Lipopolysaccharide modification enhances the inhibitory effect of clodronate liposomes on hepatic fibrosis by depletion of macrophages and hepatic stellate cells.

Hepatic fibrosis is a complex chronic liver disease in which both macrophages and hepatic stellate cells (HSCs) play important roles. Many studies have shown that clodronate liposomes (CLD-lipos) effectively deplete macrophages. However, no liposomes have been developed that target both HSCs and macrophages. This study aimed to evaluate the therapeutic efficacy of lipopolysaccharide-coupled clodronate liposomes (LPS-CLD-lipos) and the effects of liposomes size on hepatic fibrosis. Three rat models of hepatic fibrosis were established in vivo; diethylnitrosamine (DEN), bile duct ligation (BDL), and carbon tetrachloride (CCl4). Hematoxylin and eosin staining and serological liver function indices were used to analyze pathological liver damage. Masson's trichrome and Sirius red staining were used to evaluate the effect of liposomes on liver collagen fibers. The hydroxyproline content in liver tissues was determined. In vitro cell counting kit-8 (CCK-8) and immunofluorescence assays were used to further explore the effects of LPS modification and liposomes size on the killing of macrophages and HSCs. Both in vitro and in vivo experiments showed that 200 nm LPS-CLD-lipos significantly inhibited hepatic fibrosis and the abnormal deposition of collagen fibers in the liver and improved the related indicators of liver function. Further results showed that 200 nm LPS-CLD-lipos increased the clearance of macrophages and induced apoptosis of hepatic stellate cells, significantly. The present study demonstrated that 200 nm LPS-CLD-lipos could significantly inhibit hepatic fibrosis and improve liver function-related indices and this study may provide novel ideas and directions for hepatic fibrosis treatment.

Successful Revision with INTERTAN for a Blade Cut Through in PFNA Fixation: A Case Report.

BACKGROUND: Implant cut-out or cut-through remains a common cause of cephalomedullary nail failure and patient morbidity following surgical treatment of intertrochanteric femur fractures. In patients not suitable for conversion to total hip arthroplasty, which can involve long operation times and substantial blood loss, as well as a higher risk of periprosthetic fracture and dislocation postoperatively, revision with another internal fixation is an alternative option. If the femoral head can be preserved as much as possible to avoid eventual joint replacement while the internal fixation failure is solved, the quality of life of patients will be significantly improved. CASE PRESENTATION: This current case describes a successful clinical use of a salvage procedure that allows the surgeon to avoid joint arthroplasty using INTERTAN to solve internal fixation failure caused by cut-through of Proximal Femoral Nail Antirotation-II (PFNA-II). Four years after closed reduction and internal fixation of the right femur, the patient had immobilizing right hip pain and mobility disorder. X-ray examination revealed contraction of the neck of the right femur and cut-through of the helical blade of the PFNA-II. After the revision operation, he recovered well and presented no grown pain or discomfort in weight-bearing. Conventional radiographs at 1-year follow-up showed a healed fracture, with no implant migration. CONCLUSION: Main nail exchange and revision with INTERTAN can be considered a salvage procedure in selected cases to revise a failed fixation with PFNA, which solves internal fixation failure as well as preserves the femoral head.

Doxorubicin-liposome combined with clodronate-liposome inhibits hepatocellular carcinoma through the depletion of macrophages and tumor cells.

Macrophages in the liver have capacities of capturing and phagocytosing nanocarriers. Macrophages also play an important role in the inflammatory microenvironment and in the tumorigenesis, development and progression of hepatocellular carcinoma (HCC). Several studies have shown that depletion of macrophages is a viable strategy for drug delivery and tumor microenvironment regulation. We prepared liposomes containing doxorubicin and clodronate using an ammonium sulfate gradient and thin film hydration method. The repressive therapeutic effects of liposomes were compared by intrasplenic injection at different stages of a primary HCC model induced by diethylnitrosamine (DEN) in rats. Doxorubicin-liposome (DOX-LIP) and clodronate-liposome (CL-LIP) about 180-200 nm were successfully prepared and characterized. We found that DOX-LIP combined with CL-LIP could effectively inhibit the occurrence and development of liver cancer without major organ damage and side effects. The combination of doxorubicin and clodronate liposomes notably decreased hepatic CD68 + macrophages, enriched DOX in plasma and accumulated it for a long time in the liver and spleen, thus improving the tumor microenvironment, inhibiting the activation of hepatic progenitor cells (HPCs) and promoting the apoptosis of tumor cells, and finally producing the inhibitory and therapeutic effects of HCC in rats. Results of this study were expected to provide a new prospect for the chemotherapy of HCC.

