[Sorafenib regulates vascular endothelial growth factor by runt-related transcription factor-3 to inhibit angiogenesis in hepatocellular carcinoma].

Objective: To investigate the molecular mechanism of sorafenib against hepatocellular carcinoma. Methods: Sorafenib efficacy was screened and verified by the hepatocellular carcinoma patient-derived tumor xenograft (PDX) model. Veterinary B-mode ultrasonography and in vivo confocal laser scanning microscopy were used to observe PDX angiogenesis. Immunohistochemistry was used to observe the expression of proliferation and angiogenesis-related proteins in PDX tissue. Real-time quantitative PCR technology was used to observe the RUNX3 gene in PDX tissues. SPSS 17.0 statistical software was used for statistical analysis. Results: Four cases of PDX were used to screen the efficacy of sorafenib. PDX1 had a significant response to sorafenib, with an inhibition rate of 68.07%. Compared with the control group, sorafenib had significantly inhibited PDX1 relative tumor volume (5.76±2.14 vs. 11.71±2.87, P<0.05). Cell division index (39.50±7.72 vs. 67.10±9.14, P<0.05) and Ki67 expression (288.6±43.40 vs. 531.70±55.60, P<0.05) were significantly decreased. Veterinary B-mode ultrasonography showed evident blood flow signals in PDX1 tumors. In vivo confocal laser scanning microscopy results showed that sorafenib had significantly reduced the total vessel length (1573.00±236.21 vs. 2675.03±162.00, P<0.05) and area (11 145.33±1931.97 vs. 20 105.37±885.93, P<0.05)) of PDX1 tumors. Immunohistochemical results showed that sorafenib had significantly down-regulated the protein expressions of CD34 (27.55±3.76 vs. 45.47±5.57, P<0.05), VEGF (16.33±2.86 vs. 22.77±3.20, P<0.05) and MVD (38.75±6.01 vs. 55.50±8.61, P<0.05). Real-time PCR results showed that sorafenib had significantly up-regulated RUNX3 gene expression (2.14±0.71 vs. 1.00±0.36, P<0.05). However, there was a negative correlation between the expression of RUNX3 gene and the ratio of VEGF-positive cells in sorafenib group (R2=0.509 7). Conclusion: Sorafenib may inhibit the PDX angiogenesis and the growth of hepatocellular carcinoma by regulating the RUNX3-VEGF pathway.

Taraxasterol inhibits TGF-ß1-induced epithelial-to-mesenchymal transition in papillary thyroid cancer cells through regulating the Wnt/ß-catenin signaling.

Taraxasterol (TAR) is a kind of active compound extracted from dandelion and its molecular structure resembles steroid hormones. Recently, TAR has been reported to show an anti-tumor activity. However, the specific role of TAR in papillary thyroid cancer (PTC) has not been clarified. In this study, we investigated the effect of TAR on PTC cell migration, invasion and epithelial-to-mesenchymal transition (EMT) induced by TGF-ß1. PTC cells were exposed to TGF-ß1 (5 ng/mL) and then treated with different concentrations of TAR. We found that TAR showed no obvious cytotoxicity below 10 µg/mL but notably reduced migration and invasion of TGF-ß1-treated PTC cells. Moreover, TAR treatment decreased MMP-2 and MMP-9 levels, and obviously affected the expression of EMT markers. We also observed that Wnt3a and ß-catenin levels were significantly increased in TGF-ß1-treated PTC cells while TAR inhibited these effects in a concentration-dependent manner. Additionally, activation of the Wnt pathway by LiCl attenuated the suppressive effect of TAR on TGF-ß1-induced migration, invasion and EMT in PTC cells. Taken together, we highlighted that TAR could significantly suppress TGF-ß1-regulated migration and invasion by reversing the EMT process via the Wnt/ß-catenin pathway, suggesting that TAR may be a potential anti-cancer agent for PTC treatment.

