BACKGROUND: Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer, and any change of miRNAs expression will affect the degree of target regulation, thus affecting intracellular homeostasis. This study verified that miR-186-5p could inhibit the proliferation, migration and invasion of LUAD cells by regulating PRKAA2. METHODS: Previous investigations found that the expression of miR-186-5p was markedly suppressed in LUAD. Bioinformatics method is used to predict the target protein related to ferroptosis downstream and inquire about its expression level in LUAD and its influence on the survival of patients. Double luciferase verified the binding site of PRKAA2 and miR-186-5p. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of PRKAA2. The effects of miR-186-5p of LUAD cells as well as the mechanism by which miR-186-5p inhibits Fer-1's sensitivity to ferroptosis were confirmed by EdU, Transwell, and scratch assays. The effect of miR-186-5p on the amount of reactive oxygen species (ROS) in LUAD cells was discovered using ROS experiment. Malondialdehyde (MDA) and glutathione (GSH) experiments were used to detect the effects of miR-186-5p and PRKAA2 on ferroptosis index of LUAD cells. The concentration of lipid ROS (L-ROS) in LUAD cells were measured using the L-ROS tests to determine the effects of miR-186-5p and PRKAA2. RESULTS: The expression of PRKAA2 is up-regulated, and a high level of PRKAA2 expression was associated with a poor prognosis for patients with LUAD. Overexpression of miR-186-5p decreased the gene and protein expression of PRKAA2. By promoting ferroptosis, miR-186-5p overexpression prevented lung cancer cells from proliferating, invading, and migrating. ROS could be produced in higher amounts in LUAD cells due to miR-186-5p. Overexpression of miR-186-5p and knockdown PRKAA2 up-regulated MDA content and reduced GSH content in LUAD cells, respectively. miR-186-5p could increase the content of L-ROS and promote the ferroptosis sensitivity of LUAD cells by targeting PRKAA2. CONCLUSIONS miR-186-5p promotes ferroptosis of LUAD cells through targeted regulation of PRKAA2, thus inhibiting the proliferation, invasion and migration of LUAD.
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Humans ; Lung Neoplasms/genetics* ; Carcinoma, Non-Small-Cell Lung ; Ferroptosis/genetics* ; Reactive Oxygen Species ; Adenocarcinoma of Lung/genetics* ; MicroRNAs/genetics* ; 3,4-Methylenedioxyamphetamine ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; AMP-Activated Protein Kinases

Objective:To summarize the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) infected with Delta variant, so as to provide further references for clinical diagnosis and treatment.Methods:A real-world study was conducted to analyze the characteristics of 166 COVID-19 patients infected with Delta variant at Guangzhou Eighth People’s Hospital, Guangzhou Medical University.Results:The study enrolled 5 asymptomatic cases, 123 non-severe cases (mild and moderate type), and 38 severe cases (severe and critical type). Among these patients, 69 (41.6%) were male and 97 (58.4%) were female, with a mean age of 47.0±23.5 years. Thirty-nine cases (23.5%) had received 1 or 2 doses of inactivated vaccine. The incidence of severe COVID-19 cases was 7.7% in 2-doses vaccinated patients, which was lower than that of 11.5% in 1-dose and 26.8% in unvaccinated patients. The proportion of severe cases in 2 dose-vaccinated patients was 7.7%, which was lower than that of 11.5% in 1-dose vaccinated patients and 26.8% in unvaccinated patients, but the difference was not significant ( P>0.05). The most common clinical symptom was fever (134 cases, 83.2%), and 39.1% of cases presented with high-grade fever (≥39 °C); other symptoms were cough, sputum, fatigue, and xerostomia. The proportion of fever in severe cases was significantly higher than that of non-severe cases (97.4% vs. 76.4%, P<0.01). Similarly, the proportion of severe cases with high peak temperature (≥39 ℃) () was also higher than that of non-severe cases (65.8% vs. 30.9%, P<0.01). The median minimal Cycle threshold (Ct) values of viral nucleic acid N gene and ORFlab gene were 20.3 and 21.5, respectively, and the minimum Ct values were 11.9 and 13.5, respectively. Within 48 h of admission, 9.0% of cases presented with decreased white blood cell counts, and 52.4% with decreased lymphocyte counts. The proportions of increased C-reactive protein, serum amyloid A, interleukin 6, and interleukin 10 were 32.5%, 57.4%, 65.3%, and 35.7%, respectively. The proportions of elevated C-reactive protein, serum amyloid A and interleukin-6 in severe cases were significantly higher than those in non-severe cases ( P<0.01). Logistic regression analysis showed that older age and higher peak temperature were associated with a higher likelihood of severe cases ( OR>3, 95% CI: 2-7, P<0.01). In terms of treatment, traditional Chinese medicine (TCM) was used in 97.6% of non-severe cases and 100% in severe cases. Other treatments included respiratory and nutritional support, immunotherapy (such as neutralizing antibodies and plasma of recovered patients). The median times from admission to progression to severe cases, of fever clearance, and of nucleic acid conversion were 5 days, 6 days and 19 days, respectively. No deaths were reported within 28 days. Conclusions:The symptoms of Delta variant infection in Guangzhou are characterized by a high proportion of fever, high peak temperature, long duration of fever, high viral load, a long time to nucleic acid conversion, and a high incidence of severe cases. The severe cases exhibit a higher percentage of elderly patients, a longer duration of fever and have a higher fever rate and a higher hyperthermia rate than non-severe cases. Age and hyperthermia are independent risk factors for progression to severe disease. The combination of TCM and Western medicine can control the progression of the disease effectively.

Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions，9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury，injury level，severity of injury，segment and type of fracture，complications，death and other data were collected by medical record questionnaire，and analyzed according to geographical region，age and gender.Results:Medical records of 4，134 patients were included in this study，with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million （95% CI 50.122-50.846）. The highest incidence in the Eastern region was 53.791 / 1 million （95% CI 53.217-54.365）. In the whole country，the main causes of injury were high falls （29.58%），as well as in the Western region （40.68%），while the main causes of injury in the Eastern and Central regions were traffic injuries （31.22%，30.10%）. The main injury level was cervical spinal cord in the whole country （64.49%），and the proportion of cervical spinal cord injury in the Central region was the highest （74.68%），and the proportion of lumbosacral spinal cord injury in the Western region was the highest （32.30%）. The highest proportion of degree of injury was incomplete quadriplegia （55.20%），and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation，77.95% in the Western region and only 54.77% in the Central region. In the whole country，the head was the main combined injury （37.87%），as well as in the Eastern and Central regions，while the proportion of chest combined injury in the Western region was the highest （38.57%）. A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients （0.56%） died in hospital，of which 17（73.91%） died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level，incomplete quadriplegia as the main degree of injury，head as the main combined injury，and respiratory complications as the main complication.

Objective To investigate the relationship between (serum neutrophil gelatinase-associated lipocalin,sNGAL) and cardiovascular events in patients with chronic kidney disease(CKD).Methods 300 patients with CKD were divided into two groups according to the level of sNGAL:high sNGAL group (n=158) and low sNGAL group (n=142).The incidence of cardiovascular events and cumulative survival rate were analyzed by ROC curve,and the correlation between sNGAL and cardiovascular risk factors,cardiovascular events in patients with chronic renal disease was analyzed.Influencing factors of cardiovascular events in CKD patients was analyzed.Results There were significant differences in the data about BMI,diabetes proportion,CKD staging,eGFR,hsCRP,24h proteinuria,HDL,iPTH,phosphate and blood calcium between the two groups (P＜0.05).The 3-year cumulative survival rate of high sNGAL group(77.2％) was significantly lower than that of low sNGAL group(96.5％),and the 3-year incidence of cardiovascular events (37.9％) was significantly higher than that of low sNGAL group (9.8％) (P＜ 0.05).AUC in diagnosing cardiovascular events in high sNGAL group (0.746) was significantly higher than that in eGFR(0.636),age (0.504),serum calcium (0.545),HDL(0.594) and LDL (0.508,all P＜0.05).There was a significant correlation between sNGAL and eGFR,HDL,BMI,hs-CRP,iPTH and phosphate (P＜ 0.05).Both univariate and multivariate fact ors COX showed that sNGAL was a risk factor of cardiovascular events in patients with CKD (P＜0.05),((HR=1.976 and 1.588,95％ CI=1.443-2.724 and 1.144-2.143,respectively,P=0.O00 and 0.000)).Conclusions The incidence of cardiovascular events in patients with CKD with high sNGAL is significantly increased.sNGAL is an independent factor of cardiovascular events in patients with chronic renal disease.

