IFN-γ affects pancreatic cancer properties by MACC1-AS1/MACC1 axis via AKT/mTOR signaling pathway

BackgroundMetastasis-related in colon cancer 1 (MACC1) is highly expressed in a variety of solid tumours, but its role in pancreatic cancer (PC) remains unknown. Interferon gamma (IFN-γ) affecting MACC1 expression was explored as the potential mechanism following its intervention.MethodsExpressions of MACC1 treated with IFN-γ gradient were confirmed by quantitative real-time PCR (qRT-PCR) and western blot (WB). Proliferation, migration, and invasion abilities of PC cells treated with IFN-γ were analysed by CCK8, EDU, colony formation, Transwell (with or without matrix gel) and wound-healing assays. Expression of antisense long non-coding RNA of MACC1, MACC1-AS1, and proteins of AKT/mTOR pathway, (pho-)AKT, and (pho-)mTOR was also assessed by qRT-PCR and WB. SiRNA kit and lentiviral fluid were conducted for transient expression of MACC1 and stable expression of MACC1-AS1, respectively. Rescue assays of cells overexpressing MACC1-AS1 and of cells silencing MACC1 were performed and cellular properties and proteins were assessed by the above-mentioned assays as well.ResultsIFN-γ inhibited MACC1 expression in a time- and dose-dependent manner; 100 ng/mL IFN-γ generally caused downregulation of most significant (p ≤ 0.05). In vitro experiments revealed that IFN-γ decreased cellular proliferation, migration, and invasion abilities and downregulated the expression of pho-AKT and pho-mTOR (p ≤ 0.05). Conversely, overexpression of MACC1-AS1 upregulated pho-AKT and pho-mTOR proteins, and reversed cellular properties (p ≤ 0.05). Rescue assays alleviated the above changes of pho-AKT/ mTOR and cellular properties.ConclusionIFN-γ affected PC properties by MACC1-AS1/MACC1 axis via AKT/mTOR signaling pathway, which provides novel insight for candidate targets for treating PC.

[The expression and clinical significance of Bmi-1 gene in oral leukoplakia with different prognosis].

Objective: To detect the expression of Bmi-1 in oral leukoplakia (OL) cells and tissues, and analyze its role and clinical significance in the malignant transformation of OL. Methods: Immunohistochemistry was used to evaluate Bmi-1 expression in OL samples from 109 patients (51 males, 58 females, age range: 18-74 years) who were treated in the Department of Stomatology, the Affiliated Wuxi People's Hospital of Nanjing Medical University and the Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between 1996 and 2018. The correlation between Bmi-1 expression level and clinicopathological parameters and prognosis in patients with OL was analyzed. The mRNA and protein expression levels of Bmi-1 gene in normal oral mucosal epithelial cells, OL cells, oral squamous cell carcinoma (OSCC) cells, OL tissues and paired adjacent normal tissues were detected by real-time PCR and Western blotting. The effects of Bmi-1 on the proliferation, colony formation and apoptosis were investigated by silencing expression of Bmi-1 in OL cell lines Leuk-1. Results: The protein level of Bmi-1 in OL tissue with severe and mild dysplasia was statistically different (6 819±994 vs 4 713±372, P=0.017). The OSCC-free survival rate of OL patients with high Bmi-1 expression was 65.5% (36/55), which was lower than that of OL patients with low Bmi-1 expression (88.9%, 48/54, P=0.003). Multivariate Cox proportional analysis indicated that Bmi-1 expression was the independent predictor for malignant transformation of OL (HR=2.522, 95%CI: 1.128-5.640, P=0.024). The mRNA level of Bmi-1 in OL specimens was 0.455±0.120, which was higher than that in paired adjacent normal tissues (0.063±0.009, P=0.014). The Bmi-1 mRNA level in malignant transformed OL specimens was (1.405±0.397), which was higher than that in untransformed OL specimens (0.145±0.017, P<0.001). After transfection of Bmi-1-shNC and Bmi-1-shRNA2 adenovirus into OL cell line Leuk-1, there were significant differences in the number of clone formation (824±40 vs 414±38, P=0.002) and apoptosis rate (17.7%±2.3% vs 36.0%±2.0%, P=0.004). Conclusions: The up-regulation of Bmi-1 expression promotes the malignant biological behavior of OL cells. Bmi-1 expression can be used as a predictor for malignant transformation of OL.

