ObjectiveMolecular docking and animal experiments were employed to explore the protective effect and mechanism of Da Chengqitang （DCQD） on intestinal barrier in septic mice. MethodText mining method was used to screen the active ingredients in DCQD. AutoDock Tools and Discovery Studio were used to study the interactions of active components with the core target proteins ［claudin-1， tumor necrosis factor （TNF）-α， interleukin （IL）-6， endogenous antimicrobial peptide mCRAMP， Toll-like receptor 4 （TLR4）， and myeloid differentiation primary response gene 88 （MyD88）］ in sepsis. Fifty C57BL/6 mice were randomized into sham， model， low- and high-dose （4 g∙kg^-1 and 8 g∙kg^-1） DCQD， and ulinastatin groups （n=10）. Before， during， and after the day of modeling surgery， each group was administrated with corresponding drugs. The mice in other groups except the model group were subjected to modeling by cecal ligation and puncture. Enzyme-linked immunosorbent assay （ELISA） was used measure the serum level of D-lactic acid to assess intestinal mucosa permeability. Hematoxylin-eosin staining was employed to observe the histopathological changes in the ileum and assess the intestinal mucosal damage and inflammatory infiltration. Western blotting was employed to determine the expression levels of tight junction proteins claudin-1 and occludin in the ileal tissue， which were indicative of the bowel barrier function. The TNF-α and IL-6 levels were measured by ELISA to assess the intestinal inflammation. The expression of mCRAMP in the ileal tissue was observed by immunohistochemistry. The mRNA levels of mCRAMP， TLR4， and MyD88 in mouse ileal tissue were determined by Real-time polymerase chain reaction， on the basis of which the mechanism of DCQD in protecting the intestinal barrier of septic mice was explored. ResultMolecular docking results showed that most of the 10 active ingredients of DCQD that were screened out by text mining could bind to sepsis targets by van der Waals force， hydrogen bonding， and other conjugated systems. The results of animal experiments showed that compared with the model group， low- or high-dose DCQD lowered the D-lactic acid level in the serum （P<0.01）， alleviated damage to the ileal tissue and mucosal edema， protected the small intestine villus integrity， reduced inflammatory cell infiltration， promoted the expression of claudin-1 （P<0.01）， lowered the IL-6 level （P<0.01）， up-regulated the mRNA and protein levels of mCRAMP （P<0.01）， and down-regulated the mRNA and protein levels of TLR4 and MyD88 （P<0.01） in the ileal tissue. In addition， high-dose DCQD lowered the TNF-α level and promoted the expression of occludin in the ileum tissue （P<0.01）， and low-dose DCQD up-regulated the protein level of occludin in the ileum tissue （P<0.05）. ConclusionDCQD has a protective effect on intestinal barrier in septic mice. It can reduce intestinal inflammation， repair intestinal mucosal damage， improve the tight junction protein level， and reduce intestinal mucosal permeability by up-regulating the mRNA and protein levels of mCRAMP and the down-regulating the expression of genes in the TLR4/MyD88 pathway.

Objective:To investigate the association of white matter hyperintensities (WMHs) with long-term stroke recurrence in patients with recent subcortical small infarcts (RSSIs).Methods:Consecutive patients admitted to the Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University between January 2019 and August 2022 and met the clinical and imaging manifestations of RSSIs were collected. The demographic characteristics, baseline clinical data, and MRI features were collected. Using stroke recurrence as the endpoint event, the recurrence time was recorded, and Cox regression model was used to analyze relevant factors affecting stroke recurrence in patients with RSSIs.Results:A total of 202 patients were enrolled, including 138 males (68.3%), aged 67.9±10.5 years. Seventy-seven patients (38.1%) were mild WMHs, 64 (31.7%) were moderate WMHs, and 61 (30.2%) were severe WMHs. There were statistically significant differences in age, history of stroke, hypertension, hyperlipidemia, total cholesterol, infarct thickness, and infarct distribution among different WMHs severity groups (all P<0.05). The median follow-up time was 40.5 months (interquartile range, 27.7-49.0 months), and a total of 55 patients (27.2%) had stroke recurrence (ischemic stroke 54, occipital hemorrhage 1). Recurrence rates of stroke in the mild, moderate, and severe WMHs groups were 18.2%, 31.3%, and 34.4%, respectively. Cox regression analysis showed that WMHs were an independent risk factor for stroke recurrence (compared to the mild group, the risk ratio of the severe group was 2.225, 95% confidence interval was 1.116-4.436; P=0.023). Conclusion:The risk of long-term stroke recurrence in patients with RSSI is associated with the severity of WMHs.

