Objective:To investigate the protective effect and mechanism of 4-octyl itaconate(4-OI)on vascular endothelial function in diabetic mice,since endothelial dysfunction is the key and initial factor for vascular complications in diabetes.Methods:The db/db mice were used to establish a mouse model of diabetes,and high glucose(HG)-induced human umbilical vein endothelial cells(HUVECs)were used to establish a cell model of diabetes.After 4-OI treatment,HE staining,Masson staining,and reticular fiber staining were used to observe pathological changes of the thoracic aorta in the control group,the model group,and the intervention group;Western blot was used to measure the expression of α-smooth muscle actin(α-SMA),a marker for endothelial fibrosis;immuno-fluorescence assay was used to measure the expression levels of Bcl-2-associated X protein(BAX)and B-cell lymphoma-2(Bcl-2)in the thoracic aorta of mice in the control group,the model group,and the intervention group;immunoblotting was used to observe the effect of 4-OI intervention on the expression of BAX,Bcl-2,and the proteins associated with the cytochrome C(CytC)/cysteinyl aspartate specific proteinase(caspase)pathway in HG-induced HUVECs.Results:The results showed that 4-OI could significantly improve vascular endothelial dysfunction in db/db diabetic mice.Compared with the model group,the intervention group had a significant increase in the expression of Bcl-2(0.73±0.07 vs.0.52±0.04,F=49.380,P=0.009)and a significant reduction in the expression of BAX(1.41±0.14 vs.1.89±0.12,F=37.270,P=0.008)after 4-OI treatment.In the cell model of HUVECs induced by HG,compared with the high glucose group,the intervention group had a sig-nificant increase in the expression of Bcl-2(1.22±0.04 vs.0.81±0.09,F=75.410,P<0.001)and a significant reduction in the expres-sion of BAX(0.83±0.04 vs.1.12±0.04,F=268.100,P<0.001)after 4-OI treatment,as well as significant reductions in the expres-sion of CytC(0.61±0.03 vs.1.01±0.03,F=234.000,P<0.001),caspase-9(0.62±0.03 vs.1.04±0.04,F=164.300,P<0.001),and caspase-3(0.92±0.06 vs.1.74±0.04,F=424.100,P<0.001).Conclusion:In conclusion,4-OI inhibits vascular endothelial cell apoptosis in diabetic mice by affecting the expression of the CytC/Caspase pathway factors,thereby improving vascular endothelial dys-function in diabetes.

ObjectiveTo investigate the potential targets and mechanisms of Draconis Sanguis (DS), a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl (D. Sanguis, Xue Jie), in the treatment of myocardial infarction (MI).MethodsWe explored the potential mechanisms of DS in the treatment of MI using network pharmacology, bioinformatic techniques, and transcriptomic analysis, followed by validation through in vivo and in vitro experiments.ResultsNetwork pharmacology and bioinformatic analyses identified five genes (Fpr1, Glul, Mme, Mmp9, and Pla2g7) as potential targets for MI treatment. Moreover, DS significantly ameliorated cardiac function, inflammatory responses, and MI-induced myocardial fibrosis in vivo. Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI. Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene. Furthermore, DS reduced the expression of Pla2g7 (P = .0009), NLRP3 (P = .003), interleukin-18 (P .001), and interleukin-1β (P = .004) mRNAs in vivo.ConclusionsThe results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response. This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.

Objective To predict the prognosis of patients after cardiac surgery by implementing hemodynamic monitoring collective strategy—CHOLKIT protocol,and to explore the practical application value of CHOLKIT protocol,such as early intervention to improve tissue circulation and microcirculation,and predict the timing of extubation.Methods A prospective cohort study was used to analyse 88 patients who underwent cardiac surgery in the First Affiliated Hospital of Xinjiang Medical University from April to October 2020,and they were divided into the survival group (84 cases) and the death group (4 cases) with patient survival or death as the study endpoint.The CHOLKIT protocol was applied to score the central venous pressure (CVP),heart rate (HR),central venous oxygen saturation (ScvO2),lactic acid (Lac),potassium (K+),perfusion index (PI),and toe temperature (T) of patients at different time periods.The correlation between CHOLKIT score and prognosis was predicted based on the scores.Results Some monitoring indexes in the CHOLKIT protocol were related to the mortality,renal injury and duration of mechanical ventilation after cardiac surgery.Conclusion The CHOLKIT protocol can predict the timing of extubation and the change of the condition of patients after cardiac surgery,and early intervention can improve the prognosis of patients,duration of mechanical ventilation and number of days of stay in the intensive care unit.

