) adds an aesthetic appeal to many coastal areas because of their bioluminescence. An intense bloom of the red NS frequently occurs in the coastal aquaculture region of Pingtan Island in Southeastern China. However, when NS exceeds in abundance, it causes hypoxia which has devastating impacts on the aquaculture. This study was conducted in the Southeastern part of China with an aim to examine the relationship between the profusion of NS and its impacts on marine environment. Samples from four stations on Pingtan Island were collected for 12 months (January to December 2018) and were later analyzed in laboratory against five parameters, namely temperature, salinity, wind speed, dissolved oxygen, and chlorophyll a. Results showed that the NS blooms were particularly active during the months of May and June in the Pingtan Island area. The seawater temperatures during that time were recorded between 20 and 28.8 °C indicating the optimum survival temperature for NS. The NS bloom activity ceased above 28.8 °C. A principal component analysis (PCA) indicated that the richness of NS was positively associated with temperature and salinity, whereas there was a significant reverse correlation between NS accumulation and wind speed. NS is a heterotrophic dinoflagellate and relies on the predation of algae for reproduction; therefore, a significant correlation was observed between NS abundance and chlorophyll a concentration, and an inverse correlation was observed between NS and phytoplankton abundance. Additionally, red NS growth was observed immediately following the diatom bloom, suggesting that phytoplankton, temperature, and salinity are the essential factors in the evolution, progression, and termination of NS growth.

Natural progression of the pubofemoral distance with age and its correlation with future acetabular index.

OBJECTIVES: This study investigated the progression of pubofemoral distance (PFD) with age and assessed the correlation between PFD and late acetabular index (AI) measurements. METHODS: This prospective observational study was conducted between January 2017 and December 2021. We enrolled 223 newborns who underwent the first, second, and third hip ultrasounds, and pelvis radiograph at a mean age of 18.6 days, 3.1 months, 5.2 months, and 6.8 months, respectively. The difference between PFD measured at serial ultrasounds and the correlation with AI were analyzed. RESULTS: The PFD increased significantly (p < 0.001) at serial measurements. The mean PFD at the first, second, and third ultrasounds were 3.3 (2.0-5.7), 4.3 (2.9-7.2), and 5.1 (3.3-8.0) mm, respectively. The PFD at three ultrasounds were all significantly (p < 0.001) and positively correlated with AI, with the Pearson correlation coefficients being 0.658, 0.696, and 0.753 for the first, second, and third ultrasounds, respectively. Using AI as reference, the diagnostic ability of PFD was calculated by the areas under the receiver operating characteristic curve, which was 0.845, 0.902, and 0.938 for the first, second, and third PFD, respectively. For the first, second, and third ultrasounds, PFD cutoff values of ≥ 3.9, ≥ 5.0, and ≥ 5.7 mm, respectively, yielded the greatest sensitivity and specificity in predicting late abnormal AI. CONCLUSION: The PFD naturally progresses with age and is positively correlated with AI. The PFD has potential for predicting residual dysplasia. However, the cutoff for abnormal PFD values may require adjustment according to the patient's age. KEY POINTS: • The pubofemoral distance measured in hip ultrasonography naturally increases as the infant's hips mature. • The early pubofemoral distance demonstrates a positive correlation with late acetabular index measurements. • The pubofemoral distance may help physicians predict abnormal acetabular index. However, the cutoff for abnormal pubofemoral distance values may require adjustment according to patient's age.

Implementing the AAOS Guidelines for Screening of Developmental Dysplasia of the Hip Before the Age of 6 Months in Taiwan.

