BACKGROUND:Pravastatin is a clinically effective drug for the treatment of hypercholesterolemia and is now found to play a beneficial role in the treatment of CNS injury;however,the mechanism remains unknown. OBJECTIVE:To ascertain the possible mechanism of action and whether pravastatin medication can expedite functional recovery following sciatic nerve crush injury. METHODS:Male Sprague-Dawley rats were randomly assigned into:pravastatin(sciatic nerve crush injury+pravastatin gavage),negative control(sciatic nerve crush injury+saline gavage),and sham operation(sciatic nerve exposure but no injury+saline gavage).While the other two groups received comparable amounts of saline gavage,the pravastatin group received postoperative pravastatin(5 mg/kg)by gavage for 1 week.The general conditions of the rats in each group were observed after operation.Sciatic function index was evaluated at the end of the 2nd,4th,6th,and 8th week after operation,and the wet mass ratio of the gastrocnemius muscle was measured at the end of the 8th week after operation.The levels of inflammatory cytokines in serum were measured using ELISA.Histomorphometrics was used to measure the number of myelinated nerve fibers,fiber diameter,axon diameter,and myelin sheath thickness.RT-qPCR assay was used to measure the relative mRNA expression of nerve growth factor and brain-derived neurotrophic factor,and western blot was used to measure the protein expression of growth-associated protein 43. RESULTS AND CONCLUSION:Compared with the negative control group,the sciatic function index in the pravastatin group recovered faster(P<0.05)and was closer to the level of the sham operation group,the expression of tumor necrosis factor α and interleukin 6 in serum was lower(P<0.05)and close to that of the sham operation group,and the relative mRNA expression of nerve growth factor and brain-derived neurotrophic factor in the sciatic nerve increased(P<0.05 or P<0.01),the relative protein expression of growth-associated protein 43 in the sciatic nerve was also significantly increased(P<0.05),the number of myelinated nerve fibers was increased more,and the values of fiber diameter,axon diameter,and myelin sheath thickness were larger(P<0.01)and closer to those of the sham operation group.To conclude,treatment with pravastatin accelerates functional recovery from sciatic nerve crush injury by a possible mechanism of inhibiting the expression of tumor necrosis factor α and interleukin 6 and promoting the secretion of neurotrophic factors nerve growth factor and brain-derived neurotrophic factor.

BACKGROUND:Lingual movable wing is a new type of lingual orthodontic technique and the different stretching lengths of the wring affect the torque control effect of anterior teeth.However,there is yet no related biomechanical research. OBJECTIVE:To investigate the displacement trend of dentition during adduction of mandibular anterior teeth and the effect of different wing stretching lengths on the biomechanical effect of mandibular anterior teeth. METHODS:The data of the mandible and lower dentition were collected by cone-beam CT and reconstructed using Mimics software to establish a three-dimensional finite element model of mandibular anterior teeth adducted by the lingual movable wing.The ANSYS software was used to analyze the initial displacement of the mandibular anterior teeth under the following conditions:A,2 mm stretching length;B,2.5 mm stretching length;C,3 mm stretching length;and D,3.5 mm stretching length. RESULTS AND CONCLUSION:The trend of initial displacement of lower dentition:The central incisors moved lingually with depression,the lateral incisors and canines moved mildly lingually with mesial lingual torsion,the second premolar was tilted distally with a marked lingual inclination and the first molar showed an overall mesial inclination with mesial crown eversion.Therefore,in the adduction cases of mandibular tooth extraction,attention should be paid to the lingual movement of the second premolar,which could be offset by corresponding techniques in clinic.The trend of anterior tooth displacement in all directions:from condition A to condition D,in the sagittal direction,the difference value in crown-root displacement of central incisors changed from-11.891 μm to-5.757 4 μm,indicating that the central incisor changes from oblique movement to overall movement.The difference value in crown-root displacement of lateral incisors changed from-11.828 1 μm to-6.711 45 μm,and that of canines changed from-7.572 3 μm to-4.695 5 μm,indicating that the oblique movement of the lateral incisors and canines is also changing to an overall movement.In the vertical direction,from condition A to condition D,the reduction of incisors was gradually increased,while that of canines was gradually decreased.These findings indicate that the stretching length of the wing can affect the oblique movement trend of the anterior teeth.As the wing continues to stretch,the torque control of the lower anterior teeth will become better.

