Abstract:Objective To explore the influencing risk factors of perioperative technical complications and clinical prognosis of stent-assisted coiling (SAC) for acute (≤ 28 d) ruptured intracranial aneurysm (RIA). Methods Acute RIA patients, who received SAC treatment in Changhai Hospital of Naval Medical University (Second Military Medical University) between Jan. 2012 and Jun. 2018, were retrospectively enrolled. The clinical and imaging data were analyzed using univariable analysis and multivariate logistic regression analysis to identify the potential risk factors of perioperative technical complications and clinical prognosis. Results A total of 509 acute RIA patients (170 males and 339 females), who underwent SAC treatment and received 30-d follow-up, were included in this study. Perioperative ischemic complications occurred in 28 cases (5.5%), and multivariate regression analysis showed that the location of aneurysms at the bifurcation of blood vessels was an independent risk factor of ischemic complications (odds ratio[OR]=4.108, P=0.001). Perioperative hemorrhagic complications occurred in 25 cases (4.9%), and multivariate regression analysis showed that age<60 years was an independent risk factor of hemorrhagic complications (OR=3.574, P=0.014). The modified Rankin scale (mRS) scores of 81 patients (15.9%) ranged from 3 to 5 at discharge, 27 patients (5.3%) died with mRS score of 6, and the poor prognosis (mRS score>2) rate was 21.2% (108/509). Multivariate regression analysis showed that age ≥ 80 years, Hunt-Hess 3-5 class, perioperative ischemic complications, perioperative hemorrhagic complications and poor Glasgow coma scale (GCS) score were independent risk factors of poor prognosis (all P<0.01). Conclusion For the acute RIA patients treated with SAC, the location of aneurysms at the vascular bifurcation is an independent risk factor of perioperative ischemic complications; age<60 years is an independent risk factor for hemorrhagic complications; and the patients with poor GCS score at admission have a poor prognosis at discharge, and perioperative ischemic and hemorrhagic complications are independent risk factors of poor prognosis.

Abstract:Objective To determine the expression of carboxylic acid-terminal truncated hepatitis B virus X protein (Ct-HBx) in hepatocellular carcinoma (HCC) tissues and corresponding adjacent non-tumor tissues, and to explore its effect on postoperative prognosis of HCC patients. Methods Immunohistochemistry was performed to measure the expression levels of Ct-HBx in 462 HCC tissues, 263 matched adjacent tissues and 25 matched tumor thrombus tissues. The relationships between Ct-HBx expression and clinicopathological data and postoperative prognosis of HCC patients was analyzed. Results The positive rates of Ct-HBx in 263 HCC and paired adjacent tissues were 43.73% (115/263) and 11.79% (31/263), respectively. Multivariate Cox regression analysis showed that age, portal vein cancer thrombus (PVTT), preoperative aspartate aminotransferase (AST), preoperative α-fetoprotein (AFP), small daughter nodule, preoperative Barcelona Clinic Liver Cancer (BCLC) stage and postoperative antiviral treatment were independent risk factors of postoperative recurrence of HCC patients (all P<0.05), and the PVTT, preoperative AFP, tumor encapsulation, preoperative BCLC stage and Ct-HBx protein expression were independent risk factors for postoperative survival of HCC patients (all P<0.05). Analysis results of 263 paired HCC and adjacent tissues showed that the expression of Ct-HBx in the HCC tissues was related to gender, carbohydrate antigen 19-9 (CA19-9) and postoperative antiviral treatment (all P<0.05). Compared with the patients with negative Ct-HBx in HCC tissues and positive Ct-HBx in adjacent tissues, the patients with negative Ct-HBx in both HCC and adjacent no-tumor tissues had significantly higher 3-year disease free survival rate (P=0.050 1). Conclusion For HCC patients with negative expression of Ct-HBx in HCC tissues, the expression level of Ct-HBx in corresponding adjacent no-tumor tissues is related to the postoperative prognosis of HCC patients, and it may be a potential molecular biomarker to predict postoperative survival and recurrence.