Fatty infiltration of hip muscles and trochanteric soft tissue thickness are associated with hip fractures in the elderly.

PURPOSE: Apart from bone conditions, muscle and soft tissue parameters might also influence hip fractures. We aimed to evaluate the association between hip muscle and trochanteric soft tissue parameters and hip fractures. METHODS: We retrospectively reviewed 60 patients with hip fractures and 114 controls without hip fractures. Cases and controls were matched for age, sex, and body mass index using propensity score matching. Muscle cross-sectional area (CSA), mean attenuation, and fatty infiltration rate (FIR) (proportion of intramuscular fat content) were measured on CT images for the gluteus maximus, the gluteus medius/minimus, and the anterior and medial compartments of the upper thigh. Trochanteric soft tissue thickness (TSTT) and femoral neck attenuation were also measured. Univariate and multivariate analyses were conducted to identify potential risk factors of hip fractures. RESULTS: Patients with hip fractures had significantly lower femoral neck attenuation, TSTT, and CSA of the gluteus maximus and anterior compartment than controls. FIR of all hip muscle groups were significantly higher in hip fracture patients than controls. Multivariate analysis revealed that every 1% increase in FIR of medial compartment independently increased the odds of hip fractures by 23.7% (OR = 1.237, 95% CI = 1.093-1.401) and every 1 cm longer TSTT independently decreased the odds by 32.8% (OR = 0.672, 95% CI = 0.477-0.946). CONCLUSION: Fatty infiltration of hip muscles can better discriminate hip fractures than muscle area. Increased TSTT is independently associated with low fracture risk.

3,5,3'-Triiodothyronine-Loaded Liposomes Inhibit Hepatocarcinogenesis Via Inflammation-Associated Macrophages.

Background: Hepatocellular carcinoma (HCC) is inflammation-related cancer. Persistent inflammatory injury of the liver is an important factor mediating the occurrence and development of liver cancer. Hepatic macrophages play an important role in the inflammatory microenvironment, which mediates tumor immune escape, tumor growth, and metastasis. Previous studies have suggested that L-3,5,3-triiodothyronine (T3) can regulate inflammation; however, its use is associated with serious cardiac side effects, and its role in hepatocarcinogenesis remains unclear. In this study, we aimed to develop an effective T3 delivery system with reduced cardiac toxicity and to explore its effects on HCC occurrence. Methods: T3 liposomes (T3-lipo) were prepared using the thin-film hydration method, and their characteristics, including particle size, polydispersity index, zeta potential, encapsulation efficiency, drug loading, drug release, and stability, were evaluated in vitro. We assessed the effect of T3-lipo on hepatocarcinogenesis in diethylnitrosamine (DEN)-induced primary HCC in rats and examined the biodistribution of T3 and T3-lipo by high-performance liquid chromatography-mass spectrometry. Furthermore, we explored the potential molecular mechanism of T3-lipo in hepatocarcinogenesis by immunohistochemistry and immunofluorescence analyses, Bio-Plex assays, real-time polymerase chain reaction analysis, and Western blotting assays. Results: Compared with T3, T3-lipo had an enhanced inhibitory effect on hepatocarcinogenesis and reduced cardiac side effects in DEN-induced primary HCC in rats. Mechanistically, T3-lipo were absorbed by hepatic macrophages and regulated the secretion of inflammatory cytokines in macrophages by inhibiting inflammatory signaling pathways. Conclusions: T3-lipo may suppress hepatocarcinogenesis by regulating the inflammatory microenvironment in the liver and reduce the cardiac side effects meanwhile.

Screen time and health issues in Chinese school-aged children and adolescents: a systematic review and meta-analysis.

