Objective:To predict the mechanism of Panacis Quinquefolii Radix- Acori Tatarinowii Rhizoma (PQ-AT) in the treatment of diabetes encephalopathy (DE) using network pharmacology combined with molecular docking; To conduct experimental verification.Methods:The active components and targets of PQ and AT were screened by TCMSP database. The GeneCards and Disgenet were used to collect DE related target genes. String database and Cytoscape software were used to structure PPI network and perform visualization analysis. The common targets were imported into Metascape platform for GO annotation and KEGG enrichment analysis. Molecular docking was used to verify the binding ability of active components to core targets. Rats were randomly divided into a blank group, a model group, and a low-dose group of PQ-AT (1.08 g/kg), a high-dose group of PQ-AT (2.16 g/kg), and a metformin group (0.18 g/kg) using a random number table. To establish the rat model of diabetes encephalopathy, intraperitoneal injection of streptozotocin was used in addition to the blank group. After a 12-week drug intervention, TNF-α and Cyclooxygenase-2 (PTGS2) protein expression in the cerebral cortex of rats was detected using Western blot.Results:A total of 26 active components in PQ-AT and 107 related targets of DE were obtained, mainly including TNF, JUN, and PTSG2, which were mainly concentrated in TNF signaling pathway, cancer and other signal pathways. Molecular docking showed that the main active components of PQ-AT had relatively stable binding activity with TNF-α and PTGS2. Western blot results shows that compared with the model group, the expressions of PTGS2 and TNF-α significantly decreased in each administration group ( P<0.05 or P<0.01). Conclusion:PQ-AT can act on TNF, CASP3, JUN, STAT3, PTGS2 and other core targets to regulate signal pathways such as TNF, and inhibit inflammatory reaction to achieve the effect of treating DE.

Objective To explore the biomechanical mechanism of pseudoaneurysm formation at the anastomotic site of vascular patch and the inhibitory effect of transforming growth factor(TGF β1)hydrogel on aneurysm.Methods The vascular patch model and the pseudoaneurysm model were constructed separately,and the two-way fluid-structure interaction method was used to numerically simulate the blood-vessel wall dynamic response at the anastomosis.Based on the analysis of mechanical parameters such as postoperative blood velocity,vessel wall shear stress and aneurysm wall displacement,the mechanisms of postoperative pseudoaneurysm formation and inhibition were studied.Results The numerical simulation results showed that the wall shear stress increased when the blood flowed through the front end of the patch.When the pseudoaneurysm has been formed after surgery,the aneurysm wall became significantly thicker following the injection of TGF β1 hydrogel into the aneurysmal wall,and the intratumoral shear stress and the aneurysmal wall displacement were decreased.Conclusion Pseudoaneurysms are easy to form at the front end of the anastomosis after surgery,and the injection of TGF β1 hydrogel into the aneurysm wall can effectively inhibit the formation and progression of pseudoaneurysm.The numerical simulation study provides a numerical basis for the mechanical mechanism study of the formation and progression of pseudoaneurysm after patch angioplasty.

Wound infection is becoming a considerable healthcare crisis due to the abuse of antibiotics and the substantial production of multidrug-resistant bacteria. Seawater immersion wounds usually become a mortal trouble because of the infection of Vibrio vulnificus. Bdellovibrio bacteriovorus, one kind of natural predatory bacteria, is recognized as a promising biological therapy against intractable bacteria. Here, we prepared a B. bacteriovorus-loaded polyvinyl alcohol/alginate hydrogel for the topical treatment of the seawater immersion wounds infected by V. vulnificus. The B. bacteriovorus-loaded hydrogel (BG) owned highly microporous structures with the mean pore size of 90 μm, improving the rapid release of B. bacteriovorus from BG when contacting the aqueous surroundings. BG showed high biosafety with no L929 cell toxicity or hemolysis. More importantly, BG exhibited excellent in vitro anti-V. vulnificus effect. The highly effective infected wound treatment effect of BG was evaluated on mouse models, revealing significant reduction of local V. vulnificus, accelerated wound contraction, and alleviated inflammation. Besides the high bacterial inhibition of BG, BG remarkably reduced inflammatory response, promoted collagen deposition, neovascularization and re-epithelization, contributing to wound healing. BG is a promising topical biological formulation against infected wounds.

Objective Based on construction and verification of the lumbar finite element model, the simulation calculation and injury prediction on dynamic response of normal lumbar model and L5 unilateral and bilateral spondylolysis models of the pilot were carried out, so as to explore the influence of persistent flight overload on normal and spondylolysis lumbar vertebrae of the pilot. Methods The precise finite element model of lumbavertebrae was established using reverse engineering software and computer-aided engineering (CAE) technology based on CT images. The validity of the lumbar vertebrae model was verified by static and dynamic in vitro experiments. The biomechanical simulation analysis on normal and spondylolysis lumbar vertebrae of the pilotunder persistent overload was carried out, and the spinal injury was predicted and analyzed by dynamic response index (DRI) injury evaluation and prediction method. Results The maximum isthmus stress of L5 vertebra in unilateral and bilateral spondylolysis models were 105. 29 MPa and 126. 32 MPa, respectively, which were significantly higher than those in normal model. The L4-5 and L5-S1 intervertebral discs of the spondylolysis model were more prone to premature degenerative changes than those of normal model. Combined with DRI spinal injury prediction method, the probability of spinal injury in normal lumbar vertebrae, lumbar vertebrae with L5 unilateral and bilateral spondylolysis were 0. 001 4% , 2. 26% and 3. 21% , respectively, and the probability of spinal injury was significantly increased after the occurrence of spondylolysis. Conclusions The spondylolysis increases the load of lumbar isthmus under flight overload. The results provide more accurate data support for the formulation of training programs and the development of protective devices to ensure flight safety