Abstract:Objective To assess the influence of different time sampling modes on perfusion parameters and radiation dose of whole-brain computed tomography perfusion imaging (CTP), and to formulate an optimized scanning protocol for clinical diagnosis requirements. Methods Forty-seven consecutive patients, who underwent cerebral CTP scanning in our hospital between Nov. 2016 and Jun. 2017, were included in this study. Nineteen of them had acute ischemic stroke (AIS) and 28 had AIS symptoms, but no lesions were found by computed tomography or CTP. According to the time-attenuation curve, four scanning protocols were obtained:standard control group (group 1), sampling interval of 3 s (group 2), sampling interval of 3 s in pre-ascending and pro-descending period, and sampling interval of 1.5 s in the intermediate period (group 3), and smapling interval of 1.5 s between the peak of artery and vein and other sampling interval of 3 s (group 4). The perfusion parameters of all subjects were quantitatively measured. Subjective image quality was analyzed and radiation dose was calculated. Results In AIS and non-AIS groups, a total of 10 region of interests were placed in the ischemic area and contralateral brain parenchyma of each patient, and the total numbers of data points of perfusion parameters were 190 and 280, respectively. There were significant differences in blood flow, blood volume and mean transit time (MTT) between the AIS group and non-AIS group (all P<0.01). However, inter-group analysis showed that there were no significant differences in the above perfusion parameters between group 3 and group 1 in both the AIS group and non-AIS group (all P>0.05). Bland-Altman consistency analysis showed that group 3 and group 1 had good consistency of blood flow, blood volume and MTT in both the AIS group and non-AIS group. Compared with group 1 (standard control group), group 3 had better subjective score and lower radiation dose. Based on the sampling mode of group 3, 2 recommended scanning protocols were established and validated. The perfusion parameters of the 2 recommended scanning protocols were well correlated with those of group 1 in AIS patients and non-AIS patients (all P<0.01). Conclusion The scanning protocol, in which sampling interval is 3 s in pre-ascending and pro-descending period and 1.5 s in intermediate period, is in good agreement with the standard scanning mode, and can reduce radiation dose. It may be a whole-brain CTP scanning protocol for the clinical settings.

Abstract:Objective To establish a conditional knockout mouse model of transcription factor carbohydrate response element-binding protein (ChREBP), so as to provide a technical approach for exploring the biological function of ChREBP in vivo. Methods and results Using Cre/loxP gene targeting strategy, we constructed the gene targeting vector and franked the 8^th exon of ChREBP gene with loxP site in embryonic stem cells (ES cells) via homologous recombination. We microinjected the recombined ES clones into blastocysts and implanted into the uterus of pseudopregnant mice to obtain the chimeric mice and ChREBP^flox/+ mice. By crossbreeding ChREBP^flox/+ mice with Alb-Cre mice, we generated liver-specific ChREBP knockout mice. Conclusion The generation of ChREBP conditional knockout mouse model provides an important means to reveal the physiological function and pathological significance of ChREBP in different tissues.

Abstract:Objective To study the preparation method of Morinda officinalis iridoid glycosides (MOIG) and to explore the inhibitory effect on bone resorption of osteoclasts. Methods High-performance liquid chromatography (HPLC) was applied to determine the contents of monotropein and deacetyl asperulosidic acid from MOIG. The static adsorption-desorption test was used to screen the types of macroporous resins of AB-8, ADS-17, D101, HPD400, HPD600, HP20, S-8, SP850, XDA-1 and XDA-6, and to optimize the related parameters in process of enriching MOIG using macroporous resins. Furthermore, the osteoclasts induced from mouse bone marrow monocytes were used to evaluate the inhibitory effects of MOIG on osteoclastic bone resorption. Results After optimization, XDA-1 macroporous resin had better adsorption and desorption effects on MOIG. The optimized preparation conditions were as follows:mass concentration of MOIG in the sample solutions was 19.15 mg/mL, pH value was 1.0, diameter-height ratio of resin column was 1︰7, flow rate of loading samples was 2.0 BV/h (1 BV=80 mL), loading volume was 0.75 BV, and adsorption time was 11 h. 7 BV water was used to remove other constituents, and 10% ethanol was used to elute MOIG in the flow rate of 3.0 BV/h. The total content of monotropein and deacetyl asperulosidic acid in the prepared MOIG was more than 54%. MOIG had no significant effect on proliferation of the osteoclasts induced by mouse bone marrow monocytes, while it could significantly inhibit the tartrate-resistant acid phosphatase activity and the bone resorption of osteoclasts (P<0.05, P<0.01). Conclusion XDA-1 macroporous resin can be used to enrich MOIG, with more than 54% total content of monotropein and deacetyl asperulosidic acid. The MOIG can significantly inhibit the bone resorption of osteoclasts.