Objective: To explore the damaging effect of the IP3-protein kinase C pathway on human retinal vascular endothelial cells under high glucose conditions. Methods: Human retinal vascular endothelial cells in the logarithmic growth phase were taken and divided into the experimental group(10 mmol/L glucose and 20 mmol/L glucose) and the control group(5 mmol/L glucose). The morphological changes of cells were observed under different concentrations of glucose culture medium. The apoptosis of human retinal vascular endothelial cells was detected by flow cytometry. Real-time fluorescent quantitative reverse transcription polymerase chain reaction was used to detect the RNA expression level of PKC in the IP3-protein kinase C(PKC) pathway, and Western blot was used to detect the protein expression level of PKC in cells. Results: Under high glucose conditions, the volume of human retinal vascular endothelial cells increased, the degree of extension decreased, and the apoptosis rate increased. Compared with the control group, the apoptosis rate of human retinal vascular endothelial cells in the 20 mmol/L glucose group increased(P<0.05); the IP3 level of human retinal vascular endothelial cells in the 20 mmol/L glucose group(587.9±15.2) ng/ml was lower than that of the control group(738.9±1.0) ng/ml(P<0.05). Under high glucose treatment, the expression levels of PKC mRNA and protein increased(P<0.05). Conclusion The IP3-PKC pathway may be involved in the damage process of human retinal vascular endothelial cells under high glucose conditions, and thus may play a role in diabetic retinopathy.

Gas therapy has been proven to be a promising and advantageous treatment option for cancers. Studies have shown that nitric oxide (NO) is one of the smallest structurally significant gas molecules with great potential to suppress cancer. However, there is controversy and concern about its use as it exhibits the opposite physiological effects based on its levels in the tumor. Therefore, the anti-cancer mechanism of NO is the key to cancer treatment, and rationally designed NO delivery systems are crucial to the success of NO biomedical applications. This review summarizes the endogenous production of NO, its physiological mechanisms of action, the application of NO in cancer treatment, and nano-delivery systems for delivering NO donors. Moreover, it briefly reviews challenges in delivering NO from different nanoparticles and the issues associated with its combination treatment strategies. The advantages and challenges of various NO delivery platforms are recapitulated for possible transformation into clinical applications.

OBJECTIVE To study the protective effects of Dachengqi decoction （DCQD） on intestinal septic mice， and to explore the possible mechanisms from the Toll-like receptor 4（TLR4）/myeloid differentiation factor 88（MyD88） signaling pathway. METHODS The SPF male C57BL/6J mice were randomly divided into Sham group， Sham+DCQD-H group， model （CLP） group， DCQD-L group， DCQD-H group and Positive group. The model of intestinal sepsis was established by cecal ligation and puncture in CLP group， DCQD-L group， DCQD-H group and Positive group. Three days before the operation and seven days after the operation， DCQD-L group and DCQD-H group were given DCQD intragastrically at 4， 8 g/kg （calculated by crude drug）， respectively. Positive group was given ulinastatin intraperitoneally 2 h before operation and 7 d after the operation （at 50 000 U/kg）. In Sham group and Sham+DCQD-H group， only cecum of mice was exposed without ligation and puncture. Sham+DCQD- H group was given DCQD intragastrically （8 g/kg，calculated by crude drug） 3 days before the operation and 7 days after the operation. Both the Sham group and CLP group were given normal saline 0.2 mL intragstrically and intraperitoneally each day， for 10 consecutive days. After the operation， the severity of sepsis was assessed， and the 7 d survival rate of mice was assessed. One hour after the last medication， the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum and ileum of mice were determined； the pathological and morphological changes of mice’s liver， lung， kidney and ileum were observed； mRNA expressions of the TLR4 and MyD88 in ileum were tested. RESULTS Compared with CLP group， sepsis score， the levels of TNF-α and IL-6 in serum and ileum （except for IL-6 in ileum of DCQD-L group）， damage score of the liver， lung， kidney and ileum， mRNA expressions of TLR4 and MyD88 in ileum were all decreased significantly in DCQD-L group and DCQD-H group （P＜0.05 or P＜0.01）， while 7 d survival rate （except for DCQD-L group） was increased significantly （P＜0.05）. The damage to liver tissue in mice was significantly improved， and inflammation infiltration and apoptosis were reduced； lung tissue damage had been alleviated， with varying degrees of improvement in alveolar atrophy， bleeding and edema； the renal tissue damage was improved and weakened dilation of renal tubular lumen was weakened； the damage and edema of ileal tissue were significantly improved. CONCLUSIONS DCQD may exert a protective role on intestinal septic model mice. The mechanism may be related to the inhibition of systemic inflammation， the reduction of multiple organ damage， and down-regulation of TLR4/MyD88 signaling pathway.

