Objective To investigate the changes of posterior chamber intraocular lens (ICL-V4c) implantation on retinal and choroid thickness, retinal blood flow density in the macular area, and optic disc in ultra-high myopia using optical coherence tomography angiography (OCTA). Methods From April 2020 to May 2021, 15 patients (30 eyes) with binocular equivalent spherical lens (SE) ≥–10.00 D in Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled. All eyes had undergone the ICL-V4c treatment. We observed the visual acuity and intraocular pressure at the following time points: before the operation, 2-hour, 1-week, 1-month, and 9-month post-operation. OCTA was used to monitor the changes in retinal and choroid thickness in the macular area as well as retinal blood flow density around the macular area and optic disc. Results There was no statistically significant difference between uncorrected viusal acuity postoperative and best corrected viusal acuity preoperative at each time point after surgery (P>0.05). The postoperative intraocular pressure showed a downward trend, but the difference was not statistically significant. The vault at 9-month post-surgery was significantly lower than that at 1-week post-surgery, the difference was statistically significant (P=0.002). There were no statistically significant differences in deep retinal blood flow density, retinal thickness or choroid thickness in the macular area, blood flow density in the radial capillary network around the optic disc, and nerve fiber layer thickness at each postoperative time point (P>0.05). The superficial retinal blood flow density in the four directions of upper, lower, nasal, and temporal decreased significantly 2-hour after surgery, with statistical significance (P<0.05). With the extension of time, the blood flow density in each area increased significantly, and there was no statistical difference compared with that before surgery (P>0.05). Conclusion OCTA observation showed that ICL-V4c implantation had an effect on the superficial retinal blood flow density in the early stage of ultra-high myopia but would restored to the preoperative level during the time, and had no effect on the retinal choroid thickness in the remnant macular area, the blood flow density of the capillary network around the optic disc and the thickness of the nerve fiber layer.

Objective To evaluate the clinical effect of non-invasive prenatal testing (NIPT) by analyzing the efficiency of fetal chromosomal aneuploidy screening in Beijing. Methods The clinical data of 133 899 pregnant women, who underwent NIPT in eight prenatal diagnosis institutions of Beijing from January 2019 to December 2020, were collected and retrospectively analyzed. The test indications, results and prenatal diagnosis results were recorded. The positive rate of all pregnant women was calculated according to the test indications; According to the test results, it can be divided into trisomy 21 syndrome, trisomy 18 syndrome, trisomy 13 syndrome, sex chromosome abnormality, and other chromosome abnormalities. The prenatal diagnosis rate, positive rate, positive predictive value (PPV), sensitivity and specificity were calculated. Results Among the NIPT screening indicators, the detection rate of elderly pregnant women was the highest, accounting for 34.0% (45 509/133 899), followed by voluntary requirements, accounting for 32.7% (43 860/133 899). There were 1647 cases with high risk of NIPT, the positive rate was 1.2% (1647/133 899), and the positive rate of NT thickening and ultrasound structure abnormal were the highest in pregnant women. One thousand three hundred and forty-eight cases received prenatal diagnosis. The highest prenatal diagnostic rate was trisomy 18 reached to 91.5% (130/142), the lowest was the rate of sex chromosome abnormality reached to 76.4% (488/639). The overall prenatal diagnostic rate was 81.8% (1348/1647). The positive rates of trisomy 21, trisomy 18, trisomy 13, sex chromosome abnormality and other chromosomes abnormality were 0.2% (318/133 899), 0.1% (142/133 899), 0.1% (77/133 899), 0.5%(639/133 899) and 0.4% (471/133 899), respectively. The positive predictive values were 71.1% (226/318), 38.0% (54/142), 18.2%(14/77), 31.3% (200/639) and 17.8% (84/471), respectively. The sensitivity of trisomy 21, trisomy 18 and trisomy 13 was 98.7%, 96.4% and 100.0%, and all the specificity of was 99.9%. Conclusions The NIPT had high sensitivity and specificity but also still had the limitations of false positive and false negative. Therefore, prenatal diagnosis should be carried out for NIPT high-risk pregnant women, and it is important to strengthen the genetic counseling before and after testing.