IFN-γ affects pancreatic cancer properties by MACC1-AS1/MACC1 axis via AKT/mTOR signaling pathway.

BACKGROUND: Metastasis-related in colon cancer 1 (MACC1) is highly expressed in a variety of solid tumours, but its role in pancreatic cancer (PC) remains unknown. Interferon gamma (IFN-γ) affecting MACC1 expression was explored as the potential mechanism following its intervention. METHODS: Expressions of MACC1 treated with IFN-γ gradient were confirmed by quantitative real-time PCR (qRT-PCR) and western blot (WB). Proliferation, migration, and invasion abilities of PC cells treated with IFN-γ were analysed by CCK8, EDU, colony formation, Transwell (with or without matrix gel) and wound-healing assays. Expression of antisense long non-coding RNA of MACC1, MACC1-AS1, and proteins of AKT/mTOR pathway, (pho-)AKT, and (pho-)mTOR was also assessed by qRT-PCR and WB. SiRNA kit and lentiviral fluid were conducted for transient expression of MACC1 and stable expression of MACC1-AS1, respectively. Rescue assays of cells overexpressing MACC1-AS1 and of cells silencing MACC1 were performed and cellular properties and proteins were assessed by the above-mentioned assays as well. RESULTS: IFN-γ inhibited MACC1 expression in a time- and dose-dependent manner; 100 ng/mL IFN-γ generally caused downregulation of most significant (p ≤ 0.05). In vitro experiments revealed that IFN-γ decreased cellular proliferation, migration, and invasion abilities and downregulated the expression of pho-AKT and pho-mTOR (p ≤ 0.05). Conversely, overexpression of MACC1-AS1 upregulated pho-AKT and pho-mTOR proteins, and reversed cellular properties (p ≤ 0.05). Rescue assays alleviated the above changes of pho-AKT/ mTOR and cellular properties. CONCLUSION: IFN-γ affected PC properties by MACC1-AS1/MACC1 axis via AKT/mTOR signaling pathway, which provides novel insight for candidate targets for treating PC.

[Study of abnormal lipid metabolism analysis and significance of fatty acid binding protein expression in patients with hepatocellular carcinoma].

Objective: Hepatocellular carcinoma (HCC) is the fourth most dominant cancer in the world and the second leading cause of cancer-related deaths in the China. With the increase in the incidence of metabolic syndrome (MS) in the population, the correlation between MS and HCC has gradually been recognized. MS manifests as non-alcoholic fatty liver disease (shortly known as NAFLD) in the liver. A large number of research results has shown that the development of fatty liver is closely related to the occurrence of HCC, in which lipid metabolism plays a key regulatory role, and lipid metabolism is regulated by fatty acid binding protein (FABP). This study signifies the lipid metabolism analysis and the key FABP expression conditions in HCC. Methods: Data of patients who were first diagnosed with primary HCC between January 2016 to July 2019 were collected, and were divided into two groups according to the etiology, namely the viral and non-viral hepatitis-related HCC group. The relationship between MS-related factors and HCC was analyzed by t-test and chi square test. The expressions of FABP1, FABP4 and FABP5 were detected in cancer and adjacent tissues by immunohistochemistry, and the expressions of FABP1, FABP4 and FABP5 in HCC with fatty liver were detected by immunofluorescence. Finally, the expressional characteristics of the above-mentioned FABPs in HCC patients were analyzed with different clinicopathological features. Results: There were statistically significant differences in the rate of abnormal lipid metabolism and the number of abnormalities in MS-related factors between the viral and non-viral hepatitis-related HCC group. FABP1, FABP4, and FABP5 expression in HCC tissues were lower than the corresponding adjacent tumor tissues. Compared with simple HCC, FABP1, FABP4, FABP5 expression were increased in HCC tissues with steatosis, and the expression of FABP was closely related to the clinical characteristics of patients. Conclusion: Abnormal lipid metabolism is closely related to non-viral hepatitis-related HCC. The expression of lipid metabolism regulatory proteins FABP1, FABP4, and FABP5 are down-regulated in HCC tissues, but up-regulated in HCC with fatty liver, suggesting that the relationship between MS, especially dyslipidemia, and HCC should be paid attention to in clinical practice for early intervention. FABP1, FABP4, FABP5 may regulate HCC occurrence and development.

Current status and distribution of hip fractures among older adults in China.

