Objective This study is to investigate the changes in the NFATc 4/3 signaling pathway in rat hippocampus after whole brain radiation. Methods A total of 120 one?month?old male Sprague?Dawley rats were randomly divided into four groups to receive whole brain radiation using 4?MeV electron beams with doses of 0( control) ,2,10,and 20 Gy,respectively,in a single fraction. At 6 hours,12 hours,1 day,3 days,1 week,and 2 weeks after radiation,Western blot and real?time PCR were used to evaluate the changes in expression levels of CaN, NFATc 4/3, p?NFATc 4/3, and GSK?3β. Results There were no significant changes in the expression of NFATc 4/3 or p?NFATc 4/3 at 6 and 12 hours after whole brain radiation. At 1 day after radiation,compared with the control group,the expression of p?NFATc 4/3 in the radiation groups was significantly increased in a dose?dependent manner ( 2 Gy:P= 0. 014;10 Gy:P=0. 011;20 Gy:P=0. 000 );however, there was no significant difference in the expression of NFATc 4/3 between the radiation group and the control group. The expression of NFATc 4/3 was significantly decreased in the radiation groups than in the control group at day 3 ( 2 Gy:P=0. 040;10 Gy:P=0. 000;20 Gy:P=0. 000),1 week (2 Gy:P=0. 692;10 Gy:P=0. 032;20 Gy:P=0. 021),and 2 weeks (2 Gy:P=0. 001;10 Gy:P=0. 000;20 Gy:P=0. 000) after radiation,while there was no significant difference in the expression of p?NFATc 4/3 between any two groups. There were no time?or dose?dependent changes in expression of CaN or GSK?3β. Conclusions Ionization radiation has an inhibitory effect on the NFATc 4/3 signaling pathway in rat hippocampus. Combined with our previous results,this study suggests that radiation?induced cognitive dysfunction is associated with the NFATc 4/3 signaling pathway.

This study was aimed to observe the effects ofTian-ShuDripping Pills (TSDP) on cerebral hemodynamics among anesthetized dogs, in order to demonstrate its clinical treatment functional correlation on angioneurotic headache. A total of 25 hybrid dogs were randomly divided into the normal saline (NS) group, TS capsule (positive control: 0.4 g·kg-1 crude medicine) group, low-dose TSDP (0.2 g·kg-1 crude medicine) group, middle-dose TSDP (0.4 g·kg-1 crude medicine) group, and high-dose TSDP (0.8 g·kg-1 crude medicine) group.Intraduodenal administration was given once under anesthesia. Changes of mean arterial blood pressure, blood flow of vertebral artery and internal carotid artery blood flow were detected and the cerebral blood flow and cerebral vascular resistance were calculated. The results showed that TSDP of low-dose, middle-dose and high-dose group can significantly reduce the cerebral vascular resistance and increase the cerebral blood flow within 180 min after medication. It was concluded that TSDP can improve the cerebral blood circulation of anesthetized dogs. Its mechanism may be through the reduction on cerebral vascular resistance and increasing of cerebral blood flow.

Objective To observe the incidence and clinical feature of sleep-related breathing disorder in patients with idiopathic pulmonary fibrosis (IPF). Methods Thirty-four IPF patients who were measured by polysomnography (PSG) were collected in the Department of Respiration of Tianjin Medical University General Hospital. According to the results of apnea hypoventilation index (AHI), patients were divided into pure IPF group (AHI<5 events/h, n=7) and IPF combined with obstructive sleep apnea hypopnea syndrome (IPF+OSAHS) group (AHI≥5 events/h, n=27). The PSG reports of two groups were analyzed, and the correlation between AHI and pulmonary function and oxygen saturation in sleep and at wake were analyzed. Results (1)Thirty-four IPF patients were all demonstrated sleep disorders, low sleep efficiency, increased proportion of stageⅠand stageⅡand decreased proportion of stageⅢand rapid eye movement (REM). The arousal index and the proportion of stageⅠand stageⅡwere higher in IPF+OSAHS group than those of pure IPF group (P<0.01), while the proportion of stageⅢwas lower in IPF+OSAHS group than that of pure IPF group (P<0.01). There was no significant difference in stage REM between two groups. (2)Twenty-seven patients (79%) combined with OSAHS, among which five subjects (15%) were mild OSAHS with 5 events/h≤AHI<15 events/h, and 22 subjects (65%) were moderate-severe with AHI≥15 events/h. The main type of sleep-disorder breathing was hypoventilation, which mainly happened in stage REM. (3) Thirty-four IPF patients showed sleep hypoxemia, and the oxygen desaturation index (ODI) was higher in IPF-OSAHS group than those of pure IPF group (P<0.05). (4)The AHI was positively correlated with body mass index (r=0.791, P<0.05), and was negatively correlated with forced vital capacity (FVC%pred) (r=-0.574, P<0.05) and forced expiratory volume in 1 second (FEV1%pred) in IPF patients (r=-0.664, P<0.05). The lowest oxygen saturation (LSO2) and mean oxygen saturation (MSO2) in sleep were positively related with oxygen saturation at wake (r=0.421 and r=0.464, P<0.05 respectively). Conclusion The IPF patients show severe sleep disorder and hypoxemia, which can be worsen by OSAHS and produce negative effect on daily life. We should initiate active treatment in patients with sleep-related breathing disorders.