Objective To observe the changes in depression-like behavior and cAMP-PKA-CREB-BDNF signaling pathway in the hippocampus of rats with mild brain blast injury (mbTBI) caused by blast shock wave, and to explore the mechanism of neurological dysfunction caused by mbTBI. Methods 44 male SD rats were randomly divided into control group and model group, 22 in each group. The rats in the model group were placed in a gridded iron cage, with the head facing the explosion center and fixed on the ground 15 m away from the explosion center in a fan shape. At the same time, the shock wave intensity at the location of the rats was detected. After the explosion, 7 rats in each group were randomly selected and fed in separate cages. Open field test and elevated plus maze test were used to evaluate the depression-like behavior of rats at 7, 14 and 28 d after exposure. The remaining rats in each group were randomly sacrificed at 7, 14 and 28 d after exposure. The hippocampus was removed and protein extracted. Western blotting was used to detect the relative expression of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB (p-CREB), brain-derived neurotrophic factor (BDNF) and oncogenic protein c-FOS. Results After the explosion test, all the rats in the model group survived, but within 24 hours, they were apathetic, slow in action and poor in appetite. After 72 hours, the above symptoms gradually eased. There was no significant difference in body weight between the two groups at each time point (P>0.05). The results of behavioral experiments showed that compared with the control group, the total moving distance, the residence time in the central area, the number of times and the proportion of time entering the open arm of the model group were significantly reduced at 14 d after the explosion test (P<0.05). The results of Western blotting showed that compared with the control group, the expression levels of PKA, CREB, pCREB and BDNF protein in the model group were significantly decreased at 7, 14 and 28 d after explosion test (P<0.05). Compared with the control group, the expression of cAMP and c-FOS in the model group was significantly decreased at 7 and 14 d after the explosion test (P<0.05), and there was no significant difference between the two groups at 28 d(P>0.05). Compared with 7 and 14 d after the explosion test, the expression levels of PKA, CREB and BDNF in the model group were significantly increased at 28 d after the test (P<0.05). Conclusion Single blast shock wave exposure can cause depression-like behavior changes in rats, which may be related to the down-regulation of the cAMP-PKA-CREB-BDNF signaling pathway.

Latent Mycobacterium tuberculosis infection (LTBI) is a reservoir for incident tuberculosis disease, and is a constant source of new patients. 5% to 10% of the LTBI patients will develop active tuberculosis in their lifetime, and the incidence rate is higher in high-risk population. The United Nations High-Level Meeting on Tuberculosis called for a focus on LTBI management to control in 2018, further could reduce the incidence of TB due to reactivation in patients with LTBI. This paper discusses the disease burden, epidemic status, patient management, and prevention strategies, providing reference for formulating LTBI prevention strategies in China.

Spinal cord injury (SCI) is a devastating neurological and pathological condition that causes severe motor, sensory, and autonomic nerve dysfunction. Although SCI has been treated with varying degrees of success, these treatments have not yet achieved satisfactory results because the pathological molecular mechanisms of SCI are not fully understood. Recent studies have shown that astrocytes can be activated into A1/A2 phenotypes after SCI. The A1 phenotype of reactive astrocytes plays a neurotoxic role, while the A2 phenotype of reactive astrocytes plays a neuroprotective role. A full understanding of the role and activation mechanism of A1/A2 reactive astrocytes in SCI is expected to provide new ideas for the treatment of SCI. This review focuses on the role of A1/A2 reactive astrocytes in SCI, the signaling pathways that regulate the activation of A1/A2 reactive astrocytes, and SCI therapy for astrocytes.

