AIM:To investigate the mechanism of action of Wenweiyang decoction(WWYD)in treating func-tional dyspepsia in rats based on mast cell activation and stem cell factor(SCF)/receptor tyrosine kinase c-Kit signaling pathway.METHODS:Sixty SD rats were randomly divided into control group,model group,ranitidine hydrochloride capsule group,and low-,medium-and high-dose WWYD groups,with 10 rats in each group.The rat model of functional dyspepsia was established by tail clamping and irregular feeding compound senna method.After modeling,the rats in con-trol group and model group were given normal saline,while those in low-,medium-and high-dose(0.743 g/mL,1.485 g/mL and 2.970 g/mL)WWYD groups and ranitidine hydrochloride capsule(3 g/L)group were treated with corresponding drugs by intragastric administration.After treatment,the propulsion rate of the small intestine was measured by the carbon ink propulsion method.Rat duodenal mast cells were observed and counted by toluidine blue staining.ELISA was used for determination of mast cell tryptase(MCT)and histamine(HA)content in rat duodenum.The mRNA levels of SCF and c-Kit in duodenum were detected by RT-qPCR.Western blot and immunohistochemistry were employed to determine the ex-pression levels of SCF and c-Kit in the duodenum.RESULTS:Compared with model group,WWYD treatment signifi-cantly increased the propulsion rate of the small intestine in rats(P<0.05).ELISA results showed that WWYD reduced the number of mast cells and the content of MCT and HA in the duodenal mucosa tissue of rats(P<0.05).Western blot and immunohistochemistry results suggested that WWYD up-regulated the protein expression levels of c-Kit and SCF in the duodenal tissue of rats(P<0.05),and increased the numbers of SCF and c-Kit positive cells.RT-qPCR results indicated that WWYD up-regulated the mRNA expression of c-Kit and SCF in the duodenum of rats(P<0.05).Moreover,the small intestinal propulsion rate was negatively correlated with MCT and HA content,and positively correlated with the expres-sion of SCF and c-Kit.CONCLUSION:Wenweiyang decoction promotes rat duodenal motility,and its mechanism may be related to the inhibition of rat duodenal MCT and HA production and activation of SCF/c-Kit signaling pathway.

Objective:To analyze the prognostic factors of children with septic shock in the pediatric intensive care unit.Methods:The clinical data of children diagnosed with septic shock in the pediatric intensive care unit of Guiyang Maternal and Child Health Hospital from April 2018 to April 2022 were retrospectively collected,and the children were divided into the death group and the survival group according to seven days regression.The basic data of the two groups were statistically compared，and the relationship between lactic acid，vasoactive-inotropic score one hour after admission，time of antibiotic initiation，serum potassium，serum sodium，serum calcium，serum troponin T，fluid resuscitation volume in the first hour，glutamyl aminotransferase，creatinine，total leukocyte count，C-reaction protein，brain natriuretic peptide were compared.The risk factors affecting the death of children were analyzed by Logistic regression.The relationship between fluid resuscitation volume in the first hour and prognosis was analyzed using the receiver operator characteristic (ROC) curve.Results:（1）A total of 67 children were included，19 died and 48 survived.（2）The first-hour liquid resuscitation dose in the survival group was lower than that in the death group，and the difference was statistically significant（ P<0.05）.（3）The ROC curve showed that the optimal cut-off of the first-hour liquid resuscitation dose was 25 mL/kg，with a sensitivity of 57.9% and a specificity of 72.9%.（4）In unifactorial analysis，lactic acid in the first hour of admission，early lactic acid after resuscitation，serum calcium，serum troponin T，alanine aminotransferase，combined septic encephalopathy，Glasgow coma score，and pediatric critical illness score were all risk factors for death in children within seven days（ P<0.05）.(5) Multivariate Logistic regression analysis showed that serum calcium（ OR=1.435， P=0.001）and lactic acid value after resuscitation（ OR=0.040， P=0.021）were independent risk factors for death in septic shock. Conclusion:The higher the total fluid resuscitation in the first hour，the higher the fatality rate.Serum calcium and early lactic acid after resuscitation are independent risk factors for death in children within seven days.