Objective:To investigate the clinical outcomes of using the levofloxacin combined with intrauterine infusion of metronidazole for the treatment of the infertility patients with chronic endometritis (CE).Methods:Using a case-control study method. 82 infertility patients with CE admitted to Xuzhou Central Hospital from March 2018 to March 2021 were selected and randomly divided into an observation group and a control group using a random number table method, with 41 cases in each group. The control group was treated with oral levofloxacin hydrochloride, while the observation group was treated with metronidazole sodium chloride injection intrauterine infusion on the basis of the control group. Both groups were treated for 14 days. Compare the serum C-reactive protein (CRP) and tumor necrosis factor between two groups before and after treatment α(tumor necrosis factor-α, TNF-α) The levels of monocyte chemotactic protein 1 (MCP-1), natural pregnancy rate within six months, total effective rate, and incidence of adverse reactions during treatment were measured. The measurement data with normal distribution is expressed as: independent sample t-test is used for comparison between the two groups, and paired t-test is used for comparison before and after treatment within the group; The measurement data of non normal distribution is represented by M( Q1, Q3), and the comparison between groups is made by Wilcoxon Rank sum test. The counting data is represented by examples (%), and the comparison between groups is conducted using the χ 2 test. Results:Before treatment, two groups of serum CRP and TNF-α There was no statistically significant difference compared to the levels of MCP-1 (all P>0.05); After 14 days of treatment, both groups had serum CRP and TNF-α、MCP-1 were all lower than before treatment, and the observation group was lower than the control group [(4.12±1.9) ng/L vs (6.36±1.63) ng/L, (47.28±9.10) ng/L vs (62.79±9.34) ng/L, (212.04±24.82) ng/L vs (326.15±27.38) ng/L], with statistically significant differences ( t-values of 5.61, 7.62, and 19.77, all P<0.001). After 14 days of treatment, the total effective rate of the observation group was higher than that of the control group [95.12% (39/41) vs 78.05% (32/41)], with a statistically significant difference (χ 2=5.14, P=0.023). After 6 months of treatment, the natural pregnancy rate in the observation group was higher than that in the control group [53.66% (22/41) vs 31.71% (13/41)], with a statistically significant difference (χ 2=5.96, P=0.044). There was no statistically significant difference in the incidence of adverse reactions between the two groups during the treatment period (χ 2=0.55, P=0.457). Conclusions:The combination of levofloxacin and intrauterine infusion of metronidazole has a good clinical effect in treating infertility patients with CE. It can significantly improve the inflammatory state of the body, reduce serum inflammatory factor levels, increase the natural pregnancy rate within 6 months, and do not increase the incidence of adverse reactions.

Purpose: RIOK1 has been proved to play an important role in cancer cell proliferation and migration in various types of cancers—such as colorectal and gastric cancers. However, the expression of RIOK1 in breast cancer (BC) and the relationship between RIOK1 expression and the development of BC are not well characterized. In this study, we assessed the expression of RIOK1 in BC and evaluated the mechanisms underlying its biological function in this disease context. Materials and Methods: We used immunohistochemistry, western blot and quantitative real-time polymerase chain reaction to evaluate the expression of RIOK1 in BC patients. Then, knockdown or overexpression of RIOK1 were used to evaluate the effect on BC cells in vitro and in vivo. Finally, we predicted miR-204-5p could be a potential regulator of RIOK1. Results: We found that the expression levels of RIOK1 were significantly higher in hormone receptor (HR)–negative BC patients and was associated with tumor grades (p=0.010) and p53 expression (p=0.008) and survival duration (p=0.011). Kaplan-Meier analysis suggested a tendency for the poor prognosis. In vitro, knockdown of RIOK1 could inhibit proliferation, invasion, and induced apoptosis in HR-negative BC cells and inhibited tumorigenesis in vivo, while overexpression of RIOK1 promoted HR-positive tumor progression. MiR-204-5p could regulate RIOK1 expression and be involved in BC progression. Conclusion These findings indicate that RIOK1 expression could be a biomarker of HR-negative BC, and it may serve as an effective prognostic indicator and promote BC progression.

