HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems / 中华预防医学杂志

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

The role of Vav3 expression for inflammation and cell death during experimental myocardial infarction

Abstract Objectives Myocardial Infarction (MI) is the leading cause of chronic heart failure. Previous studies have suggested that Vav3, a receptor protein tyrosine kinase signal transducer, is associated with a variety of cellular signaling processes such as cell morphology regulation and cell transformation with oncogenic activity. However, the mechanism of Vav3-mediated MI development requires further investigation. Method Here, The authors established an MI rat model by ligating the anterior descending branch of the left coronary artery, and an MI cell model by treating cardiomyocytes with H2O2. Microarray analysis was conducted to identify genes with differential expression in heart tissues relevant to MI occurrence and development. Vav3 was thus selected for further investigation. Results Vav3 downregulation was observed in MI heart tissue and H2O2-treated cardiomyocytes. Administration of Lentiviral Vav3 (LV-VAV3) in MI rats upregulated Vav3 expression in MI heart tissue. Restoration of Vav3 expression reduced infarct area and ameliorated cardiac function in MI rats. Cardiac inflammation, apoptosis, and upregulation of NFκB signal in heart tissue of MI animals were assessed using ELISA, TUNEL staining, real-time PCR, and WB. Vav3 overexpression reduced cardiac inflammation and apoptosis and inhibited NFκB expression and activation. Betulinic Acid (BA) was then used to re-activate NFκB in Vav3-overexpressed and H2O2-induced cardiomyocytes. The expression of P50 and P65, as well as nuclear P65, was significantly increased by BA exposure. Conclusions Vav3 might serve as a target to reduce ischemia damage by suppressing the inflammation and apoptosis of cardiomyocytes.

MicroRNA21-5p alleviates hyperoxia-induced acute lung injury in rats through activating phosphatidylinositol 3 kinase/serine-threonine protein kinase signaling pathway by regulating type Ⅱ alveolar epithelial cell apoptosis / 中华危重病急救医学

Objective:To investigate whether microRNA-21-5p (miR-21-5p) alleviates hyperoxia-induced acute lung injury (HALI) through activating the phosphatidylinositol 3 kinase/serine-threonine protein kinase (PI3K/Akt) signaling pathway by regulating apoptosis of type Ⅱ alveolar epithelial cell (AECⅡ).Methods:Seventy-two male Sprague-Dawley (SD) rats were divided into normozone-controlled group, HALI group, PI3K/Akt signaling pathway inhibitor LY294002+HALI group (LY+HALI group), miR-21-5p overexpression+LY294002+HALI group (miR-21-5p+LY+HALI group), miR-21-5p overexpression+HALI group (miR-21-5p+HALI group), and dimethyl sulfoxide (DMSO)+HALI group by random number table method with 12 rats in each group. Animal models of HALI were prepared using 95% concentrations of oxygen. The animals in the normozone-controlled group were fed normally under normoxia. Transfection of lung tissue by miR-21-5p adeno-associated viral vector AAV6-miR-21-5p was performed by instillation of 200 μL titer (1×10 12 TU/mL) through a tracheal catheter 3 weeks prior to modeling. DMSO and LY294002 were administered via the tail vein at 0.3 mg/kg 1 hour before modeling. After 48 hours of modeling, carotid artery blood was collected to detect oxygenation index (OI) and respiratory index (RI), and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect miR-21-5p expression. Lung tissue was collected, and the levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA), and the ratio of pulmonary wet/dry weight (W/D) was determined, and the pathological changes of lung histopathology were observed under the light microscopy after hematoxylin-eosin (HE) staining. Each group was purified AECⅡ cells from 6 rats, the apoptosis rate was detected by flow cytometry, and the expression levels of phosphatase and tensin homologous gene (PTEN), and proteins from the PI3K/Akt signaling pathway were detected by Western blotting. Results:Compared with the normozone-controlled group, alveolar septal thickening and massive inflammatory cell infiltration were found after hyperoxia exposure, RI, inflammatory factors, lung W/D ratio, pathological score, AECⅡ cells early apoptosis rate, PTEN protein expression and phosphorylation level of Akt were increased, while OI and miR-21-5p expression were decreased, indicating the successful preparation of the model. After pretreatment, LY294002 could aggravate the pathological injury of lung tissue in HALI rats, RI, inflammatory factors and lung W/D ratio were further increased, and OI was further reduced compared with HALI group. At the same time, it could promote the AECⅡ cell apoptosis, further up-regulate the expression of PTEN, and reduce the phosphorylation of Akt. However, miR-21-5p pretreatment could negatively regulate PTEN, activate PI3K/Akt signal pathway, inhibit AECⅡ cell apoptosis, and reduce HALI, which was shown by the decreased level of inflammatory factors in miR-21-5p+LY+HALI group compared with LY+HALI group [TNF-α (μg/L): 100.33±3.48 vs. 116.55±2.53, IL-6 (ng/L): 141.06±3.70 vs. 161.31±3.59, IL-1β (μg/L): 90.82±3.69 vs. 112.23±2.87, all P < 0.05], RI, lung injury pathology score, lung W/D ratio, and AECⅡ cell early apoptosis rate were significantly decreased [RI: 0.81±0.02 vs. 1.05±0.07, pathology score: 0.304±0.008 vs. 0.359±0.007, lung W/D ratio: 5.29±0.03 vs. 5.52±0.08, apoptosis rate: (27.20±2.34)% vs. (34.17±1.49)%, all P < 0.05], OI and expressions of miR-21-5p were significantly increased [OI (mmHg, 1 mmHg≈0.133 kPa): 266.71±2.75 vs. 230.12±4.04, miR-21-5p (2 -ΔΔCt): 2.21±0.13 vs. 0.33±0.03, both P < 0.05], and PTEN protein expression in AECⅡ cell was significantly reduced (PTEN/GAPDH: 0.50±0.06 vs. 0.93±0.06, P < 0.05), and phosphorylation level of Akt was significantly increased [phosphorylated Akt (p-Akt) protein (p-Akt/GAPDH): 0.86±0.05 vs. 0.56±0.06, P < 0.05]. Conclusion:miR-21-5p attenuates HALI by inhibiting AECⅡ cell apoptosis, possibly through negative regulation of PTEN to activate PI3K/Akt signaling pathway.

