[Expression and significance of PD-1 and PD-L1 in the specimens of epithelial ovarian cancer].

Objective: To examine the expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) in epithelial ovarian cancer (EOC) tissues, and investigate the correlation among their expression, clinicopathological features and prognosis. Methods: The specimens of 180 patients with EOC treated in the First Affiliated Hospital of Dalian Medical University from October 2002 to December 2013 were confirmed by pathological examination. The pathological tissue specimens of subtypes ，included 120 cases of serous carcinoma, 30 cases of mucinous carcinoma, 20 cases of endometrioid carcinoma, and 20 cases of clear cell carcinoma. The normal paracancerous tissues of 50 cases randomly selected from the 180 patients as control group. Immunohistochemical SP method was used to detect the expressions of both PD-1 and PD-L1 in epithelial ovarian cancer tissues, and the relationships among their expressions,the clinicopathological parameters and prognosis were respectively analyzed. Results: （1） PD-1 was expressed in lymphocytes infiltrated in EOC tissues, and PD-L1 was expressed in the cell membranes of cancer tissues. In all EOC cases, 33 cases (18.3%, 33/180) of both PD-1 and PD-L1 were highly expressed, and only 1 (2.0%, 1/50) of control group showed high expression. There was statistically significant difference between two groups (P<0.01). (2) Among the four subtypes tissue specimens of EOC, the high expression rate of PD-1 was 25.0% (30/120) for serous carcinoma, 3/15 for endometrioid carcinoma, 0 (0/30) for mucinous carcinoma, and 0 (0/15) for clear cell carcinoma. The high expression rate of PD-L1 was 23.3% (28/120) for serous carcinoma, 3.3% (1/30) for mucinous carcinoma, 2/15 for endometrioid carcinoma, and 2/15 for clear cell carcinoma. Both PD-1 and PD-L1 expressions in the four sub-types of tissue specimens were significantly different (P<0.05). The high expression rate of both PD-1 and PD-L1 was 9.2% (8/87) in the early stage and 26.9% (25/93) in the late stage. There was a statistically significant difference between the two groups (P<0.01). Similarly, the expression of both PD-1 and PD-L1 were significantly higher in the cases of high-grade EOC （type Ⅱ） than those of low-grade （type Ⅰ） and in the cases of EOC distributed bilaterally than that distributed unilaterally, and there were statistically significant differences (P<0.05). (3) The Kaplan-Meier survival analysis showed that the survival time were respectively 35 and 36 months in the cases with high expressions of both PD-1 and PD-L1, and the survival time were the same as 61 months in the cases with low expression of both PD-1 and PD-L1, and the comparison was statistically significant (P<0.05). Conclusions: The expression levels of PD-1 and PD-L1 in EOC tissues are higher than those in adjacent tissues, especially in serous carcinomas. The expression of both PD-1 and PD-L1 is higher in specimens of the patients with advanced stages. The results showed that the high expression of both PD-1 and PD-L1 is an indicator of poor prognosis of patients suffering from EOC.

[Expression and significance of MAPK/ERK in the specimens and cells of epithelial ovarian cancer].

Objective: To detect phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) protein expression in epithelial ovarian cancer and cell lines, and to examine the effects of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor AZD6244 on cell proliferation, apoptosis as well as cell cycle of ovarian cancer cells. To explore the function and significance of MAPK/extracellular signal-regulated kinase (ERK) signaling pathway in the development of ovarian cancer. Methods: (1) A total of 104 cases of patients with ovarian cancer who accepted the treatment of gynecological surgery and being confirmed by pathological examination in First Affiliated Hospital, Dalian Medical University from January 2004 to December 2013 were selected. The expressions of p-ERK1/2 protein were detected by immunohistochemistry in ovarian cancer specimens, and the relationship between the expressions of p-ERK1/2 and the clinical features of patients was analyzed. (2) p-ERK1/2 and other related proteins were determined by western blot in various ovarian cancer cells, including SKOV3, OV2008, C13, A2780S, A2780CP, OVCAR4, OVCAR5, OVCAR8 and CAOV3 treated with or without MEK inhibitor. The cellular proliferation, apoptosis and cell cycle of ovarian cancer cells after treatment with MEK inhibitor were analyzed by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Results: (1) The immunohistochemical method showed that p-ERK1/2 between low grade serous carcinoma and clear cell carcinoma were not significantly higher expressed (P>0.05) . However, a lower level of the p-ERK1/2 expression were observed among high grade serous carcinoma, mucinous carcinoma and endometrioid carcinoma (all P<0.05) . There was no significant correlation between the protein expression of p-ERK1/2 and patients' age, pathological stage of surgery, and preoperative serum CA(125) level (P>0.05). (2) Western blot showed that the protein p-ERK1/2 was widely expressed in various ovarian cancer cell lines such as SKOV3, OV2008, C13, A2780S, A2780CP, OVCAR4, OVCAR5, OVCAR8 and CAOV3. After treatment with AZD6244 (5, 10 µmol/L), the level of p-ERK1/2 in OVCAR5 and OVCAR8 decreased significantly in dose-dependent manner. Additionally, we found a reduction of the expression level of cyclin D1, caspase-3 and appeared cleaved poly adenosine diphosphate ribose polymerase (PARP) in OVCAR5 and OVCAR8, compared with control groups. MTT assays showed that OVCAR5, OVCAR8 and A2780S were differently inhibited in the dose-dependent manner after being treated with different concentrations of AZD6244 (0, 2.5, 5, 10, 25, 50 and 100 µmol/L, all P<0.05). Further tested by flow cytometry, the results showed that AZD6244 (5, 10 µmol/L) was able to induce the apoptosis of OVCAR5, OVCAR8 and A2780S, as well as G(0)/G(1) phase arrest, both in a dose-dependent manner (P<0.05). Conclusions: As the main active and functional unit of MAPK/ERK signaling pathway, p-ERK1/2 protein is expressed in both the tissues and various ovarian cancer cell lines. AZD6244 could down-regulated the expression of p-ERK1/2 in ovarian cancer cells, accompanied by the decreased proliferation and increased cell apoptosis of ovarian cancer cells. In conclusion, MAPK/ERK signaling pathway might play a role in the development and progression of ovarian cancer, and may be provide a novel option for molecular targeted therapies of the disease.