BACKGROUNDS: Many literature reviews summarized relationships between screen time and child health, but they only included a few studies conducted in Chinese children and adolescents. The potential influence of screen time may vary by social context. The current systematic review and meta-analysis aimed to evaluate relationships between screen time and health issues among Chinese school-aged children and adolescents. METHODS: Peer-reviewed articles written in Chinese and English were retrieved from CNKI, Wanfang, PubMed, Embase, and Web of Science from inception to June 2020. The Downs & Black checklist was applied to assess study quality. Meta analyses used random effect models and mixed effects model to calculate pooled adjusted odds ratios and 95% confidence intervals. Heterogeneity, sensitivity, and publication bias were assessed using Q and I2 statistics, "one-study removed" analysis, the funnel plot, trim and fill analysis, and classical fail-safe N, respectively. RESULTS: In total, we identified 252 articles reporting 268 studies with unique samples. These studies investigated relationships between screen time and health issues of adiposity, myopia, psycho-behavioral problems, poor academic performance, cardiometabolic disease risks, sleep disorder, poor physical fitness, musculoskeletal injury, sub-health, and miscellaneous issues of height and pubertal growth, injury, sick leave, and respiratory symptoms. Proportions of studies reporting positive relationships with screen time were lowest in adiposity (50.6%) and higher in myopia (59.2%) and psycho-behavioral problems (81.8%). Other health issues were examined in 10 or less studies, all of which had more than half showing positive relationships. The pooled odds ratio from 19 studies comparing health risks with the screen time cutoff of 2 hours per day was 1.40 (95% CI: 1.31 to 1.50, I2 = 85.9%). The pooled effect size was 1.29 (95% CI: 1.20 to 1.39) after trimming 7 studies for publication bias adjustments. CONCLUSIONS: Findings exclusively generated from Chinese school-aged children and adolescents resonate those mainly from western countries. Evidence suggests that higher levels of screen time are related with greater risks of various health issues, although the relationships appear to be weak and intertwined with other confounding factors. Future studies need to investigate health-specific dose effects and mechanisms of screen time.

Clinical Risk Factors and Perioperative Hematological Characteristics of Early Postoperative Symptomatic Deep Vein Thrombosis in Posterior Lumbar Spinal Surgery.

STUDY DESIGN: A retrospective analysis (2015-2019) of data collected from patients who underwent posterior lumbar spinal surgery. OBJECTIVE: This study aims to identify the incidence, perioperative hematological characteristics, potential prognostic indicators, and risk factors of deep venous thrombosis (DVT) in the lower limbs after posterior lumbar spinal surgery. Eliminating risk factors or taking measures against patients at risk may reduce the incidence of DVT. SUMMARY OF BACKGROUND DATA: Deep venous thromboses have been extensively studied in other reconstructive surgeries. Present literatures provide limited evidence for determining the prognostic and risk factors for this complication after spinal surgery. METHODS: Patients who underwent posterior lumbar spinal surgery with internal fixation in the Spine Surgery Center of Peking Union Medical College Hospital (PUMCH) were evaluated. The patient demographics, the number of operative segments, the hematological and biochemical parameters on baseline and postoperative day 1, and the presence of DVTs were obtained from all patients. The diagnosis of DVT was established by venous ultrasound when symptomatic. A multivariate logistic regression test was subsequently performed to determine the prognostic indicators and risk factors for DVT. RESULTS: A total of 2053 patients who received lumbar spine procedures were qualified and included. Patients were followed up for 12 weeks. Early symptomatic DVT occurred in 58 individuals (2.39%; 95% confidence interval [CI], 0.4-0.7%). Advanced age, higher preoperative serum D-dimer level, and lower serum potassium level were recognized as independent risk factors for symptomatic DVT. CONCLUSION: Multiple independent risk factors were identified for early symptomatic DVT after posterior lumbar spine surgery. Postoperative prophylactic anti-coagulation treatment might be warranted for patients with high D-dimer or low potassium levels before the procedure.Level of Evidence: 4.

Ubiquitin-Fold Modifier-1 Participates in the Diabetic Inflammatory Response by Regulating NF-κB p65 Nuclear Translocation and the Ubiquitination and Degradation of IκBα.

