Objective To explore the key active ingredients and action characteristics of Wenxing Jingjintong Gel Patch in the treatment of rheumatoid arthritis(RA)based on the systematic pharmacology and LC-MS/MS technology.Methods The information of active ingredient from Wenxing Jingjintong Gel Patch was established through LC-MS/MS analysis and literature retrieval.The targets of the active ingredients were predicted using Swiss Target Prediction platform and then mapped with the RA-related targets obtained from GeneCards,DrugBank,and OMIM databases to identify the intersecting targets.The"active ingredients-effective targets"network was constructed through the Cytoscape software.The shared targets were imported into STRING database to construct a protein-protein interaction network.GO function and KEGG pathway enrichment analysis were performed using the Metascape database.Molecular docking studies were conducted using AutoDock software to investigate the interactions between key ingredients and target proteins.Results A total of 142 active ingredients were identified in Wenxing Jingjintong Gel Patch by wsing LC-MS/MS,which were further supplemented to 174 through literature retrieval.There were 175 shared targets between the active ingredients and RA.It was anticipated that Wenxing Jingjintong Gel Patch exerted immune regulation and anti-inflammatory and analgesic effects through the interaction between key active ingredients such as berberine,neobavaisoflavone,and palmatine chloride with key targets,including TNF,IL6,and AKT1 to regulate PI3K/Akt1,JAK/STAT,and MAPK signaling pathways.In 1 152 molecular docking validation,94%of them had binding energies less than-5.0 kcal·mol-1,while 51%of them had binding energies less than-7.0 kcal·mol-1.It was indicated that there was a good binding affinity between the potential active ingredients and core targets.Conclusion This study predicted the active ingredients and action characteristics of Wenxing Jingjintong Gel Patch in the treatment of RA,which provided a theoretical basis for further clinical application and quality control.

Objective:To investigate the effect of insular involvement on the outcomes of patients with acute anterior circulation ischemic stroke.Methods:Patients with acute anterior circulation ischemic stroke admitted to the Department of Neurology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2015 to December 2020 were retrospectively included. Demographic data, vascular risk factors, clinical and laboratory data, as well as treatment and outcomes were collected. Firstly, the correlation between the insular involvement and the outcomes was investigated, and then the bootstrap method was used to clarify the mediating role of infarct volume between the insular involvement and the poor outcomes.Results:A total of 450 patients with acute anterior circulation ischemic stroke were enrolled, among whom 79 cases (17.6%) had insular involvement and 41 (9.1%) had left insular involvement. There were 111 (24.7%) with poor outcomes, including 5 (1.1%) died. Compared to the non-insular involvement group, the insular involvement group had a higher proportion of patients with atrial fibrillation, shorter onset to door time, higher neutrophil-to-lymphocyte ratio (NLR), higher National Institutes of Health Stroke Scale (NIHSS) score at admission, larger infarct volume, and higher proportion of patients with poor outcomes (all P<0.05). In addition, patients with left insular involvement were younger than those with right insular involvement, had a higher baseline NIHSS score, a lower proportion of patients with minor stroke (NIHSS score ≤8), and had a longer onset to door time (all P<0.05). Compared to the good outcome group, the poor outcome group was older, with a higher proportion of female patients, higher systolic blood pressure, blood glucose, NLR, and NIHSS scores at admission, larger infarct volume, and a higher proportion of patients with insular involvement (all P<0.05). Mediation analysis suggested that the mediating effect of infarct volume between the insular involvement and the poor outcomes was significant (95% confidence interval 0.033-0.230; P=0.008). Conclusions:insular involvement in patients with acute anterior circulation ischemic stroke is associated with the poor outcomes, and this association may be mediated by infarct volume. Patients with left insular involvement may have more severe symptoms than those with right insular involvement, but there is no significant difference in the outcomes.

