Latest ArticlesObjective To observe the effect of gestational weight gain (GWG) on glucose metabolism and pregnancy outcomes in patients with gestational diabetes mellitus (GDM). Methods The clinical data of 1667 single pregnant women with GDM diagnosed in the Department of Obstetrics and Gynecology of the Sixth Medical Center of Chinese PLA General Hospital from January 2019 to December 2021 were collected and retrospectively analyzed. According to the degree of GWG, all the GDM pregnant women were divided into three groups: little weight gain group (n=882), moderate weight gain group (n=566)and excessive weight gain group (n=219). The levels of glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), fasting insulin (FIN), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), homeostasis model assessment β cell function(HOMA-β) and neonatal birth weight were compared among the three groups. Logistic regression was used to analyze the correlation between GWG and adverse pregnancy outcomes. Results The levels of HbA1c, FPG, FIN, HOMA-IR and HOMA-β in excessive weight gain group were significantly higher than those in little weight gain group and moderate weight gain group (P<0.05),and the levels of FIN, HOMA-IR and HOMA-β in little weight gain group were significantly lower than those in moderate weight gain group (P<0.05). The neonatal birth weight in excessive weight gain group was significantly higher than that in little weight gain group and moderate weight gain group (P<0.05), and the neonatal birth weight in little weight gain group was significantly lower than that in moderate weight gain group (P<0.05). Logistic regression analysis showed that both excessive weight gain and little weight gain were independent factors of hypertensive disorders of pregnancy (HDP), macrosomia and large for gestational age (LGA)(P<0.05). Conclusion Irrational weight gain during pregnancy may increase the incidence of glucose metabolism disorders and adverse pregnancy outcomes in pregnant women with GDM.
Objective To investigate the effect and mechanism of fenvalerate (Fen) on testosterone synthesis in Leydig cells of rats testis. Methods Leydig cells of SD rat testis were isolated and purified by differential adhesion method, then treated with 0, 25, 50 and 100 μmol/L Fen for 1, 12 and 24 h, and the level of testosterone was detected by ELISA. Set blank control group(treatment with 0.1% DMSO), Fen exposure group (treatment with 100 μmol/L Fen), Fen+NAC group (treatment with 100 μmol/L Fen and 5 mmol/L NAC), Fen+CsA group (treatment with 100 μmol/L Fen and 2 mmol/L CsA), and cultured for 24 h after administration. The changes of cellular reactive oxygen species (ROS) and mitochondrial membrane potential were detected by flow cytometry, the levels of testosterone, glutathione (GSH) and cAMP were detected by ELISA, and the content of ATP was detected by chemi-luminescence, Western blotting was used to detect the expressions of superoxide dismutase (SOD), steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) and cytochrome P450 cholesterol side-chain cleavage(CYP11A1). Results 100 μmol/L Fen treatment for 24 h was selected in the experiments. Compared with blank control group, the testosterone synthesis level, the contents of GSH, SOD, ATP and cAMP, mitochondrial membrane potential, and the relative expression levels of StAR, 3β-HSD and CYP11A1 decreased significantly in Leydig cells of Fen exposure group (P<0.01), the ROS content increased significantly (P<0.01). Compared with Fen exposure group, the testosterone synthesis level, the contents of GSH, SOD, ATP and cAMP, mitochondrial membrane potential, and the relative expression levels of StAR, 3β-HSD and CYP11A1 increased significantly in Leydig cells of Fen+NAC group and Fen+CsA group (P<0.05 or P<0.01), the ROS content decreased significantly (P<0.01). Conclusion Fen may cause mitochondrial damage in Leydig cells by inducing oxidative stress, resulting in the inhibition of ATP and cAMP synthesis, thereby inhibiting the expression of testosterone synthesis related proteins and enzymes dependent on cAMP/PKA signaling pathway, and ultimately leading to testosterone synthesis disorder in Leydig cells.
