Sepsis and its development of multiple organ dysfunction pose a serious threat to human life and health. Sepsis is a hot issue that experts in the critical field are committed to solve. It is a heterogeneous, infection-induced systemic inflammatory response syndrome based on endothelial dysfunction, and it is still a huge burden on the global health system. As a well recognized immune cell, the endothelium is the primary site of attack by pathogens, toxins, or endogenous injury signals, which cause activation of endothelial cells and consequently damage to their function or structure. Although the latter may help to eliminate the infection and limit the dissemination of the infection to some extent, the excessive and persistent inflammatory response will also lead to a subsequent storm of cytokine and organ damage, causing irreversible damage to the organism. Glycocalyx is the first barrier on the surface of endothelial cells, it is also the first line of defence for endothelial cells under attack in sepsis, which has a great significance on endothelial function. Many studies have found that a variety of immune inflammatory responses involving the glycocalyx also play a key role in the development of sepsis. This review will give a brief overview of the factors, mechanisms and various treatments targeting glycocalyx injury in sepsis at present.

Objective To investigate the effect and mechanism of homocysteine on apoptosis and proliferation of cardiomyocytes. Methods Cardiomyocytes were stimulated with homocysteine at the concentration of 3 mmol/L for 24 h. Cells were divided into control group and homocysteine group (Hcy group). Western blotting was detected the expression of TLR4,Myeloid differentiation factor 88 (MyD88), NF-κB, p-NF-κB, the expression of apoptosis related proteins Bax, cleaved-caspase-3 and anti-apoptotic protein Bcl-2; Flow cytometry was detected the apoptosis rate of cardiomyocyte, EdU staining was observed the proliferation of cardiomyocytes. After TLR4 interference fragment was transfected into cardiomyocytes, the interference fragment was verified by Western blotting. The cells were transfected with si-NC or si-TLR4 and treated with Hcy. Western blotting was detected the expression of MyD88, NF-κB and p-NF-κB, the expression of apoptosis related protein and anti-apoptosis protein in cardiomyocytes; The apoptosis rate of cardiomyocytes was detected by flow cytometry; The apoptosis of cardiomyocytes was observed by EdU staining. Results Compare with control group, Western blotting showed that TLR4, MyD88 and p-NF-κB significantly increased in Hcy group (P<0.01); The expression of apoptosis related proteins Bax and cleaved-caspase-3 increased and the expression of anti-apoptotic protein Bcl-2 was decreased (P<0.01); Compared with si NC+Hcy group, the expression of TLR4, MyD88 and p-NF-κB decreased (P<0.01), the expression of apoptosis related protein decreased (P<0.01), and the expression of anti-apoptosis protein increased in si-TLR4+Hcy group (P<0.01); Compare with control group, the results of flow cytometry showed that the apoptosis rate of cardiomyocytes increased in Hcy group (P<0.01); Compared with si-NC+Hcy group, the apoptosis rate of si-TLR4+Hcy group decreased (P<0.01). Compared with control group, EdU staining showed that the number of positive cells decreased in Hcy group (P<0.01); Compared with si-NC+Hcy group, the number of positive cells increased in si-TLR4+Hcy group (P<0.01). Conclusion Hcy can induce apoptosis and inhibit proliferation of cardiomyocytes, the mechanism may have something to do with TLR4/NF-κB signaling pathway.

