OBJECTIVE To screen the prescription and preparation method of Bupleurum nanoemulsion, and evaluate its quality, study the antipyretic effect. METHODS The emulsifier and co-emulsifier of the nanoemulsion were preliminarily screened, and then the prescription was screened by pseudo-ternary phase diagram. The quality evaluation of the appearance, particle size distribution, structure type, stability and content of the prepared Bupleurum nanoemulsion was performed. Wistar rats were further randomly divided into blank control group, model control group, positive control group(aspirin group), Bupleurum nanoemulsion high-dose, medium-dose and low-dose groups(18.00, 9.00, 3.00 g·kg−1). Except for the blank control group, the pathological model of fever rats was prepared in the other groups. According to the scheduled experimental requirements, rats in each group were given the corresponding drugs. And the temperature changes of rats in each group were recorded at 0.5, 1, 1.5, 2, 3 h to observe the antipyretic effect of Bupleurum nanoemulsion. RESULTS The best prescription of Bupleurum nanoemulsion: Tween-80 6 g and n-butanol 3 g, Bupleurum extract dissolved in pure water as water phase 20 mL, Bupleurum oil as oil phase 2 g. At room temperature, the Bupleurum nanoemulsion was a yellow-brown clear and transparent liquid, O/W nanoemulsion, with an average particle size of (77.21±3.66)nm, polydispersity index of 0.28±0.04, Zeta potential of (–18.81±1.42)mV, and saikosaponin content of 3.071 mg·mL−1, with good stability. In animal experiments, compared with the model control group, the rectal temperature of aspirin group and Bupleurum nanoemulsion high-dose group was significantly lower after the first administration(P<0.01), the rectal temperature of Bupleurum nanoemulsion middle-dose group was significantly lower after the first administration 2, 3 h(P<0.01). CONCLUSION The Bupleurum nanoemulsion is transparent and stable, and it has good antipyretic effect on fever rat model.

Objective:To assess the mediating effects of obesity and metabolic factors in the relationship between hyperuricemia (HUA) and prehypertension.Methods:A total of 9 399 individuals were selected using a multistage stratified whole-group random sampling method from 90 villages (neighborhood committees) in 30 towns (streets) of 5 districts (counties) in Fuzhou. A total of 4 754 study subjects were included. A linear regression model was used to analyze the association of HUA with obesity and metabolic factors. Single-factor and multi-factor logistic regression models were used to analyze the association of HUA, obesity, and metabolic factors with prehypertension. Mediating effects models were used to analyze the mediating effects of obesity and metabolic factors on the association between HUA and prehypertension.Results:After adjusting for confounders, the association between HUA and cholesterol, triglycerides, HDL-C, LDL-C, BMI, waist circumference, creatinine, and urea nitrogen were significantly correlated ( P<0.001). HUA, waist circumference, BMI, and triglycerides were significantly associated with prehypertension ( P<0.001). Waist circumference, BMI, and triglycerides mediated the relationship between HUA and prehypertension, with OR (95% CI) of 1.018 (1.007-1.027), 1.010 (1.002-1.018), and 1.010 (1.003-1.017) ( P<0.001), with mediating proportions of 7.76%, 4.31%, and 4.31% respectively. No mediating effect of cholesterol, HDL-C, LDL-C, creatinine, and urea nitrogen was found on the relationship ( P>0.05). Conclusions:Waist circumference, BMI, and triglycerides all had mediating effects in the association between HUA and prehypertension. For the general population, weight control, waist circumference, and a high-fat diet should be used to reduce the occurrence of prehypertension.

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.
Humans ; COVID-19 Vaccines ; Leukocytes, Mononuclear ; Proteomics ; COVID-19/prevention & control* ; Vaccination ; Antibodies ; Antibodies, Viral ; Antibodies, Neutralizing