Objective:To analyze the influence of application of bilateral internal mammary artery(BIMA) with different configurations in coronary artery bypass grafting(CABG).Methods:From January 2018 to December 2020, 82 patients underwent CABG using BIMA were included, with 75 males and 7 females, aged(56.9±9.8) years old. According to the target of coronary artery of BIMA, patients were divided into two groups, 23 patients(group B) who underwent the traditional operation(RIMA to the right coronary artery), and 59 patients(group L) whose RIMA were grafted to the left ventricular arteries. Also the patients were divided into two groups according to the RIMA used either in situ(group I, 57 cases) or free(group F, 25 cases). Compare the grafts flow between groups. The CTA angiography of coronary artery was completed to evaluate the grafts patency before discharge.Results:There was 1 early operative death(1.22%). The mean flow(MF) of RIMA was significantly higher in group B( P=0.013). The pulsatility index(PI) of LIMA was significantly lower and the MF of RIMA and BIMA was higher(all P<0.05), fewer patients with LIMA-MF less than 15 ml/min( P=0.023)in the group I. CTA angiography before discharge showed that only 1 RIMA to right coronary artery was occlusion. Conclusion:It is better to use BIMA in situ in CABG, RIMA used in right coronary artery can receive more satisfactory graft flow. BIMA has good patency in early stage, therefore is the ideal and stable coronary bypass graft.

Objective:To investigate the effects and significance of acute and chronic trauma on brain degree centrality (DC) in patients with post-traumatic stress disorder (PTSD) who lost their only child at resting state.Methods:Retrospectively, the study enrolled a total of 51 parents with PTSD, including 35 PTSD parents whose children was lost in emergencies (acute bereaved PTSD group) and 16 PTSD parents whose children was lost of chronic causes such as diseases (chronic bereaved PTSD group). Fifty local adults were also included as healthy controls (HC group). The clinical administered PTSD scale(CAPS) was used to evaluate the severity of the subjects' clinical symptoms.Resting-state functional magnetic resonance imaging(fMRI) data of all subjects were collected and DC values were calculated.SPSS 22.0 software was used for statistical analysis.Covariance analysis was performed among three groups, while post hoc was performed between any two groups.What's more, correlation analyses were utilized between abnormal brain regions and the scores of CAPS.Results:Significant group effects were found in multiple regions, including the right inferior temporal gyrus (MNI: x, y, z=66, -27, -21), right temporal pole (MNI: x, y, z=54, 15, -9), right orbital inferior frontal gyrus (MNI: x, y, z=42, 21, -15), bilateral medial superior frontal gyri (MNI: right x, y, z=6, 63, 12; left x, y, z=-3, 60, 18), left inferior parietal angular gyrus (MNI: x, y, z=-45, -36, 51) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51). Compared with HC group, the DC of two patient groups increased in the right inferior temporal gyrus (MNI: acute x, y, z=63, -27, -21; chronic x, y, z=63, -21, -27); the DC of acute bereaved PTSD group decreased in the right temporal pole (MNI: x, y, z=45, 21, -15) and the right orbital inferior frontal gyrus (MNI: x, y, z=48, 24, -12), while the DC of chronic bereaved PTSD group decreased in the left inferior parietal angular gyrus (MNI: x, y, z=-45, -36, 51) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51). Compared with chronic bereaved PTSD group, the DC of acute bereaved PTSD group increased in the left inferior parietal angular gyrus (MNI: x, y, z=-33, -39, 42) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51), while decreased in the right temporal pole (MNI: x, y, z=51, 12, -9), right orbital inferior frontal gyrus (MNI: x, y, z=42, 21, -15) and bilateral medial superior frontal gyri (MNI: left x, y, z=0, 57, 15; right x, y, z=3, 57, 15). In chronic bereaved PTSD group, the DC of the left postcentral gyrus was negatively correlated with C1 (avoid trauma-related thoughts, feelings) score in CAPS ( r=-0.606, P=0.028). In acute bereaved PTSD group, the DC of the left medial superior frontal gyrus was negatively correlated with D4 (high vigilance) score ( r=-0.416, P=0.020). Conclusion:There exist functional abnormalities of multiple brain regions in acute and chronic bereaved parents with PTSD.The high arousal symptoms of the former may be related with the abnormalities of prefrontal-amygdala neural circuit, while the latter show higher avoidance which may be associated with the dysfunction of somatosensory brain regions such as postcentral gyrus.