Objective:To investigate the value of left ventricular systolic synchrony assessed by gated myocardial perfusion imaging(GMPI)in predicting major adverse cardiovascular events(MACE)in elderly patients with coronary heart disease(CHD).Methods:In this retrospective study, clinical data from elderly patients who had completed a two-day assessment of resting-loading GMPI between September 2012 and February 2014 in Beijing Hospital were collected, including the summed stress score(SSS)for total ischemic burden, measured by GMPI, left ventricular ejection fraction(LVEF), peak filling rate(PFR), phase band width(PBW), phase standard deviation(PSD)and phase entropy(PE).Follow-up of MACE was conducted.Independent risk factors for MACE were analyzed using a multifactorial Cox proportional hazards regression model, and the cumulative MACE incidence was analyzed using the Kaplan-Meier survival curve.Results:A total of 427 subjects were enrolled, including 200(46.8%)men, with a mean age of 74.1±6.5(60-92)years and 323(75.6%)aged ≥ 70 years.The median follow-up time was 54.7 months.At the end of follow-up, MACE occurred in 47 patients(11.0%).Compared with the group without MACE, the incidences of hypertension, hyperlipidemia, and hyperuricemia were significantly higher( χ2=5.20, 5.62, 3.86, all P<0.05), LVEF and PFR were significantly lower( t=-5.51, -5.23, both P<0.001), and SSS, PSD, PBW, and PE were significantly higher( Z=4.78, t=5.14, 5.78, 5.62, all P<0.001)in the MACE group.The results of Cox proportional hazards regression model analysis suggested that age ≥ 70(hazard ratio: 2.57, 95% CI: 1.08-6.13), abnormal perfusion(hazard ratio: 2.60, 95% CI: 1.31-5.15), increased PSD(hazard ratio: 3.72, 95% CI: 1.72-8.05)and increased PE(hazard ratio: 4.09, 95% CI: 1.94-8.63)were independent risk factors for the occurrence of MACE(all P<0.05).Further analysis on 323 patients ≥ 70 years indicated that abnormal perfusion(hazard ratio: 2.96, 95% CI: 1.40-6.26), increased PSD(hazard ratio: 3.51, 95% CI: 1.56-7.89), and increased PE(hazard ratio: 4.49, 95% CI: 2.08-9.71)were independent risk factors for MACE( P<0.05 for all). Conclusions:Parameters of GMPI systolic synchrony analysis can very well identify the population at high risk of MACE in elderly patients with CHD.

Objective A HPLC-quantitative analysis of multi-components by single marker(QAMS)was established to determine 5 ingredients including uracil,uridine,hypoxanthine,inosine and guanosine in Periplaneta americana.Methods Separation took place on a Agilent ZORBAX SB-Aq column(250 mm×4.6 mm,5 μm)by gradient elution of methanol-0.01 mol·L-1 potassium dihydrogen phosphate at 20℃with a flow rate of 1.0 mL·min-1.The detection wavelength was 260 nm and the injection amount was 10 μL.The relative correction factors(fa/b)was calculated for the other four components with uridine as an internal standard.The content of 5 ingredients in 10 batches of Periplaneta americana was determined by QAMS.Results were compared with those of external standard method(ESM).Results Five nucleosides showed good linear relationships in their own ranges(r＞0.999 5),and the average recoveries ranged from 97.0%to 100.8%.The relative correction factors of uracil,hypoxanthine,inosine and guanosine were 0.908 0,1.005 3,1.969 5 and 1.303 4,respectively.Conclusion The established method is accurate and stable.It can provide theoretical reference for the quality control of Periplaneta americana.

The clinical and imaging data of 99 patients with Graves′ disease, 78 patients with thyroiditis and 28 patients with other diseases (resolving thyroiditis, non thyroid disease and simple goiter) who underwent thyroid scintigraphy in Beijing Shijingshan Hospital from January 2016 to March 2022 were retrospectively reviewed. The UR value of thyroid scintigraphy was calculated and ROC curve was used to assess the UR value in diagnosis of Graves′ disease. The UR value of patients with Graves′ hyperthyroidism was significantly higher than that of patients with thyroiditis and other diseases ( H=163.62, P<0.05). UR>4.84 was taken as optimal cutoff value to diagnose Graves′ hyperthyroidism, with the sensitivity and specificity of 95.0% and 98.1%, respectively.