China is a middle-risk country for hip fracture at present, which differs from previous data that it was low-risk. By 2050, the total number of hip fractures in people older than 65 years is predicted to be 1.3 million. INTRODUCTION: To assess hip fracture incidence in China and examine the heterogeneity of hip fracture in seven geographical regions of China. METHODS: There were 238,230 hip fracture patients aged 65 years or older from 2013 to 2016 from a large national in-patients database (HQMS) involving 30.6 million hospitalizations. Taking into account the total national hospitalization rate per calendar year, we estimated the incidence of hip fracture per 100,000 residents older than 65 years in China overall and in seven geographical Chinese regions. RESULTS: The proportion of men and women older than 65 years with hip fractures was 1.00:1.95. Between 2013 and 2016, the number of hip fractures per 100,000 people age 65+ was 278. China has vast territories; the number of hip fractures per 100,000 people over 65 years old was 202 in Northeast China and 374 in Northwest China. Northwest has higher altitude, lower population density, is less developed with lower urbanization than Northeast China which is low altitude, and highly urbanized. CONCLUSIONS: China should no longer be regarded as a low-risk country for hip fracture. By 2050, the total number of hip fractures in people older than 65 years in China is predicted to be 1.3 million. Higher altitude areas had higher hip fracture rates than lower altitude, higher urbanized areas.

[Clinical outcome of open reduction and internal fixation with digastric trochanteric flip osteotomy for acetabular posterior wall fracture with hip dislocation].

Objective: To evaluate the clinical outcome of open reduction and internal fixation via digastric trochanteric flip osteotomy for acetabular posterior wall fracture with hip dislocation. Methods: From January 2014 to December 2016 a total of 39 patients who suffered posterior wall acetabular fracture and hip dislocation and treated in Beijing Jishuitan Hospital were included in this retrospective study. All the patients were divided into two groups according to surgery type. There were 22 cases in osteotomy group who underwent digastric trochanteric flip osteotomy (DTFO) via Kocher-Langenbeck (K-L) approach, while 17 cases in control group who only received surgery via (K-L) approach. The Matta scale was used to evaluate fracture reduction, while functional recovery scale (FRS) and Euro-Quality of 5 Dimension (EQ-5D) were applied to measure the clinical effect. Results: The baseline characteristics were similar for both groups and the mean follow-up period was (48±11) months. All the surgeries were performed successfully. The blood loss (t=1.52, P=0.12), bed days (t=1.22, P=0.25), complication rate (χ²=2.02, P=0.16) and operation time (t=1.31, P=0.23) showed no significant difference between the 2 groups (P>0.05). The fracture reduction (χ²=0.05, P=0.81) were similar between the 2 groups but the excellent rate were higher in osteotomy group. According to evaluation scales the FRS score and EQ-5D index favored osteotomy group(85±13 vs 80±15 and 0.86±0.12 vs 0.80±0.17, respectively, t=2.87, 3.47, both P<0.05). Conclusion: K-L approach with DTFO can provide clearier surgical field which is convenient for procedure, and compared to K-L approach the clinical effect is more satisfactory.

[Effects of oxygen saturation on all-cause mortality among the elderly over 65 years old in 9 longevity areas of China].

Objective: To investigate the association between oxygen saturation (SpO2) and risk of 3-year all-cause mortality among Chinese older adults aged 65 or over. Methods: The participants were enrolled from Healthy Aging and Biomarkers Cohort Study in year of 2012 to 2014 in 9 longevity areas in China. In this prospective cohort study, 2 287 participants aged 65 or over were enrolled. Data on SpO2 and body measurements were collected at baseline in 2012, and data on survival outcome and time of mortality were collected at the follow-up in 2014. Participants were divided into two groups according to whether SpO2 was abnormal (SpO2<94% was defined as abnormal). Results: The 2 287 participants were (86.5±12.2) years old, 1 006 were males (44.0%), and 315 (13.8%) were abnormal in SpO2. During follow-up in 2014, 452 were died, 1 434 were survived, and 401 were lost to follow-up. The all-cause mortality rate was 19.8%, and the follow-up rate was 82.5%. The mortality rate of SpO2 in normal group was 21.1%, and that of abnormal group was 41.6% (P<0.001). After adjusting for confounding factors, compared to participants with normal SpO2, participants with abnormal SpO2 had increased risk of all-cause mortality with HR (95%CI) of 1.62 (1.31-2.02); HR (95 % CI) was 1.49 (0.98-2.26) for males and 1.71 (1.30-2.26) for females in abnormal SpO2 group, respectively; HR (95%CI) was 2.70 (0.98-7.44) for aged 65-79 years old, 1.22 (0.63-2.38) for aged 80-89 years old, and 1.72 (1.35-2.19) for aged over 90 years old in abnormal SpO2 group, respectively. Conclusion: Abnormal SpO2 was responsible for increased risk of 3-year all-cause mortality among Chinese elderly adults.