Cystic echinococcosis (CE) is a zoonotic infection caused by Echinococcus granulosus larvae. It seriously affects the development of animal husbandry and endangers human health. Due to a poor understanding of the cystic fluid formation pathway, there is currently a lack of innovative methods for the prevention and treatment of CE. In this study, the protoscoleces (PSCs) in the encystation process were analyzed by high-throughput RNA sequencing. A total of 32,401 transcripts and 14,903 cDNAs revealed numbers of new genes and transcripts, stage-specific genes, and differently expressed genes. Genes encoding proteins involved in signaling pathways, such as putative G-protein coupled receptor, tyrosine kinases, and serine/threonine protein kinase, were predominantly up-regulated during the encystation process. Antioxidant enzymes included cytochrome c oxidase, thioredoxin glutathione, and glutathione peroxidase were a high expression level. Intriguingly, KEGG enrichment suggested that differentially up-regulated genes involved in the vasopressin-regulated water reabsorption metabolic pathway may play important roles in the transport of proteins, carbohydrates, and other substances. These results provide valuable information on the mechanism of cystic fluid production during the encystation process, and provide a basis for further studies on the molecular mechanisms of growth and development of PSCs.

Background: and Purpose Patients with aortic disease might have an increased risk of intracranial aneurysm (IA). We conducted this research to assess the prevalence of IA in patients with aortopathy, considering the impact of gender, age, and cardiovascular risk factors. Methods: We searched PubMed and Scopus from inception to August 2019 for epidemiological studies reporting the prevalence of IA in patients with aortopathy. Random-effect meta-analyses were performed to calculate the overall prevalence, and the effect of risk factors on the prevalence was also evaluated. Anatomical location of IAs in patients suffered from distinct aortic disease was extracted and further analyzed. Results: Thirteen cross-sectional studies involving 4,041 participants were included in this systematic review. We reported an estimated prevalence of 12% (95% confidence interval [CI], 9% to 14%) of IA in patients with aortopathy. The pooled prevalence of IA in patients with bicuspid aortic valve, coarctation of the aorta, aortic aneurysm, and aortic dissection was 8% (95% CI, 6% to 10%), 10% (95% CI, 7% to 14%), 12% (95% CI, 9% to 15%), and 23% (95% CI, 12% to 34%), respectively. Gender (female) and smoking are risk factors related to an increased risk of IA. The anatomical distribution of IAs was heterogeneously between participants with different aortic disease. Conclusions According to current epidemiological evidence, the prevalence of IA in patients with aortic disease is quadrupled compared to that in the general population, which suggests that an early IA screening should be considered among patients with aortic disease for timely diagnosis and treatment of IA.

Background: Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhea and an important cause of death in hospitalized patients with diarrhea. However, there are not sufficient clinical researches on the risk factors of CDI. Aims: To investigate the risk factors of CDI in hospitalized patients with diarrhea. Methods: A total of 230 hospitalized diarrhea patients who received Clostridium difficile test from January 2015 to January 2019 at the Second Hospital of Hebei Medical University were collected. The patients were divided into CDI group and non-CDI group. Logistic regression analysis was performed to investigate the risk factors of CDI. Results: Compared with non-CDI group, patients in CDI group had a longer hospital stay (P<0.05) and a higher proportion of surgery in the past 6 months (P<0.05). The number of comorbidities in CDI group was higher than that in non-CDI group (P<0.05), and the ratio of gastrointestinal disease, cardiovascular disease, blood/immune system disease, nervous system disease in CDI group were higher than those in non-CDI group (P<0.05). Multivariate analysis showed the number of comorbidities (OR=3.215, 95% CI: 1.576-4.743; P=0.003), gastrointestinal disease (OR=4.135, 95% CI: 3.048-11.416; P=0.000), surgical history (OR=6.734, 95% CI: 2.692-15.849; P=0.000) and antibiotic use (OR=5.996, 95% CI: 2.173-15.481; P=0.000) were risk factors of CDI, especially the use of quinolone antibiotics (OR=4.769, 95% CI: 2.138-14.757; P=0.000). Conclusions: CDI can prolong the hospital stay of patients with diarrhea. Number of comorbidities, underlying gastrointestinal disease, recent history of surgery and antibiotic use, especially the use of quinolone antibiotics are risk factors of CDI in hospitalized patients with diarrhea.