Lingguizhugan Decoction (LGZG) has been investigated in basic studies, with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease (NAFLD). This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting. A randomized, double-blinded, placebo-controlled trial was performed. A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG (two groups: standard dose and low dose) or placebo for 12 weeks on the basis of lifestyle modifications. The primary efficacy variable was homeostasis model assessment of insulin resistance (HOMA-IR). Analyses were performed in two populations in accordance with body mass index (BMI; overweight/obese, BMI ⩾ 24 kg/m²; lean, BMI < 24 kg/m²). For overweight/obese participants, low-dose LGZG significantly decreased their HOMA-IR level compared with placebo (-0.19 (1.47) versus 0.08 (1.99), P = 0.038). For lean subjects, neither dose of LGZG showed a superior effect compared with placebo. Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and autophagy related 3 (ATG3) significantly increased after LGZG intervention in overweight/obese population. Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD. The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3. Lean subjects may not be a targeted population for LGZG.
Humans ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Overweight/drug therapy* ; Insulin Resistance ; Obesity/drug therapy* ; China ; DNA/therapeutic use*

Objective:To investigate the changes of proopiomelanocortin(POMC) expression in hypothalamus and corresponding metabolism in miR-21 knockout mice.Methods:miR-21 knockout or wild-type C57BL/6J mice were divided into diabetic group and control group, respectively. Diabetic mice model were forged with high-fat diet and low-dose streptozotocin. The changes of body weight and blood glucose in each group were monitored. By the end of the experiment, mice were sacrificed, and POMC protein expression and STAT3 mRNA expression in hypothalamus were detected.Results:There were no significant differences in body weight and blood glucose levels among all groups at baseline( P>0.05). The differences of body weight and blood glucose levels among various groups were compared at 3, 6, 9 and 12 weeks after the model was established. The results showed that body weight of mice in the diabetes group or miR-21 knockout+ diabetes group was higher than that in the control group at each time point( P<0.05). Moreover, there were significant difference in body weight between diabetes group and miR-21 knockout+ diabetes group at 3 and 12 weeks( P<0.05). The blood glucose levels in diabetes group were significantly higher than those in other groups at each time point( P<0.05). The blood glucose level in miR-21 knockout+ diabetes group was lower than that in diabetes group and higher than control group( P<0.05). POMC protein and STAT3 mRNA levels in diabetes group were significantly lower than those in control group, while those in the miR-21 knockout+ diabetes group were higher than those in the diabetes group. Conclusions:The expression of POMC in hypothalamus of miR-21 knockout mice is higher than that of wild-type diabetic mice. miR-21 knockout can decrease blood glucose level and body weight, and improve energy metabolism of diabetic mice.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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Objective:To explore the morphological characteristics, treatment strategies and clinical results of complex hyperextension tibial plateau fractures.Methods:From October 2017 to January 2019, data of 27 patients with complex hyperextension tibial plateau fractures were retrospectively analyzed. There were 19 males and 8 females with an average age of 43.4 years (range, 23-68 years). According to Schatzker classification of tibial plateau fractures: there are 8 cases of type IV, 5 of type V, and 14 of type VI; according to the three-column theory classification: there are 8 cases of two-column fracture and 19 cases of three-column fracture. Bicondylar fractures were treated with medial Tomofix locking plate and anterolateral L-shaped locking plate through medial and anterolateral approach; tibialmedial condylar fractures was treated with T-shaped plate and posteromedial locking plate through extended medial approach. Patients with anterior tibial fractures were treated with horizontal strip plate through modified anterior median approach. Combined soft tissue or bone injury was repaired. The fracture healing and reduction were evaluated by X-ray and CT scan. The reduction of tibial plateau fracture was evaluated by Rasmussen radiology standard, and the knee joint function was evaluated 12 months after the operation by the score of American hospital for special surgery (HSS).Results:All the 27 surgeries were performedsuccessfully. The operation time was 130-350 minutes, with an average time of 165 minutes. Twenty-seven cases were followed up for 12-24 months, with an average period of 15.8 months. All fractures were healed. The average clinical healing time was 13.5 weeks (range, 10-18 weeks). Twelve months after operation, Rasmussen's radiology score was 13-18, with an average of 16.7 points, among them there were 19 excellent and 8 good. Twelve months after the operation, the score of HSS knee joint was 82-98, with an average score of 93.2 points, and there were 22 cases excellent, 4 cases good and 1 case fair. The excellent and good rate was 96.2% (26/27).Conclusion:Complex hyperextension tibial plateau fractures often combined with tibial bicondylar, medial tibial condyle or anterior tibial fractures. According to the morphological characteristics of complex hyperextension tibial plateau fractures, using appropriate surgical approach and internal fixation, repairing ligament soft tissue structure and reconstructing knee joint stability can achieve satisfactory results.

