Myocardial fibrosis is a common pathological process from various cardiovascular diseases to heart failure, and multiple signal pathways are jointly involved in the development and progression of myocardial fibrosis. AMP-activated protein kinase (AMPK) is a trimer complex widely distributed in human body, which is a central regulator of energy homeostasis involving the regulation of various metabolic responses and signaling pathways in vivo. AMPK interacts with the network of signal pathways related to myocardial fibrosis and jointly mediates the complex pathophysiological changes of myocardial fibrosis. Intervention of AMPK signal pathway provides a new therapeutic idea for the prevention and treatment of myocardial fibrosis. This paper summarizes the role and possible mechanisms of AMPK in different diseases related to cardiac fibrosis. The mutual effects of AMPK in several signaling pathways is also discussed; then further talks about the potential correlations between three kinds of commonly used clinical drugs and AMPK aiming to provide a new idea for the clinical treatment of myocardial fibrosis.

Exosomes are microcapsules with a diameter of 30-150 nm, which contain such active substances as proteins,lipids, metabolites, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and promote tumorigenesis and development by mediating intercellular communication and regulating tumor microenvironment. miRNAs and lncRNAs are the important components of non-coding RNAs, which play an important role in the occurrence and development of breast cancer mediated by exosomes. The present paper mainly summarized the role of exosomal miRNAs and lncRNAs derived from breast cancer cells in breast cancer progression, microenvironment and drug resistance, the effects of exosomal miRNAs and lncRNAs derived from breast cancer microenvironment on the development of breast cancer, and the clinical potential of exosomal miRNAs and lncRNAs as biomarkers in breast cancer.

Reticulophagy is a process that selectively clears endoplasmic reticulum through autophagy. Selective degradation of stress endoplasmic reticulum and aggregate-prone proteins is important to maintain endoplasmic reticulum homeostasis.Reticulophagy receptors mediate selective recognition of endoplasmic reticulum by autophagosomal membrane to promote the elimination of endoplasmic reticulum by lysosome. Reticulophagy is associated with human diseases, therefore, further investigation is required to reveal its molecular mechanism. This review focuses on the most recent advances related to mechanisms and physical relevance of reticulophagy.

Irritable bowel syndrome (IBS) is the most common functional bowel disease, and diarrhea-predominant IBS(IBS-D) is the most common type of IBS in our country. There are many causes of IBS, among which abnormal bile acid metabolism and intestinal flora disorder are the main pathogenic factors. Abnormal bile acid metabolism and intestinal flora disorders are found in patients with IBS-D. Intestinal flora is critical in the regulation of bile acid synthesis. Disorders of intestinal flora may lead to abnormal bile acid metabolism. Studies have pointed out that bile acid pathway (farnesoid X receptor, FXR) agonists can improve IBS-D symptoms by regulating receptor bile acid metabolism and intestinal flora. The interaction and corresponding mechanism of bile acid-intestinal flora and IBS-D were summarized in present paper.

In recent years, there have been increasing reports of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and myelin oligodendrocyte glycoprotein-antibody disease (MOG-Ab disease) appearing simultaneously or sequentially in the same patient. Some scholars have collectively referred to this kind of disease as the overlapping syndrome of MOG-Ab disease and anti-NMDAR encephalitis (MNOS). The clinical manifestations, treatment and prognosis of these syndromes are different from simple anti-NMDAR encephalitis or MOG-Ab disease. However, due to lack of understanding, clinicians tend to diagnose these syndromes as simple anti-NMDAR encephalitis or MOG-Ab disease, resulting in delayed the disease and affected prognosis. In order to strengthen the understanding of MNOS, this paper reviews MNOS from etiological hypothesis, characteristics of affected population, clinical manifestations, imaging manifestations, antibody characteristics in disease progression and treatment, so as to provide reference for the diagnosis and treatment in the future.