Abstract:Objective To explore the effect of serum deprivation on proliferation and apoptosis of cardiomyocytes and its mechanisms. Methods Human cardiomyocytes AC16 were randomly divided into serum-deprivation group (the cells were cultured in DMEM medium without fetal bovine serum for 48 h) and control group (the cells were cultured in DMEM medium containing 10% fetal bovine serum for 48 h). CCK-8 assay was performed to test the proliferation ability, and EdU imaging was conducted to detect the DNA synthesis level. Flow cytometry was performed to analyze the apoptosis level and mitochondrial membrane potential. Western blotting was conducted to detect the protein expression levels of caspase-9, Bcl-2, P53, proliferating cell nuclear antigen (PCNA), cyclin D1, β-catenin, Wnt5a, Axis inhibition protein 1 (Axin1), dishevelled 2 (Dvl2), dishevelled 3 (Dvl3) and low-density lipoprotein receptor-related protein 6 (LRP6). Results CCK-8 assay showed that the optical density value of the control group was 1.93±0.01 and that of the serum-deprivation group was 1.08±0.08, which was 55.8% of the control group, and there was significant difference between the two groups (P<0.01). DNA synthesis was inhibited by serum deprivation, and the DNA synthesis level of the serum-deprivation group was 65.6% of the control group, with significant difference found between the two groups (P<0.05). Serum deprivation could induce cardiomyocyte apoptosis; the apoptotic rate of control group was (6.34±0.47)%, and that of serum-deprivation group was (56.83±1.90)%, which was 8.9 times of the control group, and there was significant difference between the two groups (P<0.05). Serum deprivation could decrease the mitochondrial membrane potential of cardiomyocytes, while there was no significant difference between the serum-deprivation and control groups (P>0.05). Western blotting analysis showed that serum deprivation could upregulate the protein expression of caspase-9 and downregulate the protein expression of Bcl-2, P53, PCNA and cyclin D1. Serum deprivation could inhibit the protein expression of β-catenin, Wnt5a, Axin1, Dvl2, Dvl3 and LRP6 in cardiomyocytes. Conclusion Serum deprivation can inhibit proliferation and induce apoptosis of cardiomyocytes, which may be mediated by inhibition of Wnt/β-catenin signaling pathway.

Abstract:Objective To explore the biological safety and compatibility of five kinds of acellular fish skin matrices, and to screen the materials meeting the criteria of biocompatibility. Methods Acellular fish skin matrices were prepared through decolorization, degreasing, decellularization and cross-linking using five kinds of fish skins leather jacket fish (Thamnaconus septentrionalis), black fish (Channa argus), eel (Anguillidae), carp (Cyprinus carpio) and silver crap (Hypophthalmichthys molitrix). According to the national standard (GB/T 16886.5-2017), different concentrations (10 g/L and 100 g/L) of extracts of acellular fish skin matrices were prepared, and the CCK-8 assay was used to detect the in vitro toxicity of extracts of acellular fish skin matrices to human bone marrow-derived mesenchymal stem cells. The surface structures of different collagen membranes were observed under scanning electron microscopy. The H-E and Masson staining were used to observe whether the fish skin matrix materials were completely acellular. The human bone marrow-derived mesenchymal stem cells were cultured with the medium containing standard concentration of 100 g/L acellular fish skin matrix material extracts. The blood compatibility of the meterial was tested by hemolysis test. Live/Dead, TUNEL and flow cytometry were used to detect the cell survival and apoptosis levels. Results CCK-8 assay showed that the viability indexes of the cells co-cultured with the leather jacket fish and black fish skin acellular matrix material extracts were both >70% at the concentration of 10 g/L, and the other three materials were all <70%. At the concentration of 100 g/L, the viability index of the cells co-cultured with the leather jacket fish skin acellular matrix material extracts was >70%, and that with the black fish was <70%. Scanning electron microscopy showed that the leather jacket fish skin acellular matrix materials had porous and compact structure inside, and black fish skin acellular matrix materials had smooth structure inside. The H-E staining and Masson staining showed that leather jacket fish and black fish skin acellular matrix materials were both acellular collagen fibers. The hemolysis rates (the national standard ≤ 5%) of leather jacket fish and black fish skin acellular matrix material extracts were (1.23±0.43)% and (6.35±0.47)%, respectively. Human bone marrow-derived mesenchymal stem cells survived well in the culture medium containing extracts of leather jacket fish skin acellular matrix material, but most cells died or apoptozed in the culture medium containing extracts of Black fish skin acellular matrix material. Conclusion The leather jacket fish decellularized skin matrix material has better biosafety and biocompatibility, and has the potential to be a scaffold material for tissue engineering.