Objective: To explore the effect of C1q / tumor necrosis factor-related protein 9 ( CTRP9 ) on the expression of genes and proteins related to lipid metabolism of brown adipose tissue (BAT) in mice after cold stimulation． Methods : C57BL /6J male mice were injected with adenovirus Ad-GFP (control group) or Ad-CTRP9 ( experience group) into the scapular region and kept for 7 days．After cold stimulation at 4 ℃ for 10 hours，the expression levels of BAT marker genes and proteins were detected by real time PCR and Western blot. Results: Overexpression of CTRP9 induced by cold stimulation significantly increased the mRNA level of iodothyronine deiodinase 2 (Dio2) in BAT (P＜0. 01) ．Additionally，there was no significant difference in the expression of BAT marker genes ( UCP-1，PGC-1 α , PRDM16 and ARβ3) ，and liposynthesis and lipolysis related genes (PPARγ , HSL and ATGL) ．Uncoupling protein 1 (UCP-1) protein expression was upregualted in Ad-CTRP9 compared to the Ad-GFP control group ，while the expression of lipolysis related protein adipose triglyceride lipase ( ATGL) decreased significantly (P＜0. 05) ． Conclusion In cold environment，overexpression of CTRP9 promotes the accumulation of UCP-1 protein in BAT，upregulates the expression of thyroid hormone signal related gene Dio2，and inhibits triglyceride hydrolysis to maintain a constant body temperature.

Objective To explore the possibility of β-lactoglobulin(BLG)as carrier of tamoxifen.Methods The binding mechanism of BLG and tamoxifen was studied by spectroscopic technique.Results Tamoxifen would lead to the fluorescence quenching of BLG,and its Kq value was much higher than the maximal Kq value of the dynamic quenching constant[(2.0 × 1010 mol/(L·s)].The quench-ing constant values were different under different pH values,and the values of thermodynamic parame-ters △H and △S were greater than 0.BLG can be combined with tamoxifen to form BLG-tamoxifen complex,and the endothermic process took hydrophobic force as the main force.Tamoxifen and BLG had different binding patterns under acidic and alkaline conditions,which mainly depended on the opening and closing state of the EF ring of BLG.Conclusion BLG has the ability to bind tamoxifen,which shows the potential value of BLG as a carrier of insoluble drugs.

Objective To explore the possibility of β-lactoglobulin(BLG)as carrier of tamoxifen.Methods The binding mechanism of BLG and tamoxifen was studied by spectroscopic technique.Results Tamoxifen would lead to the fluorescence quenching of BLG,and its Kq value was much higher than the maximal Kq value of the dynamic quenching constant[(2.0 × 1010 mol/(L·s)].The quench-ing constant values were different under different pH values,and the values of thermodynamic parame-ters △H and △S were greater than 0.BLG can be combined with tamoxifen to form BLG-tamoxifen complex,and the endothermic process took hydrophobic force as the main force.Tamoxifen and BLG had different binding patterns under acidic and alkaline conditions,which mainly depended on the opening and closing state of the EF ring of BLG.Conclusion BLG has the ability to bind tamoxifen,which shows the potential value of BLG as a carrier of insoluble drugs.

OBJECTIVE To study the efficacy of sinapine thiocyanate dissoluble microneedle （ST-DMN） for acupoint administration against bronchial asthma （BA）. METHODS The network pharmacology and molecular docking techniques were used to screen the core targets of sinapine thiocyanate （ST） against BA， and the pharmacodynamics of the top 3 core targets was studied. Firstly， ST-DMN was prepared （drug loading of ST was 1 mg/tablet）； secondly， 30 rats were divided into blank control group， model control group， blank microneedle group， Sinapine powder plaster group （positive control group） and ST-DMN group. Except for the blank control group， rats of other groups were sensitized with 10% ovalbumin （containing aluminum hydroxide adjuvant） and nebulized with 1% ovalbumin to induce the BA model. After modeling， blank control group did not receive any intervention； normal saline was applied to the Feishu acupoint and Dazhui acupoint of the rats in the model control group， while the blank microneedle group， Sinapine powder plaster group and ST-DMN group were given blank microneedle， Sinapis alba powder （plaster， 1.5 g） and ST-DMN （3 tablets at 2 acupoints） at same acupoint， once a day， for 28 consecutive days. After administration， the general symptoms were observed and the body mass of the rats was measured.pathological changes of lung tissues in rats was observed； the levels of prostaglandin endoperoxide synthase 2 （PTGS2）， GNYL matrix metalloproteinase-9 （MMP-9） and interleukin-2 （IL-2）in serum， bronchoalveolar lavage fluid （BALF） and lung tissues were determined. RESULTS Results of network pharmacology and molecular docking showed that the key targets of ST against BA were identified as PTGS2， MMP-9， IL-2， epidermal growth factor receptor， heat shock protein90AA1， etc. Pharmacodynamic experiments showed that compared with model control group， relieved cough， restored hair color， sensitive behavior， stable respiration and increased body weight were all found in ST-DMN group； the histopathological changes as the structure of lung tissue， infiltration of alveolar epithelial cells and pulmonary interstitial inflammatory cells were improved to different extent； the levels of PTGS2， MMP-9 and IL-2 in serum， BALF and lung tissue were significantly reduced （P＜0.05 or P＜0.01）. CONCLUSIONS The anti-BA effect of ST-DMN acupoint administration is good， the mechanism of which may be associated with decreasing the levels of PTGS2， MMP-9 and IL-2 in serum， BALF and lung tissue.