[Proximal femoral nails antirotation and dynamic hip screws for fixation of unstable intertrochanteric fractures of femur: A meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety of proximal femoral nail antirotation (PFNA) and dynamic hip screw (DHS) for unstable intertrochanteric fractures using meta-analysis. METHODS: The PubMed, Embase, Cocharane Central Register of Controlled Trials, Google Scholar, China Science and Technology Papers and Citation Database (CSTPCD) and China Journal Full-text Database (CNKI) were searched for published randomized controlled trials before January 1, 2019. Two researchers independently screened the literature in the light of the inclusion and exclusion criteria, evaluated the quality of the studies and extracted the data which were consisted of clinical efficacy indexes, such as incision length, operation time,intraoperative blood loss, weight-bearing time,fracture-healing time, Harris hip score and safety indicators like complications. Meta-analysis was performed with the Revman 5.3 software provided by Cochrane Community in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standard. RESULTS: Nine randomized controlled trials met the requirement with a total of 779 patients, of whom 383 were fixed with PFNA and 396 with DHS. Meta-analysis demonstrated that PFNA was associated with smaller surgical incision length [MD=-7.43, 95%CI (-9.31, -5.55), P<0.05], shorter operation time [MD=-22.76, 95%CI (-29.57, -11.95), P<0.05], less intraoperative blood loss [MD=-216.34, 95%CI (-275.18, - 157.49), P<0.05], earlier weight bearing after surgery [MD=-12.34, 95%CI (-17.71, -6.97), P<0.05], shorter fracture healing time [MD=-5.00, 95%CI (-7.73, -2.26), P<0.05], higher postoperative Harris hip score [MD=12.22, 95%CI (3.88, 20.55), P<0.05], higher rate of excellent Harris hip score [OR=3.56, 95%CI (1.44, 8.81), P<0.05] and lower incidence rate of postoperative complications [OR=0.48, 95%CI (0.33, 0.70), P<0.05], such as hip varus, wound infection, urinary tract infection, pulmonary infection, pressure sore, deep vein thrombosis, pulmonary embolism, heart failure and cerebral infraction when compared with DHS. No statistical difference was shown between the groups when it came to subgroup analysis by age. However, there was no significant difference (P>0.05) in the duration of hospitalization and the complications resulting in the occurrences of internal fixation loosening, such as femoral shaft fracture (during or post operation), internal fixation fracture, cut-out, displacement or retraction. CONCLUSION: Current published evidence supports the superiority of PFNA to DHS for unstable intertrochanteric fractures in terms of clinical efficacy. The conclusion was limited because of the relatively low quality of evidence with low strength of confidence. Large scale and high-quality randomized controlled trials are required to validate the safety of PFNA and DHS for unstable intertrochanteric fractures.

[Analysis of prophylactic effect of extended-duration anticoagulant drugs in elderly patients undergoing hip fracture].