Abstract:Objective To compare the safety and effectiveness of bioabsorbable stents and drug-eluting stents for cardiovascular disease. Methods We searched SinoMed, Wanfang data, Chinese National Knowledge Infrastructure (CNKI), VIP, PubMed, Medline and Embase databases to obtain the clinical trial studies published between Jan. 1980 and Oct. 2018 according to inclusion criteria. The odds ratio (OR) and 95% confidence interval (95% CI) were calculated by the R 3.5.1 software to evaluate the safety and efficacy of bioabsorbable stents and drug-eluting stents in treatment of cardiovascular disease. Results A total of 22 studies with 33 570 subjects were included. Comparing the bioabsorbable stents with the drug-eluting stents, we found that OR (95% CI) for the main safety and effectiveness indicators were as follow:cardiac death (1.01[0.88, 1.16], P>0.05), all-caused death (0.97[0.88, 1.08], P>0.05), myocardial infarction (0.98[0.87, 1.10], P>0.05), target lesion revascularization (0.99[0.89, 1.09], P>0.05), and target vessel revascularization (1.03[0.95, 1.13], P>0.05). The OR (95% CI) was (0.80[0.65, 0.99], P=0.042) for the detection of confirmed or suspected stent thrombosis, (0.97[0.69, 1.37], P=0.906) for early stent thrombus, and (0.61[0.43, 0.86], P=0.004) for late stent thrombus. Conclusion In the treatment of coronary heart disease, the results of this meta-analysis indicate that there are no differences in safety or efficacy between bioabsorbable stents and drug-eluting stents. However, bioabsorbable stents can decrease the risk of stent thrombus, especially for the late stent thrombus.

Abstract:Objective To establish a quantitative evaluation method for medical treatment effect of anthrax aerosol terrorist attacks. Methods We established an evaluation framework for the medical treatment effect of anthrax events through constructing the decision tree model of medical intervention after anthrax exposure, the allocation model of key resources consumption and the model of population state transition under different intervention measures. Then, under the scenario of the anthrax terrorist attacks in the big cities of China, we analyzed and evaluated the effects of 52 intervention strategies on the number of cases, peak value, and deaths based on the discrete event simulation method. Results The intervention effect was sensitive to time delay in intervention and resource reserve. When time delay in intervention was 1 h after the attack, the resource stock increase from 25% to 100% could reduce the deaths by 59.91%; while only about 7.33% of the deaths were reduced when the intervention was performed at 145 h after the attack. The intervention strategy had little effect on the peak time of the morbidity, with the maximum value being 10.52 d and the minimum value being 9.67 d; but it had a greater impact on the peak number of patients, with the maximum value being 255 072 patients and the minimum value being 103 943 patients. Conclusion A quantitative evaluation method for medical treatment effect of anthrax aerosol terrorist attacks is established in this study, and it may be conducive to medical rescue capacity building and emergency strategy-making.