To investigate the effects of clinical P-glycoprotein inhibitors on oral bioavailability and brain penetration of gefitinib, 16 inhibitors and gefitinib were co-administered orally to ICR mice. The suspension of gefitinib and CMC-Na were co-administered to the control group. The suspension of gefitinib and clinical P-glycoprotein inhibitors were co-administered to the control group. Blood samples and brain homogenate samples were extracted by protein precipitation with acetonitrile and determinated by LC-MS/MS. It was found that ritonavir can significantly increase the oral bioavailability of gefitinib, and the area under the plasma concentration-time curves(AUC)of gefitinib was increased by 2 times; while brain exposure was increased, there was no increment in brain penetration. Some other drugs can also increase the plasma AUC of gefitinib, but can not enhance the brain penetration; After we corrected brain concentration with fraction of unbound drug in brain, it was found that the brain concentration of gefitinib in both control group and ritonavir group did not achieve the in vitro IC50 of inhibiting non-small cell lung cancer(NSCLC)cell growth. Our results suggest that clinical doses of the 16 clinical P-glycoprotein inhibitors can not specifically increase brain tissue exposure, more specific and safer P-gp inhibitors are required. After we corrected brain concentrations with fraction of unbound drug in brain, our preclinical studies found that insufficient brain exposure may be one of the reasons for the unsatisfactory efficacy of gefitinib in the treatment of brain metastases.

Objective:To evaluate the accuracy and safety of cervical pedicle screw (CPS) placement under orthopaedic robot navigation system guidance.Methods:From March 2019 to February 2021, the data of 33 patients (19 males and 14 females, aged from 26 to 75 years, with an average age of 50.5 years) treated with pedicle screw fixation with the assistance of orthopaedic surgery robot through the posterior cervical spine were retrospectively analyzed. In clinical diagnosis, there was upper cervical fracture with instability in 14 patients (fracture nonunion in 2 patients), upper & subaxial cervical fracture in 1 patient, cervical spinal cord injury with spinal stenosis in 2 patients, cervical spinal stenosis in 9 patients, occipitocervical deformity in 2 patients, post-operative revision of cervical spondylosis in 2 patients, cervical intraspinal tumor in 3 patients. A total of 151 CPSs were inserted in C 1-C 7 using robot navigation system based on intraoperative three-dimensional C-arm fluoroscopy to assist in screw placement in posterior cervical surgery. Among them, 74 screws were implanted into upper cervical spine; 77 screws were implanted in the lower cervical spine. CT was used to obtain image data within 7 days after operation, and Neo classification was used to evaluate the accuracy of cervical pedicle screw placement. The patients were followed up for 2 weeks to observe the clinical symptoms and signs, and to determine whether there were surgical complications such as nerve and blood vessel injury and incision infection. Results:According to Neo classification, 91.4% (138/151) screws were completely contained in the pedicle without breaking through the pedicle cortex (grade 0). Among them, the accuracy of C 1 screws was 97.1% (34/35), C 2 screws was 92.3% (36/39), C 3 screws was 88.2% (15/17), C 4 screws was 71.4% (10/14), C 5 screws was 85.7% (12/14), C 6 screws was 93.3% (14/15), C 7 screws was 100.0% (17/17). The screw accuracy was highest in C 7, the lowest in C 4. The Kruskal-Wallis H test was performed on the accuracy of screw placement in different cervical level, and the results showed that there was no statistical difference (χ 2=1.31, P=0.971). However, a total of 13 screws were found to perforate the cortex of pedicle, although any neural or vascular complications associated with CPS placement were not encountered. Among them, 9 screws were found to perforate laterally, and 4 screws were found to perforate medially. No postoperative incision infection occurred in all cases. Conclusion:The safety of CPS placement can be effectively guaranteed with the assistance of the orthopaedic robot system.