OBJECTIVE: To evaluate the prophylactic effect of extended-duration anticoagulant drugs on venous thromboembolism, and to explore the time of drug prevention for venous thromboembolism after hip fracture. METHODS: A retrospective analysis of 143 patients undergoing hip fractures from November 2017 to October 2018 in Peking University People's Hospital was conducted to investigate the relationship between the extended-duration anticoagulant drug and the morbidity of venous thromboembolism and bleeding during the treatment. All the drug prevention programs for the patients included in the study were implemented in accordance with the 2016 edition of the Guidelines for Prevention of Venous Thrombosis in Orthopaedic Surgery by Orthopaedic Society of Chinese Medical Association. The patients in the two groups were followed up for venous thromboembolism and bleeding during the medication within 5 weeks after the fracture. Venous thromboembolism included symptomatic and asymptomatic deep venous thrombosis of the lower extremities, pulmonary thromboembolism, and all the patients with deep venous thrombosis of the lower extremities required vascular ultrasound results to obtain clear evidence. The results of vascular ultrasound were the basis for determining deep venous thrombosis. Bleeding conditions were included, but not limited to gastrointestinal bleeding, wound bleeding, intracranial hemorrhage, intraspinal hematoma, and fundus hemorrhage. RESULTS: There were no pulmonary thromboembolism in both groups after surgery. The morbidity of deep venous thrombosis was 22.09% and 8.77% in the 2-week and 4-week groups (P=0.037), the time to deep venous thrombosis in the two groups was (17.32±7.75) days and (29.20±0.17) days after surgery. One case of bleeding occurred during the use of anticoagulant drugs in both groups, the morbidity of bleeding during the treatment was 1.16% and 1.75% (P=0.769), respectively. CONCLUSION: Extended-duration anticoagulant drugs to 4 weeks after surgery can significantly reduce the morbidity of postoperative venous thromboembolism, and does not increase the risk of bleeding. Patients with a risk of bleeding should carefully assess the risks and benefits of drug prevention and choose the best treatment.

[Correlation analysis between rotator cuff tear and the superior migration of humeral head].

OBJECTIVE: To evaluate the association between rotator cuff tear and the proximal migration of humeral head. METHODS: In this research, we retrospectively selected 30 patients with unilateral rotator cuff tear in Peking University People's Hospital from September 2015 to May 2016, who received magnetic resonance imaging (MRI) and X-ray of the painful shoulder before enrollment in this study, the duration between the two examinations was no longer than 1 week, and also there was no past history of surgery in the selected shoulders. There was no other exclusion criteria. Upward migration index (UMI) was the ratio between the distance of humeral head center to the lower surface of acromion, and the radius of humeral head circle, which could help to minimize the effect of anatomy difference and imaging magnification, compared with the traditional acromiohumeral distance (AHD). Then we introduced this index to stratify the selected 30 patients into 3 groups, and each group contained 10 patients, UMI of group 1 was >1 and ≤1.2, UMI of group 2 was >1.2 and ≤1.4, UMI of group 3 was >1.4. As the supraspinatus was most commonly affected by pathological change among the four rotator cuff tendons, we took it as the research object. Then we used the Spearman correlation analysis to evaluate the relationship between UMI and fatty degeneration, rotator cuff tear size and the thickness of ruptured supraspinatus tendon from X-ray and MRI. RESULTS: In the A-P view, the average UMI was 1.33 (1.02-1.51, SD: ±0.22). UMI and the tear size had a significant negative correlation (R=-0.584, P<0.01), and also there was a negative correlation between the fatty degeneration of the supraspinatus (R=-0.312, P=0.033). However, there was no correlation between UMI and the thickness of ruptured supraspinatus (R=0.127, P=0.071). CONCLUSION: UMI is related with the fatty degeneration of supraspinatus and the tear size. The reduction of UMI is a predictable and reliable mark of rotator cuff tear and degeneration in clinic. Physicians can use physical examination and X-ray first when facing the patients with shoulder pain, which is convenient and helpful for evaluating rotator cuff tears.

[Comparison of the effects of two cephalomedullary nails (zimmer natural nail and proximal femoral nail antirotation) in treatment of elderly intertrochan teric fractures].

OBJECTIVE: To explore the effect of cephalomedullary nails for elderly intertrochanteric fractures: proximal femoral nail antirotation (PFNA) versus zimmer natural nail (ZNN) to provide the data support for clinical perioperative management. METHODS: A retrospective study was used to analyze the clinical data of elderly intertrochanteric fractures cases which were treated with PFNA or ZNN fixation from May 2016 to May 2017. In the study, 59 cases were followed up completely, in which 28 cases accepted PFNA, and the other 31 cases accepted ZNN. The operation time, amount of bleeding, fracture healing time, postoperative complication, postoperative radiographic measurement (tip apex distance, TAD) and the last follow-up of hip function score were analyzed. RESULTS: The patients were followed up for 6 to 19 months, with an average (10.8±4.0) months. In PFNA group, the operation time was (62.7±14.2) min, the amount of bleeding was (56.8±20.6) mL, the fracture healing time was (4.6±0.8) months, the postoperative complication was 3.6%, the TAD was (17.7±5.5) mm, and the last follow-up hip function score was 91.8±3.6. In ZNN group, the operation time was (73.6±18.3) min, the amount of bleeding was (68.7±31.6) mL, the fracture healing time was (4.5±0.7) months, the postoperative complication was 3.2%, the TAD was (16.5±4.7) mm, and the last follow-up hip function score was 92.2±3.8. The two groups of comparative experiments were carried out, the operation time of the PFNA group was less than that of the ZNN group (P<0.05). There was no significant difference in the amount of bleeding, fracture healing time, postoperative complication, TAD, postoperative hip score between the two groups (P>0.05). CONCLUSION: Although group ZNN had significant longer operation time than group PFNA, both implants were useful tools in the treatment of elderly intertrochanteric fractures. The operation of PFNA was simpler,while the design of the anterior bow of ZNN might be more suitable for the patients with a large femoral anterior bow.