Long noncoding RNA MAFG-AS1 facilitates the progression of hepatocellular carcinoma via targeting miR-3196/OTX1 axis.

OBJECTIVE: Hepatocellular carcinoma (HCC) is an invasive malignant tumor with high mortality rate. Long non-coding RNA (lncRNA) MAFG-AS1 has been showed to play an oncogenic role in several malignant tumors. Nonetheless, the exact role of MAFG-AS1 in the progression of HCC has not been fully elucidated. PATIENTS AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the mRNA and protein expression of MAFG-AS1 in HCC tissues and cells. Cell counting kit-8 (CCK-8), transwell and tubule formation assays were applied to uncover the proliferation, migration, invasion and tumor angiogenesis of HCC cells, respectively. RNA binding protein immunoprecipitation (RIP) assay and Luciferase reporter gene assay were employed to explore the molecular mechanism. In addition, Xenograft assay was used to investigate the effect of MAFG-AS1 in vivo. RESULTS: MAFG-AS1 was highly expressed in HCC tissues and cells. Attenuation of MAFG-AS1 evidently suppressed the proliferation, migration, invasion and tumor angiogenesis of HCC cells, suggesting that MAFG-AS1 played an oncogenic role in HCC. MiR-3196 was sponged by MAFG-AS1, and OTX1 was a downstream target of miR-3196 in HCC. In addition, OTX1 expression was negatively associated with miR-3196 but positively associated with MAFG-AS1 in HCC tissues. Overexpression of OTX1 could abolish the repressive influence of MAFG-AS1 inhibition on the proliferation, migration, invasion and tumor angiogenesis of HCC cells. CONCLUSIONS: MAFG-AS1 facilitated the progression of HCC via targeting miR-3196/OTX1 axis, which might be used as a new insight for HCC treatment.

[Comparative study of ultrasound-guided percutaneous microwave ablation and surgical resection for colorectal cancer with liver metastasis].

Objective: To study the clinical efficacy of ultrasound-guided percutaneous microwave ablation and surgical resection for liver metastases from colorectal cancer. Methods: Retrospective analysis of 184 patients with liver metastases from colorectal cancer in Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2012 to June 2017.Percutaneous microwave ablation or surgical resection for liver metastases were selected under ultrasound guidance. Subgroup analysis was performed according to the treatment of liver metastases. There were 98 patients in the microwave-only group (56 males and 42 females, aged (59±11) years) and 86 cases in the surgery-only group (56 males and 30 females, aged (56±11) years). The baseline data of the two groups were compared, and the results showed that the size of the metastatic lesions in the microwave-only group was smaller than that in the surgery-only group, and the remaining data didn't had statistical differences.The survival time of the two groups of patients was analyzed separately.According to the size of the metastases, the metastases were divided into groups with a diameter of<3 cm and a group of ≥3 cm. The survival time of patients in the microwave-only group and the surgery-only group were analyzed respectively.According to the different primary tumor grades of colorectal cancer, the survival time of patients in the simple microwave-only group and the surgery-only group in the primary tumors Duck A, Duck B, and Duck C were analyzed. Results: In the microwave-only group, the overall survival rates at 1, 3, and 5 years were 100%, 50.9%, and 20.9%; in the surgery-only group, the overall survival rates at 1, 3, and 5 years were 100%, 42.8%, and 20.8%, respectively. There was no significant difference in overall survival between the groups (P=0.972).Metastatic focus diameter ≥3 cm: the overall survival rates of 1, 3, and 5 years with microwave-only were 100%, 65.4%, and 12.1%; the overall survival rates of 1, 3, and 5 years with surgery-only were 100%, 59.5%, and 30.9%. There was no significant difference in overall survival between the groups (P=0.067). The long-term survival rate of the surgery-only group was greater than that of the microwave-only group (P=0.018).Metastasis diameter<3 cm: there was no significant difference in overall survival between the surgery-only group and the microwave-only group (P=0.103).In the treatment of Duck B and C liver metastases of primary colorectal cancer, there was no significant difference in overall survival between microwave alone and surgery alone (P=0.376, P=0.385).Multivariate analysis showed that the size of colorectal cancer metastases was an independent risk factor affecting the prognosis of patients with colorectal cancer liver metastases. Conclusions: Percutaneous microwave ablation has a good effect on colorectal cancer liver metastases and has a similar survival prognosis as surgery.For livers with color ≥ 3 cm in colorectal cancer, the long-term survival rate of the surgery-only group is greater than that of the microwave-only group.

