Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

This study used kidney metabolomics to investigate the underlying mechanisms of Guilingji (GLJ) on mild cognitive impairment (MCI) rats. The rats were randomly divided into 6 groups (n = 8), i.e., control group, model group, positive drug (Ginkgo biloba tablet, donepezil) group, GLJ group (low and high dose group). The MCI rat model was replicated using subcutaneous injection of D-galactose into the back of the neck along with a semi-high-fat diet for a total of 8 weeks, and drug was administered from the 5th week for 4 weeks. The kidney function and renal pathological changes of each group of rats were tested. And LC-MS based kidney metabolomics coupled with multivariate data analysis were conducted to explore the potential biomarkers, and corresponding metabolic pathways were then determined. After administration of GLJ, the level of urea nitrogen was decreased compared with those of the model group, and the abnormalities of morphology in kidney tissues were improved. The positive drugs (ginkgo biloba tablet and donepezil) had no significant modulating effect on renal function indexes. Ginkgo biloba tablet can lessen the pathological injury of kidney tissue, and donepezil had no improvement on renal histopathology. A total of 23 MCI related differential metabolites were identified in kidney, and 17 metabolites were signifcantly restored by GLJ compared with those of the model group. Additionally, we found that the cysteine and methionine metabolism, nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism were significantly involved in the regulatory effect of GLJ. The results illuminate the "cong shen zhi nao" mechanism of GLJ, and also provide a research basis for the clinical use of GLJ for the treatment of MCI. The animal experiment of this study was approved by the Ethics Committee of Shanxi University (approval number: 2020DW121).

Progressive fibrosing interstitial lung disease （PF-ILD） has a complex etiology， and is classified as lung impediment stage， impediment-atrophy combination stage， and lung atrophy stage according to the different clinical manifestations during the progression of disease. Based on the theory of opening-closing-pivoting to analyse the characteristics of yin and yang disease mechanism and the idea of prescriptions in the three stages. For lung impediment stage， main as three-Yang fail to keep inside， disharmony between Ying qi （营气） and Wei qi （卫气）， shaoyin impairment， treatment should use Mahuang （Ephedra sinica） and Guizhi （Neolitsea cassia） flexibly to form a formula， or choose pungent-dispersing formulas like Baidu Powder （败毒散） to move qi and save yang， and diffuse and disperse impediment pathogen， meanwhile combining saving-shaoyin medicinals like Fuzi （Aconitum carmichaelii） and Shudihuang （Radix Rehmanniae Praeparata） to reinforce healthy qi and dispel pathogen； for impediment-atrophy combination stage， rooted as yangming impairment and progressed by over-movement of qi， treatment should use Mahuang Shengma Decoction （麻黄升麻汤） to resolve and decrease over-activities， emphasis on both opening and closing， and improve impediment and atrophy； for lung atrophy stage with three-Yin in a bad condition simultaneously and poor prognosis， treatment should use modified Jinshui Liujun Decoction （金水六君煎） to consolidate qi and save yin， disperse phlegm and stasis， to improve the quality of life for patients with PF-ILD.

The current situation of artificial intelligence(AI)was introduced when applied in the key links of cardiovascular health management such as risk prediction,early screening,clinical decision support and health consultation and education.The deficiencies of AI during the application were analyzed,and the prospects and development directions of AI in cardiovascular health management were pointed out.[Chinese Medical Equipment Journal,2024,45(2):92-96]