Objective The novel μ opiate receptor (MOR) antagonists with biological activity was searched based on computer aided drug design method. Methods The MOR was employed as the target protein, and the Glide module of Schrodinger software was used to virtually screen the numerous compounds included in ZTNC-15 open source compound database. According to the molecular docking score, skeleton structure, binding mode and compound acquisition, one compound that may be as an antagonist was selected. The anti-fentanyl-induced acute death model of mice and the experiment of improving fentanyl-induced respiratory depression of rats were used to evaluate the biological activity of A₆ against MOR. Finally, molecular dynamics simulation method was employed to analyze the possible mechanism of MOR-A₆ interaction. Results The molecular docking score of compound A₆ was comparable to that of naloxone. The results of animal experiments showed that the LD₅₀ value of fentanyl-induced death of mice in A6 prevention administration group [13.2(95%CI 12.0-14.5) mg/kg] was 1.3 times and higher than that in model group [10.5(95%CI 9.6-11.5) mg/kg], and the mortality of mice in experimental group was significantly lower than that in model group (P<0.05); Compared with model group, the carotid oxygen saturation (SaO₂) of rats in A₆ prevention administration group increased significantly at 15, 20 and 25 min after fentanyl injection (47.91%±3.17% vs. 62.63%±4.14%, 52.99%±3.92%vs. 69.57%±3.17%, and 58.16%±2.45% vs. 77.10%±4.93%, P<0.05). Molecular dynamics simulation of A₆ and MOR showed that ASP147 amino acid residue of A₆ is consistent with the predicted results of molecular docking, and has a large contribution on binding free energy. Conclusions A novel compound A₆ has obtained by virtual screening which could effectively antagonise fentanyl-induced acute toxic death in mice and improve fentanyl-induced respiratory depression in rats. The mechanism may be related to the hydrogen bond formation of ASP147 amino acid residue with MOR.

Objective To investigate the effects of different arterial partial pressure of carbon dioxide (PaCO₂) on regional cerebral oxygen saturation (rScO₂) in robot assisted laparoscopic pyeloplasty (RALP) in children. Methods Forty-five children who received RALP in Pediatric Urology Department of the Seventh Medical Center of Chinese PLA General Hospital from February 2019 to February 2020 were selected as the study subjects, by adjusting tidal volume and respiratory rate maintained PaCO₂ at 35-45 mmHg (group N), 30-34 mmHg (group M) and 25-29 mmHg (group L) with 15 patients in each group. Before anesthesia (T₀), 10 min after endotracheal intubation (T₁), before lateral decubitus surgery (T₂), 30 min after pneumoperitoneum(T₃), 10 min after pneumoperitoneum (T₄), and 10 min after recumbent position (T₅), rScO₂ of affected side, percutaneous pulse oxygen saturation (SpO₂), heart rate (HR), mean arterial pressure (MAP), pharyngeal temperature (T), pH and hemoglobin (Hb)were recorded respectively. Arterial blood was extracted for blood gas analysis, and PaCO₂ was recorded, operation time was recorded after operation. Results Compared with T₀, rScO₂ in the three groups was increased significantly at T₁, and decreased significantly at T₃ in group L (P<0.05); compared with T₂, rScO₂ in group L at T₃ was significantly lower (P<0.05); compared with T₃, rScO₂ in group L was increased significantly at T₄ and T₅ (P<0.05). Compared with group N, rScO₂ in group L was decreased significantly at T₃ (P<0.05). Two-factor ANOVA showed that there was no interaction between group and pneumoperitoneum at T₂ and T₃, T₃ and T₄ in the three groups (P>0.05); compared with T₂, rScO₂ at T₃ in group L was significantly lower (P<0.05); compared with T₃,rScO₂ at T₄ in group L was significantly increased (P<0.05). There were no significant differences in SpO₂, HR, MAP, T, pH and Hb among the threes groups at each time point of T₀-T₅. Conclusion Pneumoperitoneum resulted in a significant decrease in rScO₂ on the affected side when PaCO₂ was within 25-29 mmHg during pediatric RALP and the risk of the cerebral oxygen supply-demand unbalance increased.