[Influence of visual impairment on mortality in the elderly aged 65 years and older in 8 longevity areas in China].

Objective: To understand the relationship between visual impairment and risk of all-cause mortality in the elderly aged 65 years and older in 8 longevity areas in China. Methods: The data of the elderly aged 65 years and older in the project in 2012 were obtained from Healthy Aging and Biomarkers Cohort Study, a sub-cohort of the Chinese Longitudinal Healthy Longevity Survey, including physical measurement and survival status, and a follow-up for survival outcomes were conducted in 2014 and 2017 respectively. Cox proportional hazard regression model was used to analyze the influence of visual impairment on mortality. Gender and age specific analysis was conducted. Results: A total of 1 736 elderly adults were included. A total of 943 deaths occurred during the 5-year follow-up period with a 5-year mortality rate of 54.3%. The 5-year mortality rate was 76.7% in the group with visual impairment, and 47.6% in the group without visual impairment (P<0.001). After adjusting for demographic information, life style and some disease factors, the risk of 5-year mortality in the group with visual impairment group was 1.30 times higher than that in the group without visual impairment (HR=1.30, 95%CI: 1.09-1.55). In the females, the risk for mortality in the group with visual impairment was 1.48 times higher than that in the group without visual impairment (HR=1.48, 95%CI:1.20-1.84). However, vision status was not associated with the risk for mortality in males (HR=1.02, 95%CI: 0.72-1.43). The risk for mortality in the group with visual impairment was 1.39 times higher than that in the group without visual impairment in the elderly aged over 90 years (HR=1.39, 95%CI: 1.13-1.70). Vision status was not associated with mortality risk in the elderly aged 65-79 years and 80-89 years (HR=1.37, 95%CI: 0.61-3.07; HR=0.95, 95%CI: 0.61-1.48). Conclusion: In the elderly people in China, visual impairment is a risk factor for mortality.

[Effects of estimated glomerular filtration rate on all-cause mortality in the elderly aged 65 years and older in 8 longevity areas in China].

Objective: To investigate the association between estimated glomerular filtration rate (eGFR) and all-cause mortality in the elderly aged 65 years and older in longevity areas in China. Methods: Data used in this study were obtained from Healthy Aging and Biomarkers Cohort Study, a sub-cohort of the Chinese Longitudinal Healthy Longevity Survey, 1 802 elderly adults were collected in the study during 2012-2017/2018. In this study, the elderly were classified into 4 groups, moderate-to-severe group [<45 ml·min(-1)·(1.73 m(2))(-1)], mild-to-moderate group [45- ml·min(-1)·(1.73 m(2))(-1)], mild group [60- ml·min(-1)·(1.73 m(2))(-1)] and normal group [≥90 ml·min(-1)·(1.73 m(2))(-1)] according to their eGFR levels. Results: After 6 years of follow-up, 852 participants died, with a mortality rate of 47.3%. Multivariate Cox regression analysis showed that the levels of eGFR were negatively correlated with all-cause mortality risk in the elderly (the HR of elderly was 0.993 and the 95%CI was 0.989-0.997 for every unit of eGFR increased, P=0.001), while compared with the group with normal eGFR, the HRs (95%CI) of the elderly in the moderate-to-severe group, mild-to-moderate group, and mild group were 1.690 (1.224-2.332, P=0.001), 1.312 (0.978-1.758, P=0.070), 1.349 (1.047-1.737, P=0.020) respectively [trend test P<0.001]. Conclusion: The decrease in eGFR was associated with higher mortality risk among the elderly in longevity areas in China.

MiR-142 inhibits lung cancer cell proliferation and promotes apoptosis by targeting XIAP.