Objective To compare the outcomes of transplant kidneys and patient survival between simultaneous pancreas-kidney transplantation(SPKT)recipients and deceased donor kidney transplant(DDKT)recipients in patients with type 2 diabetes mellitus(T2DM)complicated with end-stage renal disease(ESRD),and to analyze the risk factors affecting patient survival post-SPKT.Methods Clinical and prognostic data of patients who underwent kidney transplantation from January 27,2003,to January 1,2021,were retrieved from the United Network for Organ Sharing(UNOS)database.A total of 50 230 cases were selected based on inclusion criteria,with 48 669 cases in DDKT group and 1561 cases in SPKT group.Kaplan-Meier analysis was employed to compare transplant kidney and patient survival between the two groups,and propensity score matching(PSM)was utilized to balance confounding factors between the groups.Cox regression model was used to analyze independent risk factors affecting patient survival post-SPKT.Results Compared with DDKT group,recipients in SPKT group had a younger median age(P<0.001),a higher proportion of males(P<0.001),lower BMI(P<0.001),shorter dialysis and transplant waiting times(P<0.001),a higher percentage of private medical insurance(P<0.001),a lower proportion of previous transplants(P<0.001),a younger age at diabetes diagnosis(P<0.001),and a lower incidence of peripheral vascular disease(P=0.033).Compared with DDKT group,the donors in SPKT group had a younger median age(P<0.001),a higher proportion of males(P<0.001),lower BMI(P<0.001),and a lower prevalence of hypertension and diabetes history(P<0.001).In terms of transplant-related factors,the SPKT group had a shorter donor kidney cold ischemia time(P<0.001),a higher degree of HLA mismatch(P<0.001),and a lower Kidney Donor Profile Index(KDPI)(P<0.001)when compared with DDKT group.The SPKT group had lower serum creatinine levels at discharge(P<0.001),lower rates of postoperative delayed graft function(DGF)and acute rejection(AR)(P<0.001),but longer hospital stays(P<0.001)when compared with DDKT group.Kaplan-Meier survival analysis curves,both original and after propensity score matching(PSM),consistently showed significantly higher transplant kidney and patient survival rates in SPKT group compared with DDKT group(P<0.001).Cox regression model analysis indicated that recipient age,recipient race,donor age,and donor kidney cold ischemia time were independent risk factors influencing patient survival post-SPKT.Conclusions For ESRD patients with T2DM,SPKT offers improved long-term graft and patient survival rates compared with DDKT.Recipient age,recipient ethnicity,donor age,and cold ischemia time for the donor's kidney are independent risk factors affecting post-SPKT patient survival.

Based on the UHPLC-Q-Exactive-MS metabonomics technology, the effect of Hippocampus kuda Bleeker on the life span of Drosophila melanogaster was studied, and the change rule of endogenous metabolites in the aging process of Drosophila melanogaster after the intervention of Hippocampus kuda Bleeker japonicus was explored to clarify the anti-aging mechanism of Hippocampus. The natural aging model of Drosophila melanogaster was used. Different doses of raw Hippocampus and fried Hippocampus were given to observe the effects on the life span, climbing ability, sexual activity, and antioxidant enzyme activity of Drosophila melanogaster. Based on UHPLC-Q-Exactive-MS metabolomics technology, the metabolic profile of the aging Drosophila melanogaster was analyzed using metabonomics technology to explore the mechanism of Hippocampus kuda Bleeker delaying the aging of Drosophila melanogaster. The results showed that raw Hippocampus and crispy Hippocampus (1, 4 mg·mL^-1) could significantly prolong the average life span, median life span and maximum life span of male fruit flies, and significantly improve the climbing ability and sexual vitality of fruit flies. Catalase (CAT) and aldehyde content were increased, while malonaldehyde (MDA) content was decreased. Through metabonomics technology, it was identified that the Hippocampus can significantly recall 16 metabolites and participate in the biosynthesis of phenylalanine, tyrosine and tryptophan, starch and sucrose metabolism, tyrosine metabolism, cysteine and methionine metabolism, and histidine metabolism. The anti-aging mechanism is related to amino acid metabolism and sugar metabolism, which provides a substantial scientific basis for the development and utilization of Hippocampus and clarifying its role in senile diseases. The animal experiment of this study was approved by the Ethics Committee of Shanxi University (approval number: SXULL2021028).