Objective To explore the cumulative metabolic indicators and the related risk factors for restenosis after intervention of lower extremity arteriosclerosis obliterans (LEASO). Methods Data were collected of 110 patients with arterial occlusive symptoms of low limbs who admitted to the Department of Hypertension and Endocrinology, Army Characteristic Medical Center, Army Medical University from January 2007 to July 2021 and met the criteria. All patients underwent low limbs interventional surgery and were followed up for more than 2 years. CT angiography (CTA) and ultrasound of both low limbs arteries were performed 2 years after surgery to clarify whether restenosis occurred and, based on the results of CTA and ultrasound, patients were divided into restenosis group (n=37) and non-restenosis group (n=73). The patients' basic information, pre- and post-operative hematological indices at 6 months, 1 year and 2 years were collected to compare and analyze the differences in basic clinical information, baseline values of metabolic indices (X_baseline) and cumulative exposure values (X_cum) between patients in the restenosis group and non-restenosis group, and binary logistic regression models were used to analyze the risk factors for post-interventional revascularization in patients with LEASO. Results The incidence was 33.6% of restenosis 2 years after intervention in patients with lower extremity arterial occlusive disease. The percentage of patients with smoking, the percentage of patients with Pan Atlantic Collaborative Group (TASC) typeⅡ (hereafter referred to as TASC type Ⅱ) C or D femoropopliteal artery lesions(hereafter referred to as TASC typeⅡ), hypersensitive C-reactive protein (hs-CRP), cumulative hypersensitive C-reactive protein(hs-CRP_Cum), cumulative low-density lipoprotein cholesterol (LDL-C_Cum), and cumulative triacylglycerol (TG_Cum) were significantly higher in restenosis group than those in non-restenosis group (P<0.05). The percentage of patients with regular postoperative use of antiplatelet agents and ankle-brachial index (ABI) were significantly lower than those in non-restenosis group (P<0.05). Binary logistic regression analysis showed that smoking (OR=4.158, P=0.040), TASC Ⅱ typing (OR=4.3, P=0.036), hs-CRP_Cum (OR=1.160,P=0.013), LDL-C_Cum (OR=2.313, P=0.003), and TG_Cum (OR=1.668, P=0.015) were the risk factors for restenosis 2 years after surgery, and regular postoperative use of antiplatelet drugs was a protective factor (OR=0.038, P=0.000). Conclusions Smoking,TASC Ⅱ typing, hs-CRP_Cum, LDL-C_Cum, and TG_Cum were the risk factors for restenosis of blood vessels after intervention in patients with lower extremity atherosclerotic occlusive disease. The regular use of postoperative antiplatelet drugs was a protective factor. Continuous smoking cessation, intensive lipid lowering, and anti-inflammation are the key factors to reduce the occurrence of postoperative restenosis, and early intervention of vascular lesions (TASC A-B) has better long-term effects.

Objective Use aspirin to induce mouse inflammatory bowel disease model, and investigate whether Lactobacillus acidophilus LA-GHB1756 can alleviate this type of enteritis injury. Methods A total of 40 male BALB/c mice (6-8 weeks old) was randomized into four groups: control group, aspirin group, LA low-dose group, and LA high-dose group. Except for the control group, the remaining groups were given 0.5 mg/(100 g·d) aspirin solution by gavage for eight weeks to induce inflammatory bowel disease. The LA low-dose and high-dose groups received an additional 2000 cfu/(100 g·d) and 10 000 cfu/(100 g·d) of LA-GHB1756 bacterial liquid, respectively. Accordingly, the control and aspirin groups received the same volume of normal saline through gavage. We then monitored the mouse's body weight, defecation status, hair color, and other conventional indicators, colon macroscopic and pathological staining. We used ELISA to detect intestinal tissue MPO content, serum tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) expression. We employed Western blotting to detect intestinal tissue NF-κB p65 expression levels. Results The general observation of mice in each group showed that LA-GHB1756 could improve the diarrhea, hair, and mental status of aspirin-induced mice. In the 8th week, the body weight of mice in the aspirin group was (21.6±0.5) g. The body weight was statistically significantly improved in the LA low-dose and high-dose groups, which were (22.8±0.4) g and (23.1±0.3) g, respectively (P<0.05). The colon morphology and pathological results showed that LA-GHB1756 could alleviate intestinal mucosal edema and inflammation caused by aspirin in mice. The colon length of mice in the aspirin group was(5.80±0.43) cm, and the colon length of low-dose and high-dose LA groups was (6.17±0.15) cm and (6.50±0.26) cm, respectively. This length improvement was statistically significant (P<0.05). The results of MPO content in intestinal tissues showed that aspirin group was (95.90±11.34) pg/mg, the MPO content in LA low-dose group and LA high-dose group were (76.03±8.72) pg/mg and (51.40±9.12) pg/mg respectively, which was significantly decreased compared with aspirin group, the difference was statistically significant (P<0.05). The results of serum TNF-α and IL-6 expression showed that the concentrations of TNF-α and IL-6 in aspirin group were (238.75±17.80) pg/mg and (292.00±15.51) pg/mg, respectively, while those in LA low-dose group were (207.75±12.04) pg/mg and (250.25±11.50) pg/mg, respectively, LA high-dose group were (80.25±10.24) pg/mg and (108.50±13.38) pg/mg, respectively. Compared with aspirin group, TNF-α and IL-6 contents in LA low-dose group and LA high-dose group were statistically significantly decreased (P<0.05). The expression of NF-κB p65 was increased up to 5.07 fold in aspirin group when compared with control group. This level was statistically significantly decreased to 83.74% and 82.95% in LA low-dose and high-dose groups, respectively (P<0.05). Conclusion LA-GHB1756 can relieve intestinal inflammation in mice caused by aspirin, this effect may be related to the inhibition of MPO and NF-κB p65 expression in intestinal tissue.