OBJECTIVE: The X-linked inhibitor of apoptosis protein (XIAP) is associated with the development of various tumors. The abnormal miR-142 expression is associated with the onset of lung cancer. Bioinformatics analysis revealed a targeted relationship between miR-142 and XIAP. This report investigated whether miR-142 plays a role in regulating XIAP expression and affecting the biological processes of lung cancer cells. PATIENTS AND METHODS: The tumor tissues of lung cancer patients were collected, and the adjacent tissues were used as controls. The dual luciferase reporter gene assay validated the targeted regulation between miR-142 and XIAP. Using BEAS-2B cells as control, qRT-PCR was used to detect the expression of miR-142 and XIAP in lung cancer cells A549 and H1650. Lung cancer H1650 cells were cultured and divided into miR-NC group and miR-142 mimic group followed by an analysis of cell proliferation by EdU staining. RESULTS: Compared with those in adjacent tissues, miR-142 expression was significantly decreased and XIAP expression was increased in lung cancer tissues. The Dual-Luciferase Reporter Assay confirmed a targeted regulation relationship between miR-142 and XIAP. Compared with BEAS-2B cells, miR-142 expression in lung cancer A549 and H1650 cells was significantly decreased, and XIAP expression was significantly increased. Transfection of miR-142 mimic significantly inhibited the expression of XIAP in H1650 cells, promoted apoptosis and inhibited cell proliferation. CONCLUSIONS: Decreased miR-142 expression and increased XIAP expression is associated with the onset of lung cancer. MiR-142 can inhibit lung cancer cell proliferation and induce apoptosis through inhibition of XIAP expression.

[Postoperative distal tibiofibular synostosis: radiographic characteristics and the influence on ankle mobility].

Objective: To investigate the clinical and imaging characteristics of distal tibiofibular synostosis in postoperative ankle fractures and its effects on the ankle mobility. Methods: The clinical and imaging data of 47 patients with distal tibiofibular synostosis treated surgically from October 1991 to June 2013 were analyzed retrospectively. There were 30 males and 17 females, aged from 15 to 68 years with a mean age of (39±13) years. The original fracture types, internal fixation profiles, imaging features of distal tibiofibular synostosis were recorded. Ankle range of motion (ROM) and complications at the last follow-up were also evaluated.The ROMs of healthy and fractured sides were compared with paired sample rank test. Results: The patients were followed up for 3 to 204 months (mean 25.4 months). Of the patients, 34(72.4%) were ankle fractures, 7(14.9%) were distal tibiofibular fractures, 1(2.1%) was tibiofibular shaft fracture, 2(4.3%) were tibial shaft fractures associated with lateral malleolus fracture and the resting 3(6.4%) were Pilon fractures. In patients with ankle fractures, 76.5%(26/34) of the synostosis occurred at the distal tibiofibular syndesmosis, while 23.5%(8/34) at the proximal of the tibiofibular sydesmosis; in patients with distal tibiofibular fracture, 85.7%(6/7) of the tibiofibular synostoses occurred at the fracture sites. The synostosis occurred at the level of syndesmotic screws in 8 patients (88.9%, 8/9) fixed with distal tibiofibular syndesmotic screws. And synostosis occurred at the sites of the distal locking screws in all (3/3) of the patients fixed with intramedullary nails. At the last follow-up, the active plantarflexion, active dorsiflexion and passive dorsiflexion in the affected side was 0°(0°, 5°), 2°(0°, 5°), 5°(0°, 10°) less than those in the healthy side, respectively (Z=-3.493, -4.491, -5.130, all P<0.05).During the follow-up, 4 patients complained of lateral ankle discomfort with no impact on daily life. Conclusions: Post-operative distal tibiofibular synostosis mainly occurs at the sites of fractures, distal tibiofibular syndesmotic screw sites and the sites of the distal locking screws of tibial intramedullary nails. ROM of the injured ankle decreases in comparison with that at the contralateral side, although no obvious symptoms are observed and no intervention needed.

[The relationship between hazard ratio and median survival time].

The hazard ratio and median survival time are the routine indicators in survival analysis. We briefly introduced the relationship between hazard ratio and median survival time and the role of proportional hazard assumption. We compared 110 pairs of hazard ratio and median survival time ratio in 58 articles and demonstrated the reasons for the difference by examples. The results showed that the hazard ratio estimated by the Cox regression model is unreasonable and not equivalent to median survival time ratio when the proportional hazard assumption is not met. Therefore, before performing the Cox regression model, the proportional hazard assumption should be tested first. If proportional hazard assumption is met, Cox regression model can be used; if proportional hazard assumption is not met, restricted mean survival times is suggested.

