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.

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. 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). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.
Humans ; Pelvic Exenteration/methods* ; Pelvic Neoplasms/surgery* ; Retrospective Studies ; Neoplasm Recurrence, Local/surgery* ; Postoperative Complications

ObjectiveTo investigate inhibitory effect of extracts from Veronica peregrina （EVP） on the osteoclastic bone metastasis induced by breast cancer cells. MethodBone metastasis model was established by injection of MDA-MB-231 cells， a human breast cancer cell line， into the left ventricle of BALB/c nude mice. The expression of human cytokeratin-19 （Ck-19） gene in mouse bone marrow was determined by nested polymerase chain reaction（PCR） to assess the bone metastasis of MDA-MB-231 cells. To assess the effects of EVP on the activation of bone marrow macrophages （BMMs）， we counted the multinuclear cells and measured the secretion of Cathepsin K. Western blot was adopted to assess the effects of EVP on receptor activator of nuclear factor-κB （RANK）， Runt-related transcription factor 2 （ Runx2 ）， phosphorylated Runx2 （p-Runx2）， and matrix metalloproteinase-9 （MMP-9） in BMMs. Gelatin zymography was employed to determine the activities of matrix metalloproteinases （MMPs）. ResultCompared with that in the blank group， Ck-19 expression was down-regulated in EVP groups （P<0.05）. The multinucleated cells increased when the BMMs were induced by soluble receptor activator of nuclear factor-κB ligand （sRANKL）， which was inhibited by EVP （P<0.05）. The level of cathepsin K in the supernatant of sRANKL group increased compared with that of the blank group， while EVP groups had lower cathepsin K levels than sRANKL group （P<0.05）. Compared with the blank group， the sRANKL group showed up-regulated RANK expression， Runx2 phosphorylation， and MMP-9 expression （P<0.05）， while the expression levels of RANK， p-Runx2， and MMP-9 were down-regulated when the cells were incubated with EVP （P<0.05）. Furthermore， exposure of BMMs to sRANKL resulted in an increase in gelatin hydrolyzation compared with the blank group （P<0.01）， which， however， was reversed in EVP groups （P<0.05）. ConclusionEVP significantly inhibits bone marrow metastasis of MDA-MB-231 cells， which may be associated with the suppression of osteoclast activation by inhibiting Runx2 phosphorylation.

Humans ; Female ; Prevalence ; Breast Neoplasms ; Cancer Survivors ; Non-alcoholic Fatty Liver Disease ; Liver

To investigate the potential molecular markers and drug-compound-target mechanism of Mahuang Shengma Decoction(MHSM) in the intervention of acute lung injury(ALI) by network pharmacology and experimental verification. Databases such as TCMSP, TCMIO, and STITCH were used to predict the possible targets of MHSM components and OMIM and Gene Cards were employed to obtain ALI targets. The common differentially expressed genes(DEGs) were therefore obtained. The network diagram of DEGs of MHSM intervention in ALI was constructed by Cytoscape 3. 8. 0, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of target genes. The ALI model was induced by abdominal injection of lipopolysaccharide(LPS) in mice. Bronchoalveolar lavage fluid(BALF) was collected for the detection of inflammatory factors. Pathological sectioning and RT-PCR experiments were performed to verify the therapeutic efficacy of MHSM on ALI. A total of 494 common targets of MHSM and ALI were obtained. Among the top 20 key active compounds of MHSM, 14 from Ephedrae Herba were found to be reacted with pivotal genes of ALI [such as tumor necrosis factor(TNF), tumor protein 53(TP53), interleukin 6(IL6), Toll-like receptor 4(TLR4), and nuclear factor-κB(NF-κB)/p65(RELA)], causing an uncontrolled inflammatory response with activated cascade amplification. Pathway analysis revealed that the mechanism of MHSM in the treatment of ALI mainly involved AGE-RAGE, cancer pathways, PI3 K-AKT signaling pathway, and NF-κB signaling pathway. The findings demonstrated that MHSM could dwindle the content of s RAGE, IL-6, and TNF-α in the BALF of ALI mice, relieve the infiltration of inflammatory cells in the lungs, inhibit alveolar wall thickening, reduce the acute inflammation-induced pulmonary congestion and hemorrhage, and counteract transcriptional activities of Ager-RAGE and NF-κB p65. MHSM could also synergically act on the target DEGs of ALI and alleviate pulmonary pathological injury and inflammatory response, which might be achieved by inhibiting the expression of the key gene Ager-RAGE in RAGE/NF-κB signaling pathway and downstream signal NF-κB p65.
Acute Lung Injury/genetics* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Lipopolysaccharides ; Lung/metabolism* ; Mice ; NF-kappa B/metabolism* ; Network Pharmacology ; Receptor for Advanced Glycation End Products/metabolism* ; Signal Transduction