BACKGROUND: Ubiquitin-fold modifier-1 (Ufm1) is a recently identified ubiquitin-like protein. We previously confirmed that Ufm1 expression was increased in diabetic mice. However, its role in the development of diabetes remains undefined. METHODS: Lentivirus-mediated gene knockdown and overexpression techniques were used to observe the effect of Ufm1 on the expression of inflammatory factors, adhesion molecules and chemokines, as well as the transcriptional activity of nuclear factor kappa-B (NF-κB) in macrophages. Western blot and immunofluorescence analyses were used to analyse the mechanism by which Ufm1 affects the transcriptional activity of NF-κB. Finally, the effects of Ufm1 on inflammation and pancreatic, renal and myocardial damage were observed in db/db mice. RESULTS: Knockdown of Ufm1 by lentivirus shRNA targeting Ufm1 (Lv-shUfm1) led to decreased secretion of IL-6, IL-1ß, ICAM-1, VCAM-1, MCP-1 and CXCL2 in RAW264.7 cells that were exposed to LPS and TNF-α, while lentiviral overexpression of Ufm1 (Lv-Ufm1) caused the opposite effect. Interestingly, further investigation indicated that Ufm1 induced NF-κB p65 nuclear translocation in RAW264.7 cells via increasing the ubiquitination and degradation of IκBα. In an in vivo experiment, pretreatment of db/db mice with Lv-shUfm1 reduced the mRNA levels of TNF-α, IL-6, IL-1ß, ICAM-1, VCAM-1, MCP-1 and CXCL2 in resident peritoneal macrophages (RPMs) and decreased the plasma levels of TNF-α, IL-6, IL-1ß, ICAM-1, VCAM-1, MCP-1 and CXCL2. Additionally, in Lv-Ufm1-treated mice, the inverse results were observed. Following treatment with Lv-shUfm1 and Lv-Ufm1, NF-κB p65 nuclear translocation in RPMs was decreased and increased, respectively. Importantly, we observed that Lv-shUfm1 injection led to a decrease in plasma glycaemia, a reduction in urinary albuminuria and cardiomyocyte hypertrophy and an improvement in the histopathological appearance of pancreatic, kidney and myocardial tissue. Pretreatment of the mice with Lv-shUfm1 inhibited macrophage infiltration in the pancreas, kidney and myocardial tissue. CONCLUSION: Our data elucidate a new biological function of Ufm1 that mediates inflammatory responses. Ufm1-mediated p65 nuclear translocation occurs by modulating the ubiquitination and degradation of IκBα. Moreover, downregulating Ufm1 is an effective strategy to prevent the development of type 2 diabetes and its complications.

Soluble ST2 is associated with increased carotid intima-media thickness in patients with type 2 diabetes mellitus: A case-control study.

Soluble suppression of tumorigenicity 2 (sST2) is a free form of membrane-bound ST2, which is a member of the interleukin-1 receptor family. Previous research has shown that sST2 is associated with diabetes, but cardiovascular risk factors have not been established.To analyze the relationship between sST2 and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (T2DM).After screening, a total of 118 subjects with T2DM were divided into 2 groups according to the measurement of CIMT (normal CIMT (NCIMT), n = 58; abnormal CIMT (ACIMT), n = 60), and 60 healthy subjects (normal control (NC), n = 60) were recruited in this study. CIMT was measured by a color Doppler ultrasound, and sST2 and other metabolic parameters were measured as well.The median concentration of sST2 was elevated in the ACIMT group (31.30 ng/ml) compared with the NCIMT group (28.29 ng/ml, P < .01) and the NC group (20.15 ng/ml, P < .01). After adjustment for age and sex, log sST2 was strongly associated with smoking history (ß = 0.197, 95% CI, 0.084-0.311, P < .01), FPG level (ß = 0.302, 95% CI, 0.162-0.442, P < .01) and HbA1c level (ß = 0.296, 95% CI, 0.165-0.426, P < .01) and negatively correlated with HDL level (ß = -0.153, 95% CI, -0.259 to -0.046, P < .01). Furthermore, sST2 level was a risk factor for increased CIMT in patients with T2DM.Increased sST2 level not only was associated with indicators of glucose and lipid metabolism but also was a risk factor for increased CIMT in patients with T2DM. Thus, sST2 may be a potential novel marker to assess the progression of diabetic macrovascular complications.

Ubiquitin fold modifier 1 activates NF-κB pathway by down-regulating LZAP expression in the macrophage of diabetic mouse model.