Research progress of phosphoglycerate mutase 5-mediated mitophagy and necroptosis / 中华危重病急救医学

Mitophagy is the selective degradation of damaged mitochondria, and it is of great significance to maintain the normal quantity and quality of mitochondria to ensure cell homeostasis and survival. Necroptosis is a type of programmed cell necrosis that can be induced by excessive mitophagy. Reactive oxygen species (ROS) are produced mainly by mitochondria and can damage mitochondria. Hyperoxic acute lung injury (HALI) is a serious complication of clinical oxygen therapy, and its pathogenesis is not clear. Existing studies have shown that mitophagy and necroptosis are involved in the occurrence of HALI. There are many mechanisms regulating mitophagy and necroptosis, including tumor necrosis factor-α (TNF-α), E3 ubiquitin protein ligase (PINK1/Parkin) protein pathway encoded by PTEN-induced kinase 1/PARK2 gene, phosphoglycerate mutase 5 (PGAM5), etc. PGAM5 has been proved to be a key factor linking mitophagy and necroptosis. Previous studies of our team found that the mechanism of microRNA-21-5p (miR-21-5p) alleviating HALI was related to its pGAM5-mediated inhibition of mitophagy, but the mechanism of PGAM5-mediated mitophagy and necroptosis remains unclear. Therefore, this paper reviews the targets of PGAM5-mediated mitophagy and necroptosis, in order to find clues of lung protection of pGAM5-mediated mitophagy and necroptosis in HALI, and provide theoretical basis for subsequent basic research.

Role and mechanism of signal transducer and activator of transcription protein STAT1/3/5 in hyperoxia-induced acute lung injury / 中华危重病急救医学