Abstract:Objective To explore the mechanism by which specific agonist of farnesoid X receptor (FXR) GW4064 inhibits the growth and invasion of colon cancer cells. Methods Human colon cancer cell lines HT-29 were in vitro cultured. After treatment with GW4064 of 0, 0.1, 1, 3, 5, 7 and 10 μmol/L for 72 h, cell viability was measured by MTT assay. After treatment with GW4064 of 0, 1 and 5 μmol/L for 24 h, the cell morphology was observed under phase contrast microscope, and the mRNA expression levels of FXR and stromal cell-derived factor 1 (SDF-1) were detected by PCR. After treatment with GW4064 of 0 and 1 μmol/L for 24 h, the cell invasive ability was detected by cell scratch test. After treatment with GW4064 of 0, 1, 5 and 7 μmol/L for 24 h, the SDF-1 expression in the culture medium was detected by ELISA. Nude mouse tumorigenesis model was established by subcutaneous inoculation of HT-29 cells. After intragastric administration with GW4064 or DMSO for 16 d, the tumor growth and the mRNA expression of FXR and SDF-1 in the tumors were determined. Results GW4064 inhibited the growth of HT-29 cells in a dose-dependent manner, and there was significant difference in the cell viability of HT-29 cells between the GW4064 groups (1, 3, 5, 7 and 10 μmol/L) and the control group (0 μmol/L, all P<0.05). After treatment with GW4064, phase contrast microscopy showed contracted and rounded colon cancer cells and slender cells transforming into epidermoid cells. The cell scratch test showed that the invasion ability of the colon cancer cells was significantly reduced after treatment with GW4064 compared with the control group (0 μmol/L, P<0.05). PCR results showed that the mRNA expression level of FXR was increased in a dose-dependent manner after GW4064 treatment, while the expression of SDF-1 mRNA changed in the opposite way. ELISA results showed that the SDF-1 expression in the cell culture supernant was decreased with the increase of GW4064 concentrations, and there were significant differences between the GW4064 (1, 5 and 7 μmol/L) groups and the control group (0 μmol/L, P<0.05). GW4064 significantly reduced tumor size compared with the control group (DMSO, P<0.05). In addition, the mRNA expression of FXR in the tumors was increased, and the mRNA expression of SDF-1 was decreased. Conclusion The activation of FXR can inhibit the invasive growth of colon cancer cells and the expression of SDF-1.

Abstract:Neuroendocrine prostate cancer (NEPC) is a highly malignant subtype of prostate cancer and it mostly occurs in castration-resistant prostate cancer patients after antiandrogen therapy. The process of cell differentiation to obtain neuroendocrine phenotypes is called neuroendocrine differentiation (NED). It is a proposed mechanism of prostate cancer resistance to androgen-resistance therapy, which is associated with poor prognosis. At present, there is no consensus on the physiological and pathological characteristics of NEPC, and the treatment of this subtype is particularly difficult. This paper reviews the latest findings related to NEPC and NED, and summarizes the most studied targets, hoping to provide new ideas for peer diagnosis, treatment and research of NEPC.

Abstract:As a pathogen causing many infectious diseases, Flavivirus genus arborvirus has caused public health emergencies worldwide and posed a serious threat to human health. Attenuated vaccine is the most effective vaccine type against Flavivirus genus arborvirus. The attenuated vaccines against yellow fever virus and Japanese encephalitis virus obtained by consecutive cell passages play an important role in preventing viral infections. Recently, reverse genetics technique has been used to modify the flavivirus genome to obtain the attenuated phenotype, and this technique has made significant progress in the development of Flavivirus genus arbovirus vaccines. This review summarizes the history and the current status of attenuated vaccine of Flavivirus genus arborvirus.

Abstract:Akkermansia muciniphila (A. muciniphila) is a normal flora of human gastrointestinal tract. The A. muciniphila abundance of intestinal flora in obese patients is significantly decreased. Many evidences suggest that A. muciniphila is negatively related to obesity, diabetes, cardiovascular diseases and low-grade inflammation. A. muciniphila not only plays a metabolic protective role by protecting the integrity of intestinal epithelial cells and mucus layer, but also plays an anti-inflammatory role by regulatory T cells, endogenous cannabinoid system and non-classical Toll-like receptor in the process of inflammatory reaction. This article reviews the relationship between A. muciniphila and obesity, and the molecular mechanism and application of A. muciniphila in obesity.

Abstract:Gastric cancer is one of the main malignancies threatening human health, and its occurrence involves multistep and multigene interactions. Epithelial-mesenchymal transition (EMT) is a biological process in which epithelial cells transform to mesenchymal phenotypic cells through specific procedures. Studies have shown that long non-coding RNAs (lncRNAs) can promote or inhibit EMT by binding to target proteins and competing microRNAs as competitive endogenous RNAs, and some specific EMT-related lncRNAs are deeply involved in the invasion and metastasis of gastric cancer. In this review, we summarized the recent mechanisms of EMT-related lncRNAs in the regulating the invasion and metastasis of gastric cancer.