BACKGROUND: The prevalence of developmental dysplasia of the hip (DDH) has been considered to be low in East Asia, but this may be incorrect because of inconsistent diagnostic definitions and testing criteria. In 2015, the AAOS released guidelines for systematic screening for DDH in newborns. We implemented these guidelines and compared DDH incidence and outcomes before and after their implementation. METHODS: We used a historic comparison cohort of newborns with DDH between July 2015 and May 2017 before guideline implementation (the preguideline group); their data were retrieved using electronic medical records. In this group, the newborns received general hip screening without systemic follow-up. The postguideline group included newborns who were screened for hip dysplasia and followed up per the AAOS guidelines between July 2017 and May 2019. Their data were prospectively collected. The primary outcome in the postguideline group was DDH incidence. Other outcomes included rates of referral, surgery, and complications, and DDH prognosis. RESULTS: The preguideline and postguideline groups included 3534 and 2663 newborns, respectively, of whom 49 (1.1%) and 225 (8.4%), respectively, were referred to the pediatric orthopaedic clinic enrolled. In the postguideline group, 35 patients were diagnosed as having DDH (incidence: 1.3%, 95% CI: 0.8%-1.9%). Both the incidence and referral rates were significantly higher in the postguideline group than in the preguideline group. Furthermore, the mean age at referral was 6.7±10.06 months and 0.9±0.25 months in the preguideline and postguideline groups, respectively, indicating a potential for early treatment in the postguideline group. Finally, the female sex was identified as a risk factor for residual hip dysplasia at 6 months of age. CONCLUSION: DDH incidence in East Asia seems comparable to that in Western countries. Implementing the AAOS guidelines increased the diagnosis rate and opportunity for early treatment initiation, thus potentially avoiding surgical intervention. Nevertheless, residual DDH may be detected in some patients at 6 months of age, particularly in female infants. LEVEL OF EVIDENCE: Level IV.

Is double-crossed retrograde elastic stable intramedullary nailing an alternative method for the treatment of diaphyseal fractures in the adult humerus?

BACKGROUND: The aim of this study was to compare two techniques for the surgical treatment of diaphyseal fractures in the adult humerus: double-crossed retrograde elastic stable intramedullary nailing (DCR-ESIN) and limited-contact dynamic compression plate (LC-DCP). METHODS: This was a retrospective study conducted at a single hospital. We included 122 patients with diaphyseal fractures of the humerus who had received DCR-ESIN or LC-DCP from January 2011 to January 2017. We compared union rates, union times, disabilities of the arm, shoulder, and hand (DASH) scores at the postoperative 1-year follow-up, and complications between the two groups. RESULTS: Plating management was performed in 63 patients, while DCR-ESIN was performed in 59 patients. The union rate was higher in the DCR-ESIN group than in the LC-DCP group (100% vs. 90.5%; p = 0.052). The union time was shorter in the DCR-ESIN group than in the LC-DCP group (12.0 weeks vs. 14.8 weeks; p < 0.001). The intraoperative blood loss and operative time were less in the DCR-ESIN group than in the LC-DCP group (76.4 min vs. 129.5 min; p < 0.001; 60.9 ml vs. 244.8 ml; p < 0.001, respectively). The DCR-ESIN had superior results for the rate of overall complications (p = 0.006). At the 1-year follow-up, the DCR-ESIN group had better DASH scores than the LC-DCP group (p = 0.014). CONCLUSIONS: The DCR-ESIN technique, used to treat diaphyseal fractures of the humerus, has shorter operative times, less intra-operative blood loss, shorter union times, and better functional outcomes at 1-year follow-up than the LC-DCP technique. DCR-ESIN may be an alternative method for the surgical treatment of diaphyseal humeral fractures in adults.

Association between early sonographic findings and acetabular index at the age of 6 months: a prospective observational study.

BACKGROUND: This study investigated the association between early Graf classification and femoral head coverage (FHC) with the acetabular index (AI) at the age of 6 months. METHODS: A prospective observational study was conducted between 2017-2018. Patients requiring Pavlik harness treatment and patients with syndromic dislocation or neurogenic dislocation were excluded. In total, 169 newborns with the first ultrasound performed at the mean age of 12.3 (0-15) days, the second ultrasound performed at the mean age of 3.2 (2.5-4.1) months, and the AI measured at the age of 6.6 (4.3-7.1) months were enrolled. The correlation between the AI and first and second alpha angles and FHC measurements, and the correlation of dysplasia in early ultrasound with dysplasia in the AI were analyzed. RESULTS: At the first ultrasound, only the FHC (P = .02) demonstrated a significant negative correlation with the AI. At the second ultrasound, both the alpha angle (P < .01) and FHC (P < .01) demonstrated a significant negative correlation with the AI. With the AI as a reference, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were found to be 77%, 7%, 5%, and 81%, respectively, for the first Graf; 91%, 37%, 9%, and 98%, respectively, for the first FHC measurement; 82%, 90%, 35%, and 99%, respectively, for the second Graf; and 95%, 97%, 68% and 99%, respectively, for the second FHC measurement. CONCLUSIONS: FHC and alpha angle exhibited significant negative correlations with the AI at six months, both ultrasound parameters may have the potential to predict AI in DDH screening. Compared to the ultrasound measurements taken at 2 weeks, Graf and FHC at 3 months demonstrated superior sensitivity, specificity, PPV, and NPV to detect abnormal AI. The best timing to perform ultrasound examination may need further research.