Objective To simulate dynamic response of cervical spine of the pilot during typical maneuver flight movements using finite element method, as well as make analysis and prediction on damage failure of the pilot neck during flight by impact injury and fatigue injury model of biological tissues.Methods A geometrically accurate finite element model of the neck was constructed, and validity of the model was verified by relevant examples. Then, the acceleration curves of centrifugal trainer under different modes were loaded for numerical simulation, and impact injury and fatigue injury of tissues were predicted by using the universal cervical injury criterion and the fatigue damage model of biological tissues.Results The maximum stress of the vertebrae and intervertebral disc caused by overload impact was 66.53 MPa and 58.63 MPa respectively during typical maneuver flight. According to the Nij injury criteria, the maximum Nij was 0.096, which was lower than the injury tolerance threshold of 1, and would not cause direct acute injury to cervical tissues. Based on fatigue damage model of biological tissues, it was found that cancellous bone suffered fatigue failure under the condition of uninterrupted repeated loading for more than 40 000 times. Considering the limited flight career of the pilot, the vertebral tissues would not be fractured due to the accumulation of fatigue damage.Conclusions To a certain extent, the results can contribute to formulating pilot training and flight plans, and also provide data support for the development of its protective equipment.

Immunogenic cell death (ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system. However, effective type II ICD inducers without biotoxicity are still very limited. Herein, a tentative drug- or photosensitizer-free strategy was developed by employing enzymatic self-assembly of the peptide F-pY-T to induce mitochondrial oxidative stress in cancer cells. Upon dephosphorylation catalyzed by alkaline phosphatase overexpressed on cancer cells, the peptide F-pY-T self-assembled to form nanoparticles, which were subsequently internalized. These affected the morphology of mitochondria and induced serious reactive oxygen species production, causing the ICD characterized by the release of danger-associated molecular patterns (DAMPs). DAMPs enhanced specific immune responses by promoting the maturation of DCs and the intratumoral infiltration of tumor-specific T cells to eradicate tumor cells. The dramatic immunotherapeutic capacity could be enhanced further by combination therapy of F-pY-T and anti-PD-L1 agents without visible biotoxicity in the main organs. Thus, our results revealed an alternative strategy to induce efficient ICD by physically promoting mitochondrial oxidative stress.

Objective:To explore the practical role of reflective teaching based on Bloom's educational theory in the standardized residency training of gynecology.Methods:A total of 31 residents who participated in the standardized residency training in the Gynecology Department of Beijing Shijitan Hospital Affiliated to Capital Medical University from July 2019 to January 2020 were classified as the control group, and 33 residents who participated in the standardized training from March 2020 to September 2020 were assigned to the observation group. The control group was given routine teaching, and the observation group was given reflective teaching based on Bloom's educational theory. The theoretical test scores and skill operation test scores before and after the training were compared between the two groups, and the clinical ability and teaching satisfaction of the two groups of residents were compared. SPSS 25.0 was used for t-test and Chi-square test. Results:After the standardized training, the scores of theoretical examination [(88.78±5.69) vs. (84.56±5.23)] and skill operation test [(89.37±5.75) vs. (85.22±5.34)] in the observation group were higher than those in the control group, with statistically significant differences. After the standardized training, the team cooperation ability, diagnosis and treatment technology operation ability, problem analysis and solving ability, clinical thinking ability and doctor-patient communication ability of the observation group were higher than those of the control group, and the differences were statistically significant. After the standardized training, the satisfactions with teaching mode, stimulating learning interest, improving self-study ability, improving diagnosis and treatment thinking ability, and improving problem analysis and solving ability in the observation group were higher than those in the control group, and the differences were statistically significant.Conclusion:Reflective teaching based on Bloom's educational theory can improve the professional theoretical knowledge level, clinical operation level, clinical ability and satisfaction of the gynecological residents, and help them to adapt to the clinical work faster.