[Construction of apoptosis-stimulating of p53 protein 2 gene knockout mice and its effect on diethylnitrosamine-induced liver cancer].

Objective: To construct apoptosis-stimulating of p53 protein 2 (ASPP2) gene knockout mice using diethylnitrosamine (DEN)-induced liver cancer model to study the biological functions of ASPP2. Methods: The sgRNA oligonucleotides were constructed, and ASPP2 knockout mice were prepared with the CRISPR/Cas9 system. PCR and sequencing methods were used to identify the genotypes of F0 and F1 generations and their progeny. DEN was used to induce ASPP2+/- mice to establish liver cancer model. Results: PCR and sequencing results showed that ASPP2 gene was successfully knocked out in F0 generation mice. The genotype of F1 generation mice was accorded with ASPP2+/- and had obtained stable heredity. The success rate of DEN-induced liver cancer model (7/8 and 3 / 8) of ASPP2 + /-mice obtained by self-hybridization of F1 generation was significantly higher than that of wild-type mice. Conclusion: ASPP2 knockout mice were successfully constructed based on the CRISPR/Cas9 system. The success rate of DEN-induced liver cancer model of ASPP2 knockout mice was significantly higher than that of the wild-type mice.

[Evaluation of the systematic functional rehabilitation on rheumatoid arthritis patients following total knee arthroplasty].

Objective: To evaluate the effects of functional rehabilitation on rheumatoid arthritis patients after the total knee arthroplasty (TKA). Methods: Two hundred rheumatoid arthritis patients (259 knees) were enrolled in this study at Arthritis Clinic and Research Center, Peking University People's Hospital from January 2012 to December 2017. All patients received the primary total knee arthroplasty, followed by a systematic functional rehabilitation. The same procedure of rehabilitation was followed, which consisted of patients' education, resistance training, passive and active range of motion exercise, balance exercise, gait training and daily-activity training. According to the degree of postoperative residual flexion contracture, these patients were divided into three groups: the severe (≥30°), moderate(15°-30°), and mild (≤15°). The outcomes of functional rehabilitation were evaluated among different groups and compared with those before the rehabilitation, which included the active range of motion (AROM), the flexion and extension angle of the knee, pain on the visual analogue scale (VAS). The complications and their impacts on the process of rehabilitation were also studied. Independent t test was applied to compare the data before and after the rehabilitaton. Results: There were 17 males (20 knees) and 183 females (239 knees) in this group, aged (57±13) years with a disease course of (16±10) years. There were significant improvements after the functional rehabilitation, including the flexion angle, the extension angle, AROM and pain VAS (76°±12° vs 112°±9°, 12.9°±10.2° vs 2.4°±4.6°, 63°±15° vs 110°±10° and 3.7±1.2 vs 2.0±0.4, respectively; t=39.0, 15.1, 41.3, 21.2, all P<0.01). The residual flexion contracture after the surgery in 259 knees were all improved, among which 195 knees (75.3%) reached a complete correction. Compared with the mild flexion contracture, the moderate and severe group had a lower complete correction rate (80.2% vs 45.9%, χ(2)=20.15, P<0.05). Total of 141 patients (70.5%) suffered from anemia two days after the surgery. By offering the anti-anemia treatment during the systematic rehabilitation, all cases of anemia were healed. The length of hospital stay was longer in the patients with moderate and severe anemia when compared with that in mild anemia ((13±5) days vs (11±5) days, t=2.2, P=0.028). Conclusion: The systematic functional rehabilitation is an effective treatment for rheumatoid arthritis patients after TKA, which can not only help release the pain after surgery, but also assist patients to achieve a better function of the knee.

Exploration of effect of Odanacatib on inhibiting orthodontic recurrence in rats and on CatK and IGF-1 mRNA.