Prognostic significance of downregulated BMAL1 and upregulated Ki-67 proteins in nasopharyngeal carcinoma.

This study assessed the prognostic value of BMAL1 and Ki-67 expression in patients with nasopharyngeal carcinoma. Level of BMAL1 mRNA was assessed in tissue specimens from 36 nasopharyngeal carcinomas and 20 nasopharyngeal chronic inflammations using quantitative reverse transcriptase-polymerase chain reaction. Expression of BMAL1 and Ki-67 proteins was analyzed immunohistochemically in 90 paired nasopharyngeal carcinoma and distant normal tissues. The Kaplan-Meier curves and the Log-rank test were used to calculate prognostic significance stratified by BMAL1 and Ki67 protein expression and the COX regression model was to analyze the multivariate prognosis. BMAL1 mRNA was significantly reduced in nasopharyngeal carcinoma (4.67 ± 0.27 versus 6.64 ± 0.51 in chronic inflammation tissues, p = 0.002). Level of BMAL1 mRNA was associated with tumor distant metastasis (3.37 ± 0.66 versus 5.04 ± 0.27 compared with non-metastasis, p = 0.011). Level of BMAL1 protein was also reduced in tumor tissues and BMAL1 expression was associated with better 1-, 3- and 5-year overall survival (OS) of cancer patients (92.6%, 69.2% and 62.3% versus 59.1%, 40.9% and 0% in patients with low BMAL1 expressed tumors; p = 0.000). BMAL1 expression and age were independent prognostic factors for OS (p = 0.032). Furthermore, Ki-67 expression was high in tumor versus normal tissues and associated with poor OS of cancer patients (p = 0.035). The Pearson correlation analysis showed that there was an inverse association between BMAL1 and Ki-67 protein expression (p = 0.021). This study demonstrated that lost BMAL1 and Ki-67 overexpression were associated with poor OS of nasopharyngeal carcinoma patients.

Oxidative stress induced necroptosis activation is involved in the pathogenesis of hyperoxic acute lung injury.

Necroptosis has been found to be involved in the pathogenesis of some lung diseases, but its role in hyperoxic acute lung injury (HALI) is still unclear. This study aimed to investigate contribution of necroptosis to the pathogenesis of HALI induced by hyperbaric hyperoxia exposure in a rat model. Rats were divided into control group, HALI group, Nec-1 (necroptosis inhibitor) group and edaravone group. Rats were exposed to pure oxygen at 250 kPa for 6 h to induce HALI. At 30 min before hyperoxia exposure, rats were intraperitoneally injected with Nec-1 or edaravone, and sacrificed at 24 h after hyperoxia exposure. Lung injury was evaluated by histology, lung water to dry ratio (W/D) and bronchoalveolar lavage fluid (BALF) biochemistry; the serum and plasma oxidative stress, expression of RIP1, RIP3 and MLKL, and interaction between RIP1 and RIP3 were determined. Results showed hyperoxia exposure significantly caused damage to lung and increased necroptotic cells and the expression of RIP1, RIP3 and MLKL. Edaravone pre-treatment not only inhibited the oxidative stress in HALI, but also reduced necroptotic cells, decreased the expression of RIP1, RIP3 and MLKL and improved lung pathology. Nec-1 pretreatment inhibited necroptosis and improved lung pathology, but had little influence on oxidative stress. This study suggests hyperoxia exposure induces oxidative stress may activate necroptosis, involving in the pathology of HALI, and strategies targeting necroptosis may become promising treatments for HALI.

A randomized phase II trial of induction chemotherapy followed by cisplatin chronotherapy versus constant rate delivery combined with radiotherapy.

