Fluorine is a common chemical element. Excessive intake of fluoride can lead to fluorosis. Fluoride easily passes through the blood-brain barrier and accumulates in different brain regions, causing pathological changes in brain tissue. It leads to adverse effects on neuronal metabolism, enzyme, protein function, neurotransmitters, and redox homeostasis, and subsequently neuronal damage and neurodegenerative diseases in humans and experimental animals. This paper reviewed the effects and important mechanisms of fluoride on neurological function and behavior, involving mitochondrial toxicity, oxidative stress, cell apoptosis and autophagy, and activation of pro-inflammatory factors. It provided a reference for further studying the mechanisms of brain damage induced by fluorosis.

Objective To establish a scientific training program that takes into account both anaerobic and aerobic training for pilots,and to explore the appropriate ratio of aerobic and anaerobic training.Methods According to the physical examination standards for pilots,a total of 16 healthy subjects aged 18-24 were selected from two batches.The two batches of subjects were trained with different aerobic and anaerobic ratios.Training period was 3 months.The changes in cardiopulmonary function of the subjects before and after training were evaluated using the cardiopulmonary function exercise testing system(CPET),and the changes in anaerobic capacity were evaluated using changes in strength as an indicator.Results After training,the weight load of the subjects in the two training programs,including barbell squats,leg flexion and hard pull,and barbell under 10RM and 3RM,was significantly increased(P<0.001),and there was no statistically significant difference in anaerobic strength growth between the two groups.The results of CPET showed that the maximum load,maximum heart rate,and respiratory quotient in the two groups were significantly increased after than before the training(P<0.01).The maximum load(Experiment group 1:29.12±19.69,Experiment group 2:72.00±46.24)and respiratory quotient(Experiment grouop 1:0.11±0.09,Experiment group 2:0.28±0.16)of the subjects in experiment group 2 before and after training were greater than those in experiment group 1.The difference was statistically significant(P<0.05).Conclusion The anaerobic and aerobic capacities of the subjects in the experiment group 2 are effectively improved,indicating that ratio of aerobic and anaerobic of the training scheme is better.

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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Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients' survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.

Objective: To explore the effect of tanshinone IIA on neuronal apoptosis in the compressed spinal cord and its molecular mechanism by establishing a spinal cord compression model. Methods: Twenty-four SD rats weighing 250-300 g were the experimental animals. The spinal cord compression model was established by clamping the spinal cord with arterial clamp. Six rats in each group were randomly selected and randomly divided into sham group (Sham group, given intraperitoneal injection of normal saline at the same dose once a day) and spinal cord compression injury group (SCI group, given normal salts). Water intraperitoneal injection, once a day), tanshinone IIA group (TAN group, 30 mg/kg tanshinone IIA intraperitoneal injection, once a day), LY2904002 group (LY group, 0.3 mg/kg LY294002 intraperitoneal injection, 5 min after 30 mg/kg tanshinone IIA intraperitoneal injection, once 1 d). After 3 d of intervention, the motor function of rats were evaluated by inclined plane test and BBB score. The expression of apoptotic genes and PI3K/AKT signaling molecules in the compressed spinal cord were detected by qPCR, immunohistochemistry and Western blot. Results: The BBB score 3.31±0.45 points, inclined angle 9.31°±1.02°, GSK-3β 0.35±0.06, CyclinD1 0.25±0.06, Bcl-2 0.38±0.06, p-PI3K 0.32±0.05, p-AKT 0.29±0.07 protein expression in SCI group were lower than those in Sham group. The protein expression of Caspase-9 3.27±0.54 and Caspase-3 2.73±0.35 in SCI group was higher than that in Sham group. The BBB score 9.31±1.02 points, inclined angle 24.95°±3.52°, GSK-3β 0.74±0.09, CyclinD1 0.69±0.11, Bcl-2 0.83±0.13, p-PI3K 0.77±0.11, p-AKT 0.69±0.08 in TAN group were higher than those in SCI group BBB score 3.31 ±0.45 points, inclined angle 9.31°±1.02°, GSK-3β 0.35±0.06, CyclinD1 0.25±0.06, Bcl-2 0.38±0.06, p-PI3K 0.32±0.05, p-AKT 0.29±0.07. The protein expression levels of Caspase-9 1.78±0.22 and Caspase-3 1.64±0.2 in TAN group were lower than those in SCI group 3.27±0.54 and Caspase-3 2.73±0.35. The BBB score, oblique angle and the expression of GSK-3β 0.43±0.07, CyclinD1 0.38±0.06, Bcl-2 0.49±0.09 in LY group were lower than those in TAN group. The protein expression of Caspase-9 2.54±0.38 and Caspase-3 2.25±0.37 in LY group were higher than TAN group. Conclusion Tanshinone IIA can inhibit the apoptosis of spinal cord tissue and alleviate the spinal cord injury in spinal cord compression rats by activating the PI3K/AKT signaling pathway.