OBJECTIVE: This study aimed to investigate the inhibitory effect of Odanacatib on orthodontic recurrence in rats. MATERIALS AND METHODS: Forty rats were selected to establish a planting anchorage molar movement model, and 50 g of force was used for the mesial movement of the right maxillary first molar. Forty rats were randomly divided into the observation group (n=20) and control group (n=20). Odanacatib (60 µl, 1.25 µM) was locally injected into the mucoperiosteum around the right maxillary first molar of rats in the experimental group, and an equal amount of normal saline was injected into rats in the control group. A Vernier caliper was used for measuring the recurrence movement distance and recurrence rate of rats, Micro-CT for scanning the bone mineral density (BMD) and bone volume fraction (BVF) of the alveolar bone, TRAP special staining for observing changes in osteoclasts and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) for detecting the mRNA expressions of cathepsin K (CatK) and insulin-like growth factor 1 (IGF-1) in periodontal tissues. RESULTS: After 3 weeks of modeling, the movement distance of the first molar of rats in the two groups was 1.16±0.19 mm. The molar movement distance and recurrence rate of rats were significantly higher in the control group than those in the observation group (p<0.05). The BMD and BVF of the alveolar bone of rats were markedly lower in the control group than those in the observation group (p<0.05). There was no statistically significant difference in the number of osteoclasts between the observation group (26.15±3.92) and the control group (27.01±2.74) (t=0.882, p=0.383). The CatK mRNA expression of rats was remarkably lower in the observation group than that in the control group (p<0.05). The IGF-1 mRNA expression of rats was significantly higher in the observation group than that in the control group (p<0.05). CONCLUSIONS: By promoting the IGF-1 mRNA expression and increasing the BMD and BVF of the alveolar bone, Odanacatib inhibits orthodontic recurrence and has no effect on osteoclast activity.

Medium-term results of ceramic-on-polyethylene Zweymüller-Plus total hip arthroplasty.

INTRODUCTION: The need for better durability and longevity in total hip arthroplasty for patients with various hip joint diseases remains a challenge. This study aimed to obtain medium-term results at a follow-up of >10 years for Zweymüller-Plus total hip arthroplasty with ceramic-on-polyethylene bearing. METHODS: A retrospective study was conducted to review the results after a minimum of 12.4 years of 207 consecutive total hip arthroplasties in 185 patients in Peking University People's Hospital in China using the Zweymüller SL-Plus stem in combination with the Bicon-Plus threaded cup and ceramic-on-polyethylene bearing between October 1994 and April 2000. RESULTS: During the study period, two patients (2 hips) died and 25 patients (28 hips) were lost to follow-up. Two hips were revised for aseptic loosening of the Bicon-Plus cup. The mean clinical and radiological follow-up was 14.1 years (range, 12.4-16.5 years) for the remaining 156 patients (175 hips). The mean (standard deviation) Harris Hip score for the 175 hips increased significantly from 39.3 (3.8) preoperatively to 94.1 (2.5) postoperatively at a mean follow-up of 14.1 years (P<0.05). Focal osteolysis was observed in seven (4.0%) of 175 stems and three (1.7%) of 175 cups. The Kaplan-Meier survival with revision for any reason as the end-point was 99.03% (95% confidence interval, 95%-100%). CONCLUSIONS: The high survival rate of the cementless Zweymüller-Plus system with ceramic-on-polyethylene bearing at mid-term follow-up makes this total hip arthroplasty system reliable for patients with various hip joint diseases.

Metastasis from endometrial carcinoma to bilateral breasts presenting as inflammatory breast lesions.