Objective:To investigate the effect of coping style on the gray matter volume in patients with post-traumatic stress disorder (PTSD) who lost their only child, and the mediating role of gray matter volume in evaluating the influence of coping style in clinical symptoms of these parents.Methods:A total of 57 parents with PTSD (PTSD group) and 162 parents without PTSD (non-PTSD group) who lost their only child from September 2016 to March 2017 were enrolled from Jiangsu Province, China. Brain MRI data at resting state were collected. Voxel-based multiple regression analysis was performed to confirm the brain areas in which coping style main effect, diagnosis main effect and their interaction had significant influences in gray matter volumes. Correlations among gray matter volume of brain areas related to coping style, coping style scale scores, and clinician-administered PTSD scale (CAPS) scores were analyzed. Structural equation modeling was used to analyze the mediating role of gray matter volume in the influence of coping style in clinical symptoms of parents lost their only child.Results:(1) The coping style main effect did not significantly influence the gray matter volume in all subjects, and the diagnosis main effect had significant influence in gray matter volume in the right lingual gyrus; their interaction had significant influence in gray matter volume in the right peritalar fissure cortex and lingual gyrus. The positive coping style in the PTSD group had significant influence in the gray matter volumes of the right peritalar fissure cortex and lingual gyrus. (2) In the PTSD group, the scores of positive coping style were positively correlated with the gray matter volumes of the right talus fissure and the lingual gyrus ( P<0.05); the scores of positive coping style, and the gray matter volumes of the right talus fissure and the lingual gyrus were negatively correlated with scores of CAPS-C 5 and CAPS-C ( P<0.05). (3) In the PTSD group, positive coping style can positively predict the gray matter volumes of the right talus fissure and the lingual gyrus; the gray matter volumes of the right talus fissure and the lingual gyrus can negatively predict the avoidance-related symptoms. Conclusion:Positive coping style has influence in the gray matter volumes of the right talar fissure and lingual gyrus of PTSD patients lost their only child; and less positive coping style may affect the brain areas related to visual information processing, thus aggravating avoidance-related symptoms of PTSD patients.

OBJECTIVE: In the context of coronavirus disease 2019 (COVID-19) pandemic, the subject was designed to develop a new tracheal intubation device based on magnetic navigation technology to improve the success rate of tracheal intubation and reduce the risk of occupational exposure of medical staff. METHODS: The new tracheal intubation device was designed with the uniqueness of the magnetic field environment and magnetic steering of magnetic navigation technology. And preliminary magnetic navigation tracheal intubation experiments were performed on the tracheal intubation simulator. RESULTS: Magnetic navigation tracheal intubation can successfully implement tracheal intubation, and the time required is lower than that of traditional laryngoscopy. CONCLUSIONS The tracheal intubation based on magnetic navigation technology is feasible, with high efficiency and easy operation. That is expected to be widely used for tracheal intubation during treatment of patients outside the hospital in the future. At the same time, magnetic navigation endotracheal intubation technology will be the key technology for the development of endotracheal intubation robots.
COVID-19/therapy* ; Equipment Design ; Feasibility Studies ; Humans ; Intubation, Intratracheal ; Magnetic Phenomena ; SARS-CoV-2 ; Technology

Objective:To analyze the clinical manifestation, laboratory examination, treatment and prognosis of congenital factor Ⅺ (FⅪ) deficiency.Methods:The clinical data of 80 patients with congenital FⅪ deficiency in our hospital from September 2006 to October 2020 were analyzed retrospectively.Results:Among the 80 patients, there were 33 males (41.3%) and 47 females (58.8%) , with a median age of 32 (2-66) years. Twenty-eight cases (35.0%) had bleeding events, including 11 cases of spontaneous bleeding (13.8%) , 9 cases of ecchymosis or bleeding after skin trauma (11.3%) , 9 cases of postoperative bleeding (11.3%) . Among the female patients, there were 11 cases of menorrhagia (23.4%) and 1 case of bleeding after vaginal delivery (2.1%) . Laboratory examination were characterized by prolonged activated partial thromboplastin time (APTT) , normal prothrombin time (PT) , and decreased FⅪ activity (FⅪ∶C) . Nine patients (11.3%) were tested for FⅪ gene (F11) with 11 mutations. Twenty-seven patients (33.8%) received fresh frozen plasma (FFP) treatment, 15 patients (18.8%) were received for prophylaxis with no bleeding occurred during and after operation.Conclusion:Most patients with congenital FⅪ deficiency have no or mild bleeding symptoms. There was no significant correlation between FⅪ∶C and the severity of bleeding symptoms, and there was a well consistency between FⅪ∶C and F11 homozygous or heterozygous mutation type. Prophylactic infusion of FFP can effectively reduce the risk of operative bleeding.