Objective:To analyze the risk factors of fatal outcome in patients with severe COVID-19.Methods:The clinical characteristics of 107 patients with severe COVID-19 admitted in Renmin Hospital of Wuhan University from February 12 to March 12, 2020 were retrospectively analyzed. During the hospitalization 49 patients died (fatal group) and 58 patients survived (survival group). The clinical characteristics, baseline laboratory findings were analyzed using R and Python statistical software. The risk factors of fatal outcome in patients with severe COVID-19 were analyzed with multivariate logistic regression.Results:Univariate analysis showed that the two groups had statistically significant differences in age, clinical classification, dry cough, dyspnea and laboratory test indicators ( P<0.05 or <0.01). The random forest model was used to rank the significance of the statistically significant variables in the univariate analysis, and the selected variables were included in the binary logistic regression model. After stepwise regression analysis, the patient’s clinical type, age, neutrophil count, and the proportion of CD3 cells are independent risk factors for death in severe COVID-19 patients. Dry cough is an independent protective factor for the death of severe COVID-19 patients. Conclusion:COVID-19 patients with fatal outcome are more likely to have suppressed immune function, secondary infection and inflammatory factor storm. These factors may work together in severe patients, leading to intractable hypoxemia and multiple organ dysfunction and resulting in fatal outcome of patients. The study indicates that timely intervention and treatment measures against above factors may be effective to save the lives of patients with severe COVID-19.

Objective: To understand the incidence and mortality of colorectal cancer in tumor registration areas of Zhejiang Province,and to provide reference for prevention and control strategies for colorectal cancer. Methods: The colorectal cancer data was retrieved from fourteen tumor registries in Zhejiang Province were collected,the incidence rate and mortality rate were calculated and standardized according to the Chinese standard population in 2010 and Segi's world population in 2000. The incidence and mortality of colorectal cancer in different sex,age group and region were analyzed. Results: The crude incidence rate of colorectal cancer from 2010 to 2014 was 35.82/100 000（20 983 cases）. The standardized incidence rate by Chinese and world standard population were 20.80/100 000 and 23.01/100 000. The crude mortality rate of colorectal cancer was 15.25/100 000 （8 934 cases）. The standardized mortality rate by Chinese and world standard population were 8.01/100 000 and 9.39/100 000. The ratio of mortality to incidence was 0.43:1. From 2010 to 2014,the incidence and mortality rates of colorectal cancer were stable（P>0.05）. The incidence rates of colorectal cancer in urban and rural residents were 37.69/100 000 and 31.14/100 000,and the mortality rates were 15.73/100 000 and 14.05/100 000. The incidence rates of colorectal cancer in males and females were 41.53/100 000 and 30.11/100 000,and the mortality rates were 17.74/100 000 and 12.76/100 000. The incidence and mortality rates of colorectal cancer both increased with age. The incidence rate increased significantly in people after 40 years old,and peaked with 187.35/100 000 in people aged 80-84 years. The morbidity rate peaked with 171.27/100 000 in people aged 85 years or over. Conclusion The incidence and mortality of colorectal cancer in Zhejiang Province were stable,but the incidence was higher than the national average level. The incidence of colorectal cancer in people aged over 40 years increased significantly.