Objective To investigate the autophagy inducing effect of dihydroartemisinin (DHA) on prostate cancer PC-3 cells and its possible mechanism. Methods PC-3 cells were treated with 0, 12.5, 25, 50, 100 μmol/L of DHA. Cell viability was detected by CCK-8 method, and cell proliferation rate was detected by cell clone formation assay. Set control group, DHA group (50 μmol/L DHA for 48 h), 3-MA group (5 mmol/L 3-MA for 48 h) and DHA+3-MA group (50 μmol/L DHA+5 mmol/L 3-MA for 48 h), expressions of autophagy-related protein [microtubule associated protein light chain 3B (LC3B), yeast Atg6 homologue (Beclin-1)] were detected by Western blotting and RT-qPCR, the cell viability was detected by CCK-8 method, and the apoptosis rate was detected by flow cytometry, the formation of autophagosomes was observed by transmission electron microscope. PC-3 cells were transfected with the autophagy double labeled lentivirus mCherry-GFP-LC3B to detect the changes of autophagy flow. Set control group, DHA group (50 μmol/L DHA for 48 h), NAC group (5 mmol/L NAC for 48 h) and DHA+NAC group (50 μmol/L DHA+5 mmol/L NAC for 48 h), expressions of ROS/AMPK/mTOR signaling pathway related proteins were detected by Western blotting. After treated with 50 μmol/L DHA for 48 h, the total protein was extracted and divided into Input group (whole protein lysate), IP group (added with Beclin-1 antibody), and IgG group (added with the same mass of IgG), interaction between Beclin-1, Vps34, Bcl-2 and HMGB1 in PC-3 cells was detected by the Co-IP. Results CCK-8 assay showed that the survival rate of PC-3 cells was decreased with the increase of the concentration of DHA in a dose- and time-dependent manner (P<0.05). The half inhibitory concentration (IC₅₀) of DHA for 24 h, 48 h and 72 h were 97.12, 57.10 and 29.35 μmol/L, select 50 μmol/L DHA for 48 h for follow-up experiments. Cell clone formation assay showed that the colony formation rate of PC-3 cells decreased significantly with the increase of DHA concentration (P<0.01). Western blotting and RT-qPCR results showed that, compared with control group, the mRNA and protein expression levels of Beclin-1, LC3B increased in PC-3 cells of DHA group (P<0.01); Compared with DHA group, the mRNA and protein expression levels of Beclin-1 and LC3B significantly decreased in PC-3 cells of DHA+3-MA group (P<0.01). Transmission electron microscopy showed that there were obvious autophagosomes in PC-3 cells of DHA group, and the number of autophagosomes was significantly increased compared with control group (P<0.05). The results of mCherry-GFP-LC3B lentivirus transfection showed that the ratio of red and yellow spots per cell in DHA group was higher (P<0.01) and that in DHA+3-mA group was lower (P<0.01). Compared with DHA group, the survival rate of DHA+3-mA group decreased (P<0.05) and the apoptosis rate increased (P<0.01). Compared with DHA group, the expression levels of p-mTOR decreased in PC-3 cells of DHA group (P<0.05), the expression levels of p-AMPK increased (P<0.01); Compared with DHA group, the expression levels of p-mTOR increased in PC-3 cells of DHA+NAC group (P<0.05), the expression levels of p-AMPK decreased (P<0.01). The results of Co-IP experiments showed that the effect of Beclin-1 on Bcl-2 was weakened and the binding with Vps34 and HMGB1 was enhanced after DHA treatment. Conclusions DHA can induce autophagy in prostate cancer PC-3 cells. The mechanism may be related to the regulation of the autophagy-related genes Beclin-1, LC3 and ROS/AMPK/mTOR signaling pathways.

Objective To profile the high mobility group protein B1 (HMGB1) in exosomes derived from heat-stressed monocytes and its effect on endothelial cell inflammation. Methods The heatstroke model was established. The rats were divided into control group (n=6) and heatstroke group (n=6). Monocytes from blood were isolated and exosomes were extracted. Isobaric tags for relative and absolute quantification technology were used to identify the exosomal protein components, such as HMGB1, before functional description with annotation databases. Then, Western blotting and enzyme-linked immunosorbent assay (ELISA) were used to verify the changes of monocyte-derived exosomes HMGB1 in rats and patients. Umbilical vein endothelial cells (HUVECs) were treated with exosomes from rats in control group, heatstroke group and heatstorke+ethyl pyruvate group. The expression levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and interleukin-1β (IL-1β) were detected with RT-qPCR and Western blotting. HMGB1, NLRP3 and IL-1β expresion levels in exosomes of patient and healthy donors, were detected with ELISA. Results In heatstroke group, the number of exosomes (×10⁴/monocyte) derived from monocytes significantly increased than that in control group (11.24±2.66 vs. 1.52±0.21, P<0.001). Proteomic analysis showed that the expression of exosome HMGB1 in heatstroke group was up regulated than control group (18.63 times, P<0.001), and these proteins were enriched in NOD-like receptors and other signaling pathways. Western blotting showed that the relative expression of HMGB1 in exosomes of rats in heatstroke group was significantly higher than that in control group (4.13±0.22 vs. 1.00±0.15, P<0.001). ELISA also demonstrated that the level of HMGB1 in exosomes of patients in heatstroke group increased than that in control group [(0.29±0.11) ng/ml vs. (0.12±0.04) ng/ml, P=0.006]. qPCR and Western blotting showed that compared with control group, the mRNA and protein levels of NLRP3 and IL-1β in endothelial cells of heatstroke group were increased, which could be alleviated by the inhibitor of HMGB1, and the difference was statistically significant (P<0.05). Conclusion Heat stress increased the HMGB1 level in the monocyte-derived exosomes and might mediate endothelial cell inflammation via HMGB1.