Inflammatory response is closely related with the development of many serious health problems worldwide including diabetes mellitus (DM). Ubiquitin-fold modifer 1 (Ufm1) is a newly discovered ubiquitin-like protein, while its function remains poorly investigated, especially in inflammatory response and DM. In the present study, we analyzed the role of Ufm1 on inflammatory response in DM, and found that the proinflammatory cytokine levels (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß) and Ufm1 expression were highly increased both in the peritoneal macrophages of db/db mice and Raw264.7 cells induced by lipopolysaccharide (LPS). Western blot and luciferase reporter assay showed that NF-κB pathway was obviously activated in macrophages and the expression of LZAP, an inhibitor of NF-κB pathway, was down-regulated. With the LZAP knockdown plasmid and activation plasmid, we demonstrated that NF-κB/p65 activation was inhibited by LZAP in macrophages. The interaction of Ufm1 and LZAP was further proved with co-immunoprecipitation assay in HEK293 and Raw264.7 cells. The LZAP expression was also related with the presence of Ufm1 demonstrated by Ufm1 knockdown plasmid and activation plasmid. Besides that, we finally proved that the expression and activation of Ufm1 induced by LPS were regulated by JNK/ATF2 and JNK/c-Jun pathway with the use of SP600125. In conclusion, the present study demonstrated that Ufm 1 could activate NF-κB pathway by down-regulating LZAP in macrophage of diabetes, and its expression and activation were regulated by JNK/ATF2 and c-Jun pathway.

Implementation of flipped classroom combined with problem-based learning: an approach to promote learning about hyperthyroidism in the endocrinology internship.

BACKGROUND: With the development of medicine, new teaching methods, such as flipped classroom and problem-based learning (PBL), have received much attention in medical education. However, the implementation of flipped classroom combined with PBL in endocrinology education has not been well investigated. Considering that both two teaching methods may complement each other, therefore, the aim of this study was to evaluate students' learning effectiveness acceptability of the pedagogy between traditional lecture-based teaching methods and the combination of flipped classrooms with PBL teaching methods in the endocrinology internship. METHODS: 74 fourth-year medical students at the Bengbu Medical College were enrolled in the endocrinology internship. Hyperthyroidism was chosen for the content of this study. The participants were randomly allocated into either the combination group of flipped classroom with PBL (CG) or the traditional lecture-based classroom group (TG). Both a pre-quiz and a post-quiz were conducted before and after the classes, respectively. All questions in the quizzes were classified into two aspects, basic theoretical knowledge and clinical case analyses based on the Bloom's Taxonomy. The scores were compared and students were required to complete the questionnaire to evaluate their perceptions and experience. RESULTS: The mean post-quiz scores of both the TG and the CG were higher than those of the pre-quiz. Additionally, the post-quiz showed that students in the CG had significantly higher scores in the TG. Further analysis found that after class, only the difference in clinical case analysis between CG and TG was significant. The scores of all items in the questionnaires were higher in the CG than in the TG. More students agreed that the combined teaching method could help to improve their performance, at the same time, it could increase their workload. CONCLUSIONS: The combination of the flipped classroom and PBL teaching approach could be a better option over the traditional lecture-based classroom in the teaching of hyperthyroidism during endocrinology internship, although it can increase students' workload. To be widely accepted and implemented, further optimizations are required.

Prevalence of Diabetes and Prediabetes in Adults from a Third-Tier City in Eastern China: A Cross-Sectional Study.

INTRODUCTION: The aims of this study were to investigate the prevalence of adult diabetes and prediabetes in Bengbu (eastern China) in 2017, and to identify measures that can be taken to reduce the prevalence of diabetes and prediabetes in this region. METHODS: A stratified cluster random sampling method was used in the study. Two sampling sites were randomly selected from each of the four districts of Bengbu City, and all permanent residents (resident for ≥ 5 years) at all eight sampling sites aged 18 years or above were cluster sampled, which led to the sampling of 3388 adults. After screening, a total of 3144 respondents were enrolled in the study. The t test was utilized to compare the mean parameter values of the males and the females, and variance analysis was employed to compare the mean values of the nondiabetic, prediabetic, and diabetic groups. The chi-squared test was used to compare rates. Logistic regression was used for multivariate analysis, and the statistical significance level α was set to 0.05. RESULTS: The mean ages of the male and female groups were 51.1 ± 15.7 and 49.4 ± 15.1 years, respectively (p < 0.05). The diabetes prevalence in adults was 11.5% (8.4% after standardization), while the prevalence of prediabetes in adults was 32.0% (27.6% after standardization). The prevalence of diabetes and that of prediabetes gradually increased with age (both p < 0.05). Older age, hypertension, overweight status, obesity, central obesity, current smoker status, low serum high-density lipoprotein level, and high serum low-density lipoprotein level were all significantly associated with a higher risk of diabetes (p < 0.05). CONCLUSION: The prevalence of diabetes and that of prediabetes in adults in Bengbu City remain high. Intervention aimed at reducing the occurrence of diabetic complications and preventing prediabetes from further development is urgently required.