Objective: To investigate the resuscitation effect of aortic balloon occlusion (ABO) on the traumatic cardiac arrest (TCA) in swine. Methods: Twenty-seven male domestic swine weighing (32.7±3.8)kg were utilized. After 40% of estimated blood volume was removed within 20 minutes, the animals were subjected to 5 minutes of untreated ventricular fibrillation and then 5 minutes of cardiopulmonary resuscitation. Additionally, fluid resuscitation was initiated coincident with the beginning of cardiopulmonary resuscitation. The animals were randomly divided into model group (n=12) and ABO group (n=15). Once cardiopulmonary resuscitation was implemented, aortic balloon was concurrently inflated to stop the blood flow of descending thoracic aorta at the level of the diaphragm in the ABO group. In the model group, aortic balloon was placed in the same position without inflation. During cardiopulmonary resuscitation, the changes of coronary perfusion pressure (CPP), forehead's regional cerebral oxygen saturation (rSO₂) and pressure of end-tidal CO₂ (PETCO₂) were continuously monitored, and the rate of return of spontaneous circulation (ROSC), duration of cardiopulmonary resuscitation, number of shocks and dose of epinephrine were recorded. At 5 minutes after successful resuscitation, the levels of arterial blood gas, lactate and jugular venous blood oxygen saturation (SjvO₂) were measured. Results: Compared with the model group, the values of CPP, rSO₂ and PETCO₂ during cardiopulmonary resuscitation were significantly increased in the ABO group [CPP: (33.5±5.6)mmHg vs. (23.1±5.2)mmHg at 1 minute, (35.3±6.0)mmHg vs. (26.8±7.4)mmHg at 2 minutes, (36.3±6.3)mmHg vs. (28.2±6.3)mmHg at 3 minutes, (40.1±7.1)mmHg vs. (30.5±6.2)mmHg at 4 minutes, (38.1±7.5)mmHg vs. (29.8±5.3)mmHg at 5 minutes; rSO₂: (45.4±5.2)% vs. (39.2±5.1)% at 1 minute, (47.2±3.6)% vs. (42.0±6.4)% at 2 minutes, (47.7±3.0)% vs. (41.5±5.4)% at 3 minutes, (47.0±2.5)% vs. (42.1±5.9)% at 4 minutes, (47.1±2.0)% vs. (41.5±7.4)% at 5 minutes; PETCO₂: (17.0±3.5)mmHg vs. (12.7±4.2)mmHg at 1 minute, (18.5±3.7)mmHg vs. (14.5±2.7)mmHg at 2 minutes, (20.7±5.3)mmHg vs. (15.5±3.2)mmHg at 3 minutes, (18.7±4.5)mmHg vs. (14.9±3.5)mmHg at 4 minutes, (18.2±3.2)mmHg vs. (14.5±4.2)mmHg at 5 minutes] (all P<0.05). The rate of ROSC was significantly higher in the ABO group than in the model group[100%(15/15) vs. 75%(9/12)] (P<0.05). Additionally, shorter duration of cardiopulmonary resuscitation, less number of shocks and lower doses of epinephrine were observed in the ABO group when compared with the model group[duration of cardiopulmonary resuscitation: 5(5, 5)minutes vs. 5(5, 12.5)minutes, number of shocks: 1(1, 1)times vs. 1(1, 4)times, dose of epinephrine: 0.62(0.62, 0.74)mg vs. 0.64(0.59, 2.59)mg] (all P<0.05). At 5 minutes after resuscitation, the level of arterial lactate was significantly decreased and the value of SjvO₂ was significantly increased in the ABO group compared with the model group[Lactate: (9.6±0.8)mmol/L vs. (10.8±1.4)mmol/L; SjvO₂: (50.0±8.6)% vs. (37.9±16.3)%] (both P<0.05). Conclusions In a swine model of TCA, ABO can increase cardiac and cerebral perfusion during cardiopulmonary resuscitation and improve the efficacy of cardiopulmonary resuscitation. It might provide a novel and effective method for the resuscitation of TCA in the clinical setting.

Objective To analyze the effect of clinical application of ultrasound in microsurgical treatment of intramedullary tumors in the superior cervical spinal cord.Methods Retrospective study the clinical data of 15 patients with intramedullary tumors in the superior cervical spinal cord,which were underwent a laminectomy for microsurgical tumor resection during January,2014 and January,2018.Intraoperative ultrasound and neuromonitoring was accompanied by the whole surgical procedure for each case.The follow-up data was collected by outpatient department visits and telephone interviews.Results All the described patients were performed with microscopic tumor resection by using intraoperative neurophysiological monitoring and ultrasound.The pathological diagnosis was ependymocytoma (n=8) and astrocytoma (n=7).Gross total resections comprised 86.7％ of cases (n=13),and subtotal resections 13.3％ (n=2).The neurological outcome was as follows:Mc-Cormick scale grade Ⅰ,10 patients;grade Ⅱ,3 patients;grade Ⅲ,1 patient;and grade Ⅳ 1 patient;Follow-up was applied for (19.2±7.6) months in 13 cases and 12.0 months in 2 cases.Compared to the preoperative period,66.6％ of patients recovered postoperatively,20.0％ improved,6.7％ remained without deficit and deterioration persisted in 6.7％.Conclusion The microscopic resection of tumors is the effective way to cure this disease.By using intraoperative neurophysiological monitoring and ultrasound,the complete tumor resection and the minimal spinal cord injury were certainly achieved.