BACKGROUND: Endometrial carcinoma rarely metastasizes to the bilateral breasts and presents as an inflammatory breast lesion. In this paper, we report a case of bilateral breast metastatic endometrial carcinoma and describe the clinical and pathological features. It is the second case of this kind of disease and the first case report with full clinical data. CASE REPORT: A 56-year-old Chinese woman (G3, P3) with endometrial carcinoma received cytoreductive surgery and chemotherapy. Approximately 22 months later, she presented with pain in the right axillary region and edema of the right breast. The pathology report confirmed multifocal invasive papillary adenocarcinoma of the right mammary gland, consistent with endometrial carcinoma metastasis. Although she received many lines of chemotherapy, the disease still progressed and metastasized to the contralateral breast. Gefitinib (Iressa) improved symptoms temporarily. CONCLUSIONS: Bilateral breasts metastasis of endometrial carcinoma is rare and difficult to treat. Molecular targeted therapy may be an effective treatment for breast metastasis.

[Primary Zweymuller total hip arthroplasty for osteoarthritis secondary to congenital acetabular dysplasia].

OBJECTIVE: To evaluate the effectiveness of Zweymuller prothesis in replacing osteoarthritis secondary to congenital dysplasia of the hip. METHODS: From January 1996 to June 2000, Zweymuller prothesis was used to reconstruct 32 hips in 29 patients with congenital acetabular dysplasia(3 bilateral cases). All patients were female. According to the classification of Perner, 19 hips belonged to type I, 7 type II, 5 type III, and 1 type IV. The mean follow-up period was 27.5 months (6-53 months). The preoperative Harris hip score ranged from 25 to 59(average 44.5). RESULTS: The pain was completely relieved, and the Harris hip score ranged from 63 to 97(average 85). CONCLUSION: We consider that the Zweymuller total hip arthroplasty provides stable fixation of the cup in the presence of moderate acetabular dysplasia without structural bone grafting or cementing.

Clinical course of pediatric congenital inner ear malformations.

OBJECTIVE: To determine any factors that could improve the early detection and management of congenital inner ear malformations. STUDY DESIGN: A retrospective review was performed of all patients with a diagnosis of inner ear malformation at Loyola University Medical Center (LUMC) and the Hospital for Sick Children (HSC) between 1987 and 1995. Clinical records and audiometric data were accumulated. One neuroradiologist reviewed every temporal bone computed tomography (CT) scan. METHODS: Forty-six pediatric patients with congenital inner ear anomalies evaluated at two tertiary care hospitals. RESULTS: The average patient age at initial assessment was 25.7 months. A family history of hearing loss was noted in only five patients (12.8%). A major nonotological deformity was seen in 41% of patients. The average hearing threshold was 88 dB. All three patients with sudden hearing loss had vestibular aqueduct enlargement. Two of the three patients with common cavity anomalies had a history of recurrent meningitis. Twenty-seven patients had a vestibular aqueduct deformity, the most frequent radiographic abnormality in the series. CONCLUSIONS: Because inner ear malformation was diagnosed after 24 months of age in a significant percentage of patients, we recommend increased parental education and vigilance by primary care practitioners. Universal newborn screening may be the key to earlier detection of these infants. For children with idiopathic sensorineural hearing loss, we recommend a temporal bone CT scan. Patients with vestibular aqueduct enlargement must be counseled about the risk of progressive sensorineural hearing loss, meningitis, and the need to avoid contact sports. Patients with common cavity abnormalities should be considered for exploratory tympanotomy and also educated about the risk for meningitis.

[Low-molecular-weight heparin for preventing deep-vein thrombosis after total joint arthroplasty].

OBJECTIVE: To evaluate the efficacy and safety of low-molecular-weight heparin (LMWH) in preventing deep-vein thrombosis (DVT) after total hip and knee replacement (THR, TKR). METHODS: From November 1997 to March 1999, we performed total joint replacement for 47 control patients (34 knees, 28 hips) and for 31 patients (19 knees, 17 hips) who had been given low-molecular-weight heparin for preventing deep-vein thrombosis. All patients received venography of the operated limbs after operation. RESULTS: DVT occurred in 19.4% of the LMWH patients (26.3% in TKR, 11.8% in THR) and the reduction was significant (P < 0.05) compared to the control group (48.4%, 55.9%, 39.3% respectively). The incidence of proximal DVT was also reduced significantly (P < 0.05) from 19.4% of the control group to 2.8% of the LMWH group. CONCLUSION: Low-molecular-weight heparin can significantly reduce the incidence of deep-vein thrombosis after total joint replacement.