Objective:To investigate whether signal transducer and activator of transcription (STAT1/3/5) have a protective effect on hyperoxia-induced acute lung injury (HALI) and its mechanism.Methods:Seventy C57BL/6J mice were randomly divided into five groups: normoxia control group, HALI group, and STAT1/3/5 inhibitor groups, with 14 mice in each group. The HALI model was established by exposure to more than 90% hyperoxia for 48 hours; three STAT inhibitor groups were pretreated by intraperitoneal injection of STAT1 inhibitor 40 mg/kg and STAT3 inhibitor 5 mg/kg, and STAT5 inhibitor 10 mg/kg for 1 week. Six blood samples were randomly collected from each group, and microRNA-21 (miR-21) expression was measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). Lung tissue of the sacrificed mice was obtained, and enzyme linked immunosorbent assay (ELISA) was used to detect the contents of tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-1β), superoxide dismutase (SOD), malonic dialdehyde (MDA), and matrix metalloproteinase 9 (MMP9). The water content of lung tissue was calculated. The pathological changes in lung tissue were observed under the light microscope, and the pathological score of lung injury was performed. Western blotting was used to detect the expression of phosphorylated STAT (p-STAT1, p-STAT3, p-STAT5) in lung tissue. The 7-day cumulative survival rates of the remaining 8 mice in each group were analyzed using Kaplan-Meier survival curves.Results:Under the light microscope, the alveolar structures in the HALI group and the STAT1 inhibitor group were destroyed, a large number of neutrophils (NEU) infiltrated in the alveoli and lung interstitium, which were thickened. The pathological score of lung injury and the water content of the lung tissue was significantly increased. In STAT3 inhibitor and STAT5 inhibitor groups, the alveolar cavity was clear, the degree of NEU infiltration and the thickness of lung interstitium were lower than those in HALI group, the pathological score of lung injury and the water content of lung tissue were significantly decreased, especially in STAT3 inhibitor group. Compared with the normoxia control group, the contents of TNF-α, IL-6, IL-1β, MDA, and MMP9, and the expression levels of p-STAT3 and p-STAT5 in the HALI group were significantly increased. In contrast, the content of SOD and the expression of miR-21 were significantly decreased. Compared with the HALI group, the contents of TNF-α, IL-6, IL-1β, MDA, and MMP9 in the STAT3 inhibitor group and STAT5 inhibitor group were significantly decreased. At the same time, the content of SOD and the expression of miR-21 were significantly increased, especially in STAT3 inhibitor group [TNF-α (μg/L): 42.53±3.25 vs. 86.36±5.48, IL-6 (ng/L): 68.46±4.28 vs. 145.00±6.89, IL-1β (μg/L): 28.74±3.53 vs. 68.00±5.64, MDA (μmol/g): 20.33±2.74 vs. 42.58±3.45, and MMP9 (ng/L): 128.55±6.35 vs. 325.13±6.65, SOD (kU/g): 50.53±4.19 vs. 22.53±3.27, miR-21 (2 -ΔΔCt): 0.550±0.018 vs. 0.316±0.037, all P < 0.05]. Kaplan-Meier survival curve analysis showed that the 7-day cumulative survival rates of the STAT3 inhibitor group and STAT5 inhibitor group were significantly higher than those of the HALI group [62.5% (5/8), 37.5% (3/8) vs. 12.5% (1/8), both P < 0.05]. Conclusion:Inhibition of STAT3 hyperactivation may suppress the inflammatory response, regulate oxidative stress, improve lung permeability through regulating the expression of miR-21, which exert lung protection in HALI.

Correlation between gut microbiota and liver biochemical indicators in patients with chronic hepatitis B / 生物工程学报

Chronic hepatitis B (CHB) is a global epidemic disease caused by hepatitis B virus that can lead to hepatic failure, even liver cirrhosis and hepatocellular carcinoma. The occurrence and development of CHB are closely related to the changes in the gut microbiota communities. To explore the relationship between the structure of gut microbiota and liver biochemical indicators, 14 CHB patients (the CHB group) and 11 healthy people (the CN group) were randomly enrolled in this study. Our results demonstrate that CHB caused changes in the gut microbiota communities and biochemical indicators, such as alanine transaminase, total bilirubin and gamma glutamyl transferase. Furthermore, CHB induced imbalance of the gut microbiota. Prevotella, Blautia, Ruminococcus, Eubacterium eligens group, Bacteroides uniformis and Ruminococcus sp. 5_1_39BFAA were associated with the critical biochemical indicators and liver injury, suggesting a new approach to CHB treatment.

Transcriptome analysis of signal transduction pathway involved in light inducing astaxanthin accumulation in Haematococcus pluvialis / 生物工程学报

The unicellular green alga Haematococcus pluvialis is the best source of natural astaxanthin (AST) in the world due to its high content under stress conditions. Although high light (HL) can effectively induce AST biosynthesis, the specific mechanisms of light signal perception and transduction are unclear. In the current study, we used transcriptomic data of normal (N), high white light (W), and high blue light (B) to study the mechanisms of light inducing AST accumulation from the point of photoreceptors. The original data of 4.0 G, 3.8 G, and 3.6 G for N, W, and B were obtained, respectively, by the Illumina Hi-seq 2000 sequencing technology. Totally, 51 954 unigenes (at least 200 bp in length) were generated, of which, 20 537 unigenes were annotated into at least one database (NR, NT, KO, SwissProt, Pfam, GO, or KOG). There were 1 255 DEGs in the W vs N, 1 494 DEGs in the B vs N, and 1 008 DEGs in the both W vs N and B vs N. KEGG enrichment analysis revealed that photosynthesis, oxidative phosphorylation, carotenoid biosynthesis, fatty acids biosynthesis, DNA replication, nitrogen metabolism, and carbon metabolism were the significantly enriched pathways. Moreover, a large number of genes encoding photoreceptors and predicted interacting proteins were predicted in Haematococcus transcriptome data. These genes showed significant differences at transcriptional expression levels. In addition, 15 related DEGs were selected and tested by qRT-PCR and the results were significantly correlated with the transcriptome data. The above results indicate that the signal transduction pathway of "light signal - photoreceptors - interaction proteins - (interaction proteins - transcription factor/transcriptional regulator) - gene expression - AST accumulation" might play important roles in the regulation process, and provide reference for further understanding the transcriptional regulation mechanisms of AST accumulation under HL stress.