Objective To investigate the effect of rehmannia polysaccharide on the renal injury in offspring of pregnant mice with hyperthyroidism, and on regulating the signaling pathway of nuclear factor E₂-related factor (Nrf2)/heme oxygenase(HO-1)/Nod-like receptor protein 3 (NLRP3). Methods Fifty-six female kunming mice pregnant successfully were randomly divided into normal group (n=12), model group (n=12), positive control group (n=10), rehmannia polysaccharide low-dose group(n=11) and rehmannia polysaccharide high-dose group (n=11) to establish pregnancy with hyperthyroidism model. The positive control group was given methimazole 5 mg/kg intragastric administration, and the low and high dose groups were given rehmannia polysaccharide 20 and 40 mg/kg intragastric administration respectively, once a day, until delivery. The body weight of female mice was measured, and the contents of free triiodothyronine (FT₃), free thyroxine (FT₄) and thyroid stimulating hormone (TSH)in the serum were detected by ELISA. Kidney tissue of young mice was observed by HE staining. The contents of urea nitrogen(BUN) and creatinine (Cr) in the serum of the young mice were detected by automatic biochemical analyzer. Superoxide dismutase(SOD) activity, malondialdehyde (MDA) content, interleukin (IL)-1β and IL-18 content were detected by ELISA, and the relative expression levels of Nrf2, HO-1 and NLRP3 proteins were detected by Western blotting. Results HE staining showed that the renal tubules and glomerulus in model group were disorganized, the basement membrane thickened significantly, large number of red blood cells infiltrated, and endothelial cells were edema. Compared with model group, the kidney tissue lesion reduced obviously in positive control group and rehmannia polysaccharide low and high dose group. The body weight of mice was significantly lower in model group than that in normal group, while was significantly higher in positive control group and rehmannia polysaccharide low-dose and high-dose groups than that in model group with statistical significance (P<0.05). ELISA results showed that the contents of FT₃ and FT₄ were significantly higher in model group than that in normal group, while the TSH content was significantly lower in model group than that in normal group (P<0.05). The contents of FT₃ and FT₄ were lower, while TSH content was higher in positive control group and rehmannia polysaccharide low-dose and high-dose groups than those in model group with statistical significance(P<0.05). The contents of BUN and Cr were higher in offspring of model group than those in normal group, while were lower in positive control group and rehmannia polysaccharide low-dose and high-dose groups than those in model group with statistical significance (P<0.05). ELISA results showed that the contents of MDA, IL-1β and IL-18 were higher, while SOD activity was lower in offspring of model group than that in normal group. The contents of MDA, IL-1β and IL-18 were lower, while SOD activity was higher in positive control group, low-dose and high-dose rehmannia polysaccharide groups than those in model group with statistical significance (P<0.05). Western blotting showed that the expression levels of Nrf2 and HO-1 were lower and NLRP3 was higher in model group than those in normal group. The expression levels of Nrf2 and HO-1 were higher, while NLPR3 was lower in positive control group and rehmannia polysaccharide low-dose and high-dose groups than those in model group with statistical significance(P<0.05). Conclusion Rehmannia polysaccharide can improve the thyroid function of pregnant mice with hyperthyroidism and protect their offspring from kidney damage, and Nrf2/HO-1/NLRP3 pathway may play such a role.