Objective: To compare the clinical efficacy between proximal femoral nail antirotation (PFNA) versus InterTAN nail in the treatment of senile patients with unstable femoral intertrochanteric fracture. Methods: A retrospective study was conducted of the 164 senile patients with unstable femoral intertrochanteric fracture who had been treated at Department of Orthopedics, Shougang Hospital Affiliated to Peking University from January 2013 to March 2018. InterTAN nailing was performed in 93 of them, including 30 men and 63 women with an age of 84.5±2.4 years; by the AO classification, there were 53 cases of type 31-A2.2, 28 cases of type 31-A2.3 and 12 cases of type 31-A3. PENA fixation was performed in the other 71 patients, including 19 men and 52 women with an age of 83.8±2.3 years; by the AO classification, there were 41 cases of type 31-A2.2, 22 cases of type 31-A2.3 and 8 cases of type 31-A3. The 2 groups were compared in terms of weight-bearing time, thigh pain, hip function, imaging complications and postoperative quality of life. Results: The 2 groups were comparable because there were no significant differences between them in preoperative general data (P>0.05). In the InterTAN nail group, the incidence of imaging complications [5.4%(5/93)] was significantly lower than in the PFNA group [18.3%(13/71)], the weight-bearing time (60.0±13.6 d) significantly shorter than in the PFNA group (65.8±11.0 d), and the incidence of thigh pain [3.2%(3/93)] significantly lower than in the PFNA group [12.7%(9/71)] (all P< 0.05). Of this series, 153 patients obtained an average follow-up of 39 months (from 12 to 75 months). At the last follow-ups, the Harris scores in the InterTAN nail group (78.3±12.2) were significantly higher than in the PENA group (73.6±11.3) (P<0.05). The InterTAN nail group scored significantly higher in physical functioning (68.6±15.4), general health perceptions (78.2±10.3), vitality (74.0±12.6) and mental health (80.6±9.9) in the 36-item short form health survey (SF-36) than the PFNA groups did (64.1±9.9, 74.9±9.0, 69.9±10.9 and 77.4±8.8) (all P<0.05). Conclusions Both internal fixation procedures are able to heal the fracture and restore the hip function in the senile patients with unstable femoral intertrochanteric fracture. However, InterTAN nail may have the advantages of earlier weight-bearing, lower incidence of varus deformity and better recovery of postoperative quality of life.

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.

Objective To investigate the relationship between lipoprotein[a] (Lp[a]) level and risk of onset of spontaneous subarachnoid hemorrhage (SSAH).Methods Thirty-four patients with SSAH,admitted to our hospital from November 2014 to December 2015,were chosen as patient group,and another 40 healthy volunteers were collected as control group.Morning fasting venous blood was collected,and levels of plasma Lp (a),total cholesterol (TC),glycerol triester (TG),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C),apolipoprotein AI (ApoAI) and apolipoprotein B (ApoB) were detected.Pearson correlation analysis was used to analyze the correlations of Lp (a) with various lipid components.Results As compared with control group (84.28±57.96 mg/L),patient group had significantly higher Lp(a) level ([170.50±144.58] mg/L,P＜0.05);TC,HDL-C,LDL-C,ApoAI and ApoB levels showed no significant differences between the two groups (P＞0.05).Pearson correlation analysis indicated that Lp(a) level did not correlate to TC,HDL-C,LDL-C,ApoAI and ApoB levels (P＞0.05).Conclusion Plasma Lp (a) level is a risk factor for the onset of SSAH.

Objective To optimize the extraction process for the polysaccharide from fermented Cordyceps Sinensis powder with response surface methodology.Methods We selected the factors and levels on the basis of single factor experiment,and then designed the experiment with 3 factors and 3 levels based on the principle of Box-Behnken's design.Results The effect of the factors of extraction temperature,time and solid-liquid ratio on extraction ratio was in decreasing sequence.The optimal extraction technology obtained through the classical analysis was as follows:extraction temperature at 95 ℃,the ratio of solid to liquid being 1 ∶ 21,and extraction for 73 min.Under this condition the theoretical extraction rate was 4.31％ and the actual extraction rate was (4.20 ± 0.1)％.Conclusion The obtained values agree with the predicted values of the mathematic models,and the Box-Behnken experimental design is suitable for optimizing the extraction of the polysaccharide from fermented Cordyceps Sinensis powder.

AIM:To investigate the effects of extracellular cysteine/cystine redox potential (EhCys/CySS) on the mitochondrial function of nonalcoholic fatty liver disease ( NAFLD) hepatocytes.METHODS:LO2 cells were incuba-ted with EhCys/CySS of the oxidized (0 mV), the normal (-80 mV), or the reduced (-150 mV) status medium, then treated with oleic acid to establish NAFLD model in vitro.DCFH-DA and MitoSOX were used as the fluorescent probes for determining reactive oxygen species (ROS).Apocynin (NADPH oxidase inhibitor), MitoQ10 (mitochondria-targeted an-tioxidant), rotenone (mitochondrial respiratory chain complex I inhibitor) and antimycin A (mitochondrial respiratory chain complex III inhibitor) were used to investigate the sources of ROS.RESULTS:An increase in ROS in LO2 cells by oleic acid was aggravated by the oxidized extracellular EhCys/CySS (0 mV), which was removed by the reduced EhCys/CySS (-150 mV) .ROS generation by 0 mV was significantly eliminated by MitoQ10 .ROS levels were dependent on ex-tracellular Eh Cys/CySS in rotenone treated LO2 cells.A decline of mitochondrial membrane potential in the cells with NAFLD was aggravated by 0 mV and reversed by -150 mV.CONCLUSION:The oxidized extracellular Eh Cys/CySS via inhibitiing of complex I intensifies ROS generation and reducing the mitochondrial membrane potential in the NAFLD hepa-tocytes, which were reversed by reduced Eh Cys/CySS.

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