Chronotherapy is no longer a novel concept in cancer treatment after approximately 20 years of development. Many clinical trials have provided strong supporting evidence that chronomodulated treatment yields better results than a traditional dosage regimen. This study aimed to evaluate the adverse reactions, effect on immune functions, and therapeutic efficacy of chronomodulated infusion versus flat intermittent infusion of cisplatin (DDP) combined with intensity-modulated radiation therapy (IMRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 148 patients with biopsy-diagnosed untreated stage III-IVb NPC were randomly assigned to undergo two cycles of chronomodulated infusion (study group) or flat intermittent infusion (control group) of DDP (100 mg/m2 on day 1, 21 days/cycle) synchronized with radical radiotherapy. Patients in the study group received chronomodulated infusion, with peak delivery of DDP at 16:00 pm. Patients in the control group received a routine constant rate of infusion. Both groups were treated with the same radiotherapy techniques. Over a median follow-up of 20 months, the study group had better outcomes for adverse effects and immune functions compared with the control group. During the phase of concurrent chemoradiotherapy, the incidence of nausea, vomiting, and oral mucositis in the study and control groups was 66.7% and 79.5% (p < 0.05), 47.9% and 71.2% (p < 0.05), and 73.9% and 87.7% (p < 0.05), respectively. There was no significant difference in 2-year overall survival, progression-free survival, and distant metastasis-free survival between the two groups (p > 0.05). Chronochemotherapy significantly reduced the incidence of adverse reactions and enhanced the tolerance for treatment without affecting survival. It is worth mentioning that reduced destruction of immune function is a novel area of exploration in chronotherapy research.

[Expression and significance of IKKε in the specimens and cells of epithelial ovarian cancer].

Objective: To examine the expressions of IKKε protein in the specimens and cells of epithelial ovarian cancer and investigate the effect of IKKε inhibitor on cell proliferation and apoptosis. Methods: (1) A total of 118 cases of patients with the median age of 59 who have accepted surgical treatment due to ovarian cancer in the First Affiliated Hospital of Dalian Medical University from January 2006 to April 2013 were selected. Twenty cases of patients with the median age of 55 who have accepted hysterectomy and salpingo-oophorectomy due to uterine leiomyoma during the same period were selected as the control. The expressions of IKKε protein were detected by immunohistochemistry in normal ovarian tissues and epithelial ovarian cancer specimens, and the relationship between the expressions of IKKε and the clinical features of patients was analyzed. IKKε protein was determined by western blot in various ovarian cancer cells, including SKOV3, OV2008, C13, A2780S, A2780CP, OV4, OV5, OV8, and CAOV3 treated with or without IKKε inhibitor. The cellular proliferation and apoptosis of ovarian cancer cells after 48 hours treatment of IKKε inhibitor were analyzed by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Results: (1) The immunohistochemical results showed that IKKε was highly expressed in epithelial ovarian cancer specimens with the expression rate 66.1% (78/118), compared with normal ovarian tissue with the expression rate 35.0% (7/20), which exhibited statistically significant difference (χ(2)=6.993, P=0.008). The expression of IKKε protein was correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, the level of CA(125) in preoperative serum and distribution of the tumor (P<0.05), but no correlation with age, histological type, the incidence pattern, and tumor size (all P>0.05). (2) IKKε was widely overexpressed in different levels in SKOV3, OV2008, C13, A2780S, A2780CP, OV4, OV5, OV8, and CAOV3 cells, and the expression of IKKε decreased as the increase of the concentration of IKKε inhibitor (0.1 and 0.5 µmol/L) in OV2008, C13, A2780S, and A2780CP cells after 48 hours treatment. Different concentrations of IKKε inhibitor (0.05, 0.1, 0.5, 1, 5, 10, and 25 µmol/L) significantly inhibited the proliferation of OV2008, C13, A2780S, A2780CP, and SKOV3 cells in a concentration-dependent manner (P<0.05), and the half maximal inhibitory concentration (IC(50)) was 0.43, 0.86, 0.10, 0.19, and 0.24 µmol/L, respectively. The cell apoptotic rate of OV2008, C13, A2780S, A2780CP, and SKOV3 cells was significantly increased after 48 hours treatment of IKKε inhibitor with the concentration of 0.1 and 0.5 µmol/L (P<0.05). Conclusions: The IKKε protein in epithelial ovarian cancer specimens and cells is overexpressed. IKKε inhibitor could inhibit cellular proliferation and induce apoptosis in a concentration-dependent manner. Together, the result indicated that IKKε may be a candidate target for the treatment of ovarian cancer in future.

[Morphology character and reduction methods of sagittally unstable intertrochanteric fractures].