Effect of autophagy gene DRAM on proliferation, cell cycle, apoptosis, and autophagy of osteoblast in osteoporosis rats.

OBJECTIVE: The research aimed at detecting the autophagy level of osteoblast in osteoporosis rat, and investigating the effect of autophagy gene damage-regulated autophagy modulator (DRAM) on osteoblast proliferation, cell cycle, apoptosis, and autophagy. METHODS: The level of osteocalcin (OCN) and C-telopeptide (CTX) in serum of ovariectomized (OVX) rats was detected by enzyme-linked immunosorbent assay (ELISA). The Oil Red-O staining was used to observing bone histological changes. The messenger RNA level and protein expression level of Runt-related transcription factor 2 (Runx2; osteoblast markers) and other autophagy-related genes were revealed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The changes of autophagy in osteoblasts were detected by immunofluorescence staining. The following experiments were performed in osteoblasts of OVX rats through transfected with silencing DRAM to detecting cell proliferation, cell cycle, and apoptosis by Cell Counting Kit-8 assays and flow cytometry. RESULTS: The result of ELISA showed a significantly elevated of OCN and CTX in OVX rats as well a high fat content compared with sham-operated rats. The expression of Runx2 in bone of proximal tibia was higher by qRT-PCR and western blot analysis. The immunofluorescence staining and transmission electron microscope observe revealed that pcDNA3-DRAM could promote the autophagy in OVX rats. Besides that, overexpression of DRAM inhibited cell proliferation, promoted apoptosis, and enhanced autophagy in osteoblasts. The results of Oil Red-O staining indicated that overexpression of DRAM enhanced lipid accumulation in osteoporosis rats. CONCLUSIONS: The autophagy level of OVX rats was weakened, but overexpressed DRAM could increase the autophagy level of osteoblast, suppress proliferation, and induce apoptosis of osteoblast.

Improved vacuum sealing drainage for treatment of surgical site infection following posterior spinal internal fixation: A case report.

RATIONALE: Surgical site infection (SSI) following spine surgeries involving internal fixation often require removing the instrument; however, this can cause spinal instability. Previous reports have demonstrated the usefulness of vacuum sealing drainage (VSD) therapy, but the cases require wound opening, aseptic condition to replace the VSD device, and a secondary operation to close the wound. Thus, to improve the VSD treatment and develop a maneuverable procedure, make sense in spine surgery. PATIENTS CONCERNS: A 59-year-old male patient with a T12 vertebral fracture was affected by SSIs after spinal osteotomy with internal fixation. DIAGNOSES: The patient complained of wound exudation and had a fever 3 weeks after posterior spinal surgery. Initial serum investigations showed elevated white blood cell count and bacterial cultures of wound exudate were positive for Enterococcus faecalis. Therefore, SSI is confirmed. INTERVENTIONS: The infection was not controlled after 2 debridements, so the patient was treated with VSD treatment. The VSD foam dressings containing a drainage tube were placed into the wound from the exudation site of the wound until they contacted the internal fixation devices. After covering external fixation devices, continuous drainage was performed for 24 h. The VSD device was replaced every 4 to 5 days until the wound effusion stopped. All of the operations were performed at the bedside without complex manipulation or secondary closure under harsh aseptic condition. OUTCOMES: Wound exudation decreased remarkably and the infection was controlled 2 weeks after the application of VSD treatment. After 5 weeks, inflammatory indicators all decreased to normal levels and the exudate of the wound had stopped. The VSD treatment was then terminated and the drainage site of the wound was sutured. After 7 weeks, complete wound healing was achieved and no infection recurred during the 6-month follow-up. LESSONS: VSD could be a reliable treatment for SSIs that require preservation of internal fixation. Complete opening of the wound during the VSD treatment and secondary wound closure surgery were avoided.

Lumbar Scoliosis Induction in Juvenile Dogs by Three-dimensional Modulation of Spinal Growth Using Nickel-Titanium Coil Springs.