Objective To investigate the effects of GCN5-mediated histone H3 acetylation (ac) on the proliferation, apoptosis and inflammatory factors of lipopolysaccharide (LPS) -induced alveolar epithelial cells. Methods A549 cells were randomly divided into 6 groups: control group, LPS group, NC+LPS group, GCN5+LPS group, MB-3 (GCN5 inhibitor) +LPS group and GCN5+MB-3+LPS group. Expression levels of H3K9ac, H3K14ac, H3K23ac, GCN5, and cell viability, cell proliferation, apoptosis, levels of inflammatory factors were compared between different groups. Quantitative polymerase chain reaction (qPCR) was used to detect the GCN5 mRNA expression; CCK-8 kit was used to detect cell viability; Cell proliferation was detected by EdU assay; apoptosis was detected by flow cytometry. The expression of GCN5, H3K9ac, H3K14ac, H3K23ac, Caspase-3 and Bcl-2 proteins were detected by Western blotting. The levels of inflammatory factors [interleukin (IL) -1β, IL-6 and tumor necrosis factor (TNF) -α] were determined by enzyme-linked immunosorbent assay (ELISA). Results Compared with control group, the levels of H3K9ac, H3K14ac and H3K23ac were decreased, the mRNA and protein expression of GCN5 were down-regulated, and the cell viability and proliferation were decreased, cell apoptosis was increased, Caspase-3 protein expression was up-regulated while Bcl-2 was down-regulated, the levels of inflammatory factors were increased in LPS group (P<0.05). Compared with the LPS group, no significant changes existed in the levels of the mRNA and protein expression of GCN5 in NC+LPS group (P>0.05), the mRNA and protein expression of GCN5 were up-regulated, the levels of H3K9ac, H3K14ac and H3K23ac were increased, and the cell viability and proliferation were increased, cell apoptosis was decreased, Caspase-3 protein expression was down-regulated while Bcl-2 was up-regulated, the levels of IL-1β, IL-6 and TNF-α were decreased in GCN5+LPS group (P<0.05). Compared with GCN5+LPS group, the levels of H3K9ac, H3K14ac and H3K23ac were decreased, and the cell viability and proliferation were reduced, cell apoptosis was elevated, the levels of IL-1β, IL-6 and TNF-α were increased in GCN5+MB-3+LPS group (P<0.05). Conclusion GCN5 overexpression could resist LPS-induced injuries of alveolar epithelial cells such as abnormal proliferation and apoptosis and inflammatory factors production, which could be related to the increase of histone H3 acetylation level.