Objective To evaluate preoperative apparent diffusion coefficient (ADC) and exponential apparent diffusion coefficient (eADC) in diffusion weighted imaging (DWI) on microvascular invasion (MVI) of hepatocellular carcinoma (HCC).Methods We retrospectively reviewed 43 HCC patients with DWI data confirmed by surgery and pathology.ADC and eADC values were measured both in neoplasm and hepatic tissue,the ratio of tumor to liver (T/L) on ADC and eADC was calculated.The correlation between MVI and ADC value,T/L of ADC value,eADC value and T/L of eADC value was analysed,the best cut-off value of variables was analysed by ROC curve,multi factor analysis was carried out by Logistic regression model.Results The ADC value,T/L of ADC,eADC value and T/L of eADC were (1.458 ± 0.444) × 10-3 mm2/s,0.787 ± 0.186,0.289 ± 0.144 and 1.383 (1.179,1.655),respectively.Among them,the positive MVI group were (1.232 ± 0.480) × 10-3 mm2/s,0.683 ± 0.229,0.323 ±0.123 and 1.630(1.387,2.066),respectively.The negative MVI group were(1.545 ±0.404) × 10-3mm2/s,0.844 ±0.149,0.277 ±0.152 and 1.303(1.176,1.545),respectively.There was significant difference in ADC value,T/L of ADC value and T/L of eADC value (t =2.164,2.654,z =-2.058,all P ＜0.05),the area under the ROC curve were (1.085 × 10-3) mm2/s,0.685 and 1.475 using MVI as a diagnostic standard.Multivariate analysis showed that T/L of ADC value was an independent factor affecting MVI of HCC (OR=0.002,95％CI:1.380E-5-0.311,P＜0.05).Conclusions The ADC value in HCC patients with positive MVI is lower than in HCC patients with negative MVI,T/L of eADC value is higher than in HCC patients with negative MVI,and T/L of ADC value is an independent factor predicticing MVI of HCC.

Objective To evaluate the effect of mild hypothermia on inositol-requiring enzyme 1 (IRE1) signaling pathway during myocardial injury after cardiac arrest and resuscitation in swine.Methods Twenty-one healthy male white swine,weighing 33-41 kg,were divided into 3 groups using a random number table method:sham operation group (group S,n =5),cardiac arrest-cardiopulmonary resuscitation group (group CA-CPR,n=8),and mild hypothermia group (group MH,n=8).The model of cardiac arrest and resuscitation was established based on the previously reported method.The catheters placed in the left femoral artery and right internal jugular vein were connected to the PiCCO Monitor system,and another pacing catheter was advanced from the right external jugular vein into the right ventricle.Ventricular fibrillation was induced by using a 1 mA alternating current through the pacing catheter.Once ventricular fibrillation was successfully induced,mechanical ventilation was discontinued for 8 min,and then cardiopulmonary resuscitation was initiated.Epinephrine 20 μg/kg was administered at 2.5 min of resuscitation followed by repetition every 3 min.Defibrillation was delivered at 5 min of resuscitation,and then spontaneous circulation was evaluated.If return of spontaneous circulation was not achieved,cardiopulmonary resuscitation was immediately resumed for 2 min and then defibrillation was delivered again.Mechanical ventilation was continued for 30 h after successful resuscitation.Animals in group S only underwent surgical preparation without experiencing cardiac arrest and resuscitation.At 5 min after successful resuscitation,body temperature was cooled down to 33 ℃ by using a cooling blanket,and then maintained at this level until 24 h after resuscitation,followed by 5 h of re-warming at a rate of 1 ℃/h in group MH.The temperature was maintained at 37.5-38.5 ℃ with the aid of surface cooling blanket in the other two groups.At 1,6,12,24 and 30 h after resuscitation (T1-5),the values of stroke volume (SV) and global ejection fraction (GEF) were recorded,and meanwhile 2 ml of blood samples was obtained via the femoral vein to measure the concentration of serum cardiac troponin Ⅰ (cTnI) (by enzyme-linked immunosorbent assay) and activity of serum creatine kinase-MB (CK-MB) (by immunosuppression).The swine were sacrificed at 30 h after resuscitation,and then myocardial specimens from the left ventricle were obtained for determination of the expression of caspase-3 (by immunohistochemistry),cell apoptosis (by TUNEL),and expression of IRE1 and casepase-12 (by Western blot).Apoptosis index was calculated.Results Compared with group S,SV and GEF were significantly decreased and the serum CK-MB activity was increased at T1-5,the concentration of serum cTnI was increased at T2-5,the expression of IRE1,caspase-12 and caspase-3 in myocardium was up-regulated,and apoptosis index was increased in CA-CPR and MH groups (P＜0.05).Compared with group CA-CPR,the SV and GEF were significantly increased and the concentration of serum cTnI was decreased at T2-5,the activity of serum CK-MB was decreased at T3-5,the expression of IRE1,caspase-12 and caspase-3 in myocardium was down-regulated,and apoptosis index was decreased in group MH (P＜0.05).Conclusion The mechanism by which mild hypothermia mitigates myocardial injury after cardiac arrest and resuscitation may be related to inhibiting IRE1 signaling pathway in swine.