Objective: To analyze the clinical, pathological and radiological characteristics of paragonimiasis in children for accurate diagnosis and therapy. Methods: A total of 31 patients with paragonimiasis treated from 2002 to 2016 were selected, including 17 cases from migrant areas and 14 cases from Wenzhou area. Results: In migrant children group, the serum IgE was significantly higher than that in Wenzhou area group [(2 379±944) IU/mL∶(1 552±1 121) IU/mL, t=-2.23, P<0.05], and the duration of therapy was remarkable longer [(13.8±6.5) days∶(9.9±3.4) days, t=-2.15, P<0.05]. Among all cases, 10 showed polyserositis including pleural effusion, ascites and pericardial effusion at different degrees on chest CT scans. Five cases with cerebral paragonimiasis were confirmed by MR imaging. Most of the lesions were located in the parietal lobe with slight low signal on T1WI but high signal on T2WI surrounded by disproportionate edema. Annular enhancement was prominent by Gd-DTPA. Paragonimiasis serum antibody was positive in all cases by ELISA. Pathologic features included formation of irregular lacunae or sinus tracts, presence of paragonimus bodies, and eosinophilic infiltration in the adjacent tissues. Conclusions Clinical manifestations of paragonimiasis are complex and non-specific in children.In migrant children group, clinical manifestations are diverse, more serious with more complications and difficulties in treatment, while patients in Wenzhou area group have favorable prognosis and less complicated treatment. The early diagnosis and timely treatment should be determined by patient′s detailed history, eosinophilic count, radiologic findings and immunological test to avoid serious complications.

BACKGROUND:The establishment of a safe, reliable and easily repeatable mouse model of nonalcoholic fatty liver disease is the prerequisite for the study of the diagnosis and treatment of the disease.
OBJECTIVE:To establish a C57BL/6 mouse model of nonalcoholic fatty liver disease and observe changes of biochemical indicators, which can provide a theoretical basis for its pathogenesis and drug treatment.
METHODS:Sixty healthy male C57BL/6 mice were randomly divided into a control group of 30 cases (normal diet), and a model group of 30 cases (high fat diet). Models of nonalcoholic fatty liver were established. At 8 weeks, body mass, liver index, and homogenate superoxide dismutase activity in the liver were detected. Changes in serum alanine aminotransferase, aspartate aminotransferase, triglyceride glycerol, cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were observed. Pathological examination was performed.
RESULTS AND CONCLUSION:(1) Pathological sections showed that large droplets and smal lipid droplets in the mouse liver and spread the whole liver. Swel ing of the liver cel s, visible cytoplasmic vacuoles and obviously inflammatory changes in liver cel s were observed in the model group. (2) Body weight and liver index were significantly higher in the model group than in the control group (P<0.05). Superoxide dismutase activity was significantly reduced in the liver (P<0.05). (3) Triglycerides, cholesterol, and low-density lipoprotein cholesterol levels were significantly higher, but high-density lipoprotein cholesterol levels were significantly lower in the model group than in the control group (P<0.05). (4) Nonalcoholic fatty liver mouse model is ideal for high-fat diet-induced animal model. The method is simple, repetitive, and can provide a stable animal model for the study on the mechanism of nonalcoholic fatty liver disease and drug treatment.