Objective To investigate the interaction between staphylococcal nuclease domain containing protein 1 (SND1)and tissue differentiation-inducing non-coding RNA (TINCR), and the effect of SND1 on TINCR expression level and keloid growth. Methods Keloid tissue samples (n=27) were collected from patients with Ⅱ- or Ⅲ-degree burns who received treatment in Shaanxi Provincial People's Hospital from June 2016 to May 2018. Bioinformatics methods were used to predict RNA methylation sites in TINCR sequences; human primary normal skin fibroblasts (HFs) and keloid fibroblasts (KFs) were cultured and divided into HFs group and KFs group. KFs in logarithmic growth phase were taken, and divided into: (1) control group, empty vector group and methyltransferase-like protein 3 (METTL3) overexpression group, (2) control group and 3-deazaadenosine (DAA) group, and(3) control group, SND1 recombinant proteome group and SND1 proteome+DAA group. The relative expression level of TINCR in HFs and KFs was determined by real-time quantitative PCR (RT-qPCR); methylated RNA immunoprecipitation (MeRIP) followed by RT-qPCR was performed to analyze the methylation levels of TINCR; Western blotting was used to detect the relative expression levels of SND1 and METTL3 protein; the half-life of TINCR was determined by actinomycin D treatment combined with RT-qPCR,and the cell proliferation capacity was assessed with CCK-8 and clone assays. A keloid xenograft model was generated with 18 BALB/c nude mice, and then randomly divided into three groups (6 mice in each group): keloid group, keloid+SND1 recombinant protein group, and keloid+SND1 recombinant protein+DAA group. Keloid tissue growth was observed by HE staining; the expression level of SND1 in keloid tissue was detected by immunohistochemistry staining and Western blotting. Results The third exon of TINCR contains seven potential RNA methylation sites. The relative expression level and methylation level of TINCR elevated obviously in KFs than in HFs (5.43±0.35 vs. 1.00±0.11, P<0.01; 19.73%±1.56% vs. 10.25%±1.13%, P<0.01), and the protein levels of SND1 and METTL3 in KFs were significantly increased (P<0.01), methylated TINCR could bind both SND1 and METTL3. Compared with empty vector group, overexpression of METTL3 stimulated the mRNA and protein expression of METTL3 (mRNA: 6.03±0.55 vs. 1.09±0.09, P<0.01; protein: 4.33±0.35 vs. 0.96±0.08, P<0.01) and increased the methylation level of TINCR (32.89%±2.88%vs. 19.04%±1.72%, P<0.01) and relative expression level (4.65±0.32 vs. 1.00±0.10, P<0.01). Compared with control group,DAA treatment reduced the stability [(8.50±1.13) h vs. (12.90±1.41) h, P<0.001] and the methylation level (7.43%±0.55% vs.18.88%±1.76%, P<0.01) of TINCR, and inhibited the viability and clonogenic ability of KFs (P<0.01). Compared with control group, SND1 recombinant protein treatment increased the stability of TINCR [(23.95±1.25) h vs. (13.10±1.33) h, P<0.01],cell viability and clonogenic ability (P<0.01), but showed no significant effect on TINCR methylation levels (20.15%±1.74% vs.19.04%±1.77%, P>0.05); DAA treatment may abolish the effect of SND1 recombinant protein on TINCR stability [(12.00±1.21) h vs. (23.95±1.44) h, P<0.01], cell viability and clonogenic ability (P<0.01). Compared with the keloid group, a large number of fibroblasts and collagen fibers existed in the dermal layer of keloid+SND1 recombinant protein group. Furthermore, the percentage of positive SND1 cell and the relative expression level of protein in keloid tissue increased significantly (63.43%±3.32% vs.21.16%±4.67%, P<0.01; 2.54±0.13 vs. 1.00±0.10, P<0.01); However, DAA treatment made large amount of loose fibrous collagen in keloid tissue, and the percentage of positive SND1 cells and the relative expression level of protein decreased significantly(38.52%±6.88% vs. 63.43%±3.32%, P<0.01; 1.07±0.09 vs. 2.54±0.13, P<0.01). Conclusion TINCR is hypermethylated in KFs. SND1 can recognize and bind the methylation sites of TINCR, accelerate the stability of TINCR and promote the growth of TINCR mediated keloid.