Objective To develop a probe for photoacoustic imaging and fluorescence imaging targeting integrin αvβ6 . Methods The probe was separated by RP‐HPLC .Molecular weight and the maximum absorption wavelength of the probe were detected by mass spectrum instrument and optical spectrum instrument . Various concentrations of the probe were detected by photoacoustic imaging and fluorescence imaging . The stability of the probe was evaluated when exposed under laser . Targeting of the probe on integrinαvβ6 was evaluated in cell uptake assay with integrinαvβ6 positive and negative cells . The minimum number of cells that could be detected by photoacoustic imaging and fluorescence imaging was also evaluated . Results The probe ICG‐peptide was separated from reaction mixture by RP‐HPLC .The probe had a retention time of 21 .4 minutes and m/z of 4 727 . The labeling ratio of the probe was 1∶1 . The maximum absorption wavelength of the probe was 790 nm . The photoacoustic signal was linearly dependent on the concentration of the probe . The fluorescence signal was linearly dependent on the concentration of the probe when the concentration was smaller than 1 .5 × 10 -5 mol/L . The lowest concentration of the probe that could be detected above the background by photoacoustic imaging and fluorescence imaging was 0 .09 × 10-5 mol/L and 0 .05 × 10-5 mol/L ,respectively . No obvious decrease of the photoacoustic signal was observed after the probe was scanned 20 times ( each time lasted for 1 min) by laser . There existed differences ( P <0 .001) in cell uptake of the probe with various concentrations and reaction time between A431 cells (αvβ6 positive) and 293T cells (αvβ6 negative) . Cell uptake was inhibited by the addition of 5μmol/L unlabeled peptide in A431 cells ( P = 0 .001 ) . The lowest number of the labeled A431 cells detected by photoacoustic imaging and fluorescence imaging was 0 .4 × 106 and 0 .05 × 106 ,respectively . Conclusions The dual functional photoacoustic and fluorescence probe targeting integrin αvβ6 was successfully developed . The targeting and sensitivity of the probe makes it potentially useful in early detection of αvβ6 positive tumors .

An instrumental analysis method for the determination of stable silicon isotope ratio using multi-collector inductively coupled plasma mass spectrometry ( MC-ICP-MS) was established. In dry plasma mode, silicon isotopes suffered from the spectrum polyatomic interferences of C, N, O, H at medium resolution. The sample gas flow had significant effect on the silicon sensitivity and signal stability. Besides, higher sample gas flow lead to higher production of 14N16O. Consistent δ29Si and δ30Si within 0. 04‰ (1σ) could be obtained over a mass range of ca. 9 milli-amu at the lower mass side of silicon at medium resolution. The analyte concentrations of the sample and reference material were matched within 20% to avoid concentration effect on the determination of silicon isotopes using standard-sample-bracketing correction method. The measurements were not sensitive to the acid molarity and Cl matrix. An internal precision of less than 8×10-6(1σ) could be achieved for 29 Si/ 28 Si and 30 Si/ 28 Si by taking an integration time of 8 seconds. The long-term reproducibility of 0 . 06‰-0 . 10‰ ( 2σ, n=20 ) was obtained for δ29 Si and δ30 Si by repeating the analysis of the silicon reference materials, whilst the determined isotopic value for GBW04421 and GBW04422 were in good agreement with the recommended data, suggesting the precision and robustness of this method. The measured silicon isotopic values of fresh waters ( river and lake waters ) , saline waters and seawater demonstrated the capability of applying this method to trace the biogeochemical processes of silicon in natural waters.