Objective To evaluate the diagnostic value of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) in intrathoracic tuberculosis(TB).Methods We retrospectively analyzed patients underwent EBUS-TBNA with a final diagnosis of intrathoracic TB at Shanghai Chest Hospital from October 2009 to March 2013 and observed that the diagnostic efficacy by pathology and microbiology and safety of EBUS-TBNA for intrathoracic TB.Results 75 patients were diagnosed with pulmonary TB or intrathoracic tuberculous lymphadenitis,and accuracy was 80％ (60/75) by EBUS TBNA.A total of 60 patients had pathology,acid-fast bacilli(AFB) staining and mycobacterial culture test results,of whom 52 (86.67％)were diagnosed.Pathological findings were consistent with TB in 77.33％ patients (58/75),in 20.31％ (13/64) the smear were positive for AFB and in 46.67％ (28/60) were positive for cuhure.One hundred and twenty-nine mediastinal or hilar lymph nodes and 10 intrapulmonary lesions were biopsied in 75 patients,the average target number of per patient were 1.85.Pathological findings were consistent with TB in 66.19％ samples(92/139),in 13.91％ (16/115) were positive for AFB and in 38.32％ (41/107) were positive for culture.Multivariate regression revealed that short-axis diameter was an independent risk factor associated with positive pathology,smear and euhure.Additionally,more aspiration times cause higher pathology positive rate,pathology showing necrosis and positive smear were independent risk factors associated with positive cuhure.There were two patients occurred complications during operation.Conclusion EBUS-TBNA was a safe and effective method for the diagnosis of intrathoracic tuberculosis.

Objective To discuss the advantage of hispectral index(BIS) monitoring used in gastrointestinal endoscopy,and to observe elinical effects of target-controlled infusion(TCI) propofol combined with remifentanyl in elderly patients.Methods 120 patients aged from 65 to 78 with ASA physical status Ⅰ ～ Ⅱ were randomly divided into two groups,i,e.Group A (propofol with fentanyl ),Group B ( TCI propofol and remifentanyl with BIS).The amount of propofol was adjusted by consciousness and hemodynamics in Group A,while by BIS value in Group B.BIS was controlled at 55 ～60.The total amount of propofol and the time of wake-up,the incidence of complicatiors in each group were recorded.Results Compared with Group A,the changes of MAP and HR at T1 and T2 were smaller in Group B(P ＜ 0.05 ) ; Compared with Group A,the total amount of propofol and the time of wake-up were less in Group B ( P ＜ 0.05 ) ;Compared with Group A,the incidence of intraoperative respiratory depression and bradycardia were increased in Group B( P ＜ 0.05 ),there were no differences in the rest between the two groups.Conclusion Under BIS monitoring,TCl propofol and remifentanyl in elderly patients undewent gastrointestinal endoscopy may reduce propofol,and reach rapid recovery from anesthesia,but it needs additional management of respiration and circulation.

Objective To investigate the role of rotational alignment reference landmarks of the proximal tibia in total knee arthroplasty.Methods Fifteen healthy adult volunteers were enrolled in this study,including 10 males and 5 females,aged from 21 to 38 years (average,28.1±6.0).CT scans of 26 knees were taken as the knees were placed in full extension.Two anteroposterior axes were drawn on the CT images:one line connected the middle of the posterior cruciate ligament insertion site and the medial edge of the patellar tendon,and another line connected the middle of the posterior cruciate ligament insertion site and the middle-medial 1/3 of the patellar tendon.The surgical epicondylar axis was also drawn on the CT images.Angles were measured between a line perpendicular to the surgical epicondylar axis and the two anteroposterior axes,and the angles were compared with the ideal tibial rotational alignment reference axis (0°).Results Angles between the line perpendicular to the surgical epicondylar axis and the line connecting the middle of the posterior cruciate ligament insertion site and the medial edge of the patellar tendon averaged 0.7°±2.8° (range,-5.1°-5.8°),there was no significant difference compared with 0°.Angles between the line perpendicular to the surgical epicondylar axis and the line connecting the middle of the posterior cruciate ligament insertion site and the middle-medial 1/3 of the patellar tendon averaged 6.9°±5.3° (range,-3.4°-14.1°),there was significant difference compared with 0°.Significant difference existed in angles between the two anteroposterior axes and the line perpendicular to the surgical epicondylar axis.Conclusion The line connecting the middle of the posterior cruciate ligament insertion site and the medial edge of the patellar tendon is a more reliable reference axis for the tibial component rotational alignment,which makes the femoral and tibial components in a more matching rotational position.