Abstract:Annexin A2 (AnxA2) is a multifunctional protein and has complex functions regulated by post-translational modifications. Protein phosphorylation is the most popular post-translational modification of AnxA2. Ser11, Ser25 and Tyr23 are the three most important phosphorylation sites. The possible impact of phosphorylation of AnxA2 function regulation has always been a hot topic. Recently, AnxA2 has been found in the exosomes of tumor cells, and the research of AnxA2 and its phosphorylation has been expanded from intracellular to extracellular. Remarkable achievements in the study of AnxA2 and its phosphorylation have been made in many clinical disciplines. This paper reviewed the advances on the impact of phosphorylation of Ser11, Ser25, Tyr23 sites on AnxA2 function regulation and the research about AnxA2 in exosomes.

Abstract:Medical geographic information plays an important role in prevention, treatment, rescue and delivery of the wounded, prevention and control of diseases, and supplement and use of medicines and equipment. We collected and collated the natural geography, social geography, medical geography and military geographic information of 181 coastal countries and regions in the world, and constructed a global naval medical geographic information database. This database can provide fast and efficient information support and decision support, and contribute to implementing naval medical support timely and effectively and promoting the comprehensive development of China's naval health services.

Abstract:Objective To explore the effect of glucocorticoid on ocular surface changes in the patients with thyroid-associated ophthalmopathy. Methods Sixty eyes of 30 patients with thyroid-associated ophthalmopathy were examined for the break-up time of tear film (BUT), blinks, incomplete blinks, tear film lipid layer thickness (LLT) and the fluidity of tear film lipid layer before and after glucocorticoid treatment. The differences of each detection index were compared and analyzed. Results The BUT of the patients with thyroid-associated ophthalmopathy was significantly longer after glucocorticoid treatment versus before glucocorticoid treatment (the medians were 5.0 s and 7.0 s, respectively; P<0.01). The average, maximal and minimal values of LLT were significantly increased after glucocorticoid treatment than those before glucocorticoid treatment (average, maximal and minimal values of LLT before and after treatment were 59 nm and 64.5 nm, 73.5 nm and 78.8 nm, and 52.4 nm and 57.5 nm, respectively; all P<0.01). There were no significant differences in the blinks, incomplete blinks or the fluidity of tear film lipid layer between before and after glucocorticoid treatment (all P>0.05). Conclusion Glucocorticoid treatment can improve the lipid secretion of tear film, thus maintaining the stability of tear film.

Abstract:Objective To analyze the expression of suppressor of cytokine signaling 1 (SOCS1) in gastric cancer tissues and its relationship with the clinicopathological parameters, and to explore the clinical significance of SOCS1 as the prognostic indicator of gastric cancer patients. Methods Sixty-seven pairs of gastric cancer tissue and adjacent tissue specimens were collected to establish tissue microarray from the gastric cancer patients without preoperative radiotherapy or chemotherapy history, and the expression level of SOCS1 was detected by immunohistochemical SP method. χ² test was used to analyze the relationship between SOCS1 protein expression and clinicopathological parameters of the patients. Kaplan-Meier survival curve and log-rank test were used to analyze the relationship between SOCS1 protein expression and survival of patients. Cox proportional hazards regression model was used to analyze the relationship between SOCS1 protein expression and prognosis. Results The positive expression rate of SOCS1 was 80.6% (54/67) in gastric cancer tissues and 61.2% (41/67) in adjacent tissues, and the difference was significant (P<0.05). Incidence of lymph node metastasis in the patients with positive expression of SOCS1 was significantly higher than that in the patients with negative expression of SOCS1 (74.1%[40/54] vs 38.5[5/13], P<0.05). Kaplan-Meier survival analysis showed that the total survival rate of the patients with positive expression of SOCS1 was significantly lower than that of the patients with negative expression of SOCS1 (P<0.05). Cox proportional hazards regression model showed that SOCS1 and TNM stage were independent prognostic factors in patients with gastric cancer. Conclusion SOCS1 is highly expressed in gastric cancer, and it may be used as an important indicator for predicting lymph node metastasis and evaluating prognosis of gastric cancer patients.

Abstract: