Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common sleep disorder, which is caused by collapse and obstruction of upper airway during sleep, accompanied by snoring, daytime drowsiness and sleep structure disorder. OSAHS is closely related to cardiovascular disease, metabolic disorder, diabetes, cognitive impairment and tumors. The prevalence rate of OSAHS is relatively high, which significantly increases the social and economic burden. Therefore, early diagnosis and treatment of OSAHS is necessary. miRNA is a non-coding small RNA molecule, which can play important role in a variety of important biological functions by regulating the expression of target genes. In recent years, some studies indicated that miRNA could be used as a biomarker for early diagnosis of hypertension, coronary heart disease, diabetes and tumors. Recently, a large number of studies showed that miRNA can be used in diagnosis, assessment, and therapeutic target of OSAHS with its complications. This review summarizes the research progress on the role of miRNA in OSAHS with its complications.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (MTB) that seriously affects human health. As one of the TB high-burden countries worldwide, there is a need to strengthen the prevention and treatment of tuberculosis in China. It is estimated that the proportion of people with latent TB infection (LTBI) in China is close to 20% of the total population. Effective identification of LTBI, thus enabling early diagnosis and preventive treatment, is one of the key measures to control the TB epidemic. Existing methods of diagnosing TB infection are unable to distinguish LTBI from active TB (ATB), and cannot accurately predict progression of LTBI to ATB, while biomarkers are expected to have the potential in differentiating LTBI from ATB and predict progression. In this paper, we summarize the recent advances in biomarkers associated with LTBI and address the future development trends, in order to provide ideas for finding new markers for precisely identifying LTBI.

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.

Tuberculosis (TB) is still a big threat to public health. TB in newborns includes congenital TB and neonatal TB. Although not common, rapid progress and high mortality rates must attract the attention of clinicians. Congenital TB is transmitted vertically from mother, mainly acquired in utero through haematogenous spread via the umbilical cord or at the time of delivery through aspiration or ingestion of infected amniotic fluid or cervicovaginal secretions. Neonatal TB is acquired after birth through exposure to a person with infectious TB. It is often difficult to distinguish congenital TB and neonatal TB. But treatment and management is the same. This paper discusses the prenatal (epidemiology, early detection and reasonable treatment of TB in pregnancy) and postpartum (evaluation and treatment of newborns with high risk factors for TB) management of tuberculosis in newborns in order to provide useful information for clinicians to identify congenital tuberculosis and neonatal tuberculosis in the early stage and take reasonable and effective treatment measures as soon as possible.

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 analyze the value of tumor growth pattern (TGP) and tumor budding (TB) on judgment of the prognosis of patients with stage Ⅰ-Ⅲ colorectal cancer. Methods The clinical data of 152 patients with stage Ⅰ-Ⅲ colorectal cancer, admitted and undergone radical operation from December 2012 to June 2020 in Hainan Hospital of Chinese PLA General Hospital, were collected and retrospectively analyzed. TGP and TB were interpreted with HE staining and patients were divided into TGP-A (dilatant growth type and intermediate type) or B (invasive growth type), TB-low or TB-high subgroups. The differences of clinicopathological features among these subgroups were analyzed; Kaplan-Meier analysis was performed to analyze the disease-free survival (DFS) and overall survival (OS) of these subgroups. Finally, Cox proportional risk model was used to analyze the risk factors influencing prognosis of colorectal cancer patients. Results Statistical differences of tumor differentiation degree and N stage existed in TGP-A or TGP-B, TB-low or TB-high subgroups (P<0.01); in addition, the characteristics were more obvious of high CEA level (P=0.03), T₃+T₄ stage (P<0.01) and TNM Ⅲ stage (P<0.01) in TGP-B groups. Between TGP-A and TGP-B subgroups, and between TB-low and TB-high subgroups, the statistical significantly difference existed in DFS (TGP: Log-rank=10.06, P<0.01; TB: Log-rank=6.62, P=0.01) and OS (TGP: Log-rank=6.53, P=0.01; TB: Log-rank=4.90, P=0.03). TGP was an independent risk factor for both DFS (HR=2.95, 95%CI 1.54-5.63, P<0.01) and OS (HR=2.37, 95%CI 1.14-4.94, P=0.02). Conclusion Both TGP and TB were more reliable prognostic markers for patients with stage Ⅰ-Ⅲ colorectal cancer, the ones presented TGP with infiltrative pattern or TB ≥10/0.785 mm² would have poor prognosis.