[Mechanism of Potentilla discolor in treating UC by regulating mitochondrial autophagy].

To evaluate the therapeutic effect of Potentilla discolor on 2,4,6-trinitrobenzensulfonic acid(TNBS)-induced experimental ulcerative colitis(UC) in rats and to determine its therapeutic mechanism through mitochondrial autophagy, immune cells, and cytokines. A rat model of UC was established by TNBS-ethanol enema. Rats were divided into six groups: control, UC model, sulfasalazine(positive drug), and high-dose, moderate-dose, and low-dose ethanol extract groups. After 14-day continuous administration of the corresponding drugs, the disease activity index(DAI) and hematoxylin and eosin(HE) were evaluated. The morphological structure of mitochondria was observed by using transmission electron microscope(TEM), mitophagy-related mRNA expression was detected by using Real-time quantitative polymerase chain reaction(qRT-PCR), immune cell differentiation in rat serum was detected by using flow cytometry(FCM), and cytokine expression in colon tissues of rats was detected by protein microarray. The results showed that compared with the model group, each dose group of P. discolor could significantly reduce the DAI of UC model rats, and decrease the degree of inflammatory cells infiltration in the colon tissue of UC model rats. Meanwhile the expressions of T cells and Th cells in the serum increased significantly, the expression of Tc cells in the serum decreased significantly. Transmission electron microscope found that there was fusion of mitochondria and lysosomes in the colon tissue of the administration group. The expressions of mitochondrial autophagy related genes NF-κB, p62 and parkin were significantly increased in colon tissues. The results of protein chip showed that compared with the model group, the high dose group of P. discolor could significantly regulate the expression of cytokines. In conclusion, these results suggested that P. discolor improved TNBS-induced acute ulcerative colitis in rats by regulating the mitochondrial autophagy and the inflammatory factor expression.

Effects of Visfatin on Intracellular Mechanics and Catabolism in Human Primary Chondrocytes through Glycogen Synthase Kinase 3ß Inactivation.

Osteoarthritis (OA) is still a recalcitrant musculoskeletal disease on account of its complex biochemistry and mechanical stimulations. Apart from stimulation by external mechanical forces, the regulation of intracellular mechanics in chondrocytes has also been linked to OA development. Recently, visfatin has received significant attention because of the clinical finding of the positive correlation between its serum/synovial level and OA progression. However, the precise mechanism involved is still unclear. This study determined the effect of visfatin on intracellular mechanics and catabolism in human primary chondrocytes isolated from patients. The intracellular stiffness of chondrocytes was analyzed by the particle-tracking microrheology method. It was shown that visfatin damages the microtubule and microfilament networks to influence intracellular mechanics to decrease the intracellular elasticity and viscosity via glycogen synthase kinase 3ß (GSK3ß) inactivation induced by p38 signaling. Further, microtubule network destruction in human primary chondrocytes is predominantly responsible for the catabolic effect of visfatin on the cyclooxygenase 2 upregulation. The present study shows a more comprehensive interpretation of OA development induced by visfatin through biochemical and biophysical perspectives. Finally, the role of GSK3ß inactivation, and subsequent regulation of intracellular mechanics, might be considered as theranostic targets for future drug development for OA.

Interobserver agreement and clinical disparity between the Graf method and femoral head coverage measurement in developmental dysplasia of the hip screening: A prospective observational study of 198 newborns.