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

Objective:To explore the feasibility of cardiac T 2 weighted dark blood sequence (T 2W-DB) based on artificial intelligence assisted compression-sensing(ACS) in clinical cardiac MR examination, compared with the conventional cardiac fast spin-echo T 2W-DB sequence. Methods:A total of 38 patients referred for cardiac MR examination in Tongji Hospital were enrolled prospectively from August to December 2021. The conventional T 2W-DB scan and the single-shot ACS T 2W-DB scan were acquired at continuous short-axial slices covering the whole left ventricle in all patients, and the acquisition time of each scan was recorded. The image quality of the two sequences was evaluated by the objective quantitative parameters and the subjective scoring methods, respectively. The signal to noise ratio (SNR), the contrast to noise ratio of the interventricular septum to blood pool (CNR), and the sharpness of the images were calculated. The subjective scoring was to evaluate the overall image quality, the effect of blood pool suppression, the visibility of right ventricular free wall, left ventricular free wall, and interventricular septum with a 5-point Likert scale. The intraclass correlation coefficient and Kendall W were calculated to evaluate the interobserver agreement of the objective quantitative parameters and subjective scoring. The paired t-test or Wilcoxon test was used to compare the difference in acquisition time, objective quantitative parameters and subjective scoring between the conventional T 2W-DB and the single-shot ACS T 2W-DB. Results:The inter-observer agreement between the single-shot ACS T 2W-DB and conventional T 2W-DB was good in all the objective quantitative parameters and subjective scoring of image quality ( P<0.05 for all). Compared with conventional T 2W-DB, acquisition time of single-shot ACS T 2W-DB was remarkably shortened [(85.8±14.7) s vs. (16.9±3.0) s, t=35.42, P<0.001]. Compared with SNR (66.4±29.0) and CNR(61.8±28.6) of conventional T 2W-DB, single-shot ACS T 2W-DB had significantly higher SNR(110.8±36.8, t=-8.13, P?0.001) and CNR(88.2±31.1, t=-5.89, P?0.001). Compared with conventional T 2W-DB, single-shot ACS T 2W-DB had better blood pool inhibition effect (4.6±0.6 vs. 4.7±0.5, Z=-2.64, P=0.008). There was no significant difference in overall image quality, visibility of right ventricular free wall, left ventricular free wall, and interventricular septum between the two sequences( P>0.05 for all). Conclusions:In cardiac MR examination, compared with the conventional T 2W-DB sequence, the single-shot ACS T 2W-DB sequence can significantly shorten the acquisition time and obtain better image quality.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Objective To evaluate the quality of postoperative recovery of patients undergoing cardiac great vessels surgery by 15-item Recovery Quality Score Scale(QoR-15),to retrospectively analyze the influence of perioperative multi-factors on postoperative recovery quality,and to establish the predictive model.Methods Clinical data of patients who underwent cardiac great vascularsur-gery from March 2020 to September 2022 were collected through electronic medical record system and the postoperative QoR-15 score were evaluated.The data including gender,age,postoperative follow-up time,American Society of Anesthesiologists(ASA)classification,preoperative lactate level,co-morbidities,emergency or not,extracorporeal circulation or not,etc.were collected.The modified frailty index(mFI)was also calculated.Surgical patterns,operation time,extracorporeal circulation time,aortic block time,type of heart recurrence,perioperative fluid therapy,extracorporeal circulation temperature,and other postoperative data as well as postoperative data including ICU retention time after surgery,total length of stay and QoR-15 score were recorded.The univariate and multivariate Logistic regression analysis were then applied to construct a prediction model,and its accuracy was validated.Results A total of 213 patients were included,in which 15 patients were excluded,and 198 postoperative QoR-15 score sheets were received.Gender,ASA classification,preoperative lac-tate level,postoperative follow-up time,and mFI were significant influencing factors on the quality of rehabilitation of patients undergoing cardiac or great vascular surgery.The prediction model of ln(p/1-p)=-5.571+0.862 × gender+3.844 × ASA classification+3.143 × preoperative lactate level+2.001 × postoperative follow-up time+3.712 × mFI,which had good predictive and classifi-cation effects.Conclusion Gender,ASA classification,preoperative lactate level,postoperative follow-up time and mFI are influencing factors on the recovery quality of patients after cardiac great vascular surgery.

Objective To evaluate the quality of postoperative recovery of patients undergoing cardiac great vessels surgery by 15-item Recovery Quality Score Scale(QoR-15),to retrospectively analyze the influence of perioperative multi-factors on postoperative recovery quality,and to establish the predictive model.Methods Clinical data of patients who underwent cardiac great vascularsur-gery from March 2020 to September 2022 were collected through electronic medical record system and the postoperative QoR-15 score were evaluated.The data including gender,age,postoperative follow-up time,American Society of Anesthesiologists(ASA)classification,preoperative lactate level,co-morbidities,emergency or not,extracorporeal circulation or not,etc.were collected.The modified frailty index(mFI)was also calculated.Surgical patterns,operation time,extracorporeal circulation time,aortic block time,type of heart recurrence,perioperative fluid therapy,extracorporeal circulation temperature,and other postoperative data as well as postoperative data including ICU retention time after surgery,total length of stay and QoR-15 score were recorded.The univariate and multivariate Logistic regression analysis were then applied to construct a prediction model,and its accuracy was validated.Results A total of 213 patients were included,in which 15 patients were excluded,and 198 postoperative QoR-15 score sheets were received.Gender,ASA classification,preoperative lac-tate level,postoperative follow-up time,and mFI were significant influencing factors on the quality of rehabilitation of patients undergoing cardiac or great vascular surgery.The prediction model of ln(p/1-p)=-5.571+0.862 × gender+3.844 × ASA classification+3.143 × preoperative lactate level+2.001 × postoperative follow-up time+3.712 × mFI,which had good predictive and classifi-cation effects.Conclusion Gender,ASA classification,preoperative lactate level,postoperative follow-up time and mFI are influencing factors on the recovery quality of patients after cardiac great vascular surgery.