Ginsenoside Rg1 induces ferroptosis by regulating the focal adhesion kinase/protein kinase B-forkhead box O3A signaling pathway and alleviates sepsis-induced myocardial damage.

It is significant to note that 50% of patients with sepsis show cardiac insufficiency. Ginsenoside-Rg1 (G-Rg1) has been shown to have a cardiovascular protective effect. However, whether G-Rg1 is involved in the mechanism of action of sepsis-induced myocardial damage (SIMD) is unclear. This study aimed to investigate the protective effect of G-Rg1 on SIMD and to further investigate its mechanism and mechanisms of regulation of downstream pathways. An in vivo model of sepsis was established in mice by cecal ligation and puncture (CLP), and mice was administered intraperitoneally 35 or 70 mg/kg G-Rg1 after surgery. The damage to cardiac tissue was detected by hematoxylin and eosin (HE) staining. Forkhead transcription factor O subfamily member 3a (FOXO3A) in SIMD mice was detected by immunohistochemistry. Apoptosis in mouse myocardial tissue was determined by TUNEL staining. The effect of G-Rg1 on SIMD cardiomyocytes was evaluated by incubating the cells with lipopolysaccharide to induce inflammation as an in vitro model of SIMD. Cardiomyocyte viability and apoptosis were evaluated by cell counting kit-8 (CCK-8) and flow cytometry. Lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and Fe2+ markers of heart damage were detected by the kit. The concentrations of tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1ß) in heart tissue and H9c2 cells were determined by ELISA. The factors related to the focal adhesion kinase (FAK)/protein kinase B (AKT)-FOXO3A signaling pathway were determined by RT-qPCR and Western blot. High-dose G-Rg1 had a significant inhibitory effect on SIMD mouse model and lipopolysaccharide (LPS)-induced H9c2 cardiomyocytes, reducing serum levels of LDH, CK-MB, and cTnI concentrations, which effectively alleviated SIMD. G-Rg1 restored the abnormally elevated levels of TNF-α, IL-1ß, and iron ions and promoted the expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) expression, inhibiting apoptosis and inflammatory responses. In addition, G-Rg1 reversed the inhibitory effect of G-Rg1 on LPS-induced H9c2 cardiomyocyte injury through activation of the FAK/AKT signaling pathway and up-regulation of FOXO3A. G-Rg1 promoted the activation of the FAK/AKT signalling pathway and up-regulation of the protein expression levels of pathway-associated proteins, p-FAK and p-AKT. Therefore, G-Rg1 mediated the FAK/AKT-FOXO3A signaling pathway and played a role in the treatment of SIMD. We conclude that G-Rg1 inhibited apoptosis and inflammation of cardiomyocytes induced by sepsis and reduced iron ion levels by regulating FAK/AKT-FOXO3A signaling pathway.

[Clinical study on the effects of global end-diastolic volume index-directed fluid resuscitation on the prognosis of chronic heart failure patients with septic shock].

Objective: To investigate the effect of global end-diastolic volume index (GEDI)-guided fluid resuscitation on the prognosis of patients with chronic heart failure and septic shock. Methods: This study was a prospective randomized controlled study. Consecutive eligible patients were divided into 2 groups according to the random number table method: control group (n=21) and experimental group (n=20). On the basis of routine treatment, patients in the control group received early goal-directed therapy until the central venous pressure (CVP) reaching 8-12 mmHg (1 mmHg=0.133 kPa), mean arterial pressure reaching over 65 mmHg, urine volume reaching over 0.5 ml·kg(-1)·h(-1), and central venous oxygen saturation reaching more than 70%. On the basis of routine treatment, patients in the experimental group were monitored continuously on cardiac output with pulse indication and fluid resuscitation guided by volume index GEDI. The GEDI should be maintained on the range of 680-800 ml/m(2). The remaining resuscitation goals were the same as control group. General clinical data of the two groups were collected at admission. Negative fluid balance onset time, duration of mechanical ventilation, ICU mortality and 28-day mortality were compared between the two groups. The outcomes were recorded as listed: start time of negative fluid balance, duration of mechanical ventilation, mortality in ICU and 28-day mortality. Results: There was no significant difference in age, sex, weight, APACHE Ⅱ score, SOFA score and NYHA functional class score between the two groups (all P>0.05). The negative liquid balance onset time in the control group was 3.5 (2.5, 4.0) days, which was significantly longer than that in the experimental group (2.6 (2.0, 3.0) days,U=115.0, P=0.012). The duration of mechanical ventilation was 355 (118, 552) hours in the control group, which was significantly longer than that in the experimental group (132 (36.75, 233.3) hours, U=130, P=0.038). The ICU mortality was 38.1% (8/21) in the control group, tended to be higher than that in the experimental group (20.0%(4/20), χ(2)=1.620, P=0.203). The 28-day mortality was 42.9% (9/21) in the control group, similar as in the experimental group (25.0%(5/20), χ(2)=1.482,P=0.477). Conclusion: Fluid resuscitation guided by volume index (GEDI) may improve the prognosis of patients with chronic heart failure complicated with septic shock.