Objective: We aimed to investigate whether 2-[ 18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[ 18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. Materials and Methods: This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[ 18F]FDG PET/CT for endoscopy-detected ampullary tumors 5–87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. Results: The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in earlyphase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13–36.18;P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80–13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41–19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00–14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16–21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874–0.956] vs. 0.815 [0.732–0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816–0.967) in candidates for endoscopic papillectomy. Conclusion Adding 2-[ 18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.

Objective:To evaluate the effect of surgery under propofol anesthesia during mid-pregnancy on the cognitive function and hippocampal histone deacetylase 2 (HDAC2)-cAMP response element-binding protein (CREB)-N-methyl-D-aspartate (NMDA) receptor 2B subunit (NR2B)-containing NMDA receptor (NR2B) signaling pathway in the offspring rats.Methods:Thirty healthy Sprague-Dawley rats at 14 days of gestation were divided into 3 groups ( n=10 each) using a random number table method: propofol anesthesia group (P group), surgery under propofol anesthesia group (S group) and control group (C group). In S group, propofol 20 mg/kg was injected via the caudal vein, and then propofol was continuously infused at a rate of 20 mg·kg -1·h -1 to maintain anesthesia for 4 h, and exploratory laparotomy was performed. Group P received no exploratory laparotomy and the other treatments were similar to those previously described in group S. The equal volume of normal saline was given instead in group C. The learning and memory of the offspring rats was assessed using Morris water maze test on postnatal day 30. The expression of HDAC2, phosphorylated CREB (p-CREB), NR2B, brain-derived neurotriphic factor (BDNF) and phosphorylated tyrosine kinase B (p-TrkB) in offspring′s hippocampi was evaluated by Western blot. Apoptosis in hippocampal neurons was detected by TUNEL staining. Results:Compared with group C, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the time spent in the second quadrant was shortened, the expression of HDAC2 was up-regulated, the expression of p-CREB, NR2B, BDNF and p-TrkB was down-regulated, and the apoptosis rate of the hippocampal neurons was increased in P and S groups ( P<0.05). Compared with P group, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the time spent in the second quadrant was shortened, the expression of HDAC2 was up-regulated, the expression of p-CREB, NR2B, BDNF and p-TrkB was down-regulated, and the apoptosis rate of the hippocampal neurons was increased in S group ( P<0.05). Conclusions:Surgery under propofol anesthesia during mid-pregnancy can decrease the cognitive function of offspring rats, and the mechanism is related to the regulation of HDAC2-CREB-NR2B signaling pathway and the promotion of apoptosis in hippocampal neurons.