Objective:To investigate the effects and mechanisms of curcumin on insulin resistance in streptozocin-induced diabetic rats.Methods:Diabetic rats were induced by intraperitoneal injection of STZ, then all the rats were randomly divided into diabetes (DM), diabetes+ curcumin (DM+ Cur), and diabetes + buffer control (DM+ NC) groups. Normal SD rats were used as control group (NC). The DM+ Cur group was treated with curcumin, while the DM+ NC group was treated with equal-volume buffer. The test lasted 12 weeks. The blood glucose was detected, and hyperinsulinemic-euglycemic clamp test was performed to estimate peripheral insulin resistance. At the end of the experiments, rats were killed and the total protein and cell membrane protein were extracted from skeletal muscle. The levels of phosphorylated PI3K, phosphorylated AKT, total PI3K, and total AKT were measured by Western blot. The levels of total GLUT4 and GLUT4 of cell membrane were also detected by Western blot, GLUT4 levels in skeletal muscle cell membranes were detected by immunofluorescence.Results:Blood glucose levels of DM+ Cur group were lower than those of DM group [(18.67±1.99 vs 24.38±2.88) mmol/L, P<0.05], and insulin resistance was also improved[the average GIR(14.69±0.29 vs 10.25±0.30) mg·kg -1·min -1, P<0.01]. The phosphorylation levels of PI3K and AKT were increased, and GLUT4 translocation to the cell membrane was increased. Conclusion:By activating the PI3K/AKT pathway, curcumin promotes GLUT4 translocation, increases skeletal muscle glucose uptake, and finally improves insulin resistance.

OBJECTIVE: To investigate the effect of orthodontic traction on the microstructure of dental enamel. METHODS: Forty-eight isolated premolars were randomly divided into 6 groups (=8), including Group A (blank control group), in which the teeth were bonded with the orthodontic brackets without any loading force; Groups B1, B2, and B3 where the teeth were bonded with the orthodontic brackets using clinical adhesives and loaded with 50 g force for 6 months, 200 g force for 6 months, and 200 g force for 1 month, respectively; and Groups C1 and C2, where the teeth were bonded with straight wire brackets using light curing bonding and chemical curing bonding techniques, respectively. All the teeth were embedded with non-decalcified epoxy resin. Scanning electron microscope (SEM), atomic force microscope (AFM), and energy spectrometer (EDS) were used to analyze interface morphology and elemental composition of the teeth sliced with a hard tissue microtome. RESULTS: Compared with those in Group A, the teeth in the other 5 groups showed increased adhesive residue index with microcracks and void structures on the enamel surface under SEM; AFM revealed microcracks on the enamel surface with angles to the grinding direction. A larger loading force on the bracket resulted in more microcracks on the enamel interface. The interface roughness differed significantly between Groups A and C2, and the peak-to-valley distance differed significantly between Groups A, C, and C2. CONCLUSIONS Orthodontic traction can cause changes in the microstructure of normal dental enamel.
Dental Enamel ; Materials Testing ; Orthodontic Brackets ; Resin Cements ; Surface Properties ; Traction