Objective To investigate the role and mechanism of circRNA BRAF_2 in proliferation and apoptosis of placental trophoblast cells in preeclampsia (PE). Methods Placental tissues of pregnant women with normal pregnancy and PE were collected (n=21) in the General Hospital of Ningxia Medical University from January 2018 to February 2019. The expression level of circRNA BRAF_2 in placental tissues of the two groups was detected by qRT-PCR, and the correlation between circRNA BRAF_2 expression level and blood pressure was analyzed. Human placental trophoblast cell lines (HTR8-S/Vneo) were cultured in vitro, (1) Cells were divided into control group and hypoxia group, and the expression of circRNA BRAF_2 were detected by qRT-PCR. (2) HTR8-S/Vneo was transfected with circRNA BRAF_2 lentivirus empty vector and circRNA BRAF_2 overexpression lentivirus, and then divided into control group, circRNA BRAF_2 negative control group and circRNA BRAF_2 overexpression group. The overexpression of circRNA BRAF 2 was verified with qRT-PCR. (3) Based on the successful transfection of circRNA BRAF_2 overexpressing lentivirus, the cells were divided into control group, circRNA BRAF_2 negative control group, circRNA BRAF_2 overexpression group, hypoxia group, hypoxia +circRNA BRAF_2 negative control group, and hypoxia +circRNA BRAF_2 overexpression group. EdU and CCK-8 methods were used to detect the proliferation. Flow cytometry was used to detect the changes of apoptosis level. Western blotting was used to detect the expression levels of apoptosis-related proteins caspase-3, caspase-9,Bcl-2 and Bax. qRT-PCR was used to detect the expression levels of circRNA BRAF_2 in HTR8-S/Vneo cytoplasm and nucleus.Bioinformatics analysis was performed to screen out the miRNA that might bind circRNA BRAF_2 and detect their expression levels in tissues and cells. Results Compared with normal pregnancy group, the expression level of circRNA BRAF_2 was significantly decreased in placenta of PE group (P<0.001), and of circRNA BRAF_2 was negatively correlated with systolic pressure and diastolic pressure (r=-0.4531, P<0.01; r=-0.4381, P<0.01). qRT-PCR showed that compared with control group, the expression level of circRNA BRAF_2 in hypoxia group was significantly decreased (P<0.01), and the relative expression level of circRNA BRAF_2 in negative control group showed no significant difference when ompared with control group (P>0.05). Compared with that in circRNA BRAF_2 negative control group, the circRNA BRAF_2 expression level increased significantly in circRNA BRAF_2 overexpression group (P<0.001). The detection results of EdU and CCK-8 showed that, compared with control group, the percentage of positive EdU cells decreased significantly (P<0.001) in hypoxia group, trophoblast proliferation ability decreased (P<0.001); Compared with the hypoxia +circRNA BRAF_2 negative control group, the percentage of EdU positive trophoblast cells increased significantly in hypoxia +circRNA BRAF_2 overexpression group (P<0.001), and the proliferation ability of trophoblast cells was significantly enhanced (P<0.001). The detection results of flow cytometry showed that, compared with control group, the apoptosis rate of hypoxia group increased obviously (P<0.001); Compared with the hypoxia +circRNA BRAF_2 negative control group, the apoptosis rate of the hypoxia + circRNA BRAF_2 overexpression group decreased significantly (P<0.001). Western blotting showed that compared with control group, the relative expressions of caspase-3, caspase-9 and Bax proteins increased (P<0.01 or P<0.001), and of Bcl-2 protein decreased (P<0.01) in hypoxia group; Compared with the hypoxia + circRNA BRAF_2 negative control group, the relative expressions of caspase-3, caspase-9 and Bax proteins decreased (P<0.001 or P<0.01), and of Bcl-2 protein increased (P<0.05) in hypoxia + circRNA BRAF_2 overexpression group. The results of qRT-PCR showed that circRNA BRAF_2 was expressed mainly in cytoplasm, and bioinformatics analysis showed that binding sites existed between circRNA BRAF_2 and miR-7855-5p. and miR-7855-5p was highly expressed in PE placental tissue than that in normal pregnancy group (P<0.05); Compared with control group, miR-7855-5p was obviously highly expressed in hypoxia group (P<0.001). Conclusion circRNA BRAF_2 can promote proliferation and inhibit apoptosis of PE placental trophoblast cells, and the mechanism may be related to miR-7855-5p.
Perioperative hypothermia is not rare in surgical patients, and is closely related to a variety of complications,which is not conducive to postoperative recovery of patients. At present, many studies focus on the risk factors, adverse outcomes and prevention strategies of perioperative hypothermia, and few studies analyze the changes of perioperative hypothermia from a multidimensional perspective. By summarizing and analyzing the previous research results, this paper reviews the physiology of body temperature, perioperative hypothermia, perioperative monitoring and maintenance of body temperature, and the new opinions and derived parameters of perioperative hypothermia, which is expected to bring some new perspectives for researchers and clinicians to develop better strategies for the prevention and treatment of perioperative hypothermia.
Cardiac arrest (CA) induced by army combat trauma is a specific type of traumatic cardiac arrest. Since it is inextricably intertwined with tactical combat casualty care (TCCC), the diagnosis and therapeutic strategy is dependent on various stages, i.e., care under fire/threat, tactical field care, and tactical evacuation care. In addition, active abdominal compression-decompression cardiopulmonary resuscitation (AACD-CPR) should be considered among patients with lung, pleural and heart injury resulted from chest trauma. Moreover, portable ultrasound to identify reversible etiologies in CA should be highlighted.