Treatment of calcaneal fracture with calcaneal reduction forceps and external fixation / 中国医师进修杂志

Objective:To study the clinical effect of the minimally invasive treatment of calcaneal fractures by closed reduction using calcaneal plastic reduction forceps combined with threaded-pin external fixation.Methods:Clinical data of 16 patients with unilateral calcaneal fractures admitted to Affiliated Zhongshan Hospital of Dalian University from January 2015 to December 2017, including 14 males and 2 females, with a unilateral calcaneal fracture were analyzed retrospectively. The Bohler angle, Gissane angle, and calcaneal width, height and length were measured before and after the operation. The ankle function was evaluated according to the AOFAS score at 6 and 12 months after the operation.Results:The Bohler angle, Gissane angle, width, height and length 3 d and 6 months after operation were significantly better than before operation: (28.82 ± 1.72)° and (25.84 ± 1.96)° vs. (16.71 ± 2.74)°, (120.92 ± 3.85)° and (119.65 ± 3.84)° vs. (103.63 ± 4.62)°, (35.23 ± 1.94) and (36.51 ± 2.01) mm vs. (39.52 ± 1.26) mm, (48.52 ± 2.16) and (48.86 ± 1.98) mm vs. (46.94 ± 2.48) mm, (71.23 ± 2.49) and (70.94 ± 2.36) mm vs. (67.53 ± 2.53) mm, there were statistical differences ( P<0.05); there were no statistical difference in those indexes before 6 months after operation and 3 d after operation ( P>0.05). The average AOFAS score 12 months after operation was significantly higher than 6 months after operation (80.6 scores vs. 60.1 scores), there was statistical difference ( P<0.01). At the final follow-up, the AOFAS score was excellent, good, moderate, and poor in 11 cases, 3 cases, 1 case and 1 case. The average AOFAS score was 60.1 at 6 months after the operation and 80.6 at 12 months after the operation, which was significantly higher than the average AOFAS score at 6 months after the operation ( P < 0.01). At the final follow-up, the AOFAS score was excellent, good, moderate, and poor in 11 cases, 3 cases, 1 case and 1 case, respectively. Conclusions:The application of closed reduction using calcaneal plastic reduction forceps combined with threaded-pin external fixation is effective for the treatment of displaced calcaneal fractures, with a simple procedure, minimal trauma, fewer skin and soft tissue complications, and satisfactory clinical results.

Hypofibrinogenemia Caused by Hemocoagulase Injection: A Retrospective Study on Clinical Laboratory Findings / 中国医学科学杂志(英文版)

Objective Hemocoagulase injection based on the venom of is widely used in the treatment of hemorrhagic disorders. This study aimed to characterize the clinical laboratory findings of hemocoagulase-induced hypofibrinogenemia as the associated adverse reaction of hemocoagulase injection.Methods We retrospectively enrolled 27 in-patients who were treated with hemocoagulase injection for hemoptysis and developed hypofibrinogenemia during the period of January 1, 2015 to March 31, 2018. Clinical data were collected and investigated, including clinical manifestations, hemostatic and fibrinolytic parameters, dosage of hemocoagulase, the medication time, and the cryoprecipitate blood product infusion. Differences in fibrinogen, D-dimer, and fibrin/fibrinogen degradation products (FDP) before, during, and after the application of hemocoagulase injection were analyzed statistically.Results Plasma fibrinogen level during medication of hemocoagulase injection decreased significantly compared to that before the treatment (=1.80, <0.001), with the average decrease of 2.28 g/L (0.63-3.9 g/L). After withdrawal, fibrinogen level increased significantly compared to that during the medication (=-1.20, <0.001), but was still lower than that before the medication (=0.59, =0.03). The D-dimer level and the FDP level after withdrawal decreased significantly compared to the levels during the medication (=0.83, =0.002; Wilcoxon-test, =-4.54, <0.001). Spearman's correlation analyses did not find either fibrinogen change during-before the administration or FDP change after-during the administration was associated with the dosage of hemocoagulase (=-0.17, =0.40; =-0.28, =0.15; respectively) and the time of recovery from hypofibrinogenemia (=-0.45, =0.05; =0.13, =0.61; respectively).Conclusion Monitoring both clotting and fibrinolysis parameters is essential in the management of hemoptysis patients treated with hemocoagulase injection. Clinicians should be aware of hypofibrinogenemia and consider discontinuation of the administration of hemocoagulase whenever necessary.

