Ischemic heart disease (IHD) is one of the diseases with the highest mortality in the world, which endangers human health for a long term. Reperfusion, the preferred treatment strategy, can lead to myocardial deterioration and accelerate injury, known as myocardial ischemia-reperfusion injury (MIRI), which seriously affects the clinical efficacy and prognosis of patients. At present, the prevention and treatment of MIRI is still an unsolved clinical problem. Numerous studies have shown that adaptor protein p66Shc plays an important regulatory role in the occurrence and development of various diseases, including MIRI.The mechanism of adaptor protein p66Shc involved in oxidative stress, inflammatory response and vascular endothelial function in MIRI, and the relevant treatment strategies targeting p66Shc were reviewed in present paper in order to provide a reference for further research on prevention and treatment of MIRI.

Objective 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 (HbA_1c), 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 HbA_1c, 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.

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 investigate the effect of early injection of umbilical cord mesenchymal stem cells (UC-MSCs)on the progression of diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM) mice and its mechanism. Methods Twenty 5-week-old male db/db mice were used to establish T2DM model and randomly divided into stem cell treatment group(MSCs group, n=10) and T2DM group (DM group, n=10); In addition, age-matched db/m mice were set as normal control group(NC group, n=10). Human UC-MSCs (1×10⁶/0.2 ml saline) were infused into the tail vein of mice in MSCs group for 6 weeks,while the same volume of saline was infused into the tail vein of mice in NC and T2DM groups once a week for 6 consecutive times. Blood glucose and body weight of mice in each group were monitored weekly. At the end of the sixth treatment, the mice in each group were killed by heart perfusion, and the blood and kidney tissues were collected for biochemical and histopathological examination. Western blotting was used to detect the expression of silent information regulator 2 homolog 1 (SIRT1) and Claudin-1,and immunohistochemistry was used to detect the expression of SIRT1, Claudin-1, type 1 collagen (Col Ⅰ) and Col Ⅳ. The morphology of glomeruli was observed by electron microscope. HK-2 cells in logarithmic growth phase were divided into control group, high glucose induced model group (HG group), high glucose induced siRNA group (HG+siRNA group), MSC groups(HG+MSC group) and SIRT-1 siRNA group (HG+MSC+siRNA group). The expression levels of apoptosis-related proteins were detected by Western blotting. Results After the sixth treatment, compared with NC group [(7.66±0.37) mmol/L], the levels of blood glucose increased significantly (P<0.01) in T2DM group and MSCS group [(32.54±0.36) mmol/L, (29.74±1.04)respectively]; Compared with T2DM group, the level of blood glucose in MSCs group decreased significantly (P<0.05).Pathological results showed that compared with NC group, glomerular sclerosis, diffuse thickening of basement membrane and renal interstitial fibrosis were significantly increased in T2DM group; compared with T2DM group, glomerular sclerosis, deposition of mesangial extracellular matrix and renal interstitial fibrosis were alleviated in MSCs group. The results of Western blotting and immunohistochemistry showed that compared with T2DM group, the expression level of SIRT1 protein in MSCs group increased significantly (P<0.01), the expression of Claudin-1 protein decreased significantly (P<0.01), and of α-smooth muscle actin (α-SMA)protein decreased significantly in MSCs group (P<0.05). In addition, the immunohistochemical results showed that the percentage of Col Ⅰ and Col Ⅳ positive area in MSCs group was significantly lower than that in T2DM group (P<0.01). Compared with NC group, T2DM group showed marked destruction of glomerular filtration barrier, diffuse thickening of basement membrane, and extensive fusion and disappearance of foot processes. Compared with T2DM group, the structure of glomerular foot process in MSCs group was regular and complete. Western blotting results showed that SIRT-1 protein content was significantly lower in HG group than that in control group (P<0.01), while apoptosis-related Cytochrome-C protein contents were significantly higher in HG group than that in control group (P<0.01). Compared with HG group, the protein content of SIRT-1 in HG+MSC group was significantly higher (P<0.01), and the content of apoptosis-related Bax and Cytochrome-C protein decreased significantly (P<0.01).Compared with HG+MSC group, the protein content of SIRT-1 in HG+MSC+siRNA group was significantly decreased (P<0.01),while the protein content of apoptosis-related Bax and Cytochrome-C increased significantly (P<0.01). Conclusion UC-MSCs treatment may play a protective role for kidney of T2DM mice and delay the development of DN by up-regulating the expression of SIRT1 and down-regulating the expression of Claudin-1.

Mucosal-associated invariant T (MAIT) cells are evolutionarily conservative and non-conventional innate T cell subsets, having the characteristics of both innate and adaptive immune cells. They have antibacterial and tissue repair functions,and are the important part of the immune system. MAIT cells are highly abundant in human liver and play a complex role in various liver diseases. Current studies have shown that the markedly reduced number of MAITs and the dysfunction of immunomodulatory effect in various liver diseases were closely related to the occurrence and progression of liver diseases. This paper mainly reviews the characteristics of MAIT cells and their latest progress in chronic viral hepatitis, autoimmune liver disease, non-alcoholic fatty liver disease, alcoholic liver disease and hepatocellular carcinoma, and further discuss the potential mechanisms underlying the loss of MAIT cells, so as to provide some references for follow-up research.

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 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.

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 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.