ABSTRACT: Ultrasonography is the ideal tool for assessing hip morphology in infants younger than 6-month-old. This study assessed the interobserver agreement and clinical disparities of the 2 most widely used ultrasound (US) methods, the Graf method, and femoral head coverage (FHC) measurement.A prospective observational study (STROBE compliant) of 2024 newborns was conducted between January 2017 and December 2018. Hip US was conducted on all newborns with abnormal Barlow and Ortolani maneuvers as well as on 50 randomly selected normal newborns. The physical examination and US were performed by a senior pediatric orthopedic surgeon with musculoskeletal sonography certification. Three observers with different levels of experience interpreted the images by using the Graf method and FHC. We analyzed the intraclass correlation coefficient, Cohen kappa, and the disparity between the clinical findings of the 2 methods.A total of 198 newborns (9.8%) presented with clinical instability, including 193 subluxatable hips in 168 patients (84.8%) and 45 dislocatable/dislocated hips in 30 patients (15.2%). The mean age at US examination was 11.69 days (range: 0-18 days). The intraclass correlation coefficient was .71 (95% CI: 0.55-0.83) for FHC, 0.63 (95% CI: 0.38-0.78) for the alpha angle, and 0.47 (95% CI: 0.16-0.69) for beta angle. The Cohen kappa coefficients of Graf type were 0.19 (95% CI: 0.03-0.35), 0.39 (95% CI: 0.20-0.58), and 0.17 (95% CI: 0.02-0.32) between observers 1 and 2, observers 1 and 3, and observers 2 and 3, respectively. Based on the Graf method, 14% of the stable hips had abnormal USs; by contrast, 19.2% of the subluxatable hips and 17.8% of the dislocatable/dislocated hips had normal Graf morphologies. In USs interpreted using FHC, 16% of stable hips demonstrated abnormal coverage, whereas 13.5% of subluxatable hips and 4.4% of dislocatable/dislocated hips had normal FHC.Incidence of clinically detectable hip instability was 9.8% among newborns in our series. Both alpha angle and FHC ratio revealed substantial interobserver agreement while beta angle achieved moderate agreement. FHC ratio possesses higher sensitivity and similar specificity compared with the Graf method when screening unstable hips.Level II, development of diagnostic criteria on basis of consecutive patients.

[Diversity and community characteristics of organic phosphate-mineralizing bacteria in the sea area between Minjiang Estuary to Pingtan.] / 闽江口-å¹³æ½­æµ·åŸŸæœ‰æœºè§£ç£·èŒå¤šæ ·æ€§åŠç¾¤è½ç‰¹å¾.

Microbial mineralization of organic phosphorus is an important component of marine phosphorus cycle. The research on organic phosphate-mineralizing bacteria (OPB) is helpful to reveal microbial driving mechanism of organic phosphorus mineralization in eutrophic sea area. The diversity and community characteristics of OPB were examined by Illumina high-throughput sequencing using the primer sets phoX in the sea area between Minjiang Estuary to Pingtan in April (spring) and July (summer) 2019. The results showed that the Shannon index of OPB in the surface seawater samples ranged from 3.21 to 7.91, and that the diversity at each station was greater in spring than that in summer. Shannon index of OPB in the sediment samples ranged from 2.04 to 8.70, which was greater in summer than that in spring. Shannon index of OPB in surface seawater of each station was higher than that of sediment in spring, while it was in adverse in summer. Nine phyla of OPB were detected in surface seawater, with Proteobacteria and Cyanobacteria being the most abundant. Tweleve phyla of OPB were detected in the sediments, with Proteobacteria and Bacteroidetes being the most dominant. OPB community composition at the genus level showed obvious spatio-temporal variation. Leisingera, Phaeobacter, Thalassococcus, and Pseudomonas were the major genera in the seawater in spring, while Synechococcus, Halioglobus, Roseovarius, Phaeo-bacter, Sulfitobacter, and Hyphomonas were the major genera detected in summer. Leisingera, Phaeobacter, Vibrio, and Sulfitobacter were major genera in the sediment in spring, while Azospirillum, Aminobacter, Sulfurifustis, Burkholderia, and Thiohalobacter were the major genera in summer. A large number of unclassified OPB were detected in both surface seawater and sediment. The redundancy analysis results showed that dissolved oxygen, water temperature, pH, dissolved inorganic nitrogen, NO2--N, and NO3--N had great influences on community distribution of OPB in the surface seawater. The abundant OPB in the surface seawater and sediment might play an important role in phosphorus cycle in this sea area.

Stearoyl-CoA Desaturase-1 Attenuates the High Shear Force Damage Effect on Human MG63 Osteosarcoma Cells.