Objective To compare the differences between exosomes derived from three-dimensional (3D) cultured human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and conventional (2D) cultured hUC-MSCs in promoting osteoblast differentiation, and to explore the application possibility of exosomes derived from 3D-cultured hUC-MSCs in treatment related to promoting bone formation. Methods hUC-MSCs were divided into 2D group and 3D group, and cultured respectively.The morphological characteristics of the both groups were observed under optical microscope, and the viability of 3D-cultured hUC-MSCs was detected by calcein AM/PI double staining of living and dead cells. Transcriptome sequencing was performed to screen the differentially expressed genes between 2D group and 3D group, and GO enrichment analysis was conducted. Exosomes of 2D group and 3D group were extracted and divided into 2D-Exo group and 3D-Exo group. Characterization of exosomes was conducted by transmission electron microscope, nanoparticle tracking analysis and Western blotting. The exosomes excreted by 2D group and 3D group were applied to C57BL/6J mouse calvarial osteoblasts, respectively, and osteogenic differentiation was induced in vitro. The effects of exosomes cultured in 2D and 3D on osteogenic differentiation were identified by alizarin red staining, alkaline phosphatase staining and RT-qPCR. Results Comparing to 2D group, cells in 3D group were equal in size and grew into spherical shape. 3D-cultured hUC-MSCs showed higher rate of viability verified by calcein AM/PI double staining of living and dead cells.Transcriptome sequencing results showed that the up-regulated genes in 3D group were enriched in bone mineralization, cartilage development, composition of extracellular matrix, osteoblast differentiation, angiogenesis, cell proliferation and gene expression.The down-regulated genes were enriched in negative regulation of cell proliferation, cell migration, and apoptotic process, etc.Transmission electron microscope observation showed that the exosome diameter in both 2D-Exo group and 3D-Exo group were around 100 nm and exhibited typical cup shape features, and expressed exosome related marker proteins CD9, CD63 and CD81.Staining results of osteoblasts in calvaria of newborn rats showed that the number of calcium nodules stained with alizarin red and the intensity of alkaline phosphatase staining increased significantly in 3D-Exo group than in 2D-Exo group. Results of RT-qPCR showed that the relative expression levels of osteogenic differentiation related genes Bglap, Runx2, Alp, Col1a1 and Spp1 mRNA increased significantly in 3D-Exo group than in 2D-Exo group with statistically significant differences (P<0.05). Conclusion Exosomes from 3D-cultured hUC-MSCs can up-regulate the expressions of osteogenic genes Bglap, Runx2, Alp, Col1a1 and Spp1,and have stronger capabilities to promote osteogenic differentiation compared with 2D-cultured exosomes.
Bullet vascular embolism is a serious complication of firearm injury, which is caused by military weapons in wartime and civil guns in peacetime. However, small caliber bullets and small mass fragments are mostly used in military weapons now, which makes it more likely that bullets/fragments will be left in the body, leading to a higher incidence of bullet vascular embolism. Therefore, the incidence of bullet vascular embolism in wartime in the future would be higher than it in the past. Bullet vascular embolism after firearm injury is more harmful to human body, and more emergency treatment is needed. This article reviews the mechanism, vulnerable vessels, embolization types, diagnostic methods and treatment points of bullet vascular embolism, so as to provide reference for clinical diagnosis and treatment of bullet vascular embolism.