Chemotherapy is the main treatment for triple-negative breast cancer (TNBC) due to the lack of effective targeted therapy. At present, neoadjuvant chemotherapy (NAC) is one of the standard treatment strategies. However, the response of patients to NAC is different, and how to identify effective or resistant individuals before treatment is an urgent clinical problem to be solved. The research progress on the prediction of NAC response for TNBC has many aspects, including imageomics, tumor immunology and genomics. Combining different factors to build a prediction model can better improve the prediction efficiency. With the development of gene detection technology, single-cell sequencing technology can exclude the influence of non-tumor cells in tumor microenvironment, accurately determine tumor subtypes, reveal drug resistance mechanisms, and may be applied to NAC in the future to improve the accuracy of prediction. This article reviews the latest research progress in predicting the efficacy of TNBC NAC.

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.

Traumatic brain injury (TBI) is a serious public health problem, and it is estimated that more than 50 million patients worldwide su ff ered from TBI each year. At present, the diagnosis of TBI mainly relies on scoring scales, and it is extremely necessary to screen objective biomarkers of TBI. A large number of studies have focused on the screening of protein markers of TBI, however, protein markers have short half-life and low sensitivity, so it is important to screen new biomarkers of TBI for its rapid diagnostic and treatment. As a lack of effective therapeatic drugs, TBI was mainly treated according to symptoms. microRNAs (miRNAs) are a class of small non-coding RNAs whose altered expression levels are associated with a variety of diseases in central nervous system including TBI and play an important role in the regulation of neuroplasticity and repair of neuronal damage. In addition, its small molecular weight make it crossing the blood-brain barrier conveniently and be easily detected in peripheral fluids. Therefore, miRNAs have the potential to be used as diagnostic markers and therapeutic targets for TBI. This paper aims to review the features of miRNAs and their applications on diagnosis and treatment of TBI, and provide a reference for their potential clinical applications.

Objective To investigate the effect and mechanism of mitochondrial translocation regulation of translocase of outer mitochondrial membrane 70 (Tom70) /polyribonucleotidyltransferase 1 (PNPT1) in hypoxic injury of rat myocardial cells. Methods (1) Rat H9C2 cardiomyocytes were divided into control group (treated with normoxia for 12 hours) and hypoxia group (treated with hypoxia for 12 hours). The apoptosis rate of cardiomyocytes was detected by flow cytometry, the expression of TUBA mRNA was detected by qPCR, and the expression of PNPT1 protein was detected by Western blotting. (2) H9C2 cells were infected with lentivirus vector carrying Tom70 sequence to up-regulate the expression of Tom70. The cells were then divided into NC group (lentivirus negative control group, containing lentivirus empty vector only), Tom70 over-expression group (lentivirus vector carrying Tom70 sequence), hypoxia+NC group, hypoxia+Tom70 over-expression group. Western blotting was used to detect the expression level of Tom70, PNPT1 protein in cells, and flow cytometry was used to detect the apoptosis rate of hypoxia+NC group and hypoxia+Tom70 over-expression group, the expression of TUBA mRNA in the hypoxia+NC group and hypoxia+Tom70 overexpression group were detected by qPCR, and the interaction between Tom70 and PNPT1 in the cells was detected by immunoprecipitation technique. Results (1) The results of flow cytometry showed that compared with control group, the apoptosis rate of myocardial cells in hypoxic group was significantly higher (P<0.05). The results of qPCR showed that compared with the control group, the content of TUBA mRNA in cells of hypoxia group was significantly decreased (P<0.05). Western blotting showed that compared with control group, the expression level of PNPT1 protein in mitochondria of hypoxic group was significantly decreased, while the expression level of PNPT1 protein in cytoplasm was significantly increased (P<0.05). (2) Western blotting showed that compared with control group and NC group, the expression of Tom70 in the Tom70 over-expression group was significantly increased (P<0.05); Under normal oxygen conditions, there was no significant difference in the expression of mitochondrial PNPT1 and cytoplasmic PNPT1 between NC group and Tom70 over-expression group; Under hypoxia condition, compared with hypoxia+NC group, the expression level of mitochondrial PNPT1 in hypoxia+Tom70 over-expression group was significantly higher, and the expression level of cytoplasmic PNPT1 was significantly lower (P<0.05). The results of immunoprecipitation showed that Tom70 and PNPT1 in cardiomyocytes could bind each other. The results of flow cytometry showed that compared with hypoxia+NC group, the apoptosis rate of hypoxia+Tom70 over-expression group decreased (P<0.05). The results of qPCR showed that compared with hypoxia+NC group, the content of TUBA mRNA in the hypoxia+Tom70 overexpression group increased (P<0.05). Conclusion Tom70 can alleviate hypoxic injury of rat myocardial cells by regulating the expression of PNPT1 mitochondria and reducing the degradation of apoptosis-related mRNA.