Objective:To investigate the optimal keV value of a novel dual-layer spectral detector CT virtual monoenergetic images (VMI) for displaying esophageal cancer lesions and to evaluate its diagnostic efficacy for preoperative T staging of esophageal cancer.Methods:The data of 50 patients with esophageal carcinoma in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from October 2019 to August 2020 were retrospectively analyzed. There were 42 males and 8 females, aged 49-78(65±7) years. All patients underwent novel dual-layer spectral detector CT chest enhanced scan before treatment, the conventional CT images and 40-200 keV VMI were reconstructed. One-way ANOVA and Kruskal-Wallis H rank sum test were used to compare the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) among conventional CT images and 40-200 keV VMI.The 5-grade grading method were applied for subjective evaluation, and the Friedman test was used to compare the differences in the subjective evaluation of image quality in each group.Spearman test was used to analyze the correlation of images at different energy levels with SNR and CNR. Fisher exact test was used to compare the accuracy of conventional CT and optimal keV value images for preoperative diagnosis of T staging of esophageal cancer. Results:There were significant differences in SNR and CNR among conventional CT images and 40-200 keV VMI images ( P<0.001), and the SNR and CNR of 40 keV images were superior to those of conventional CT images and 70-200 keV VMI images ( P<0.05). The energy level of 40-200 keV VMI was negatively correlated with SNR and CNR (SNR: r=-1.000, P<0.001; CNR: r =-1.000, P<0.001). The overall difference in subjective image quality scores among conventional CT images and 40-200 keV VMI was statistically significant (χ 2=498.37, P<0.001), of which the subjective image quality of 40-60 keV VMI was superior to that of conventional CT images ( P<0.05). The accuracy of preoperative diagnosis of T-stage of esophageal cancer was 62.9% (22/35) for both 40 keV VMI and conventional CT images. Conclusion:The novel dual-layer spectral detector CT of 40 keV VMI has the best display of esophageal cancer, and the accuracy of preoperative diagnosis of T staging is similar to that of conventional CT.