Mechanical regulation is known as an important regulator in cancer progression and malignancy. High shear force has been found to inhibit the cell cycle progression and result in cell death in various cancer cells. Stearoyl-CoA desaturase (SCD)-1, one of the important lipogenic enzymes, has recently been indicated as a potential pharmaceutical target in cancer therapy. In this study, we determined whether the cell fate control of shear force stimulation is through regulating the SCD-1 expression in cancer cells. Human MG63 osteosarcoma cells were used in this study. 2 and 20 dynes/cm2 shear forces were defined as low and high intensities, respectively. A SCD-1 upregulation in human MG63 osteosarcoma cells under 20, but not 2, dynes/cm2 shear force stimulation was shown, and this induction was regulated by Smad1/5 and peroxisome proliferator-activated receptor δ (PPARδ) signaling. Moreover, gene knockdown of PPARδ and SCD-1 in human MG63 osteosarcoma cells attenuated the differentiation inhibition and resulted in much more cell death of high shear force initiation. The present study finds a possible auto-protective role of SCD-1 upregulation in high shear force-damaged human MG63 osteosarcoma cells. However, its detailed regulation in the cancer fate decision of high shear force should be further examined.

[Community characteristics of polyphosphate accummulating organisms in the heart sediment of three reservoirs in Fujian Province, China.] / 福建省3座水库库心沉积物聚磷菌的群落特征.

Polyphosphate accummulating organisms (PAOs) play an important role in the phosphorus metabolic cycling in the sediment of reservoir. We assessed the diversity and community structure of PAOs in the sediments by T-RFLP and clone sequencing which targeted ppk1 gene at the hearts of three reservoirs (Jiulongjiangxipi reservoir, Sanshiliujiao lake reservoir and Dongyaxi reservoir) in Fujian Province. The results showed that the diversity of PAOs varied among different reservoirs, though not statistically significant. The diversity of PAOs in the Sanshiliujiao lake reservoir was highest (Shannon index H=2.89±0.03, Simpson index D=0.06±0.01). The community structure of the PAOs in the Sanshiliujiao lake reservoir was most complicated, consistent with the results of the T-RFLP. The differences of dominant PAOs genera in three reservoirs were distinct, mainly concentrated in the Proteobacteria, Actinobacteria and Acidobacteria. The percentage of those three phylum accounted for 74.5%, 85.0% and 75.0%, respectively, of the total PAOs. The dominant groups in each reservoir sediment were Anaeromyxobacter and Solibacter. Various forms of phosphorus had certain influence on the diversity of PAOs. There were significantly correlation between Fe/Al-P and PAOs diversity and community structure. The dominant genus in the three reservoirs, Anaeromyxobacter, was positively correlated with all forms of phosphorus and significantly correlated with insoluble phosphorus such as OP and Ca-P, while Solibacter was negatively correlated with all forms of phosphorus. The results suggested that PAOs had important impacts on the phosphorus cycle of sediment in eutrophicatied reservoirs.

Augmentation Plate Fixation for Treating Subtrochanteric Fracture Nonunion.

BACKGROUND: The treatment of subtrochanteric fracture nonunion is challenging. Although revision with either an intramedullary or extramedullary device had been advocated with acceptable results, complications that require secondary procedures still arise. The use of an intramedullary device with augmentation plate fixation is a well-known approach for femoral or tibial diaphyseal nonunion. However, this approach has not previously been reported for subtrochanteric fracture nonunion. MATERIALS AND METHODS: A series of 21 cases of subtrochanteric fracture nonunion treated with an intramedullary device in combination with augmentation side plating were collected and retrospectively reviewed after an average of 18 months of followup. Fourteen patients with a prior well-fixed intramedullary device were treated with side plating and bone grafting. Seven patients underwent revision nailing in addition to side plating and bone grafting. RESULTS: All fractures united well without major complication. The average time to union was 7.1 months. CONCLUSION: The use of an intramedullary device with augmentation plate fixation is a reliable and decisive procedure for treating subtrochanteric fracture nonunion that produces satisfactory results with a low complication rate.

Radiographic risk factors for predicting failure of geriatric intertrochanteric fracture treatment with a cephalomedullary nail.