[Clinical analysis of 13 infected total knee replacements].

OBJECTIVE: To investigate the cause, treatment and its result of infected total knee replacements (TKRs). METHODS: Between 1987 and 1999, 13 infected TKRs in 13 patients were treated with surgical debridement and one-stage or two-stage reimplantation. The preoperative average ROM of knees was 55 degrees and the average Hospital for Special Surgery (HSS) knee score was 36.5 points. Clinical results were evaluated after average follow-up for 3 years and 5 months. We analyzed the factors for TKR infection. RESULTS: No recurrent infection was noted, and pain was significantly alleviated in all patients. The average ROM of knees was 85 degrees and the average HSS knee score was 73.5 points. CONCLUSIONS: The high risk factors for TKR infection are rheumatoid arthritis, steroid administration, associated diabetes mellitus, hinged prosthesis and previous knee surgery. Early surgical debridement with intravenous antibiotics is necessary as soon as deep infection is detected. Two-stage reimplantation is more effective in eradicating deep infection than single debridement or one-stage reimplantation.

[Reconstruction of hip, knee, and ankle bony fused in non-functional position of ankylosing spondylitis patients].

OBJECTIVE: To evaluate the reconstruction of hip, knee and ankle joints with bony fusion at non-functional positions for patients with severe late-stage ankylosing spondylitis (AS). METHODS: From January 1996 to May 1997, simultaneous ipsilateral total hip, knee and ankle replacement was performed under single anesthesia on 2 patients (3 sides) with multiple joint deformity including bony fusion at non-functional positions. They were followed for 29 months on average. RESULTS: Satisfactory range of motion and function were observed. HSS knee score on average was improved by 45 points and Harris hip score by 37.7 points. There were no wound healing problems or late infection. No aseptic loosening was found. CONCLUSIONS: Simultaneous ipsilateral total hip, knee and ankle replacement not only reduced cost for hospitalization, but also facilitated early rehabilitation. To our knowledge, this is the first report on this type of surgery, named ipsilateral tri-arthroplasty.

[The relationship between laminin-receptor and nm23 protein expression and its correlation with interstitial microvascular density and tumor metastasis in breast carcinoma].

OBJECTIVE: To study the relationship between 67,000 laminin, laminin-receptor (LN-R) and nm23 protein expression, interstitial microvascular density (MVD) and tumor metastasis in breast carcinomas. METHODS: The expression of laminin (LN), LN-R, FVIIIRAg and nm23 protein were detected in 73 cases of breast carcinoma with immunohistochemical technique and analyzed. RESULTS: A significant difference in LN expression was found in breast carcinoma according to their pathological grade. A positive relation exists between LN-R expression and lymph node metastasis. A positive relationship exists between the degree of LN-R and MVD expression. A significant difference in lymph node metastasis cases exists between nm23 protein positive expression group and negative expression group. When the expression of nm23 protein was inhibited, the degree of LN-R, MVD expression increased and positively related with lymph node metastasis. CONCLUSION: LN-R expression enhancement, microvascular density increase and nm23 expression inhibition may be the reliable markers for predicting tumor metastasis and prognosis.

[Reinfusion of autologous shed blood after joint replacement].