Objective To investigate the effects of different target hypothermia on the cardiovascular function and prognosis of rats after cardiopulmonary resuscitation. Methods A total of 44 male SD rats were induced with electrical stimulation to ventricular fibrillation (VF) for 8 minutes, then cardiopulmonary resuscitation (CPR) was performed for 8 minutes followed by electric defibrillation (DF). Totally 28 SD rats survived VF, and randomized into either 37 ℃ normothermia group, 35 ℃hypothermia group, 33 ℃ hypothermia group or 28 ℃ hypothermia group (7 each) after restoration of autonomic circulation(ROAC). Hypothermia was immediately induced with surface cooling to the target temperature. The target temperature was maintained for 4 hours before rewarming to (37±0.2) ℃. Survived animals were observed for up to 72 hours. Mean aortic pressure(MAP), ejection fraction (EF), heart rate (HR), blood lactate level (Lac), microcirculation of buccal flow (MBF), duration of survival, survival rate and neurological deficit score (NDS) were measured during hypothermia and post-rewarming. Results During CPR, there were no difference in coronary perfusion pressure (CPP), times of DF, duration of VF-ROAC (P>0.05). During hypothermia treatment, the slowest HR was observed in the 28 ℃ hypothermia group, and the highest HR was observed in the 37 ℃ normothermia group; The levels of MAP and EF were higher in hypothermia groups than in normothermia group, among which the EF level (%) was obviously higher in 33 ℃ hypothermia group and 28 ℃ hypothermia group than in 35 ℃ hypothermia group [(63.8±6.1, 67.8±8.4)% vs. (54.0±5.2)%, P<0.05]; the Lac level was markedly lower in 33 ℃ hypothermia group and 35 ℃ hypothermia group than in 37 ℃ normothermia group and 28 ℃ hypothermia group (P<0.05); the MBF levels were lower in hypothermia groups than in normothermia group, while no statistical significant difference existed in MBF level among the 3 hypothermia groups (P>0.05). After rewarming, the EF level was markedly higher in 35 ℃ hypothermia group than in the 33 other groups [(52.9±3.3)% vs. (46.9±6.2, 38.5±7.5, 35.8±7.3)%, P<0.05]; MBF was obviously recovered in 33 ℃ and 35 ℃hypothermia groups compared with that in 28 ℃ hypothermia group [(2.8±0.4, 2.4±0.5) vs. (1.6±0.6), P<0.05], but no difference existed between 33 ℃ and 35 ℃ hypothermia group. The duration of survival, survival rate and NDS score were much better in 33 ℃ and 35 ℃ hypothermia groups than in 28 ℃ hypothermia groups and 37 ℃ normothermia group, but no difference between 33 ℃ and 35 ℃ hypothermia groups (P<0.05). Conclusions Hypothermia therapy with 33 ℃ and 35 ℃ target temperature may protect the blood circulation function of rats after CPR, reduce nerve function injury and improve prognosis. Hypothermia therapy with 35 ℃ target temperature might be a new choice for treatment of patients with clinical cardiac arrest after recovery.