Objective To explore establish a risk prediction model for patients with nonvalvular atrial fibrillation (NVAF) after ablation based on serum miRNA levels. Methods A total of 389 NVAF patients who received ablative therapy in the Second Affiliated Hospital of Fujian Medical University from August 2018 to December 2020 were selected as the study objects. 70.0% (272 cases) were randomly selected as the training set, 20.0% (78 cases) as the test set, and 10.0% (39 cases) as the verification set. The patients were followed up for 1 year, and the Kaplan-Meier cumulative recurrence risk curve was drawn. According to the recurrence of patients during the follow-up period, the patients were divided into recurrence group and non-recurrence group. The factors influencing the risk of recurrence after ablation in the training set of NVAF patients were explored through univariate and multivariate analysis, and the prediction model of recurrence risk after ablation was constructed. The prediction efficiency of this model was further tested by the consistency index (C-index) and receiver operating characteristic (ROC) curve. Then the model effectiveness of the test set is verified. Results As of December 21, 2021, a total of 30 cases were lost to follow-up (18 cases in the training set, 10 cases in the test set, and 2 cases in the validation set), and 359 actual cases were finally included (254 cases in training set, 68 in test set, and 37 in validation set). Of which 58 cases recurred in training set, and the recurrence rate was 22.8%. The baseline epicardial adipose tissue (EAT) volume was higher in recurrent group than that in non-recurrent group (P<0.05). The levels of miRNA-21, miRNA-150 and miRNA-192-5p in relapse group before and at the end of follow-up were higher than those in non-recurrence group, while the levels of miRNA-29 were lower than those in non-recurrence group with statistical significance (P<0.05). Multivariate logistic analysis showed that EAT volume (OR=1.060, 95%CI 1.012-1.109), miRNA-192-5p (OR=1.759, 95%CI 1.135-2.726), miRNA-21 (OR=32.508, 95%CI 9.224-114.577), miRNA-150 (OR=18.704, 95%CI 5.513-63.456) are independent risk factors for recurrence after ablation, miRNA-29b (OR=0.166, 95%CI 0.049-0.560) are protective factors for recurrence after ablation (P<0.05). Based on the above factors, the recurrence risk prediction model predicted that the C-index of NVAF patients after ablation was 0.929 (95%CI 0.890-0.958). ROC curve results of verification set showed that the specificity and sensitivity of this model were 83.2% and 88.0%, and the optimal critical value of area under ROC curve (AUC) was 0.711. The test data showed that the sensitivity, specificity and accuracy of the model were 86.7%, 88.7% and 88.3%. Conclusion The post-NVAF ablation recurrence risk model constructed by EAT volume, miRNA-192-5p, miRNA-29b, miRNA-21, miRNA-150 and other factors has a high predictive value for the recurrence risk after NVAF ablation.

Objective To explore the relationship between perioperative hemoglobin (HGB) concentration and acute kidney injury (AKI) after pulmonary lobectomy. Methods Patients, who received selective pulmonary lobectomy under general anesthesia in Peking University First Hospital from July 2017 to December 2019, were recruited and divided into low HGB group (HGB<120.0 g/L; n=230) and normal group (HGB≥120.0 g/L, n=1522) according to the HGB concentration before surgery. And the primary endpoint was the incidence of AKI after surgery. Multivariate logistic regression model was used to analyze the influence of preoperative HGB, minimum HGB concentration during surgery and the decrease of HGB concentration after surgery on postoperative AKI. Results A total of 1752 patients were involved in the study, and the overall incidence of postoperative AKI was 2.3%. The incidence of AKI was significantly higher in low HGB group than in normal group [5.7% (13/230) vs. 1.8% (28/1522), RR=3.197, 95%CI 1.631-6.266, P=0.001]. Multivariate logistic regression analysis showed that the risk of postoperative AKI increased to 3.590 (95%CI 1.765-7.303, P<0.001) times if preoperative HGB concentration being lower than 120.0 g/L, and that the risk of postoperative AKI increased to 2.751 (95%CI 1.633-4.635, P<0.001) times for every 15.0 g/L reduction of preoperative HGB. Moreover, the independent risk factors involved preoperative eGFR <60 ml/ (min.1.73 m²), intraoperative infusion rate <5 ml/ (kg·h) and intraoperative urine output <0.8 ml/ (kg·h) (P<0.05). In addition, multivariate logistic regression models also showed that minimum HGB concentration during surgery (OR=0.933, 95%CI 0.780-1.114, P=0.442) and the decrease of HGB concentration after surgery (OR=0.900, 95%CI 0.630-1.287, P=0.565) were not independent risk factors of postoperative AKI. Conclusion Preoperative HGB <120.0 g/L is an independent risk factor of postoperative AKI after pulmonary lobectomy.