OBJECTIVE: To investigate the morphology character of sagittally unstable intertrochanteric fractures and reduction methods. METHODS: A retrospective study was used to analyze the clinical data of sagittally unstable intertrochanteric fractures cases, which were treated with proximal femoral nail anti-rotation (PFNA) fixation from March 2009 to June 2016. In the study, 36 cases were followed up completely, in which 17 cases accepted open reduction, and the other 19 cases accepted minimally invasive reduction. The operation time, amount of bleeding, the fluoroscopy times, postoperative radiographic measurements, such as tip-apex distance (TAD) and sliding distance of the spiral screw, and hip Harris scores were analyzed. The morphology character of the fractures was documented and investigated. RESULTS: The average follow-up time was 15 months. The amount of bleeding of the open reduction group was (170.5±19.7) mL, and the amount of bleeding of the minimally invasive group was (54.7±12.5) mL. The amount of bleeding of the minimally invasive group was significantly less than that of the open reduction group (P<0.001). Between the two groups, there were no significant differences in other evaluation parameter, including operation time (P=0.054), the fluoroscopy times (P=0.053), fracture healing time (P=0.305), postoperative radiographic measurements, such as TAD (P=0.317) and sliding distance of the spiral screw (P=0.206), and hip Harris scores (P=0.459). In regard to morphology character of the fractures, the proximal anterior unstable fractures with separation displacement were more common than the proximal posterior unstable fractures with impaction. The characteristic feature of the proximal anterior unstable fractures was the proximal anterior and medial long oblique fracture, and a V shape cortical defect in the distal fracture fragment on the externally rotation X-ray. CONCLUSION: Sagittally unstable intertrochanteric fractures can be divided into the proximal anterior unstable fractures with separation displacement, and the proximal posterior unstable fractures with impaction. The two types have their own morphology character individually. The reduction should be performed by minimally invasive techniques.

Significantly enhanced osteoblast response to nano-grained pure tantalum.

Tantalum (Ta) metal is receiving increasing interest as biomaterial for load-bearing orthopedic applications and the synthetic properties of Ta can be tailored by altering its grain structures. This study evaluates the capability of sliding friction treatment (SFT) technique to modulate the comprehensive performances of pure Ta. Specifically, novel nanocrystalline (NC) surface with extremely small grains (average grain size of ≤20 nm) was fabricated on conventional coarse-grained (CG) Ta by SFT. It shows that NC surface possessed higher surface hydrophilicity and enhanced corrosion resistance than CG surface. Additionally, the NC surface adsorbed a notably higher percentage of protein as compared to CG surface. The in vitro results indicated that in the initial culture stages (up to 24 h), the NC surface exhibited considerably enhanced osteoblast adherence and spreading, consistent with demonstrated superior hydrophilicity on NC surface. Furthermore, within the 14 days culture period, NC Ta surface exhibited a remarkable enhancement in osteoblast cell proliferation, maturation and mineralization as compared to CG surface. Ultimately, the improved osteoblast functions together with the good mechanical and anti-corrosion properties render the SFT-processed Ta a promising alternative for the load-bearing bone implant applications.

Core-shell structured titanium-nitrogen alloys with high strength, high thermal stability and good plasticity.

Multifunctional materials with more than two good properties are widely required in modern industries. However, some properties are often trade-off with each other by single microstructural designation. For example, nanostructured materials have high strength, but low ductility and thermal stability. Here by means of spark plasma sintering (SPS) of nitrided Ti particles, we synthesized bulk core-shell structured Ti alloys with isolated soft coarse-grained Ti cores and hard Ti-N solid solution shells. The core-shell Ti alloys exhibit a high yield strength (~1.4 GPa) comparable to that of nanostructured states and high thermal stability (over 1100 °C, 0.71 of melting temperature), contributed by the hard Ti-N shells, as well as a good plasticity (fracture plasticity of 12%) due to the soft Ti cores. Our results demonstrate that this core-shell structure offers a design pathway towards an advanced material with enhancing strength-plasticity-thermal stability synergy.

Renin-angiotensin system and its role in hyperoxic acute lung injury.

Oxygen is essential to sustain life, but at a high partial pressure oxygen may cause toxicity to the human body. These injuries to the lung are known as hyperoxic acute lung injury [HALI]). To date, numerous studies have been conducted to investigate the pathogenesis of HALI, for which some hypotheses have been proposed. Accumulating evidence indicates that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of some lung diseases, including acute lung injury (ALI), chronic obstructive pulmonary disease (COPD) and HALI. In this review, we briefly introduce the classic RAS, local (tissue) RAS and intracellular RAS, and we summarize findings on the relationship between local/classic RAS and HALI. The importance--and ambiguity--of the results of these studies indicate a need for further investigations of the RAS and its role in the patho- genesis of HALI.

[Clinical auxiliary diagnosis value of high frequency ultrasonographic measurements of the thickness of transverse carpal ligaments in carpal tunnel syndrome patients].