Objective:To investigate the clinical significance of a new classification system for atlas fractures based on pre- and post-treatment CT features, with a focus on diagnosis and treatment.Methods:A retrospective analysis was conducted on 75 cases of cervical vertebra fractures treated at the Sixth Hospital of Ningbo City between January 2015 and December 2020. The study included 44 males and 31 females, with an average age of 53.3±13.0 years (range: 27-81 years). The fractures were classified according to the Landells classification, resulting in 12 cases of type I, 13 cases of type II, 33 cases of type III, 9 cases that were difficult to classify due to fracture lines located at anatomical junctions, and 8 cases that could not be classified using the Landells classification due to diverse injury mechanisms. To establish a new preliminary classification for cervical vertebra fractures, the researchers considered whether the fracture line in the CT images involved the facet joint surface of the atlas, the impact on bilateral half-rings, and the displacement distance of the fracture ends. Five spinal surgeons were randomly selected to classify the CT images of the 75 patients using the new classification method. After one month, the imaging data of the 75 cases of cervical vertebra fractures were randomized and reclassified to assess the reliability and repeatability of the classification.Results:The new cervical vertebra fracture classification method comprised three types based on whether the fracture line involved the facet joint surface of the atlas: type A (no involvement of the facet joint surface of the atlas), type B (involvement of one side of the facet joint surface with intact contralateral half-ring), and type C (involvement of one side of the facet joint surface with fractured contralateral half-ring). Additionally, based on the maximum displacement distance between the fracture ends (>4 mm), six subtypes were identified: subtype 1 (≤4 mm displacement) and subtype 2 (>4 mm displacement). Consequently, the subtypes were classified as A1, A2, B1, B2, C1, and C2. According to the new classification method, the 75 patients included 17 cases of A1, 12 cases of A2, 7 cases of B1, 13 cases of B2, 12 cases of C1, and 14 cases of C2. The classification demonstrated excellent consistency, as assessed by the five doctors, with Kappa values of 0.85 and 0.91 for reliability and repeatability, respectively. At the final follow-up, all conservatively treated patients achieved bone healing, while four surgically treated patients experienced non-union of the fracture ends but exhibited good fusion between the atlas and axis. The remaining surgically treated patients achieved bony union without complications such as loosening or fracture of internal fixation.Conclusion:The new cervical vertebra fracture classification method, based on CT imaging features, comprehensively covers common clinical cases of cervical vertebra fractures and demonstrates excellent consistency. It provides valuable clinical guidance for the diagnosis and treatment of cervical vertebra fractures.

To study the chemical constituents of petroleum ether extract from the stems and leaves of Humulus scandens (family of Moraceae), fifteen compounds were isolated from the stems and leaves of H.scandens by silica gel, Sephadex LH-20, ODS, and preparative HPLC chromatography.The structures were identified by physicochemical data and spectroscopic method as tectochrysin (1), chrysin (2), 5-hydroxy-3, 4'', 6, 7-tetramethoxyflavone (3), (2S)-5-hydroxy-7, 8-dimethoxyflavanone (4), imperatorin (5), phellopterin (6), ethyl 4-hydroxy-3-(3''-methyl-2''-butenyl)benzoate (7), p-hydroxy-phenylpropionic acid (8), ethyl p-hydroxycinnamate (9), p-hydroxybenzaldehyde (10), anofinic acid (11), 5,6-dehydrokavain (12), physcion (13), olean-12-ene-3,?11-dione (14) and ergosta-4, 6, 8 (14), 22-tetraen-3-one (15), respectively.All compounds were isolated from this plant for the first time.

Objective:To explore the difference in properties of anterior occipital condyle plate screws compared with common anterior occipitalcervical fusion internal fixation.Methods:A 28-year-old healthy adult male volunteer's CT data of the occiput and neck was selected to establish finite element models：including the normal model，simple artificial vertebral fixation model（special-shaped titanium cage+clival screws），anterior occipital condyle plate and screw fixation model，and clival plate and screw fixation model，then a 50 N gravity and a torque of 1.5 N m were exerted upon the upper surface of the occipital bone to make the model produce flexion and extension，lateral bending and rotation. The motion range，internal fixation stress distribution and occipital bone stress distribution of each model under varying conditions were compared.Results:Under the conditions of flexion，extension，lateral bending and rotation，the range of motion of the normal model was 18.65°，15.35°，9.82° and 34.68°，respectively；that of the simple artificial vertebral fixation model was 3.20°，3.63°，2.94° and 3.92°，respectively；that of the clival plate and screw fixation model was 0.40°，0.50°，0.35° and 0.89°，respectively；that of the anterior occipital condylar plate and screw fixation model was 0.27°，0.33°，0.13° and 0.30°，respectively. Compared with the simple artificial vertebral fixation model，the range of motion of the clival plate and screw fixation model decreased by 87.5%，86.2%，88.1% and 77.3% in flexion，extension，lateral bending and rotation. The range of motion of the anterior occipital condylar plate and screw fixation model decreased by 91.5%，90.1%，95.6% and 92.3%，respectively. Under the conditions of flexion and extension，lateral bending and rotation，the stress peak of the simple artificial vertebral fixation model was 52.3 MPa，51.9 MPa，52.6 MPa，respectively；that of the clival plate and screw fixation was 100.1 MPa，158.1 MPa，170.6 MPa，respectively；that of the anterior occipital condylar plate and screw fixation was 114.2 MPa，62.9 MPa，132.9 MPa，respectively. Under the condition of flexion and extension，lateral bending and rotation，the stress peak of the occipital bone in the simple artificial vertebral body internal fixation model was 52.9 MPa，50.9 MPa and 62.3 MPa，respectively；that of the clival plate and screw fixation model was 19.7 MPa，55.9 MPa and 38.3 MPa，respectively；that of the anterior occipital condylar plate and screw fixation model was 37.8 MPa，15.0 MPa and 16.3 MPa，respectively. The stress in bone near the hypoglossal canal was close to 0 MPa，much smaller than the stress peak in occipital bone.Conclusion:Anterior occipital condylar plate and screw fixation in front of the special-shaped titanium cage can improve the stability of occipitocervical fusion with little effect on the occipital bone and hypoglossal canal or without obvious stress concentration，and hence is a safe and reliable anterior fixation method for upper cervical spine instability.

