[Objective]To summarize results of treating complex proximal tibia fractures with less invasive stabilization system(LISS),and to explore the concept and technology of LISS.[Method]From January 2004 to March 2006,39 cases of complex proximal tibia fractures were treated with less invasive stabilization system,including 26 male and 13 female.The mean age of the patients was 34.8 years(range 22 to 54 years).According to the AO/OTA fracture classification,there were 19 cases in type 41-A3,12 cases in type 41-C2,4 cases in type 41-C3,4 cases in proximal type 42.Seven cases were open fractures and were classified as 3 grade Ⅰ,4 grade Ⅱ open fracture according to the system of Gustilo.Eleven patients were multitraumatic patients.[Result]All the cases were followed up for averaging 15.6 months(10～21 months).The mean operation time was 75 min(60～130 min).All fractures healed,the averaging healing time was 13 weeks(11～16weeks).The averaging blood lost was 300 ml(170～500 ml).The postoperative alignment of 33 fractures was satisfactory,5 cases had 6?～ 8 ?valgus auglation,one case had 5?varus auglation in coronal plane.The mean time of weight bearing was 14.2 weeks(11～18 weeks).The range of movement was 100?～120?.All the cases had no infection,breakage of screws and plates,failed fixation and so on.According to HSS scores system,there were 26 excellent cases,7 good cases,5 fair cases,1 poor case,the excellent and good rate was 84.6%.[Conclusion]Less invasive stabilization system,providing stable fixation and optimizing early bone union and functional rehabilitation,is a realistic therapy in treatment of complex proximal tibia fractures.Exact comprehension of LISS concept and procedure,adjustment according to cases,are very important to assure satisfactory results.

Objective:To explore the changes of mitophagy- and apoptosis-related protein expressions after spinal cord injury in rats and its related mechanism.Methods:Ninety-six healthy female SD rats were divided into sham surgery group ( n=48) and spinal cord injury group ( n=48) according to the random number table. Each group was divided into six time points of 1, 3, 7, 14, 21 and 28 days with 8 rats at each time point. In the sham surgery group, the T 8-9 spinous processes and vertebral plates were removed without damage to the spinal cord; in the spinal cord injury group, the spinal cord injury model was established using Allen′s method. At each post-injury time point in two groups, BBB score was used to evaluate the motor function of the rats; HE staining was used to observe the histopathological changes of the spinal cord; immunofluorescence was used to observe the co-localized positive cells of the voltage-dependent anion channel protein 1 (VDAC1) with microtubule-associated protein 1 light chain 3 (LC3) II, E3 ubiquitin ligase (Parkin), and polyubiquitin-binding protein (p62); Western blotting was used to observe expressions of the mitochondrial LC3 II/LC3 I, cytoplasmic Parkin, mitochondrial Parkin, cytoplasmic p62, mitochondrial p62, cytoplasmic apoptotic proteins (Bax), mitochondrial Bax, cytoplasmic cytochrome C (Cyt C), and mitochondrial Cyt C. Results:(1) Compared with the sham surgery group [(21.00±0.00)points at all time points], the BBB scores in the spinal cord injury group were (0.94±0.50)points, (1.69±0.70)points, (4.13±0.99)points, (11.81±1.03)points, (15.06±1.12)points and (18.38±0.83)points at 1, 3, 7, 14, 21 and 28 days after injury, respectively ( P<0.01). (2) Compared with the sham surgery group, the structure in the spinal cord injury group was significantly disrupted at 1 and 3 days after injury, when a large number of hemorrhagic foci, inflammatory cell infiltration, neuronal swelling, and cavity formation were observed. At 7 and 14 days after injury, the number of hemorrhagic foci was markedly reduced compared with the earlier period, when