BACKGROUND: Current treatments for scoliosis have some defects and complications. To study spinal deformities and test novel scoliosis treatments, many animal models of scoliosis have been developed. These models applied a single load to the spine and could not precisely modulate the spinal growth in different dimensions. In this study, we applied posterior tethering in various directions with the application of nickel-titanium (NT) coil springs in dog's spine to modulate spinal growth in the coronal, sagittal, and transverse planes and create a scoliosis model possess curves that mimic adolescent idiopathic scoliosis (AIS) three dimensionally. METHODS: Scoliosis was surgically induced in eight 8-week-old female dogs (weight: 1.95-2.30 kg) using bone screws and NT coil springs. The deformity was induced through the placement of posterior NT coil springs that tethered the spine by bone screw fixation. All dogs were monitored with serial radiographs to document changes in deformities. RESULTS: All experimental animals developed scoliotic curves convex to the left in the lumbar segment. The mean coronal Cobb angle was 18.0° immediately postoperatively and 54.5° at 22 weeks. The mean lordosis increased from 6.2° postoperatively to 35.0° at final follow-up. Apical axial rotation increased from 4.5° postoperatively to 31.2° at 22 weeks. CONCLUSIONS: With the application of NT springs in dogs that allowed posterior tethering in various directions, lumbar spinal deformity was achieved in three planes: coronal, sagittal, and transverse planes. Notably, the lumbar spine in surgically treated dogs developed lordoscoliosis with obvious rotation and the curves mimic AIS three dimensionally well. This method allows lumbar scoliosis to develop without deep dissection of muscle and maintains the essential anatomical elements along the spinal curve. Moreover, the spinal growth modulation technique could yield information that would provide a basis for developing novel early-stage treatments for children with scoliosis.

Successful treatment of pachydermoperiostosis patients with etoricoxib, aescin, and arthroscopic synovectomy: Two case reports.

RATIONALE: Pachydermoperiostosis (PDP) is a rare hereditary disorder that affects the skin and bones. PDP is characterized by periostosis, digital clubbing, and pachydermia. Previous studies demonstrated that increased prostaglandin E2 (PGE2) levels resulting from defective protein degradation pathways play a crucial role in PDP pathogenesis, and males were more commonly and severely affected than females. Moreover, nearly all PDP patients suffer from refractory arthralgia. Although several different treatment modalities are used for PDP, therapy for this disease remains challenging. PATIENTS CONCERNS: Two cases of PDP showing symptoms consistent with polyarthritis and arthralgia that mainly affected the knees and ankles. DIAGNOSES: The diagnostic criteria for PDP include digital clubbing, periostosis, and pachydermia. The 2 patients were diagnosed as PDP based on the finger clubbing, facial cutis furrowing, knee and ankle arthritis, and radiographic evidence of periosteal proliferation. INTERVENTIONS: Patient 1 had massive joint effusion that was treated by oral administration of etoricoxib and aescin combined with arthroscopic synovectomy, whereas Patient 2 had mild joint swelling and accepted only oral medication. OUTCOMES: Clinical symptoms of the 2 patients greatly improved after the treatment. During the 1-year follow-up, the patient experienced no adverse effects or recurrence. LESSONS: The therapeutic results showed that oral etoricoxib could reduce inflammation and retard progression of pachydermia, or even relieve facial skin furrowing, but had limited efficacy for arthralgia. However, oral aescin had satisfactory efficacy for arthralgia. Thus, etoricoxib combined with aescin is a safe and effective treatment for PDP. Meanwhile, arthroscopic synovectomy can be used to treat joint effusion, but had no therapeutic effect on arthralgia. Therefore, postoperative oral medications would be needed as subsequent therapy for joint problems. In conclusion, this study proposes an effective and safe treatment plan to address symptoms experienced by PDP patients.

[Effect of preoperative factors on the clinical outcome of total knee arthroplasty].

OBJECTIVE: To analyze the effect of preoperative factors on the clinical outcome in patients receiving total knee replacement. METHODS: From January 2011 to September 2013, 145 patients (206 knees; 22 males, 31 knees; 123 females, 175 knees)receiving total knee arthroplasty were successfully included in this study and followed up. The average ages was (66.5±7.6) years old(range, 51-83 years old). The data of preoperative factorsincludedgender, age, body mass index (BMI), preoperative range of motion (ROM), the knee varus angle, flexion deformity and preoperative the hospital for special surgery (HSS) scorewere collected. The correlation between preoperative factors and the clinical outcome (postoperative HSS score, postoperative ROM)after total knee replacement was evaluated statistically. RESULTS: The average follow-up time was 35 months (range, 24-56 months). The HSS score was increased from (55.1±7.6) preoperativelyto (89.3±5.1) postoperatively. ROM elevated from (95.6±10.0)°preoperatively to (115.1±7.8)° postoperatively.The correlation analysis showed that the postoperative ROM was positively correlated with the preoperative ROM, and was negatively correlated with the BMI, the knee varus angle(r=-0.864, -0.353, all P<0.01). The postoperative HSS score was positively correlated with preoperative ROM, preoperative HSS score(r=0.101, 0.244, P=0.033, P<0.01), and was negatively correlated with the BMI (r=-0.277, P=0.039). CONCLUSIONS: Total knee arthroplasty can definitely improve the function of knee joint. The BMI, the preoperative ROM, the knee varus angle and preoperative HSS score have influence on postoperative function of patients receiving total knee arthroplasty.