Objective To investigate the effect and the underlying molecular mechanism of zinc finger protein Zpr1 on differentiation and the insulin signaling pathway of pre-adipocytes. Methods A high-fat diet-induced insulin resistance mouse model (IR group, n=7) was established by feeding 8-week-old C57BL/6J male mice using high-fat feed for 16 weeks, with conventional diet feeding mice as control group (n=7). Glucose tolerance and insulin tolerance tests were used to observe the blood glucose values of mice in each group and verify the insulin resistance phenotype of mice in the induction group. Western blotting and RT-PCR were performed to detect the protein and mRNA expression of Zpr1 in subcutaneous and visceral adipose tissue from high-fat diet induced insulin resistance mice and regular diet mice. Bioinformatic prediction combined with dual-luciferase reporter gene system were employed to detect the influence of single nucleotide polymorphism (SNP) rs964184 GG genotype and CC genotype in human ZPR1 against miR-4286 binding to the 3'UTR of ZPR1. After mouse preadipocyte 3T3-L1 transfected with miR-4286 simulant to observe the effect of miR-4286 regulating Zpr1 expression on adipocyte differentiation and insulin signaling pathway. Results The protein and mRNA expression levels of Zpr1 decreased obviously in the subcutaneous and especially in the visceral adipose tissues of high-fat diet induced insulin resistant (IR) mice compared with the mice in control group (P<0.05, P<0.01).The rs964184 SNP locus of ZPR1 made it difficult that ZPR1 3'UTR forms a multi-hairpin structure, but may promote miR-4286 to recognize and bind to ZPR1 3'UTR. The miR-4286 level increased obviously in subcutaneous and especially in visceral adipose tissues of IR model group mice (P<0.05); meanwhile, the protein expression level decreased of Zpr1 in mouse pre-adipose cells 3T3-L1 regulated by miR-4286 simulacrum (P<0.05). At the same time, after transfection of miR-4286 simulacrum, the expression levels of fat cell differentiation and insulin signaling pathway-related proteins PPAR-γ, Perilipin A, pAkt, and IRS-1 in 3T3-L1 cells were reduced markedly (P<0.05). Conclusions The GG genotype rs964184 locus can promote the post-transcriptional regulation of Zpr1 by miR-4286. The decreased expression of Zpr1 can inhibit the differentiation of 3T3-L1 preadipocytes and interfere the insulin signaling pathway.
Objective To investigate the early diagnosis value of neutrophil-side-fluorescence intensity (NE-SFI) on heat stroke (HS)-related disseminated intravascular coagulation (DIC). Methods According to the International Society of Thrombosis and Haemostasis (ISTH) scoring criteria, thirty-four HS patients admitted to the General Hospital of Southern Theater Command from January 1, 2017 to December 31, 2018 were selected and divided into HS without DIC group (DIC score <5 points, n=23)and HS with DIC group (DIC score ≥5 points, n=11). The patient's general information, NE-SFI, and neutrophil extracellular traps (NETs)-related markers such as, dsDNA (double-stranded DNA), myeloperoxidase (MPO) and citrullinated histone (CitH3)were compared between the two groups. Receiver operating characteristic (ROC) curve was used to analyze the early diagnostic value of NE-SFI in HS with DIC. Results There was no significant difference in age, maximum body temperature, white blood cell count and neutrophil count between the two groups (P>0.05). The proportion of patients in the HS with DIC group whose core temperature dropped below 38.5 ℃ within 3 hours and the GCS (Glasgow Coma Scale) score were lower than those in the HS without DIC group, while the alanine aminotransferase (ALT), creatinine, ISTH (International Society of Thrombosis and Haemostasis) score, and the proportion of concurrent multiple organ dysfunction syndrome (MODS) in the HS with DIC group were higher than those in the HS without DIC group (P<0.05). On the 1st to 3rd day of onset, the NE-SFI values of the HS with DIC group were higher than those of the HS without DIC group (P<0.001). Compared with the serum dsDNA, MPO, and CitH3 in HS without DIC group [respectively (30.14±7.01) ng/ml, (56.39±34.64) pg/ml, (320.26±89.60) ng/μl], the serum dsDNA, MPO and CitH3 levels in HS with DIC group [respectively (372.93±135.77) ng/ml, (108.32±38.58) pg/ml, (600.18±183.74) ng/μl]are significantly increased (P<0.001). Spearman correlation analysis showed that the value of NE-SFI on day 1-3 were positively correlated with the levels of dsDNA, MPO and CitH3 on day 1 (P<0.05 or P<0.01). ROC curve analysis showed that NE-SFI on day 2 had a high value for the early diagnosis of HS complicated with DIC, and its AUC was 0.921 (95%CI 0.820-1.000, P<0.001). Conclusion NE-SFI can be used as an effective indicator for the early diagnosis in HS complicated with DIC.
Chronic hepatitis C virus (HCV) is a worldwide epidemic and the main cause of liver cirrhosis and hepatocellular carcinoma (HCC). The anti-HCV treatment has gone through two eras of pegylated interferon-α plus ribavirin (PR therapy) and direct-acting antiviral agent (DAA). Generally, achieving a sustained virological response (SVR) can reduce the incidence of HCC through antiviral treatment. In recent years, increasing researchers pay more attention to the issue whether DAA treatment might increase the risk of HCC occurrence or recurrence. This article aims to review the related studies on the risk of HCC after PR therapy and DAA treatment, summarize the risk factors, and explore the mechanism of HCC and its impact on the efficacy of DAA, in order to help clinicians to determine the timing of initiation of antiviral therapy and provide clinical evidence for individualized management.