Effect of overexpression of microRNA-21-5p on early apoptosis of typeⅡalveolar epithelial cells in rats with hyperoxic acute lung injury / 中华危重病急救医学

To investigate the effect of overexpression of microRNA-21-5p (miR-21-5p) on early apoptosis of type Ⅱalveolar epithelial cells (AECⅡ) in rats with hyperoxic acute lung injury (HALI). Methods The Sprague-Dawley (SD) rats were randomly divided into four groups: control group (CON group), hyperoxia group (H group), overexpression group (OE group) and empty vector group (EV group), with 20 rats in each group. HALI animal model was made by inhaling high concentration oxygen (oxygen concentration ≥90%); CON group was arranged to inhale room air. The miR-21-5p adeno-associated virus-6 (AAV-6) overexpression vectors or empty vectors were dripped into the lungs of OE group and EV group through tracheal tube, respectively. The hyperoxia model was prepared after 3 weeks of feeding. At 0, 24, 48 and 60 hours after making model, 5 rats were selected to detect lung injury parameters:oxygenation index (OI), respiratory index (RI), wet/dry ratio (W/D), pathological injury score of lung tissue; real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-21-5p in AECⅡ, and flow cytometry was used to detect the early apoptotic rate of AECⅡ. Results ① The lung injury parameters: in H group, the OI gradually decreased with time, but the RI, lung W/D ratio and pathological score increased gradually with time, the difference between CON group was statistically significant at 24 hours [OI (mmHg, 1 mmHg = 0.133 kPa):336.04±5.79 vs. 400.22±19.70, RI: 0.20±0.02 vs. 0.10±0.06, lung W/D ratio: 5.04±0.09 vs. 4.85±0.09, lung tissue pathological score: 0.13±0.01 vs. 0.07±0.01, all P < 0.05]. It indicated that HALI model could be successfully established by inhaling high concentration oxygen continuously. ② The expression of miR-21-5p: the miR-21-5p was gradually increased in H, OE and EV groups, and the expression of miR-21-5p was significantly higher than that in CON group at 24, 48 and 60 hours. Compared with H group, the expression of miR-21-5p was significantly increased further in OE group at 0, 24, 48 and 60 hours (2-ΔΔCt: 3.75±0.11 vs. 0.98±0.14, 3.98±0.12 vs. 1.18±0.13, 4.28±0.18 vs. 1.49±0.06, 4.66±0.12 vs. 1.80±0.12, all P < 0.05). ③ The early apoptosis of AECⅡ: the early apoptosis rate gradually increased with time in H, OE and EV groups, and the early apoptosis of AECⅡ was significantly higher than that in CON group at 24, 48 and 60 hours. Compared with H group, the early apoptosis rate was significantly decreased in OE group at 24, 48 and 60 hours [(1.22±0.63)% vs. (2.84±0.59)%, (5.76±0.18)% vs. (13.10±2.01)%, (29.48±0.48)% vs. (49.04±1.36)%, all P < 0.05]. ④ There was no significant difference in the expression of miR-21-5p and the early apoptosis of AECⅡ cells between EV group and H group at each time point. Conclusion Overexpression of miR-21-5p could inhibit the early apoptosis of AECⅡ in rats with HALI.

Application of critical care ultrasound in hemodynamic monitoring of septic shock / 中华危重病急救医学

Critical?care?ultrasound?(CCUS)?has?gradually?become?an?indispensable?monitoring?tool?in?intensive?care?unit?due?to?noninvasive,?real-time?and?repeatability?and?is?playing?an?important?role?in?etiological?screening,?disease?diagnosis,?treatment?and?efficacy?evaluation,?especially?in?hemodynamic?monitoring?of?septic?shock.?The?etiology?of?septic?shock?is?so?complicated?that?often?affect?the?hemodynamic?status?of?patients,?increasing?the?difficulty?of?diagnosis?and?treatment.?CCUS?can?dynamically?monitor?the?changes?in?volume?and?organ?function?through?cardiopulmonary?and?renal?examination,?which?is?combined?with?clinical?information?and?other?monitoring?methods?to?manage?the?patient's?diagnosis?and?treatment?and?evaluate?their?prognosis?more?accurately,?timely?and?comprehensively.?The?aim?of?this?article?is?to?enhance?the?understanding?and?clinical?utility?of?ultrasonic?knowledge?and?provide?reference?in?patients'?hemodynamic?monitoring?methods?for?clinicians?after?reviewing?the?application?of?CCUS?in?hemodynamic?monitoring?of??septic?shock.