[Study of rat lumbar vertebral endplate via micro computed tomography].

OBJECTIVE: To reconstruct the 3-dimensional (3D) models of vertebral endplate and internal canal structure based upon the micro computed tomography (MicroCT) scanning data and clarify the structural characteristics and changes of bone, canals and lumbar vertebral endplates with advancing age in SD rats. METHODS: Lumbar spines from male SD rats aged 3, 9 and 16 months (n = 15 each) were subjected to MicroCT scan. Mimics software was used to reconstruct the 3D models of lumbar vertebral endplate and internal canal structure. The bone volume fraction (BV/TV) of endplate was measured by CTAn software. RESULTS: The rebuilt 3D models of vertebral endplate showed that lumbar endplate was a thin layer of bone and the canals within vertebral endplate formed a ring-shaped canal network after reconstruction. Communicating branches existed between the adjacent canals. Every ring-shaped canal connected with trunk canals lying in the ventral and dorsal portions of endplate. The BV/TV of endplate in the ventral portion was lower than that in dorsal portion (ventral side: 79.9% ± 7.3%; dorsal side: 90.6% ± 6.2%, P < 0.05) and BV/TV increased with advancing age. CONCLUSION: The canals within rat lumbar vertebral endplate are not haphazard, but regularly arrayed to form a ring-shaped network of many circular canals, communicating branches and ventral and dorsal trunk canals. This canal network provides channels for blood vessels within endplate. The ratio of older rat canals decreases in endplate.

Novel experimental scoliosis model in immature rat using nickel-titanium coil spring.

STUDY DESIGN: Follow-up of animals after surgically initiated scoliosis. OBJECTIVE: To develop quantitatively asymmetric loads on rat lumbar to create scoliosis. SUMMARY OF BACKGROUND DATA: Current animal models for scoliosis use mostly rigid or flexible posterior asymmetric tethers. The curve progression can only be expected for the growth potential, leading to insufficient growth potential for validation of corrective techniques. METHODS: Scoliosis was induced in 55 five-week-old female Sprague-Dawley rats using a nickel-titanium coil spring. The experimental rats were randomly divided into 2 groups: in group A (n = 15), the nickel-titanium coil spring was not removed until these rats reached physical maturity (age, 12 wk). Group B (n = 40) was further randomly subdivided into 5 subgroups (n = 8 for each subgroup): removal of the spring after 1 week (group B1), 2 weeks (group B2), 3 weeks (group B3), 4 weeks (group B4), and 5 weeks (group B5). All rats were followed for a 7-week period with serial radiographs to document change of the deformity. RESULTS: All experimental animals of group A developed progressive, structural scoliotic curves convex to the left in the lumbar segment. In group B, the deformity of the lumbar progressed after the spring load was applied and regressed after the spring was removed. The scoliosis in group B1-B3 (the spring removed before sexual maturity) regressed after spring removal until the rats reached sexual maturity (4 wk after spring implant surgery). The scoliosis in group B4-B5 (the spring removed after sexual maturity) regressed only during the first week after spring removal surgery. The average coronal Cobb angle was 7.8° ± 1.3° (range: 6.0° -10.2°) in group B1 at the final follow-up, and there was only 1 experimental rat that maintained a curve more than 108. The models of group B2-B5 maintained stable scoliotic curves (coronal Cobb angle of L2-L5 > 10°) convex to the left in the lumbar segment at the final follow-up. CONCLUSION: This study establishes a rat lumbar scoliosis model via asymmetric load. This method develops lumbar scoliosis in a short time and maintains the essential elements along the curve. It is suitable for the investigation of scoliosis.