Objective To explore the effect of the maximum dilatation pressure of percutaneous transluminal angioplasty(PTA) balloon on the patency rate of arteriovenous fistula stenosis within 12 months after PTA, and screen out the independent risk factors that affect restenosis after PTA. Methods A hundred patients, admitted and successfully undergone PTA in the Department of Nephrology, the Third Hospital of Hebei Medical University during January to December 2019, were recruited as the subjects, and of them the basic information, primary medical history, comorbidities, related serological indicators and types of fistula stenosis were collected. The internal fistula patency of patients for 12 months after PTA surgery was traced and collected through outpatient or telephone follow-up. According to the maximum pressure required to expand the stenosis during the operation, the patients were divided into high-pressure group (the maximum balloon pressure required to expand the stenosis ≥20 atm) and low-pressure group (the maximum balloon pressure required to expand the stenosis <20 atm), The basic information, primary medical history, comorbidities, related serological indicators and postoperative patency rate were compared between the two groups, and the risk factors leading to restenosis of internal fistula after PTA were analyzed by COX survival analysis. The receiver operating characteristic (ROC) curve was employed to evaluate the predictive value of the maximum balloon inflation pressure for restenosis within 12 months after PTA. Results A total of 100 patients were enrolled in present study, including 48 males and 52 females with average age of (53.21±15.75) years, the median dialysis age at PTA of 24.0 (12.0, 49.5) months, and the median duration of fistula of 12.6 (5.1, 37.4) months. All patients were completely followed up. The rates of diabetic kidney disease in primary diseases,hypertension and the restenosis rate within 12 months after PTA were higher in high-pressure group than those in low-pressure group with statistically significance (P<0.05). The patency rate within 12 months after PTA was higher in low-pressure group than that in high-pressure group (Log-rank test, χ²=5.399, P=0.020). Cox multivariate survival analysis showed that the maximum expansion pressure required to expand the stenosis and hypomagnesemia were the independent risk factors for restenosis after PTA(P<0.05). ROC curve analysis showed that the area under the curve (AUC) of the maximum balloon inflation pressure during PTA was 0.619 (95%CI 0.496-0.742, P<0.05), which has diagnostic value. The best critical value for the maximum balloon dilatation pressure was 19atm, the sensitivity was 60.5%, and the specificity was 66.1%. Conclusions Patients who require higher expansion pressure during PTA are more likely to have restenosis within 12 months after PTA. The maximum expansion pressure required to expand the stenosis during PTA and hypomagnesemia are the independent risk factors for patency after PTA.

Objective To detect the expression level of cell division cycle gene 20 (CDC20) in prostate cancer (PC) tissues and analyze the effect on the clinicopathological characteristics and prognosis of PC patients. Methods To collect the prostatic tissues of 134 PC patients and benign prostate hyperplasia tissues of 134 patients with benign prostate hyperplasia who underwent surgical treatment in the 988th Hospital of Joint Logistics Support Force from January 2016 to December 2018. qRT-PCR, Western blotting and immunohistochemical method were used to detect the expression of CDC20 in PC tissues and benign prostate hyperplasia tissues. According to the immunohistochemical score, the PC patients were divided into CDC20 high expression group(n=69) and CDC20 low expression group (n=65). The clinicopathological characteristics, 3-year overall survival rate and disease progression-free survival rate were compared between the two groups. Cox regression analysis were performed to analyze the risk factors affecting the survival of patients after surgery. Results The results of qRT-PCR and Western blotting showed that the relative expression levels of CDC20 mRNA and protein were higher in PC tissues than in benign prostate hyperplasia tissues with statistically significant difference (mRNA: 1.96±0.34 vs. 0.37±0.12, P=0.003; protein: 1.02±0.08 vs. 0.15±0.06, P<0.001). The immunohistochemical test results showed that the positive expression rate and high expression rate of CDC20 were higher in PC tissues than in benign prostate hyperplasia tissues [CDC20 positive expression rate: 80.6% (108/134) vs. 8.9% (12/134), P<0.001;CDC20 high expression rate: 51.5% (69/134) vs. 0.0% (0/134), P<0.001]. The 3-year overall survival rate and disease progression-free survival rate were lower in CDC20 high expression group than in CDC20 low expression group with statistically significant difference [3-year overall survival rate: 69.6% (48/69) vs. 87.7% (57/65), P=0.012; 3-year disease progression-free survival rate: 62.3% (43/69) vs. 80.0% (52/65), P=0.020]. Gleason score >7 points, cT stage >cT_2c stage, T stage >T₂ stage, and CDC20 immunohistochemical score ≥8 points were independent risk factors affecting postoperative survival of PC patients (P<0.05). Conclusions The increased expression of CDC20 in PC tissue might mean the progress of PC. CDC20 immunohistochemical score ≥8 points suggests a poor prognosis for patients, so is expected to become a tumor marker for judging the prognosis of PC.