An analysis of GNAS and THRA gene mutations in children with congenital hypothyroidism / 中国当代儿科杂志

OBJECTIVE@#To preliminarily investigate the relationship between stimulatory G protein α subunit (GNAS) and thyroid hormone receptor α (THRA) gene mutations and clinical phenotypes in children with congenital hypothyroidism (CH).@*METHODS@#A total of 70 children with CH diagnosed by neonatal screening were enrolled. Their peripheral blood samples were collected to extract genomic DNA. GNAS and THRA genes were screened for mutations using next-generation sequencing. Bioinformatics software was used to analyze the pathogenicity of gene mutations.@*RESULTS@#Of the 70 children with CH, nine missense mutations (three known mutations and six novel mutations) in the GNAS gene were detected in three patients (4%), and one gene polymorphism, c.508A>G(p.I170V), in the THRA gene was detected in four patients. The analysis results of bioinformatics software and ACMG/AMP guidelines showed that the two GNAS gene mutations [c.301C>T(p.R101C) and c.334G>A(p.E112K)] were more likely to be pathogenic. Three children with GNAS gene mutations showed different degrees of hypothyroidism.@*CONCLUSIONS@#GNAS gene mutations are related to the development of CH, and children with CH have different clinical manifestations. THRA gene mutations may not be associated with CH.

Research progress on autophagic mechanism in acute lung injury/acute respiratory distress syndrome / 中国中西医结合急救杂志

Autophagy is a fundamental cellular process that plays a role in the turnover of sub-cellular organelles to protein. The activation of autophagy may prevent the pathophysilogical progression of oxidative stress-induced protein damage or organelle damage. The selective form of autophagy can maintain organelle renewal by degrading damaged proteins. In this article, the research progress on the mechanism of autophagy in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) was summarized in order to understand more deeply on this topic and arouse more researchers to pay attention to the role of autophagy in lung protection of ALI/ARDS.

Establishment of multiple organ dysfunction syndrome early warning score in patients with severe trauma and its clinical significance: a multicenter study / 中华危重病急救医学

Objective To explore the risk factors of multiple organ dysfunction syndrome (MODS) in severe trauma patients, put forward a new warning scoring system of MODS, and to provide a more accurate scoring method for doctors to judge the clinical condition and prognosis of patients. Methods Clinical data of 342 patients with severe trauma admitted to intensive care unit (ICU) of the Affiliated Hospital of Zunyi Medical College and Daping Hospital of the Third Military Medical University from January 1st, 2015 to December 31st, 2016 were retrospectively analyzed. The patients were divided into MODS groups (n = 251) and non-MODS group (n = 91) according to clinical outcomes. The clinical data of patients, including gender, age, heart rate (HR) and blood pressure within 24 hours after admission to the hospital, indicators of blood routine and blood biochemistry, severity of disease, severity of trauma, whether received the emergency intubation or surgery within 24 hours or not, whether developed sepsis or acute respiratory distress syndrome (ARDS) during hospitalization, were recorded, and univariate analysis was conducted. The indicators with statistical significance found by univariate analysis were enrolled in multivariate Logistic regression analysis, and the risk factors for MODS in patients with severe trauma were screened and assigned, and the final total score was MODS warning score. Receiver operating characteristic (ROC) curve was plotted to evaluate MODS warning score for predicting the occurrence of MODS in patients with severe trauma. Results Compared with non-MODS group, HR, Na+, serum creatinine (SCr), activated partial thromboplastin time (APTT), injury severity score (ISS), new injury severity score (NISS), acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score and sequential organ failure assessment (SOFA) score in MODS group were significantly increased, pH value, red blood cell (RBC), platelet (PLT), albumin (Alb) and Glasgow coma score (GCS) were remarkably decreased, and multiple injury, the patients with shock at admission, blood transfusion, central venous catheter, emergency intubation and infection were also increased, and more patients suffered from sepsis and ARDS. Multivariate Logistic regression analysis showed that the number of injured places equal or more than 2, shock at admission, APACHEⅡ score ≥ 15, SOFA score ≥ 4 and APTT > 40 s were risk factors for MODS in patients with severe trauma, with total MODS warning score of 7.5. ROC curve analysis showed that the area under ROC curve (AUC) of MODS warning score for predicting MODS in patients with severe trauma was 0.822, which was significantly higher than that of APACHEⅡ score (AUC = 0.698, P < 0.001), APTT (AUC = 0.693, P < 0.001) and SOFA score (AUC = 0.770, P = 0.025). When the cut-off value of MODS warning score was 2.5, the sensitivity was 61.35%, the specificity was 90.11%, and Youden index was 0.515. Conclusions MODS warning score is composed of five factors, including the number of injured places, shock at admission, APACHEⅡ score, SOFA score and APTT, which could be regarded as early warning score system for predicting MODS in patients with severe trauma. MODS warning score can be more comprehensive and timely to assess the possibility of MODS and prognosis of patients with severe trauma, and the prediction result is better than the single use of APTT, APACHEⅡ or SOFA score.