BACKGROUND: The cephalomedullary nail is the most common device used to treat unstable intertrochanteric fractures (ITFs) (AO/OTA 31-A2 and A3) in the geriatric population. However, there is lack of radiological parameter to evaluate the entry point; hence, this study reports a new radiological parameter to evaluate the entry point of the nail. Besides, other risk factors were also examined. METHODS: A retrospective study on the geriatric population with unstable ITFs was conducted from July 2011 to December 2014. A total of 136 patients were enrolled in this study; they received treatment with Gamma-3 nails (Stryker, Mahwah, NJ, USA) and were followed for at least 1 year. Demographic data, radiological parameters, and side-difference of the distance from the piriformis fossa to the greater trochanteric tubercle in the anteroposterior view (dPG) were compared between the union and failure groups. Student's t test, χ test, and multiple logistic regression were used in the statistical analyses. RESULTS: The overall failure rate was 13.23% (18 patients). Sex, tip-apex distance (TAD), and dPG were significantly different between the failure and union groups in multivariate analyses. Using a dPG > 6 mm as a reference, patients with a dPG > 6 mm had an odds ratio of 7.64 for failure relative to a dPG < 6 mm. CONCLUSION: This study provides additional evidence demonstrating that sex and TAD have significant effects on the outcomes of unstable ITFs after nailing. Moreover, the newly reported radiological parameter, dPG, can be used to predict the failure of ITFs treated using cephalomedullary nails.

The efficacy of a drug holiday test on two-stage revision for infected total knee arthroplasty.

BACKGROUND: We compared the clinical efficacy of normal C-reactive protein (CRP) expression (<1.0 mg/dL), with a 2-week drug holiday test (DHT) and no drug holiday test (DHT) as a reimplantation criterion, based on subsequent infections after a two-stage revision of a total knee arthroplasty of a periprosthetic joint infection (PJI). METHODS: In a 10-year review of 58 patients (mean age: 73.3-years-old; mean follow-up: 46.2 months), there were 31 patients in the DHT group and 27 patients in the DHT group. Primary outcome was recurrent infection rate. Secondary outcomes included length of hospital stay in the revision stage and CRP resurge one day before revision. RESULTS: We reported that the CRP resurge rate in the DHT group (0%) was significantly (p = 0.029) lower than that in the DHT group (16.1%) one day before the revision. The DHT group also had a significantly shorter mean length of stay (LOS) in the hospital (9.6 vs 12.7 days, p = 0.015) and a nonsignificantly lower subsequent infection rate (14.8% vs 29%, p = 0.195). CONCLUSION: We found that disciplined use of DHT as a reimplantation criterion reduced CRP resurges before reimplantation and yielded a shorter LOS afterward. DHT positively affected the subsequent mid-term infection rate after PJI treatment.

The elderly have similar outcomes compared to younger patients after ORIF with locking plate for comminuted proximal humerus fracture.

OBJECTIVE: The aim of this study was to compare clinical and radiological outcomes of elder and younger patients with comminuted proximal humerus fracture treated with osteosynthesis with locking plate. METHODS: A total of 70 patients (30 males and 40 females; mean age 65.4 years) operated on for Neer 3- or 4-part proximal humeral fractures between 2010 and 2016 and followed for at least one-year were included in the study. The reduction was achieved through intraosseous window to minimize soft tissue stripping in all patients and structural allograft at metaphyseal diaphyseal junction was used aggressively to resist varus force. Group 1 consisted of 32 patients aged 70 or older (14 males and 18 females; mean age: 77.8 ± 5.1), while Group 2 consisted of 38 patients younger than 70 (16 males and 22 females; mean age: 58.2 ± 9.3). The groups were compared for their clinical and radiological outcomes. RESULTS: There was no significant difference in clinical outcomes by Oxford score (54.8 ± 2.7 vs 56.6 ± 3.4, p = 0.13) and ASES score (89.7 ± 5.7 vs 90.8 ± 8.2, p = 0.68). Two groups had similar radiological outcomes regarding neck shaft angle, greater tip height and offset. However, group 2 had better final shoulder forward elevation (162.6 ± 8.7 vs 135.4 ± 14.7ß, p < 0.05) and shorter duration to achieve maximal range of motion (4.37 ± 2.37 vs 8.14 ± 3.25 months, p < 0.05) than group 1. Two groups had similar complication rates (9.4% vs 7.9%). All the complications were related to greater tuberosity including mal-reduction and avulsion. CONCLUSION: With the prerequisite of good alignment with robust medial cortical support and untouched soft tissue over medial metaphysis area via intra-osseous reduction, comminution of proximal humeral fracture can achieve satisfactory result and low complication rate by osteosynthesis with locking plate system, regardless of age. In addition, we suggested to use structural bone graft for comminuted medial cortex fracture with multiple fragments or bony defect more than 2 cm. LEVEL OF EVIDENCE: Level III Therapeutic study.

2 dyn/cm2 shear force upregulates kruppel-like factor 4 expression in human chondrocytes to inhibit the interleukin-1ß-activated nuclear factor-κB.