Dystonia is a type of movement disorder disease characterized by abnormal movements and postures, which seriously affects patients' social life and quality of life. However, there are certain difficulties in positioning judgment of early intervention, efficacy analysis and prognostic evaluation at present. Resting state functional magnetic resonance imaging (rs-fMRI)is an advanced technique for measuring the brain's spontaneous nerve activity at rest. It is widely used in the study of dystonia due to its advantages of non-invasiveness, simplicity and ease of use, and diverse analysis methods. Studies have shown that dystonia is not simply a basal ganglia dysfunction, but a neural network disorder. This article briefly describes the principle and clinical application of rs-fMRI, focusing on the research progress of rs-fMRI in various dystonia diseases, which will help to further understand the pathogenesis of focal dystonia to provide functional imaging basis for the development of more effective therapeutic drugs.

Objective To investigate the effect of Rhopaladins' analogs RPDPC on cell biological properties of human cervical cancer HeLa cells and miR-21-5P/PTEN/PI3K signaling pathway. Methods CCK-8 assay was used to detect the effects of different concentrations of RPDPC on the cell viabilities of HeLa cells treated for different time. DMSO (control), 12.5 μmol/L,25.0 μmol/L and 50.0 μmol/L RPDPC were selected to treat HeLa cells for 48 h. Hoechst 33258 staining and Annexin-FITC/PI double staining were used to detect the effect of RPDPC on HeLa cell apoptosis; The expression levels of miR-21 and mRNA of E6,E7, PTEN, PI3K, Akt were detected by qRT-PCR; The expression levels of PTEN, p-PI3K, p-PI3K, p-Akt and Akt were detected by immunoblotting (WB). Results Compared with the control group, viabilities of HeLa cells decreased significantly treated by RPDPC in different concentration and time (P<0.05); The apoptosis rate of HeLa cells tended to increase with increasing concentration of RPDPC (P<0.05); qRT-PCR results showed that compared with the control group, the expression level of miR-21-5P and mRNA of E6, E7, PI3K, Akt decreased significantly (P<0.05), the expression levels of PTEN mRNA increased significantly(P<0.05). WB results showed that compared with the control group, the expression level of PTEN protein increased significantly(P<0.05); The expression levels of p-PI3K, PI3K, p-Akt and Akt proteins decreased significantly (P<0.05). Conclusions RPDPC could inhibit the proliferation and promote the apoptosis of cervical cancer cells. The mechanism may be the inhibition of expression of E6 and E7, and may be related to mir-21/PTEN/PI3K/Akt signaling pathway.