OBJECTIVE: To evaluate the meaning and value of high-frequency ultrasound in the diagnosis of carpal tunnel syndrome (CTS). METHODS: In this study, 48 patients (unilateral hand) with CTS were analyzed. The thickness of transverse carpal ligaments at the pisiform bone was measured using high-frequency ultrasound. Open carpal tunnel release procedure was performed in the 48 CTS patients, and the thickness of transverse carpal ligaments at the hamate hook bone measured using vernier caliper under direct vision. The accuracy of thickness of transverse carpal ligaments was evaluated using high-frequency ultrasound. high-frequency ultrasound measurement of thickness of transverse carpal ligaments at the hamate hook bone and pisiform bone, and determination of the diagnostic threshold measurement index using receiver operating characteristic (ROC) curve, sensitivity and specificity were performed and the correlation between the thickness of transverse carpal ligaments and nerve conduction study (NCS) analyzed. RESULTS: The thickness of transverse carpal ligaments in the CTS patients were (0.42±0.08) cm (high-frequency ultrasound) and (0.41±0.06) cm (operation) at hamate hook bone, and there was no significant difference between the two ways (t=0.672, P>0.05). The optimal cut-off value of the transverse carpal ligaments at hamate hook bone was 0.385 cm, the sensitivity 0.775, and the specificity 0.788. The optimal cut-off value of the transverse carpal ligaments at the pisiform bone was 0.315 cm, the sensitivity 0.950, and the specificity 1.000. The transverse carpal ligaments thickness and wrist-index finger sensory nerve conduction velocity (SCV), wrist-middle finger SCV showed a negative correlation. CONCLUSION: High frequency ultrasound measurements of thickness of transverse carpal ligaments is a valuable method for the diagnosis of CTS.

[Clinical characteristics and risk factors of newly developed vertebral fractures after vertebral augmentation].

OBJECTIVE: To identify the characteristics and risk factors of the refractures after percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP). METHODS: A retrospective analysis of 148 patients who had undergone PKP or PVP between March 2006 and October 2013 in Peking University People's Hospital was conducted. In the study, 29 patients with 42 refractured vertebra and 119 patients without refracture were included. All the patients were observed for a time of (34.4±26.8) months. Clinical, imaging and procedure related factors (gender, age, height, weight, body mass index, the level of the injured vertebra, the time interval between the procedure and the refracture, the level of the refractured vertebra, the bone cement volume injected, performed PKP or PVP,performed unilateral or bilateral, the percentage of anterior vertebral height restoration, the correction of the Cobb angle, cement diffusion, bone mineral density, presence or absence of diabetes mellitus, history of fractures of the whole body, anti-osteoporosis treatment, cement leakage) for each group were analyzed by Cox proportional hazards regression analysis. RESULTS: Of all the patients,16 (55.17%, 16/29) had refractures in the adjacent vertebra, and 13 (44.83%, 13/29) had refractures in the nonadjacent vertebra. Refractures within 3 months accounted for 31.03% (9/29) of all the refractures, and within 1 year accounted for 55.17% (16/29). Both older age (P=0.027, HR=1.051, 95% CI=1.006-1.098) and a history of fractures of the whole body (P=0.012, HR=0.386, 95% CI=0.184-0.812) were statistically significant as the independent risk factors for predicting refractures. Others were not associated with refractures (P>0.05). CONCLUSION: Older age and a history of fractures of the whole body are the independent risk factors of the refractures after PKP and PVP. The mechanism of the refractures after PKP and PVP is mainly the natural development of osteoporosis.

[Applying percutaneous placement of guide wire combined with true lateral view fluoroscopy proximal femoral nail anti-rotation fixation].

OBJECTIVE: To apply modified proximal femoral nail anti-rotation (PFNA) fixation techniques performed by percutaneous placement of guide wire combined with true lateral view and to make the procedures simpler. METHODS: A retrospective study was used to analyze the clinical data of femoral intertrochanteric fractures cases, which were treated with conventional PFNA fixation or modified PFNA fixation performed by percutaneous placement guide wire combined with true lateral view in our hospital, from March, 2011 to May, 2014. In the study, 60 cases were followed for average 13 months. The operation time, the amount of bleeding, the fluoroscopy time, postoperative radiographic measurements (tip apex distance, TAD) and hip function scores were analyzed. RESULTS: In modified PFNA group, the amount of bleeding, the operation time and the fluoroscopy time were (34.9±6.1) mL, (70.5±12.5) min, (63.6±9.7) s respectively. In conventional PFNA group,they were (47.8±6.7) mL, (80.6±17.1) min, (68.5±8.7) s respectively. There were significant differences in the above respects between the two groups (P were 0.006, 0.013, and 0.022 respectively). There were no significant differences in TAD, fracture healing time, postoperative hip scores between the two groups (P>0.05). CONCLUSION: Fracture line is a natural entry point for some cases of femoral intertrochanteric fractures when we use proximal femoral nail anti-rotation to fix the fracture. Applying percutaneous insertion of the guide pin combined with true lateral view could reduce the operation time, amount of bleeding, and fluoroscopy time significantly, make the procedures simpler and acquire satisfactory results .