The shear force effect on human chondrocytes is time and magnitude dependent. Recently, kruppel-like factor (KLF) 4 has been identified as a pleiotropic protein and its activity in cells is dependent on different stimuli and/or cell types. The role of KLF4 in chondrocytes is still unclear and there has been no report determining whether shear force regulates KLF4 levels in chondrocytes. Hence, this study was carried out to investigate the role of KLF4 in human chondrocytes under shear force stimulation and the underlying mechanism. Human primary and SW1353 chondrocytes were used in this study. The shear forces at 2, 5, or 15 dyn/cm2 intensity were applied to both types of human chondrocytes. The specific small interfering RNAs, activators, and inhibitors were used to study the detailed mechanism of shear force. The presented results showed that 2, but not 5 and 15, dyn/cm2 shear force increases KLF4 expression in human primary and SW1353 chondrocytes. Extracellular signal-regulated kinase 5 induced peroxisome proliferator-activated receptor γ transcription activity to increase KLF4 transcription. Moreover, the KLF4 induction in human chondrocytes in response to 2 dyn/cm2 shear force could attenuate interleukin (IL)-1ß-stimulated nuclear factor-κB activation. These results elucidate the role of KLF4 in antagonizing the effect of IL-1ß in human chondrocytes under 2 dyn/cm2 shear force stimulation and provide a possible mechanism to demonstrate the protection of moderate forces or exercises in cartilage.

HLA-B*07, HLA-DRB1*07, HLA-DRB1*12, and HLA-C*03:02 Strongly Associate With BMI: Data From 1.3 Million Healthy Chinese Adults.

Strong associations between HLA alleles and infectious and autoimmune diseases are well established. Although obesity is also associated with these diseases, the relationship between HLA and obesity has not been systematically investigated in a large cohort. In the current study, we analyzed the association of HLA alleles with BMI using data from 1.3 million healthy adult donors from the Chinese Marrow Donor Program (CMDP). We found 23 HLA alleles, including 12 low-resolution and 11 high-resolution alleles, were significantly associated with BMI after correction for multiple testing. Alleles associated with high BMI were enriched in haplotypes that were common in both Chinese and European populations, whereas the alleles associated with low BMI were enriched in haplotypes common only in Asians. Alleles B*07, DRB1*07, DRB1*12, and C*03:02 provided the strongest associations with BMI (P = 6.89 × 10-10, 1.32 × 10-9, 1.52 × 10-9, and 4.45 × 10-8, respectively), where B*07 and DRB1*07 also had evidence for sex-specific effects (Pheterogeneity = 0.0067 and 0.00058, respectively). These results, which identify associations between alleles of HLA-B, DRB1, and C with BMI in Chinese young adults, implicate a novel biological connection between HLA alleles and obesity.

Leptin induces MMP1/13 and ADAMTS 4 expressions through bone morphogenetic protein-2 autocrine effect in human chondrocytes.

The induction of bone morphogenetic protein (BMP)2 in injured and arthritis articular cartilage has been proposed, but the precise mechanism has not been clearly clarified. Our previous study has found that leptin could stimulate the BMP2 autocrine effect to increase the anabolic collagen II expression when it initiates the catabolic response in human chondrocytes. It has been suggested that this BMP2 autocrine effect contributes to a reparative role in leptin-stimulated human chondrocytes. In this study, we further determined whether this BMP2 autocrine effect also affect the expressions of catabolic matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS). Human primary and SW1353 chondrocytes were used in this study. It was shown that leptin could induce the expressions of MMP1, 3, and 13 and ADAMTS4 and 5 in both human primary and SW1353 chondrocytes. Leptin-increased MMP1/13 (not MMP3) and ADAMTS4 (not ADAMTS5) expressions were affected by the leptin-upregulated BMP2 and its specific downstream Smad1/5 signaling. Moreover, both HDAC3 and 4 are involved in regulating leptin-induced BMP2 upregulation and then affect MMP1 and 13 and ADAMTS4 expression. Both HDAC3 and 4 also affect leptin-increased MMP3 mRNA expression but not through BMP2 autocrine effect of leptin induction. Our results further elucidated the role of BMP2 autocrine effect in matrix-degrading enzymes expressions under leptin stimulation. The findings in this study provide new insights into the possible mechanism of BMP2 induction in leptin-stimulated chondrocytes and in leptin-induced OA development.