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 compare the clinical efficacy of arthroscopy-assisted and open reduction and internal fixation in the treatment of Schatzker type I-III tibial plateau fractures.Methods:The data of patients with Schatzker type I-III tibial plateau fractures who were treated from August 2017 to July 2019 were retrospectively analyzed. According to the treatment, the patients were divided into the arthroscopic-assisted minimally invasive reduction and internal fixation group (arthroscopy group) and the conventional open reduction and internal fixation group (incision group). In the arthroscopy group, there were 30 patients, 19 males and 11 females were included; the age was 45.13±7.12 years old (range, 29-60 years). Among them, 13 cases were Schatzker type I fractures, 14 cases were Schatzker type II fractures, and 3 cases were Schatzker type III fractures. In the incision group, there were 30 patients, 17 males and 13 females were included; the age was 43.53±7.79 years old (range, 31-58 years). Among them, 11 cases were Schatzker type I fractures, 15 cases were Schatzker type II fractures, and 4 cases were Schatzker type III fractures. The operation time, intraoperative blood loss, postoperative ambulation time, postoperative complete weight-bearing time and postoperative complications were recorded. The degree of knee joint swelling, knee flexion and extension range of motion and the American knee society knee score (AKS score) were compared between the arthroscopy group and the incision group.Results:Both groups were followed up. The follow-up time of the arthroscopy group were 10-18 months, with an average of 14 months; the follow-up time in the incision group were 12-18 months, with an average of 15 months. In the arthroscopy group, the operation time (87.60±9.20 min vs. 94.33±10.65 min), intraoperative blood loss (57.16±9.63 ml vs. 71.93±11.15 ml), postoperative ambulation time (5.13±1.28 d vs. 6.17±1.53 d) and postoperative complete weight-bearing time (12.83±1.68 weeks vs. 14.23±1.77 weeks) were superior to the incision group, and the differences were statistically significant ( t=2.62, 5.49, 2.83, 3.94; all P<0.05). The healing time was 13.33±1.37 weeks in the arthroscopy group and 14.86±1.63 weeks in the incision group, and the difference was statistically significant ( t=3.94, P<0.001). At 1 year after surgery, the range of flexion and extension of knee joint in the arthroscopy group was 116.77°±12.46°, which was better than that in the incision group, which was 109.13°±9.89°, and the difference was statistically significant ( t=2.63, P=0.011). The AKS score in the arthroscopy group was 164.57±11.16 points, and the score in the incision group was 149.53±14.77 points, and the difference was statistically significant ( t=4.45, P<0.001). There were no malunion or compartment syndrome in the arthroscopy group and the incision group. The total incidence of complications in the arthroscopy group was 13% (4/30), including 2 cases of poor wound healing, 2 of poor knee range of motion after operation. The total incidence of complications in the incision group was 23% (7/30), including 4 cases of poor wound healing, 1 of wound infection, 2 of poor knee range of motion after operation. And the difference between the two groups in complication incidence was not statistically significant (χ 2=1.00, P=0.317). Conclusion:Arthroscopic-assisted reduction and internal fixation in the treatment of Schatzker I-III tibial plateau fractures has the advantages of less trauma, less bleeding, early mobility, fewer complications, and better knee joint function, and there are no obvious arthroscopic-related complications, which is a safe and reliable treatment method.