Objective:To study the relationship between preoperative serum carbohydrate antigen 19-9 (CA19-9) levels and long-term prognosis after partial hepatectomy in patients with hepatocellular carcinoma (HCC).Methods:The clinical data of 1102 patients with HCC who underwent partial hepatectomy at the Affiliated Tumor Hospital of Guangxi Medical University from January 2012 to December 2017 were retrospectively analyzed. There were 960 males and 142 females, with an average age of 51 years. The X-tile software determined the best cut-off value of CA19-9 to be 55U/ml. The enrolled patients were then divided into the low-level (CA19-9≤55 U/ml, n=956) and high-level (CA19-9 >55 U/ml, n=146) groups. The Kaplan-Meier method was used to analyze survival, and the log-rank test was performed to evaluate survival rates. The prognostic risk factors of HCC were calculated by the Cox proportional hazards model. Results:The 1, 3, and 5-year survival rates for the low-level group were 85.0%, 68.2%, and 60.9%, respectively, which were significantly higher than those of the high-level group of 80.1%, 58.2%, and 47.0%, respectively ( P<0.05) . The 1, 3, and 5-year recurrence-free survival rates of the low level group were 60.5%, 44.6%, and 37.9% respectively, which were significantly higher than those in the high-level group of 53.4%, 33.3%, and 25.1%, respectively ( P<0.05). Cox regression analysis showed that patients with CA19-9 >55 U/ml ( HR=1.323, 95% CI: 1.070-1.636, P=0.010) had a higher risk of recurrence after hepatectomy, while patients with CA19-9 >55 U/ml ( HR=1.511, 95% CI: 1.163-1.964, P=0.002) had a poor prognosis after hepatectomy. Conclusions:Preoperative serum level of CA19-9>55 U/ml was an independent risk factor for survival and recurrence of HCC patients after partial hepatectomy. CA19-9 had a significant predictive value for prognosis of HCC patients who underwent partial hepatectomy.

Objective To study the antipyretic effect of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules on the fever model induced by LPS and dry yeast in rats.Methods Fever was induced by ip injecting LPS (100 μg/kg) or sc injecting dry yeast (20％) in rats.We observed the changes of temperature of the rats after administration of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets (the acetaminophen contents were 205.67,102.83,and 51.42 mg/kg)and Chaiqin Qingning Capsules (1110.60,555.30,and 277.65 mg/kg).Maximum temperature rise height (△T) and temperature response index (TRI) were calculated,and the curve of average rise in temperature was drawn.Results Each dose group of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules had obvious antipyretic effect on the fever model induced by LPS and dry yeast in rats,and there was a certain dose-effect relationship.Conclusion Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules has certain antipyretic effect on LPS and dry yeast fever model in rats,and on the whole,the Western medicine acts rapid but continue for a short time,while the traditional Chinese medicine acts slow but continues for a long time.

Objective To study the time-toxicity and dose-toxicity relationship of hepatotoxicity induced by Paracetamol Tablets (PT),Compound Paracetamol and Amantadine Hydrochloride Tablets (CPAH),Compound Dextromethorphan Hydrobromide Tablets (CDH),and Chaiqin Qingning Capsules (CQC) with single dose in mice.Methods In the Time-Toxicity relationship study,Kunming mice were randomly divided into control,PT,CPAH,CDH,and CQC group,and mice of.each drug administration group were randomly divided into nine subgroups according to the time (1,2,4,8,12,24,48,72 and 96 h after administration) of blood collection.The acetaminophen contents in PT,CPAH,and CDH groups were 425.98 mg/kg,and the dose of CQC group was 3 680.50 mg/kg.In the Dosage-Time relationship study,mice were randomly divided into control,PT,CPAH,CDH,and CQC high,medium and low dose group.The acetaminophen contents of high,medium,and low dose were 266.24,425.98,and 681.57 mg/kg in PT,CPAH,and CDH group,and the dose of CQC group was 1437.70,2300.31,and 3680.50 mg/kg,10 mice in each group,sex in half.Blood was collected 12 h after administration.Animal behavior was observed every day,blood and organs were collected at the corresponding time points,serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),and alkaline phosphatase (ALP) level were detected,and the organs index of spleen and thymus,liver were calculated.Results There were no significant changes of ALT,AST,ALP,and organs index after once ig administration of CQC at dosage of 1437.70 mg/kg to 3680.50 mg/kg in mice.The study on time-toxicity relationship indicated that,after once administration of PT,CPAH,and CDH at 425.98 mg/kg,mice showed toxic symptom such as hypokinesia,dry hair and so on,12 h was the most obvious,24 ～ 72 h disappeared.The level of ALT,AST,and ALP in serum increased and reached to the peak at 12 h and then restored near normality after 72,24,and 24 h in PT,CPAH,and CDH group.Their organ index of liver,spleen and thymus all had no significant changes.The study on the dosage-toxicity relationship indicated that,there were no significant changes of animal behavior,ALT,AST,ALP,and organs index after once ig administration of PT,CPAH,and CDH at 266.24 mg/kg.Obvious liver injury can be induced by the three drugs with dosage of 425.98 to 681.57 mg/kg and the level of ALT,AST,and ALP increased significantly with the increase of dosage.Their liver index increased significantly with dosage of 681.57 mg/kg,but the organs index of spleen,thymus had no significant changes.Conclusion There was no hepatotoxicity after once ig administration of CQC with dosage of 3680.50 mg/kg in mice.Mice were once ig administration ofPT,CPAH,and CDH with a large dose,may induce acute liver injury and show obvious time-toxicity and dose-toxicity relationships.