Diabetic nephropathy (DN) is a chronic microvascular disease mainly secondary to diabetes. Its pathogenesis is affected by gene polymorphism, environmental factors, and so on. More and more studies have shown that epigenetic regulation mechanism without gene sequence changes plays an important role in occurrence and development of DN. The epigenetic regulation mechanism changes dynamically with the change of the surrounding environment. Transient environmental change, such as short-term high glucose, can lead to epigenetic regulation mechanism changes, affect histone exposed amino acid residue modification, DNA methylation level, etc., regulate the expression of related genes, and eventually promote the pathophysiological changes such as inflammation, hyperplasia and fibrosis. More interestingly, although the environmental stimulus disappeared, the epigenetic influence triggered by the initial stimulus still existed, with the phenomenon of "metabolic memory", suggesting that the change of epigenetic mechanism related to environmental stimulation may be the fundamental reason for the continuous progress of complications in diabetes patients, so effective intervention at the level of epigenetic mechanism also reveals new clinical therapeutic targets. The role of epigenetic regulation in the occurrence and development of DN has been reviewed in present paper, including epigenetic differences in DN, and the role of these differences-mediated signal pathway changes on kidney disease, and pay attention to the progress of epigenetic mechanism in treatment of the diseases, so as to provide a basis for clinical diagnosis and treatment of DN through epigenetic mechanism.

Since the outbreak of the coronavirus disease 2019 (COVID-19), machine learning has been widely used in forecasting the epidemic trend of COVID-19, screening and tracking high-risk people, early diagnosis and monitoring of patients, etc., which has greatly improved the efficiency of information processing during the epidemic period and provided efficient decision support for clinicians. However, due to the different data types and scales and training methods used to develop models, machine learning that perform diagnosis or prognosis tasks also have different limitations. This review introduces the application of machine learning in the diagnosis and prognosis of COVID-19 from the aspects of machine learning combined with imaging data, laboratory results, and the model trained by integrating these two aspects, trying to provide more practical ways for machine learning in training and application.

With aging of population and improvement of medical technology, the number of elderly patients receiving surgical treatment is increasing. Cardiovascular events after noncardiac surgery are one of the leading causes of death. Perioperative cardiovascular events have a high risk and incidence rate, thus severely affecting the prognosis of patients. In recent years, a growing number of studies have focused on the prevention and treatment of perioperative cardiovascular events in elderly patients. Assessing the risk of perioperative cardiovascular events and using effective interventions can effectively reduce the incidence of cardiovascular events and improve the prognosis of elderly patients. This article discusses cardiovascular risk assessment and management in elderly patients during noncardiac surgeries from the perspective of preoperative, intraoperative, postoperative periods, and perioperative medication used to provide assistance to clinical practice.

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.

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.

Currently, the bacillus Calmette-Guerin (BCG) is the only licensed vaccine against tuberculosis, but its protective effect is highly controversial. Therefore, it is particularly important to develop a new and effective tuberculosis vaccine. Meanwhile, with the in-depth understanding of the pathogenic mechanism of Mycobacterium tuberculosis and the continuous update of vaccine research and development technology, there will be a major breakthrough in tuberculosis vaccine. Considering the safety, economic cost and protective effect, multi-stage antigen subunit vaccine or multi-epitope vaccine has good application prospects. This paper systematically reviews the types and characteristics of current tuberculosis vaccines, and discuss the problems and challenges in four aspects: antigen selection, animal model selection, the evaluation indicators of vaccine efficacy and the population specificity in the research of new tuberculosis vaccines, which lays a theoretical foundation for the research of new tuberculosis vaccine.

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.

Objective To investigate the effect and mechanism of berberine (BBR) on the activity and proliferation of hepatoma cells. Methods Normal human hepatocytes (MIHA) and human hepatoma cells (Hep3B, HepG2) were respectively divided into control group (high glucose) and different concentration (0, 12.5, 25, 50 μmol/L) of BBR groups (glucose-free). CCK-8 and clone formation experiment were used to explore the effect of BBR on the viability and clone formation. SYTOX Green nucleic acid stain was used to determine the cell death and flow cytometry to detect the changes in reactive oxygen species (ROS) levels in hepatoma cells. The changes of Nrf2 and its related proteins after BBR incubation were measured by Western blotting. We incubated the proteasome inhibitor MG132 and the protein synthesis inhibitor cycloheximide (CHX) with BBR to study its effect on the Nrf2 protein. We quantified the expressions of Nrf2 and HO-1 in Hep3B cells cultured with BBR using Quantitative real-time PCR (qRT-PCR). We established a tumor model by subcutaneous injection of Hep3B cells into nude mice. To observe the effect of BBR on tumor growth, we injected tumor-bearing nude mice in the BBR groups and the control group with BBR or the same amount of normal saline, respectively. We evaluated the effect of BBR on Nrf2 and its related proteins in vivo with HE and immunohistochemical staining. Results The viability of Hep3B and HepG2 cells decreased after BBR incubation in a glucose-free environment (P<0.05). No appreciable changes were observed in MIHA cell viability under the same experiment condition. BBR could inhibit clone formation and promote the death of hepatoma cells in a concentration-dependent manner (P<0.05). We observed an increase in the ROS and a decrease in Nrf2, HO-1, and c-Myc with no significant change in Keap1 in hepatoma cells after BBR treatment. While total GSK3β remained unchanged, the treatment-induced decrease in P-GSK3β (Ser9) decreased but increase in P-GSK3β (Tyr216). MG132 co-treatment reversed the BBR-induced reduction of Nrf2 protein while CHX enhanced the BBR-induced reduction of Nrf2 protein in hepatoma cells. BBR treatment-induced increase in Nrf2 mRNA and a decrease in HO-1 mRNA (P<0.05). BBR could significantly inhibit the growth of Hep3B cells in vivo in nude mice. BBR treatment increased tumor tissue necrosis and suppressed the expression of Nrf2 and c-Myc but did not affect the Keap1 level. Conclusions BBR could inhibit the activity and proliferation of hepatoma cells and promote cell death. In vivo experiments showed that BBR injection could significantly inhibit the growth of tumor cells and lead to increased necrosis of tumor cells. We verified that BBR may lead to the death of hepatoma cells through the non-Keap1-dependent Nrf2/GSK3β pathway. We infer that the degradation of Nrf2 protein through the ubiquitin-proteasome system by the non-Keap1-dependent Nrf2/GSK3β pathway, thereby reducing the anti-oxidative stress ability of tumor cells and leading to the death of hepatoma cells ultimately.

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.

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.