The emergence of regular short repetitive palindromic sequence clusters (CRISPR) and CRISPR- associated proteins 9 (Cas9) gene editing technology has greatly promoted the wide application of genetically modified pigs. Efficient single guide RNA (sgRNA) is the key to the success of gene editing using CRISPR/Cas9 technology. For large animals with a long reproductive cycle, such as pigs, it is necessary to screen out efficient sgRNA
Animals ; CRISPR-Cas Systems/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; Gene Editing ; RNA, Guide/genetics* ; Swine

Objective:To investigate the safety of posterior atlantoaxial transarticular screw combined with atlas pedicle screw fixation in Chinese.Methods:CT data of upper cervical spine in 48 patients were collected from Ningbo No.6 Hospital, including 26 males and 22 females aged 26-58 years [(37.3±13.5)years]. All CT data was transformed into 3D dimensional model and inserted with virtual screws by Mimics 19.0. Firstly, the vertical plane P 1 and the horizontal plane P 2 of the atlas were built in those atlantoaxial models, secondly the atlantoaxial transarticular screw S 0 was inserted by Margel method, and it's insertion point was located at 3 mm lateral and 2 mm cephalad in the C 2 inferior articular process. Finally, four atlas pedicle screws were inserted at the midline of atlas lateral mass. The four screws are inserted as follows. S 1: the screw was tangent to the lateral side of the S 0 or the medial of the atlas pedicle. S 2: the screw was tangent to the lateral wall of the atlas pedicle. S 3: the screw was tangent to the upper wall of the atlas pedicle. S 4: the screw was tangent to the inferior wall of the atlas pedicle. The angles between S 1, S 2 and P 1 as the camber angle, and the angle between S 3, S 4 and P 2 as the gantry angle were measured. Then the safety range of camber angle and gantry angle were calculated, and the screw length of S 1, S 2, S 3 and S 4 was measured. In all models, the camber angle and gantry angle of the screws were adjusted an interval of 2°, the number of successful cases was calculated and the success rate of insertion was calculated. Results:All 3D models were inserted successfully. The minimum value, maximum value and safety range of the camber angle of atlas pedicle screws were (-6.7±5.2)°, (10.4± 4.3)°, (17.1±3.7)°, respectively; and of the gantry angle were (-0.5±3.5)°, (11.0±5.8)°, (11.5±4.9)°, respectively. The length of screw placement was S 1: (31.1±2.4)mm, S 2: (28.3±2.5)mm, S 3: (29.2±3.8)mm, S 4: (29.6±3.0)mm, respectively ( P<0.05). When the camber angle was from -1°to 5°, the success rate of screw placement was 87.5%; when inserting with 2° camber angle, the success rate was 100%; when the gantry angle was 5°, the success rate was 93.8%. Conclusion:The posterior atlantoaxial transarticular screw combined with atlas pedicle screw can achieve satisfy insertion length and success rate.