Objective: To investigate the clinical significance of endothelin A receptor (ETAR) expression in high-grade serous ovarian carcinoma (HGSOC). To design ETAR carboxyl terminal (ETAR-C) amino acids derived polypeptide and to study the inhibitory effect on ovarian epithelial carcinoma cells in vitro. Methods: (1) A total of 126 patients who received surgical treatment and were diagnosed with HGSOC by postoperative pathological examination in Central Hospital of Xuzhou from January 1, 2007 to December 31, 2017 were selected. All patients had completed clinicopathological data and follow-up data. Cancer tissue samples were collected and ETAR mRNA expression in HGSOC tissues was detected by reverse transcript-PCR. The clinical significance was analyzed. (2) ETAR-C fusion polypeptide was designed based on the sequence of carboxyl terminal amino acids of ETAR, expressed and purified in vitro. The effects of ETAR-C fusion polypeptide on migration and invasion ability of ovarian cancer SKOV3 and CAOV3 cells were detected by scratch test and invasion test, respectively. The effect of ETAR-C fusion polypeptide on chemosensitivity of cisplatin-resistant ovarian cancer SKOV3/cDDP and CAOV3/cDDP cells was determined by methyl thiazolyl tetrazolium (MTT) colorimetric assay. The effect of ETAR-C fusion polypeptide on β-arrestin-1 expression in ovarian cancer SKOV3 and CAOV3 cells was detected by western blot. Results: (1) The relative expression level of ETAR mRNA in HGSOC tissues was 18.6±5.1. Patients with HGSOC were divided into high ETAR mRNA expression (n=76) and low ETAR mRNA expression (n=50) with 61.7% as cut-off value analyzed by X-Tile software. High expression of ETAR mRNA was significantly correlated with abdominal water volume, platinum drug resistance, and cancer antigen 125 (CA₁₂₅) value in HGSOC patients (all P<0.05), but was not related to the age of patients with HGSOC and the size of postoperative residual lesions (all P>0.05). The 5-year progression free survival rates were 18.4% and 28.0%, and the 5-year overall survival rates were 38.2% and 52.0% in HGSOC patients with high and low ETAR mRNA expression respectively, there were statistically significant differences (P=0.046, P=0.034). (2) The results of scratch test and invasion test showed that the scratch healing rate and cell invasion rate of SKOV3 or CAOV3 cells treated with endothelin-1 (ET-1) and ET-1+ETAR-C were respectively compared, and the differences were statistically significant (all P<0.05). MTT assay showed that the inhibition rates of ETAR-C fusion polypeptide treated in SKOV3/cDDP and CAOV3/cDDP cells were significantly higher than those of control cells after the addition of 4, 6, 8, 10, 12, and 24 μg/ml cisplatin (all P<0.05). Western blot analysis showed that the relative expression levels of β-arrestin-1 in SKOV3 or CAOV3 cells treated with ET-1 and ET-1+ETAR-C were 1.85±0.09 and 1.13±0.09 (SKOV3 cells), 2.14±0.15 and 1.66±0.12 (CAOV3 cells), respectively. The differences were statistically significant (all P<0.05). Conclusions: The prognosis of HGSOC patients with high expression of ETAR mRNA is significantly worse than those with low expression of ETAR mRNA. ETAR might be a new target for HGSOC treatment. The ETAR-C fusion polypeptide that interferes with the interaction of ETAR and β-arrestin-1 has good inhibitory effect on ovarian cancer cells in vitro, and might have clinical application potential.
Female ; Humans ; Amino Acids/therapeutic use* ; beta-Arrestins/therapeutic use* ; Cell Line, Tumor ; Cisplatin/pharmacology* ; Clinical Relevance ; Ovarian Neoplasms/pathology* ; Receptor, Endothelin A/therapeutic use* ; RNA, Messenger/metabolism*

Humans ; Lupus Erythematosus, Systemic/therapy* ; Thrombotic Microangiopathies/complications*

This study constructed a nano-drug delivery system, A3@GMH, by co-delivering the stapled anoplin peptide(Ano-3, A3) with the light-harvesting material graphene oxide(GO), and evaluated its oncolytic immunotherapy effect on triple-negative breast cancer(TNBC). A3@GMH was prepared using an emulsion template method and its physicochemical properties were characterized. The in vivo and in vitro photothermal conversion abilities of A3@GMH were investigated using an infrared thermal imager. The oncoly-tic activity of A3@GMH against TNBC 4T1 cells was evaluated through cell counting kit-8(CCK-8), lactate dehydrogenase(LDH) release, live/dead cell staining, and super-resolution microscopy. The targeting properties of A3@GMH on 4T1 cells were assessed using a high-content imaging system and flow cytometry. In vitro and in vivo studies were conducted to investigate the antitumor mechanism of A3@GMH in combination with photothermal therapy(PTT) through inducing immunogenic cell death(ICD) in 4T1 cells. The results showed that the prepared A3@GMH exhibited distinct mesoporous and coated structures with an average particle size of(308.9±7.5) nm and a surface potential of(-6.79±0.58) mV. The encapsulation efficiency and drug loading of A3 were 23.9%±0.6% and 20.5%±0.5%, respectively. A3@GMH demonstrated excellent photothermal conversion ability and biological safety. A3@GMH actively mediated oncolytic features such as 4T1 cell lysis and LDH release, as well as ICD effects, and showed enhanced in vitro antitumor activity when combined with PTT. In vivo, A3@GMH efficiently induced ICD effects with two rounds of PTT, activated the host's antitumor immune response, and effectively suppressed tumor growth in 4T1 tumor-bearing mice, achieving an 88.9% tumor inhibition rate with no apparent toxic side effects. This study suggests that the combination of stapled anoplin peptide and PTT significantly enhances the oncolytic immunotherapy for TNBC and provides a basis for the innovative application of anti-tumor peptides derived from TCM in TNBC treatment.
Humans ; Animals ; Mice ; Photothermal Therapy ; Triple Negative Breast Neoplasms/pathology* ; Antimicrobial Cationic Peptides ; Immunotherapy/methods* ; Cell Line, Tumor ; Phototherapy/methods* ; Nanoparticles/chemistry*

Child ; Humans ; Renal Insufficiency, Chronic ; Kidney Failure, Chronic