Objective: To investigate the inhibitory effect of polydopamine (PDA) on enamel demineralization in isolated teeth and the induction of hydroxyapatite (HA) production on the surface of demineralized enamel to provide a novel protocol for the prevention and treatment of enamel demineralization. Methods: Twenty isolated bovine teeth were cut into 20 enamel slices and randomly divided into an experimental group and a control group, with 10 slices in each group. The enamel slices in the experimental group were immersed in 2 mg/mL freshly prepared dopamine solution and incubated for 24 hours at room temperature in the dark to prepare the PDA coating, while the control group was left untreated. Then, the isolated bovine teeth, with and without PDA coating, were immersed in artificial demineralization solution at 37 °C for 3 days, followed by 7 days in simulated body fluid (SBF), and the immersion solution was changed daily. The surface morphology of enamel was observed by scanning electron microscopy (SEM), the calcium/phosphorus ratio of the enamel surface was analyzed by energy dispersive spectroscopy (EDS), and the characteristic functional groups in enamel deposits were analyzed by Fourier transform infrared spectroscopy (FTIR). Results: Compared with the control group, the number of demineralized pores produced after 3 d of enamel demineralization with polydopamine coating was less, and the diameter was smaller. EDS elemental analysis showed that the Ca/P ratio after enamel demineralization was 2.37 in the experimental group, which was smaller than the 2.53 ratio in the control group. In the remineralization experiment, after 7 days of remineralization of PDA coated enamel in the experimental group, lamellar grains were produced on the enamel surface, and the growth showed obvious directionality, growth regularity and uniform arrangement. In the control group, the surface of enamel was flocculent mineral deposit, and the crystallinity was poor. The FTIR results proved that the enamel surface deposit of PDA-coated enamel was HA after 7 d of remineralization. Conclusion PDA can affect the nucleation process of HA and promote the production of HA on the surface of demineralized enamel.

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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Hepatocellular carcinoma has a high morbidity and mortality, which has seriously harmed human health. Several targeted therapies have been approved for the first- and second-line treatment of advanced hepatocellular carcinoma. The emergence of immunotherapy has brought the treatment of hepatocellular carcinoma into a new era. Targeted and immunotherapeutic agents have synergistic effects in mechanism, also the combination of these two therapies has been clinically beneficial to patients with advanced hepatocellular carcinoma. At the same time, in addition to the systemic therapy of targeted combined immunological, applying appropriate local therapy can provide a longer survival period or even a chance of cure for that some patients. The authors introduce the diagnosis and treatment of a case of advanced hepatocellular carcinoma who achieved pathological complete remission by first-line immunotherapy combined with anti-angiogenesis targeted therapy.

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 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.

Objective:To investigate the correlation between urinary 8-oxo-7, 8-dihydroguanosine(8-oxo-Gsn)and physical function in community-dwelling elderly people.Methods:A total of 210 community-dwelling elderly people aged 75 years and over were enrolled in this cross-sectional analysis.According to the scores of short physical performance battery(SPPB), subjects were divided into three groups: the high performance group(summary score 10-12), the intermediate performance group(summary score 7-9)and the low performance group(summary score 0-6). All participants received a comprehensive geriatric assessment.Urinary 8-oxo-dGsn, serum high-sensitivity C-reactive protein(hs-CRP)and white blood cell count were measured.The correlation between urinary 8-oxo-Gsn and physical function was analyzed by using Pearson correlation analysis and the ordered Logistic regression model.Results:The scores of activities of daily living(ADL), instrumental activities of daily living(IADL), grip strength and gait speed were lower in the low performance group than in the other two groups( H=47.002, 110.902, F=11.962, 235.952, all P<0.001). Levels of urinary 8-oxo-Gsn and serum hs-CRP were higher in the low performance group than in the other two groups( F=23.780 and 13.259, both P<0.001). There was no significant difference in levels of urinary 8-oxo-dGsn or white blood cell count between the three groups(both P>0.05). Urinary 8-oxo-Gsn was negatively correlated with gait speed, grip strength and SPPB score( r=-0.559, -0.302 and-0.450, all P<0.001)and was positively correlated with the time of five-times-sit-to-stand test( r=0.290, P<0.001). Adjusting for age, gender and Charlson comorbidity index, the ordered Logistic regression analysis showed that elevated levels of urinary 8-oxo-Gsn( OR=1.38, 95% CI: 1.06-1.77, P<0.05)and hs-CRP( OR=1.23, 95% CI: 1.04-1.48, P<0.05)decreased physical function. Conclusions:Urinary 8-oxo-Gsn is independently associated with the decline of physical function in community-dwelling elderly adults, suggesting that the oxidative stress level is increased in the elderly with poor physical function.