Advances in genetic research of congenital hypothyroidism in China / 中国当代儿科杂志

Congenital hypothyroidism (CH), which results from insufficient thyroid hormone biosynthesis, is one of the most common neonatal endocrine disorders. Thyroid dysgenesis and thyroid dyshormonogenesis are the two causes of CH and either one will lead to deficiencies of enzymes during thyroid hormone biosynthesis and insufficient thyroid hormone biosynthesis. Recently, researchers have performed extensive studies on genetics of CH. This paper reviews genes reported to be associated with CH in China.

Polymorphisms of 19 STR Loci in Guizhou Han Population and Their Forensic Application / 法医学杂志

Objective To investigate the allelic distribution of 19 autosomal STR loci in Guizhou Han population,and to estimate the forensic application value.Methods The 19 autosomal STR loci in 520 unrelated healthy individuals from Guizhou Han population were studied using GoldeneyeTM 20A kit.The 310 genetic analyzer was used for capillary electrophoresis,and the GeneMapper(R) ID v3.1 for genotyping.Results The heterozygosis,the discrimination power,the probability of exclusion,the polymorphism information content,the cumulative discrimination power and the cumulative probability of exclusion of the 19 STR loci were 0.603 8-0.9164,0.7900-0.985 6,0.295 5-0.8269,0.553 5-0.9089,1-1.2300×10-22 and 0.999 999 99,respectively.Compared with other five Han populations in pairwise allelic frequencies,Guizhou Han only had significant differences with Shandong Han,Liaoning Han and Shanxi Han.Conclusion The 19 autosomal STR loci such as D19S433 have a highly genetic polymorphic in Guizhou Han population,which have application values in the researches of population genetics and forensic genetics.

Analysisof the incidence of gallbladder cancer in Qido ng, Jiangsu Province from 1993 to 2012 / 上海预防医学

Objective To analyze the incidence of gallbladder cancer in Qidong City from 1993 to 2012 . Methods The clinical data of gallbladder cancer from January 1993 to December 2012 for patients with census registration in Qidong were sorted out from the cancer registration center in Qidong . Annual percent change ( APC ) models were applied to describe the annual percent changes of disease incidence and the standardized incidence trend over time.The incidence was standardized with the age structure of standard population from a national census taken in 2000 . Results A total of 493 new cases were diagnosed from 1993 to 2012 , occupying 0 .81%of new-onset malignant tumors for the same period . The crude incidence rate of gallbladder cancer was 2 .41/100 000 population and the standardized incidence thereof was 1 .42/100 000 population .Both the crude incidence and the standardized incidence thereof increased on a yearly basis from 1993 to 2012 ( APC=12 .83; APC =12 .04 ) while the annual crude incidence thereof for females increased faster than that for males ( APC=14 .51; APC=10 .60 ) . Old people aged 65 years and above were a high-risk group for gallbladder cancer , occupying 63 .49%of the incidence thereof for all ages . Conclusion The incidence of gallbladder cancer increases in Qidong , Jiangsu province of China on a yearly basis from 1993 to 2012 , with the incidence thereof for females increasing faster than that for males .