OBJECTIVE: To evaluate the results of reinfusion of autologous shed blood after joint replacement. METHODS: From February 1996 to March 1998, we selected 36 patients for 56 joint replacements. Apart from preoperative donation of autologous blood, all patients received transfusion of unwashed autologous drained blood from hips and knees after arthroplasty. The CBCIIConstaVac blood conservation system was used to salvage shed blood. Among the patients, 8 hips and 48 knees were involved. 12 patients had rheumatoid arthritis, 16 osteoarthritis, 5 ankylosing spondylitis, and 3 other arthritis. RESULTS: 36 patients received 24 260 ml (50%) autologous shed blood, 9 700 ml (20%) reserved autologous blood, and 14 600 ml (30%) allogenic blood. 15 patients experienced transient febrile reaction at the time of reinfusion, no other clinic abnormalities were discovered after reinfusion. CONCLUSIONS: Reinfusion of autologous shed blood is a safe and effective to decrease the use of allogenic blood and avoid the complications of its transfusion.

Toronto's Hospital for Sick Children study of traumatic sudden sensorineural hearing loss.

OBJECTIVE: Traumatic sudden sensorineural hearing loss (SHL) is by definition a hearing loss of greater or equal to 30 dB occurring within 3 days of trauma. The objective of this study was to assess the rate of traumatic sudden SHL. Etiology is discussed with statistical references, and appropriate treatment is proposed. A case study of an enlarged vestibular aqueduct illustrates the above. METHOD: The authors retrospectively studied cases at The Hospital for Sick Children, Toronto, between the years 1980 and 1995. High-resolution CT scans of the temporal bones with bone algorithms and coronal/axial views were performed on all children presenting with SHL after 1988. RESULTS: Of the 12 children studied, 9 had high-resolution CT scans, revealing a 33% incidence each of inner-ear malformations, temporal bone fractures, and other miscellaneous CT findings. CONCLUSION: By corollary, the authors recommend a high index of suspicion for congenital temporal bone abnormalities in all cases of sudden sensorineural hearing loss, particularly those associated with trauma.

[One-stage reimplantation for the salvage of total knee arthroplasty complicated by infection].

One-stage reimplantation for the salvage of infected total knee arthroplasty in 8 patients was reviewed at an average follow-up of 20.1 months late infections occurred in 7 (87.5%) patients. The timing of the diagnosis of the infection after knee arthroplasty was of the prosthesis averaged 11.5 months. No one had recurrent infection and pain was relieved significantly in all patients. Our results suggest that one-stage reimplantation is a reasonably reliable procedure for the management of an infected prosthesis. The use of Gentamicin-impregnated bone cement and the Streptomicin bead mixed with Gentamicin improve the success of treating or preventing recurrence of the infection. Early one-stage reimplantation was needed as soon as the deep infection was defined in order to decrease more destruction of the bone.

[Total knee replacement of severe flexion contracture deformities greater than 60 degree].

The technique of total knee arthroplasty for the patients with severe flexion contractures of more than 60 degrees is not clear. Recently, We have performed 37 total knee arthroplasties in 23 patients with flexion contracture of more than 60 degrees (average 77.97 degrees). Among them, 14 knees (37.9%) with flexion contracture of more than 90 degrees, and 7 knees (18.0%) with 90 degrees flexion fusion deformities. Significant improvements occurred after averaged 4.3-year follow-up. Complications occurred in four patients: three had transient peroneal-nerve palsy, and one had temporary circulatory disturbance of the lower extremity. They recovered after conservative therapy. We consider that severe flexion contracture of more than 60 degrees is not a contraindication of TKR. Staged bone resection and thoroughly soft-tissue release of the posterior capsule and collateral ligament balance were the critical procedure. If necessary, additional distal femoral condyle resection with posterior cruciate ligment sacrifice can be considered.

[Simultaneous bilateral total knee replacement for the patients with serious rheumatoid disease].

This retrospective study reviews 57 patients with serious rheumatoid disease who had bilateral total knee arthroplasties simultanneously between 1987 and 1994. The short follow-up results revealed that there was no increase in complications in the patients with simultaneous bilateral procedures, and nearly identical postoperative results to those observed among patients with single joint replacement. Advantage of simultaneous bilateral total arthroplasty include reduction in hospital cost, the need for less invasive surgical event and the ability to rehabilitate the patient symmetrically.