[Characteristics and perioperative management of hemophilia patients with fractures].

OBJECTIVE: To investigate the characteristics and perioperative management of hemophilia patients with fracture. METHODS: Retrospectively, we analyzed 8 patients with hemophilia combined with fracture, who were admittted to our department from 2005 to 2013. Six patients were with hemophilia A and two with hemophilia B; Based on the severity of hemophilia, 2 cases were light, 3 moderate and 3 severe; Based on the location of fracture, 4 cases were femoral neck fractures, 1 femoral intertrochanteric fracture, 1 bilateral distal femur fractures, 1 tibiofibula fracture, and 1 humerus intercondylar fracture. Blood coagulation factor replacement therapy was conducted preoperatively, intraoperatively and postoperatively, All the patients underwent closed or open reduction and internal fixation or joint replacement. Also, we analyzed the perioperative complications and observed whether the fracture healed. RESULTS: The average age was 33.5 years (14 to 47 years); In 6 cases, fractures occurred at femur, accounting for 75% of all the fractures; Femoral neck fracture was treated by closed reduction and hollow screws fixation; Femoral intertrochanteric fracture, distal femur fracture, and tibiofibula fracture were treated by open reduction and internal fixation with plate; Humerus intercondylar fracture was treated by elbow joint replacement. Intraoperative bleeding was from 50 to 600 mL, an average of 262 mL; Perioperatively, the average use of FVIII/activated prothrombin complex concentrates (APCC) was 358 U/kg (125 to 554 U/kg). Postoperatively, poor wound healing was observed in 2 patients, and the condition improved after symptomatic treatment; In patients with internal fixation, all the fractures united, and the average healing time was 14 weeks. No complications such as fixation loosening or rupture occurred after internal fixation. CONCLUSION: Hemophilia combined with fracture mainly occurred in the young, and the site of fracture was given priority to femur. With perfect preoperative preparation, on the basis of the replacement therapy, hemophilia combined with fractures was safe for surgical treatment, and postoperative fractures healing wasgood. But the risk of poor wound healing was high.

Radiological evaluation of reduction loss in unstable proximal humeral fractures treated with locking plates.

PURPOSE: The aim of this study was to radiologically evaluate the risk of reduction loss after locking plate fixation of proximal humerus fractures. METHODS: From September 2007 to April 2009, 71 patients (28 males, 43 females) with unstable proximal humeral fracture were treated with open reduction and internal fixation by locking plate. The mean follow-up time was 31.2 months (range: 26-47). The head-shaft angulation (HSA) and the humeral head height (HHH) in true anteroposterior (AP) were recorded and compared over time. All complications were noted. Shoulder function was measured by the Constant score. RESULTS: Patients with ΔHSA >10° (t=2.740, P=0.008) and ΔHHH >5mm (t=2.55, P=0.019) were more likely to have impaired shoulder function. Varus collapse occurred most frequently in patients with initial reduction of HSA <125° (χ(2)=19.17, P<0.001, Fisher's exact test F<0.001). Patients with >5mm HHH decrease were strongly associated with loss of reduction (χ(2)=24.23, P<0.001, F<0.001). CONCLUSIONS: Dynamic change of HSA >10° and HHH >5mm were radiological factors that indicated poor shoulder function. Intra-operative HSA >125° should be achieved to avoid reduction loss following locking plate fixation of proximal humerus fracture. LEVEL OF EVIDENCE: level IV.

Validated HPLC Method for the Determination of Paclitaxel-related Substances in an Intravenous Emulsion Loaded with a Paclitaxel-Cholesterol Complex.

A high-performance liquid chromatography method was developed for the determination of related substances in an intravenous emulsion loaded with a paclitaxel-cholesterol complex. The separation was achieved using Agilent Eclipse XDB-C18 column (150×4.6 mm, 3.5 µm), which was kept at 40°. The gradient mobile phase consisted of acetonitrile and water with a flow rate of 1.2 ml/min. The ultraviolet detection wavelength was set at 227 nm. The preparation of the sample solution began with the addition of anhydrous sodium sulphate to break the emulsion. Then, methanol and ethyl ether were added to pick up the drug and remove the accessories of the emulsion by extraction and centrifugation. Finally, paclitaxel was enriched by a nitrogen blow method and resolved with a mixture of methanol:glacial acetic acid (200:1). The method was proven to be selective, sensitive, robust, linear, repeatable, accurate and suitable for the determination of paclitaxel-related substances in the emulsion formulations, and the major degradation products in the potential pharmaceutical product were 7-epipaclitaxel and 10-deacetylpaclitaxel.