Objective:To establish a risk prediction model for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) using regression analysis and verify the model.Methods:The risk factors and acute exacerbation of 1 326 patients with chronic obstructive pulmonary disease (COPD) who entered the stable phase and followed up for 6 months in the four completed multi-center large-sample randomized controlled trials were retrospectively analyzed. Using the conversion-random number generator, about 80% of the 1 326 cases were randomly selected as the model group ( n = 1 074), and about 20% were the verification group ( n = 252). The data from the model group were selected, and Logistic regression analysis was used to screen independent risk factors for AECOPD, and an AECOPD risk prediction model was established; the model group and validation group data were substituted into the model, respectively, and the receiver operating characteristic (ROC) curve was drawn to verify the effectiveness of the risk prediction model in predicting AECOPD. Results:There were no statistically significant differences in general information (gender, smoking status, comorbidities, education level, etc.), body mass index (BMI) classification, lung function [forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), etc.], disease status (the number and duration of acute exacerbation in the past year, duration of disease, etc.), quality of life scale [COPD assessment test (CAT), etc.] and clinical symptoms (cough, chest tightness, etc.) between the model group and the validation group. It showed that the two sets of data had good homogeneity, and the cases in the validation group could be used to verify the effectiveness of the risk prediction model established through the model group data to predict AECOPD. Logistic regression analysis showed that gender [odds ratio ( OR) = 1.679, 95% confidence interval (95% CI) was 1.221-2.308, P = 0.001], BMI classification ( OR = 0.576, 95% CI was 0.331-1.000, P = 0.050), FEV1 ( OR = 0.551, 95% CI was 0.352-0.863, P = 0.009), number of acute exacerbation ( OR = 1.344, 95% CI was 1.245-1.451, P = 0.000) and duration of acute exacerbation ( OR = 1.018, 95% CI was 1.002-1.034, P = 0.024) were independent risk factors for AECOPD. A risk prediction model for AECOPD was constructed based on the results of regression analysis: probability of acute exacerbation ( P) = 1/(1+ e- x), x = -3.274 + 0.518×gender-0.552×BMI classification + 0.296×number of acute exacerbation + 0.018×duration of acute exacerbation-0.596×FEV1. The ROC curve analysis verified that the area under ROC curve (AUC) of the model group was 0.740, the AUC of the verification group was 0.688; the maximum Youden index of the model was 0.371, the corresponding best cut-off value of prediction probability was 0.197, the sensitivity was 80.1%, and the specificity was 57.0%. Conclusion:The AECOPD risk prediction model based on the regression analysis method had a moderate predictive power for the acute exacerbation risk of COPD patients, and could assist clinical diagnosis and treatment decision in a certain degree.

Objective:To evaluate the efficacy of holographic image technology in robot-assisted laparoscopic radical prostatectomy (RARP).Methods:The clinical data of 34 patients with prostate cancer who underwent RARP in our hospital during October 2020 and December 2020 was analyzed retrospectively. The average age of the patients was 67.8 (52-78) years. The mean BMI was 25.8 (18.0-32.3) kg/m 2. The median level of PSA before surgery was 13.4 (2-149) ng/ml. Median prostate volume was 31.7 (9.5-159.1) ml. EAU risk groups for biochemical recurrence of localised and locally advanced prostate cancer were list as below: 5 cases of low-risk, 7 cases of medium-risk, 22 cases of high-risk. There were 9, 16, 9 cases with the ASA score of 1, 2, 3 point, respectively. Preoperative Gleason score of 34 patients were list as below: 9 cases in score ≤6 group, 15 cases in score=7 group, 10 cases in score ≥8 group. For clinical stage before the surgery, 13 cases ≤T 2a stage, 1 case in T 2b stage, 20 cases ≥T 2c stage. The engineers established holographic images of 34 patients based on multiparametric magnetic resonance imaging (mpMRI) and the reports before the operation. Surgeons can obtain the size and location of tumors, surrounding neurovascular bundles visually by revolving, assembling, disassembling and concealing images, which was helpful for pre-surgery planning. By manipulating the holographic images extracorporeally, surgeons can discriminate Internal sphincter of urinary bladder and vesicoprostatic muscle, neurovascular bundles, membranous part, seminal vesicle easily, which improves the operation accuracy. Results:All 34 cases underwent operation successfully without transferring to open surgery. The median operative time was 157.5 (95-276) min with an estimated blood loss of 50 (20-300) ml. The median drainage removal time was 2 d and median hospitalization time was 3.5 d, respectively. The catheters were removed within an average time of 20.5 d. For postoperative Gleason score, there were 2 cases in score ≤6 group, 16 cases in score =7 group, 8 cases in score ≥8 group and 8 cases can’t make a score. For clinical stage after the surgery, 10 cases were ≤T 2a stage, 1 case was T 2b stage, 23 cases were ≥cT 2c stage. 22 cases underwent pelvic lymph node dissection, including a patient with right iliac fossa lymph node metastasis. There were 2 cases with positive surgical margin and 3 cases with Clavien-DindoⅠcomplications. The rate of 1-month and 3-month urinary continence were 47.1% and79.4%, respectively, 8 cases recovered erectile function after 3 month. Conclusions:Holographic image technology can promote cancer dissection completely, achieve urinary continence early and reduce perioperative complications tremendously. The technology is the "intraoperative security" for the accurate surgical treatment of prostate cancer.