ObjectiveTo systematically review the clinical of artificial liver support system (ALSS) in the treatment of drug-induced liver failure. MethodsPubMed, Embase, The Cochrane Library, CMB, CNKI, and VIP databases were searched for related randomized controlled trials or randomized controlled trials on ALSS in the treatment of drug-induced liver failure published up to October 2019, and a statistical analysis was performed. Odds ratio (OR) was the effect size for categorical data, and the difference between groups was the effect size for continuous data. The weighted mean difference (WMD) method was used for the pooled analysis of effect size, and 95% confidence interval (CI) was calculated for each effect size. I2 and P values were used to evaluate the heterogeneity of the articles included in the analysis; a fixed effect model was used when I2＜50% and P＞0.1, otherwise a random effects model was used. ResultsA total of 16 articles with 945 patients were included, with 520 patients in the ALSS+routine medical treatment (RMT) group and 425 in the RMT group. The meta-analysis showed that compared with the RMT group, the ALSS+RMT group had a significantly lower mortality rate of drug-induced liver failure (OR=0.27, 95%CI: 0.20-0.36, P＜0.001), significant improvements in albumin (Alb) (MD=1.21, 95%CI: 0.18-2.25, P=0.02) and prothrombin activity (PTA) (MD=11.84, 95%CI: 6.34-17.35, P＜0.001), and a significant reduction in total bilirubin (TBil) (MD=-104.97, 95%CI: -163.63 to -46.30, P＜0.001). Further analysis of Alb, TBil, and PTA after the withdrawal of ALSS showed that ALSS significantly improved Alb (MD=1.74, 95%CI: 1.20-2.27, P＜0.001) and PTA (MD=4.45, 95%CI: 2.80-6.10, P＜0.001) and significantly reduced TBil (MD=-128.41, 95%CI: -217.22 to -39.59, P=0.005). ConclusionCompared with RMT alone, RMT combined with ALSS can significantly improve the main biochemical indicators of patients with drug-induced liver failure and reduce their mortality rate.

Objective:To discuss how to make the surgical strategy for tibial tubercle fracture associated with bicondylar tibial plateau fracture.Methods:Data of thirty-five patients of tibial tubercle fractures associated with bicondylar tibial plateau fractures who were treated from October 2014 to May 2018 were retrospectively analyzed. There were 26 males and 9 females with an average age of 37.6 years (range, 21-68 years). According to Schatzker classification in tibial plateau fracture, 16 cases were type V and 19 cases were type VI. According to the integrity of tibial tubercle fracture and cortical bone of the proximal tibia in bicondylar tibial plateau fracture, they were divided into four types: type A, tibial tubercle fracture fragment and cortical bone of the proximal tibia are both complete; type B, tibial tubercle fracture fragment is complete but cortical bone of the proximal tibia is comminuted; type C, tibial tubercle fracture fragment is comminuted but cortical bone of the proximal tibia is complete; type D, both of them are comminuted. The surgical approaches and fixation methods of all the tibial tubercle fractures were according to the four different types. There were 22 cases with type A and B that were treated via an anterolateral and a medial incision, 13 cases with type C and D were treated via an anterior midline and a medial incision. There were 4 cases belonging to type A fixed with lag screws singly, 18 cases with type B fixed with 1/4 tubular plates, 7 cases with type C and 6 cases with type D fixed by 1/4 tubular plates combined with lag screws.Results:Thirty-five patients were followed up for 16.8 months (range, 12-24 months). All fractures healed with an average time of 4.7 months (range, 3-6 months). Loss of reduction didn’t occur in 34 cases except one. According to Rasmussen radiographic evaluation, the average score was 14.1 (range, 10-18) and clinical outcomes were rated with excellent in 11 cases, good in 19, fair in 5. The excellent and good rate was 85.7% (30/35) . The mean Hospital for Special Surgery (HSS) scores of all cases were 86.8 (range, 64-98) and the functional scores were excellent in 22 cases, good in 10 cases and fair in 3 cases with the excellent and good rate of 91.4% (32/35) . Surgical complications included fat liquefaction in 2 cases, superficial wound infection in 1, loosening of implant in 1and traumatic arthritis in 1.Conclusion:This kind of tibial tubercle fracture associated with bicondylar tibial plateau fracture is rare and special. Therefore, the preoperative plan should be made by considering the morphological features of the tibial tubercle fragments and the cortical bone of the proximal tibia. The middle longitude approach is the best way to expose tibial tubercle fragments which should be fixed with 1/4 tubularplate and/or lag screws.