LncRNA HOTAIR contributes to the tumorigenesis of nasopharyngeal carcinoma via up-regulating FASN.

OBJECTIVE: The therapeutic options for nasopharyngeal carcinoma (NPC) treatment have been restricted mainly to radiotherapy or chemotherapy, and the clinical treatment effect remains unsatisfactory. The primary purpose of this study was to investigate the molecular mechanisms of NPC and to find effective novel therapeutic targets for NPC. PATIENTS AND METHODS: In order to analyze the expression level of lncRNA HOTAIR and FASN in human NPC clinical tissues or NPC cells, total RNA was extracted with TRIzol and the relative mRNA expression levels were detected by quantitative Real-time PCR. The endogenous expression of HOTAIR was modulated using lentivirus vectors transfection. The protein levels of Fatty acid synthase (FASN), p21 and MMP-9 in NPC cells were determined by Western blot when HOTAIR was knockdown. A free Fatty acid quantitation assay was performed to detect the intracellular free Fatty acid in NPC cells. The CCK-8 and colony formation assays were performed for cell viability and proliferation determination. The cell cycle of NPC cells was also determined by flow cytometric analysis. A matrigel invasion assay was performed to analyze the invasive ability of NPC cells. RESULTS: In this study, we observed a significant upregulation of lncRNA HOTAIR in NPC cells and clinical NPC specimens. The expression of Fatty acid synthase (FASN) was positively correlated to HOTAIR in NPC specimens. Knockdown of HOTAIR led to downregulation of FASN in NPC cells, thus suppressing cell proliferation and invasion. Additionally, de novo synthesis of cellular free fatty acid in NPC cells was inhibited when HOTAIR was knockdown. Furthermore, the protein levels of MMP-9 and p21 were downregulated when HOTAIR was knockdown. CONCLUSIONS: We suggest that HOTAIR is important in the progression and recurrence of NPC, perhaps through upregulating FASN. Targeting HOTAIR may be an effective therapeutic strategy for NPC.

[Experimental study on the pathogenesis of Entamoeba gingivalis].

OBJECTIVE: To study the pathogenesis of Entamoeba gingivalis (E. g.) and its relation to periodontal diseases. METHODS: Rats were treated with immuno-inhibitor for one week and the neck of incisor teeth of the rats was bound with steel wire. They were randomly divided into three groups: the first group was infected by E. g. in the periodontal tissue, the second group was infected by symbiotic bacteria (s. b.), and the third group was given physiological saline as control. Observation on the periodontal inflammation was made for each group of rats, and the purulent secretion from periodontal abscess was examined for living pathogens. RESULTS: The incidence of periodontal diseases in rats infected by E. g. was higher than that of symbiotic bacteria group and that of control (P < 0.05), the incidence of periodontal diseases in rats infected by s. b. was higher than that of control group (P < 0.05). Living pathogens were found in the abscess liquid. CONCLUSION: E. g. is an opportunistic pathogen, which, together with synergistic symbiotic bacteria, can cause periodontal diseases in hosts with low immunity.

[An experimental study on the relationship between the estimation of early postmortem interval and DNA content of liver cells in rats by image analysis].

15 rats were used in this experiment. After rats were killed, cells of liver were collected, smeared, fixed with Formalin in every hour within the first 24 hours then stained with Feulgen's method, With an auto-TV-image system, mean and integral optical density and abnormal index of cell DNA were measured and analyzed statistically. The results showed that the DNA degeneration rate of liver cells had a linear relationship to early postmortem period in rats.

Indoor radon measurements in the Beijing area.

Average indoor air radon concentration of 30 Bq/m3 was determined in various types of dwellings in the Beijing area using activated carbon detectors. In this study, several related factors were also investigated: radon area exhalation rates of 136 building materials and from soil surfaces; Ra-226 contents of 143 soil samples, 34 building materials and 28 coal samples; and radon concentrations in gaseous fuel, outdoor air and drinking water. The magnitude and relative importance of different sources in terms of indoor radon are discussed, compared and evaluated. The results show that the underlying soil and building materials are important sources of indoor radon. Cracks in floors or walls are major pathways for the entry of radon into houses. Measurements of the annual effective dose equivalent from radon daughters for different types of aboveground and underground buildings gave average values of 1.1 and 1.5 mSv, respectively.

Indoor 222Rn measurements in the region of Beijing, People's Republic of China.

Passive integrating activated C detectors were used to study the regional distribution and temporal variation of 222Rn in indoor air in dwellings in the Beijing region. Measurements were made in 537 dwellings, which were either detached houses or multi-family apartments. The city-wide study was completed in 1985. The distributions are approximately log-normal with 90% of the dwellings having 222Rn levels less than 60 Bq m-3. The weighted average 222Rn concentration has been found to be 22.4 Bq m-3. Averages for detached houses and multi-family dwellings are 25.9 and 15.2 Bq m-3, respectively. Assuming an equilibrium factor of 0.5 and an occupancy factor of 0.8, the average equilibrium equivalent concentration of 222Rn progeny is 11.2 Bq m-3 and the annual average effective dose equivalent is 1.1 mSv.