Objective: To observe the clinical efficacy of auricular point pricking-bloodletting plus auricular point sticking therapy for acne vulgaris. Methods: A total of 66 patients with acne vulgaris were randomized into an observation group and a control group by the random number table, with 33 cases in each group. The observation group was treated with auricular point pricking-bloodletting plus auricular point sticking therapy, and the control group was treated only with auricular point sticking therapy. The treatments of both groups were performed twice a week, 4 weeks as a course of treatment, for 3 courses in total. The scores of skin lesions and dermatology life quality index (DLQI) scores were recorded before and after treatment to assess the clinical efficacy. Results: During the trial, there were 3 cases of drop-out both in the observation group and the control group. After 3 courses of treatment, the total effective rate of the observation group was 96.7％, while that of the control group was 76.7％. The difference between the two groups was statistically significant (P<0.05). The intra-group comparison showed that the scores of skin lesion and DLQI were both decreased with the increase of treatment times, that was, the scores were lower than those at the previous time point (allP<0.05). After 1, 2, and 3 courses of treatment, the scores of skin lesion and DLQI of both groups were statistically different from those of the same group before treatment (allP<0.05). At every time point during the treatment, the scores of skin lesion and DLQI of the observation group were lower than those of the control group, and the differences between the two groups were statistically significant (all P<0.05). Conclusion: Auricular point pricking-bloodletting plus auricular point sticking has a better curative effect than auricular point sticking therapy alone in the treatment of acne vulgaris, and has a time-effect correlation.

Objective　Mini-invasive Carisolv is an aid to treat dental caries for patients with dental phobia. The article was to investigate the level of pain in caries removal using mini-invasive Carisolv III gel and mechanical methods with four psychological indicators.　Methods　We collected 120 primary molar tooth caries of 60 children treated in our hospital. Two primary molar tooth caries of each child were respectively treated with Carisolv III gel (Group A) and mechanical method (Group B) for caries removal. Psychological indicators including the visual analog scale (VAS), the Frank1 behavior rating scale (Frank1), the Kuttner law (Kuttner), and the Houpt behavior rating scale (Houpt) were used to assess the level of pain, degree of cooperation, pain tolerance and comfort. The clinical efficiency after six months and treatment time were compared between the two groups.　Results　There was no statistically significant difference before treatment between the two groups using the four psychological indicators (P>0.05) , while significant differences were found during and after the treatment between the two groups (P<0.05). Then, Carisolv III gel and mechanical groups for careis removal were compared before, during and after treatment themselves. In the Carisolv III gel group, there was no statistically significant difference using the four psychological indicators (P>0.05). In the mechanical group, there were statistically significant differences before and during treatment or before and after treatment using the four psychological indicators (P<0.05). The treatment time in Carisolv III gel group was longer than in mechanical group (P=0.001). There was no statistical difference between the two groups in filling examination after six months (P=0.082).　Conclusion　Carisolv III gel for caries removal can effectively avoid pain, improve comfort and decrease fear in children, which can be promoted in clinical application.

Shuyu Yiban decoction(SYYB) has significant effect in treating the patients with coronary heart disease combined with chronic psychological stress. In this study, in order to observe the effects of SYYB on early formation of atherosclerosis(As) and inflammation response induced by chronic psychological stress, high-fat diet+intraperitoneal injections of Vitamin D3 were given to establish As early lesion models, and based on these models, chronic unpredictable mild stress(CUMS) was used to observe whether the chronic psychological stress could increase coronary atherosclerotic lesions investigate the intervention effect of SYYB(6.6, 13.2, 26.4 mg•kg⁻¹). The tail suspension test and novelty-feeding test were adopted to detectadrenocortico-tropic hormone(ACTH), cortisol(Cor) andnoradrenaline(NE) in serum and weigh thymus and adrenal gland, in order to assess the effects of SYYB on CUMS model rats. The pathological changes of vascular tissues in aortic arch were observed by using hematoxylin and eosin(HE) staining, and then the levels of triglycerides(TG), total cholesterol(TC) and high density lipoprotein(HDL-C) in serum were determined to assess effects of SYYB on As lesions. The effects of SYYB on the inflammatory response in As rats were assessed by detecting high-sensitivity C-reactive protein(hsCRP), interleukin-1β(IL-1β) and interleukin-6(IL-6) in serum. The results showed that as compared with the blank control group, TC and TG levels in As group were increased while HDL-C was markedly decreased; furthermore, the aortic wall was thickened in HE staining. Meanwhile, foam cells were formed, and the behavioral assessment and serum stress hormone test showed that there was a chronic stress response, indicating successful establishment of As+CUMS models in this study. The experiment demonstrated that SYYB could lower the levels of serum TC and TG, reduce foam cells, calcification and inflammatory cells infiltration. Moreover, SYYB could obviously lower levels of ACTH, Cor and NE and the As related inflammatory indicatorhs-CRP, IL-1β and IL-6 in serum.These results indicated that SYYB had protective effect on chronic psychological stress induced in As rats, and the mechanism was associated with balancing the neuroendocrine-immune network system and regulating inflammation response.

Objective To investigate the repeatability of three-dimensional (3-D) cephalometric measurements for the clinical application of 3-D cephalometry.Methods Forty-nine measurements that widely used in traditional cephalometric analyses were defined in 3-D cone-beam CT(CBCT) images.Three examiners identified landmarks on CBCT images of 17 subjects with normal occlusion,respectively,and 3-Dmeasurements were exported automatically by software SimPlant.Inter-examiner reliability correlation coefficients(ICC) were obtained for all measurements.Results Repeatability of 36 measurements was high (ICC value greater than 0.9),including SNA,SNB.Repeatability of 11 measurements was moderate (ICC value between 0.8 and 0.9),including CoL-GoL,CoL-MSP.Repeatability of 2 measurements was low (ICC value lower than 0.8),including Gn-MSP and MPR-MSP.Conclusions Most 3-D cephalometric measurements based on CBCT had high repeatability.However,some 3-D cephalometric measurements had limited repeatability.