[Block randomization in clinical trials].

Randomization is the key to ensure the balance of confounders between the comparison groups in clinical trials, and it is the statistical basis for making the study results comparable. A simple randomization in a clinical trial with large sample-size allows for a balanced comparison of the number of subjects and confounding factors between groups, but in a clinical trial with small sample-size, it is necessary to use a restricted randomization method (the blocked randomization). Block randomization ensures that the number of subjects between groups is basically equal, maximize the effectiveness of clinical trials as the standard error of the treatment-effect estimate is decreased, which affords big rewards in scientific accuracy and credibility.

[Deltoid ligament augmentation and repairing in ankle fracture associated with deltoid ligament injury and syndesmosis diastasis].

Objective: To evaluate the outcome of the deep component augmentation and superficial component repairing and syndesmosis screw fixation in treating ankle fracture associated with deltoid ligament injury and syndesmosis diastasis. Methods: From January 2014 to December 2017, 16 patients with ankle fracture combined with deltoid ligament injury and syndesmosis diastasis were treated with the deep component augmentation and superficial component repairing in Beijing Jishuitan Hospital.Of the patients, 13 were males and 3 were females, with an average age of (38±10) years (21-57 years). Nine cases were athletic injuries, 4 cases were daily-life injuries and 3 cases were traffic injuries.According to the Weber classification, 6 cases were type B, 10 cases were type C. According to the Lauge-Hansen classification, 6 cases were supination external rotation Ⅳ injury, 9 cases were pronation external rotation Ⅳ injury, 1 case was pronation abduction Ⅲ injury.The surgical treatment method was rigid fixation of the lateral malleolus and deep deltoid ligament augamentation instead of syndesmosis screw fixation.The effect of the surgical method was observed. Results: The average follow up was (24±12) months (6-40 months). The mean degree of dorsiflexion was 17.8°±6.8° (5°-30°), with 3.8°±6.0° (0°-15°) less than that in normal side, the mean degree of plantar flexion was 46.9°±7.9°, with 1.9°±3.9° (0°-10°) less than that in normal side.The mean Philips and Schwartz score was 96.8±5.1 (82-100), the American Orthopaedic Foot and Ankle Society (AOFAS) Score was 97.4±4.6 (84-100). Conclusion: In the treatment of ankle fracture associated with deltoid ligament injury and syndesmosis diastasis, the deep component augmentation and superficial component repairing and proper rehabilitation can benefit the functional recovery.

Research on values of GDF-15 level in the diagnosis of primary liver cancer and evaluation of chemotherapeutic effect.

OBJECTIVE: To investigate the values of growth differentiation factor-15 (GDF-15) level in the diagnosis of primary liver cancer and evaluation of chemotherapeutic effect. PATIENTS AND METHODS: 92 patients with liver cancer treated from June 2015 to May 2016 were selected as liver cancer group; 53 patients with benign liver lesion were selected as benign liver disease group, and 40 healthy subjects receiving physical examination were selected as healthy control group. Fasting venous blood was drawn from objects of study in the early morning at 1 d after admission and at the last day after chemotherapy (liver cancer group), and the serum GDF-15 level was measured. RESULTS: The serum GDF-15 levels in patients in liver cancer group and benign liver disease group were significantly higher than those in healthy control group and benign liver disease group (p<0.05). The serum GDF-15 levels in patients with stage III and IV liver cancer were significantly higher than those in patients with stage I and II liver cancer, and the serum GDF-15 level in patients with stage IV liver cancer was significantly higher than that in patients with stage III liver cancer (p<0.05). There was no significant difference in serum GDF-15 level among patients with different clinical data (p>0.05). The ROC curve analysis showed that the threshold value of GDF-15 was 1573.23 ng/L, and the sensitivity, specificity, and accuracy were 81.23%, 83.99%, and 83.62%, respectively. The serum GDF-15 level in patients with progressive disease was significantly higher than those in patients with partial remission and stable disease, and the serum GDF-15 level in patients with stable disease was significantly higher than that in patients with partial remission (p<0.05). CONCLUSIONS: The serum GDF-15 level has certain clinical values in the diagnosis of primary liver cancer and evaluation of chemotherapeutic effect.