Objective To construct a PAEH/PEG DA hydrogel sustained-release system containing combined Pseudomonas aeruginosa (PA) outer membrane protein F (OprF) and Pseudomonas V antigen (PcrV) gene DNA vaccine, and evaluate the in vivo immune efficacy of the system. Methods The PAEH/PEG DA hydrogel containing combined PA DNA vaccine was prepared with a simple mixing method. The gelation time was tested, and the cytotoxicity (DC 2.4), degradation and cumulative release rate in vitro of the hydrogel were evaluated. Nine mice were randomly divided into 3 groups (3 each): 30 min group, 2 d group and 7 d group, the in vivo degradability and security of the hydrogel were evaluated by gelation volume changes at the injection site and histopathological sections of the skin, respectively. Eighteen mice were randomly divided into 6 groups (3 each): control group (PBS),hydrogel group (Gel), En/pVAX1-OprF group (O), En/pVAX1-PcrV group (P), En/(pVAX1-OprF+pVAX1-PcrV) group (OP), and hydrogel + En/(pVAX1-OprF+pVAX1-PcrV) group (GOP). Mice were immunized 3 times with a 10-day interval, then sacrificed 2 weeks after last immunization. The levels of serum specific IgG antibody, splenic lymphocyte stimulation index (SI) and interferon-γ(IFN-γ) in the supernatant of splenic lymphocytes were detected. Results The PAEH/PEG DA hydrogel sustained-release system required only about 30 min to form a gelation state. There was no significant toxicity to DC 2.4 cells in vitro, and approximately 85%of plasmid DNA was released after 36 hours of in vitro release. The degradation time of the hydrogel was nearly the same in vitro and in vivo. It could be almost completely degraded in about 7 days, and had good in vivo biodegradability and biosafety. The results of in vivo immune test showed that, compared with PBS group, no significant changes existed in the levels of specific IgG antibodies,splenic lymphocyte SI and IFN-γ in the Gel group (P>0.05). Compared with the corresponding DNA vaccine groups (O group or P group) and PBS group, the specific IgG antibody levels, spleen lymphocyte SI and IFN-γ level increased obviously in OP group and GOP group (P<0.05, P<0.01). While compared with OP group, the levels of specific IgG antibodies, splenic lymphocyte SI and IFN-γ increased markedly in GOP group (P<0.05, P<0.01). Conclusion The PAEH/PEG DA hydrogel sustained-release systems containing PA OprE and PcrF gene combined DNA vaccines, which can slowly release the combined DNA vaccine and further enhance the immune efficacy of combined DNA vaccine, are one of the promising strategies for the development of PA vaccines.

Objective To compare the clinical and multidetector computed tomography (MDCT) features of gastroduodenal heterotopic pancreas (HP) and gastrointestinal stromal tumors (GIST) smaller than 3 cm in diameter. Methods A total of 61 patients pathologically confirmed as gastroduodenal HP (n=28) and GIST (diameter <3 cm, n=33) in Daping Hospital during 2012-2021 were included. Their clinical and MDCT features (including lesion location, growth mode, morphology, contour,size and MDCT multi-phase enhancements) were retrospectively reviewed and compared. The characteristics with significant difference between the two were searched as the index of differential diagnosis, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficiency of each parameter. Results No significant difference existed in gender, body mass index (BMI), clinical symptoms and signs between the patients with gastroduodenal HP and GIST (P>0.05), while statistically significant differences existed in age, MDCT morphological features (location, growth pattern, lobulation sign) and CT values (plain CT value, portal venous phase CT value and enhancement value) between the two groups (P<0.05, P<0.01). Among them, age,location, and portal venous phase CT value had better efficiency, and the areas under ROC curves (AUC) were all greater than 0.700.When the 3 MDCT morphological features (location, growth pattern, lobulation sign) were combined in use, the AUC was improved to 0.954 (95%CI 0.867-0.991). The plain scan CT value, portal venous phase CT value and enhancement value can be separately used to distinguish HP and GIST respectively, and the portal venous phase CT value has the best efficiency. The optimal cut-offs of age, plain scan CT value, portal venous phase CT value and enhancement value were 50 years, 40.33 HU, 72.53 HU and 37.33 HU,respectively, which could be used as reference indicators to differentiate HP from GIST. Conclusion By comprehensively analyze the patient's age, lesion MDCT morphological features and multi-phase enhanced quantitative parameters, a preliminary differential diagnosis can be made between gastroduodenal HP and GIST smaller than 3 cm in diameter.