swollen neuronal cytosols, inflammatory cell infiltration and a large number of cavities were found. At 21 and 28 days after injury, a large number of cells were seen to be involved in the repair and the arrangement of cells was disorganized. (3) Compared with the sham surgery group, the number of co-localized positive cells of VDAC1 with LC3 II, Parkin and p62 separately in the spinal cord injury group, markedly increased at 1 and 3 days after surgery, and gradually decreased after that. (4) In the sham surgery group and at 1, 3, 7, 14, 21 and 28 days after injury in the spinal cord injury group, the mitochondrial LC3 II/LC3 I expression levels were 0.56±0.05, 1.00±0.05, 1.19±0.11, 0.86±0.05, 0.80±0.08, 0.66±0.13 and 0.51±0.11, respectively; the cytoplasmic Parkin expression levels were 0.80±0.13, 0.47±0.08, 0.29±0.06, 0.57±0.07, 0.70±0.05, 0.97±0.09 and 0.88±0.12, respectively; the mitochondrial Parkin expression levels were 0.67±0.09, 1.07±0.18, 1.27±0.15, 0.82±0.12, 0.59±0.09, 0.53±0.13 and 0.57±0.14, respectively; the cytoplasmic p62 expression levels were 1.25±0.08, 1.04±0.04, 0.94±0.05, 1.09±0.05, 1.19±0.06, 1.20±0.04 and 1.27±0.05, respectively; the mitochondrial p62 expression levels were 0.61±0.06, 0.88±0.07, 1.09±0.09, 0.98±0.07, 0.70±0.08, 0.68±0.08 and 0.60±0.09, respectively; the cytoplasmic Bax expression levels were 0.92±0.08, 0.67±0.07, 0.36±0.08, 0.48±0.08, 0.69±0.06, 0.88±0.11 and 0.94±0.08, respectively; the mitochondrial Bax expression levels were 0.57±0.04, 0.74±0.04, 0.91±0.05, 0.76±0.05, 0.63±0.08, 0.61±0.05 and 0.57±0.05, respectively; the cytoplasmic Cyt C expression levels were 0.28±0.05, 0.81±0.07, 1.12±0.08, 0.64±0.07, 0.67±0.13, 0.60±0.11 and 0.37±0.06, respectively; and the mitochondrial Cyt C expression levels were 1.02±0.07, 0.91±0.14, 0.37±0.07, 0.73±0.06, 0.91±0.11, 0.95±0.13 and 1.10±0.15, respectively. Compared with the sham surgery group, in the spinal cord injury group mitochondrial LC3II/LC3I had the highest expression level at 3 days after injury; cytoplasmic Parkin had the lowest expression level at 3 days after injury; mitochondrial Parkin had the highest expression level at 3 days after injury; cytoplasmic p62 had the lowest expression level at 3 days after injury; mitochondrial p62 had the highest expression level at 3 days after injury; cytoplasmic Bax had the lowest expression level at 3 days after injury; mitochondrial Bax had the highest expression level at 3 days after injury; cytoplasmic Cyt C had the highest expression level at 3 days after injury; and mitochondrial Cyt C had the lowest expression level at 3 days after injury. Conclusion:Mitochondrial autophagy and apoptosis are enhanced after spinal cord injury in rats, and the potential mechanism may be associated with the transfer of Parkin and P62 from the cytoplasm to the damaged mitochondria for enhanced mitophagy and the release of a large amount of Cyt C from the mitochondria caused by the transfer of Bax from the cytoplasm to the damaged mitochondria for enhanced apoptosis.

Fluorosis is an endemic disease caused by prolonged exposure to excessive fluoride and is considered a serious public health problem in many countries. In recent years, the damage of chronic fluorosis to the central nervous system has attracted extensive attention from scholars at home and abroad. The mechanisms of neurotoxicity caused by fluorosis include oxidative stress, inflammatory reaction, autophagy, neurotransmitters and related enzymes, changes in neural signaling pathways, abnormal neuronal energy metabolism of neurons, cell apoptosis, etc., causing permanent damage to human brain structure, impaired learning ability, memory dysfunction and behavioral problems. This article reviews the effects of fluorosis on the nervous system and related mechanisms, and provides a reliable basis for prevention and treatment of fluorosis.

Fluorine is an important element widely present in nature, and moderate intake can prevent dental caries and promote bone development. However, long-term excessive intake can lead to fluorosis, damaging tissues or organs such as teeth, bones, heart muscle, and blood vessels. Bone marrow mesenchymal stem cells (BMSCs) play an important role in the repair process of bone injury due to their excellent multi-directional differentiation potential. Therefore, studying BMSCs is of great value in the treatment of fluorosis caused by fluoride poisoning. This article summarize the progress on the effect of fluoride on BMSCs, providing new ideas for the study of the pathogenesis and clinical treatment of fluorosis.

Objective:To investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with sorafenib and sequential microwave ablation (MWA) versus TACE combined with sorafenib in the treatment of hepatocellular carcinoma (HCC) with tumor diameter over 5 cm, and to analyze risk factors affecting the prognosis of patients.Methods:The prospective cohort study was conducted. The clinicopathological data of 61 HCC patients with tumor diameter over 5 cm who were admitted to two medical centers (30 in the Laiyang Central Hospital of Yantai City Affiliated to Weifang Medical College and 31 in the Qingdao Central Hospital Affiliated to Qingdao University) between July 2012 and November 2013 were collected. Patients who were treated with TACE combined with sorafenib and sequential MWA were allocated into observation group, and patients who were treated with TACE combined with sorafenib were allocated into control group. Observation indicators: (1) treatment, complications and adverse drug reactions; (2) short-term efficacies; (3) follow-up and survival situations; (4) analysis of prognostic factors. Follow-up was performed by inpatient, outpatient examinations or telephone interview once a month within the first 6 months after treatment and once every 3 months thereafter up to November 2018. The follow-up included laboratory indicators, tumor markers, abdominal enhanced computed tomography or magnetic resonance imaging examinations. The survival of patients and disease progression were fully documented. Measurement data with normal distribution were expressed as Mean± SD, and comparison between groups was performed by the t test. Measurement data with skewed distribution were described as M (range), and comparison between groups was performed using the Wilcoxon rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was performed using the chi-square test or pearson-corrected chi-square test. Ranked data were analyzed using the Wilcoxon rank sum test. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Comparison of survival rates between time points was performed using the Bonferroni method to adjust the test level. Univariate and multivariate analyses were performed using the multiple COX proportional hazard model. Results:A total of 61 HCC patients were selected for eligibility, including 36 males and 25 females, aged (58±8)years, with a range from 43 to 73 years. Of the 61 patients, 31 were in the observation group and 30 in the control group. (1) Treatment, complications and adverse drug reactions: ① treatment information. The treatment times of TACE, treatment times of MWA, time from the first TACE to the first sorafenib medication, and duration of sorafenib medication in the observation group were 1 time (range, 1-5 times), 2 times (range, 1-4 times), 5 days (range, 5-9 days), 24 months (range, 6-72 months), respectively. The above indicators of patients in the control group were 3 times (range, 1-5 times), 0, 6 days (range, 5-9 days), and 16 months (range, 6-60 months). There were significant differences in the treatment times of TACE, treatment times of MWA, and duration of sorafenib medication between the two groups ( Z=4.701, -7.213, -2.614, P<0.05). There was no significant difference in the time from the first TACE to the first sorafenib medication between the two groups ( Z=0.573, P>0.05). ② Complications: there was no TACE related complications in the two groups. There were 3 patients with MWA related complications in the observation group, including 2 cases of minor hemorrhage under the liver capsule and 1 case of pleural effusion, and they were relieved after conservative treatment. ③ Adverse reactions to sorafenib: after 2 months of sorafenib medication, patients in the observation group and control group had at least one kind of sorafenib related stage Ⅰ-Ⅲ adverse reaction, without stage Ⅳ adverse reaction. The numbers of cases with hand-foot skin reaction, rash, pruritus, loss of skin pigmentation, diarrhea, decreased appetite, nausea and vomiting, pain in the liver area, fever, fatigue, liver dysfunction, bone marrow suppression were 8, 3, 4, 3, 10, 18, 20, 20, 20, 15, 3, 2 in the observation group, and 9, 3, 3, 2, 13, 19, 23, 12, 21, 12, 6, 2 in the control group, respectively, showing no significant difference in the above indices between the two groups ( χ2=0.133, 0.000, 0.000, 0.000, 0.796, 0.177, 1.082, 3.674, 0.208, 0.435, 0.601, 0.000, P>0.05). Patients with adverse reactions to sorafenib were relieved by symptomatic treatment, reducing the dose of sorafenib or intermittent drug withdrawal. (2) Short-term efficacies: the level of alpha fetoprotein was 16 μg/L (range, 3-538 μg/L) in the observation group and 292 μg/L (range, 9-642 μg/L) in the control group after one month of treatment, showing a significant difference between the two groups ( Z=3.744, P<0.05). After 3 months of treatment, cases with tumor complete remission, cases with tumor partial remission, cases with stable disease, cases with progressive disease, objective response rate, and disease control rate in the observation group were 14, 11, 6, 0, 80.6%(25/31) , 100.0%(31/31), respectively. The above indicators in the control group were 2, 13, 12, 3, 50.0%(15/30), 90.0%(27/30). There was a significant difference in the objective response rate between the two groups ( χ2=6.343, P<0.05), but no significant difference in the disease control rate between the two groups ( χ2= 1.473, P>0.05). (3) Follow-up and survival situations: 61 HCC patients were followed up for 9.0-75.0 months, with a median follow-up time of 22.0 months. During the follow-up, 28 patients in the observation group had progressive disease, including 8 cases of local tumor progression, 4 of portal vein tumor thrombi, 11 of intrahepatic metastasis, and 5 of pulmonary metastasis. Thirty patients in the control group had progressive disease, including 13 cases of local tumor progression, 6 of portal vein tumor thrombi, 6 of intrahepatic metastasis, and 5 of pulmonary metastasis. Among the 61 patients, 28 patients in the observation group and 29 patients in the control group died. The median overall survival time and median progression-free survival time of the observation group was 28.0 months and 18.0 months, versus 19.5 months and 11.5 months of the control group, showing significant differences between the two groups ( χ2=8.021, 10.506, P<0.05). The 1-, 3-, 5-year overall survival rates of the observation group were 97%, 37% and 20%, respectively, versus 83%, 13% and 7% of the control group, showing significant differences in the above indicators between the two groups ( Z=23.635, 4.623, 3.139, P<0.0167). The 1-, 2-, 3-year progression-free survival rates of the observation group were 77%, 40%, and 27%, respectively, versus 43%, 13%, and 7% of the control group, showing significant differences in the above indicators between the two groups ( Z=9.965, 4.900, 3.684, P<0.0167). (4) Analysis of prognostic factors: results of univariate analysis showed that treatment method, maximum tumor diameter, Barcelona clinical liver cancer (BCLC) stage, liver cirrhosis, hepatitis B virus(HBV) infection, and Child-Pugh classification were related factors for overall survival time [ hazard ratio ( HR)=0.483, 6.196, 12.646, 5.049, 2.950, 4.791, 95% confidence interval ( CI): 0.284-0.823, 3.198-12.003, 5.031-31.785, 2.586-9.858, 1.366-6.369, 2.507-9.155, P<0.05] and progression-free survival time ( HR=0.427, 5.804, 7.032, 5.405, 2.925, 4.410, 95% CI: 0.248-0.735, 3.043-11.070, 3.071-16.101, 2.685-10.881, 1.364-6.270, 2.331-8.342, P<0.05). Results of multivariate analysis showed that treatment method, maximum tumor diameter, BCLC stage, liver cirrhosis, and HBV infection were independent influencing factors for overall survival time ( HR=0.183, 5.886, 17.544, 4.702, 3.801, 95% CI: 0.090-0.370, 2.648-13.083, 5.740-53.622, 1.928-11.470, 1.368-10.562, P<0.05) and progression-free survival time ( HR=0.201, 3.850, 3.843, 3.598, 3.726, 95% CI: 0.098-0.411, 1.761-8.414, 1.526-9.682, 1.444-8.963, 1.396-9.947, P<0.05). Conclusions:Compared with TACE combined with sorafenib, TACE combined with sorafenib and sequential MWA is safe and effective in the treatment of HCC with tumor diameter over 5 cm. The treatment method, maximum tumor diameter, BCLC stage, liver cirrhosis, and HBV infection are independent influencing factors for overall survival time and progression-free survival time of patients.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.