Optimization of fiber reconstituted technology for preparation of nasopore using fish scale collagen / 中国组织工程研究

BACKGROUND: Nowadays, fish collagen biomedical materials still exhibit obvious deficiency in thermal stability,in vivo degradation stability and in vivo material morphology stability. To expand the application of fish source collagen, it is urgent to improve the material performance by increasing the density and collagen molecule tightness of freshwater fish collagen sponge materials using technique methods.OBJECTIVE: To optimize the reconstitute process for nasopore preparation using fish scale collagen.METHODS: The optimal process for nasopore preparation through the reconstitution of fish scale collagen was ascertained by taking tilapia fish skin as a raw material to extract enzymatic soluble collagen at a temperature lower than the collagen denaturation temperature and recombinant rate of collagen fibers as index. Optimization of the conditions for nasopore preparation was carried out using single factor test and orthogonal test. The prepared nasopore was analyzed through infrared spectroscopy and microstructure analysis.RESULTS AND CONCLUSION: The optimal conditions for nasopore preparation were determined through the single factor test and orthogonal test as follows: 20 ℃ for 10 hours at pH 7.4 using a mixture of 65 mmol/L NaCl and 1 g/L collagen, by which the reconstitute rate of collagen fibers was up to 68.6%. The prepared nasopore is characterized by a refined porous structure constituted by threadlike collagen fibers, and has complete three-dimensional spiral structure,which is a potential intracavitary hemostatic material with fine properties.

Clinical application of percutaneous iliosacral screws combined with pubic ramus screws in Tile B pelvic fracture / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the application and effect of minimally invasive percutaneous anterior pelvic pubic ramus screw fixation in Tile B fractures.</p><p><b>METHODS</b>A retrospective review was conducted on 56 patients with posterior pelvic ring injury combined with fractures of anterior pubic and ischiadic ramus treated between May 2010 and August 2015, including 31 males and 25 females with an average age of 36.8 years old ranging from 35 to 65 years old. Based on the Tile classification, there were 13 cases of Tile B1 type, 28 cases of Tile B2 type and 15 cases of Tile B3 type. Among them, 26 patients were treated with sacroiliac screws combined with external fixation (external fixator group) and the other 30 patients underwent sacroiliac screw fixation combined with anterior screw fixation (pubic ramus screw group). Postoperative complications, postoperative ambulation time, fracture healing, blood loss, Majeed pelvic function score and visual analogue scale(VAS) were compared between two groups.</p><p><b>RESULTS</b>Fifty-four patients were followed up from 3 to 24 months with a mean of 12 months. There were no significant difference in the peri-operative bleeding and operation time between two groups(>0.05). The postoperative activity time and fracture healing time of pubic ramus screw group were shorter than those of the external fixator group, the differences were statistically significant(<0.05). The Majeed score, VAS score of pubic ramus screw group were higher than those of the external fixator group, the differences were statistically significant(<0.05). The incidence of postoperative complications of pubic ramus screw was lower than that of the external fixator group, the difference was statistically significant (<0.05).</p><p><b>CONCLUSIONS</b>Percutaneous iliosacral screws fixation combined with the pubic ramus screw is an effective and safty treatment method to the Tile B pelvic fracture. It has advantages of early ambulation, relief of the pain and few complications.</p>

Molecular mechanism of total flavonoids in Isodon amethystoides on adjuvant arthritis in rats / 中国中药杂志

Our preliminary study showed that the total flavonoids in Isodon amethystoides(TFIA), a local medicinal herb in Suzhou, had a certain therapeutic effect on adjuvant arthritis, and this therapeutic effect may be achieved through the up-regulation of miR-152 expression. In this paper, the molecular mechanism of TFIA on the pathogenesis of adjuvant arthritis(AA) rats was further studied. AA rats were prepared with complete Freund's adjuvant, and then treated with TFIA by intragastric administration. Real-time qPCR was used to detect the effects of TFIA on the negative regulatory loop of miR-152, methylase DNMT1 and methyl-CpG binding protein MeCP2 in fibroblast like synoviocytes(FLS) of AA rats, as well as the effects of TFIA on the classic Wnt signaling pathway and the expression of fibronectin gene in AA rats. Intragastric administration of TFIA significantly inhibited the expression of DNMT1 and reversed the negative regulatory loop composed of miR-152, DNMT1 and MeCP2 in the pathology of AA rats. After transfection of miR-152 inhibitors into the FLS in treatment group, DNMT1 expression was significantly restored. TFIA significantly up-regulated the expression of SFRP4 and inhibited the expression of β-catenin, C-myc and ccnd1, the key genes of canonical Wnt signaling pathway. TFIA also significantly inhibited the expression of fibronectin, an AA gene. The effect of TFIA on the expression of SFRP4, β-catenin, C-myc, ccnd1 and fibronectin was reversed after transfection with miR-152 inhibitors in the treatment group FLS. TFIA may inhibit the DNMT1 expression, up-regulate the SFRP4 expression, inhibit the expression of classical Wnt signaling genes β-catenin, C-myc, and ccnd1 as well as the RA gene fibronectin expression through the up-regulation of miR-152 expression.