ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

This paper aimed to use non-targeted urine metabolomics to reveal the potential biomarkers of toxicity in rats with hepatic injury induced by aqueous extracts of Dictamni Cortex(ADC). Forty-eight SD rats were randomly assigned to a blank group and high-dose, medium-dose, and low-dose ADC groups, with 12 rats in each group(half male and half female), and they were administered orally for four weeks. The hepatic injury in SD rats was assessed by body weight, liver weight/index, biochemical index, L-glutathione(GSH), malondialdehyde(MDA), and pathological alterations. The qPCR was utilized to determine the expression of metabolic enzymes in the liver and inflammatory factors. Differential metabolites were screened using principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA), followed by a metabolic pathway analysis. The Mantel test was performed to assess differential metabolites and abnormally expressed biochemical indexes, obtaining potential biomarkers. The high-dose ADC group showed a decrease in body weight and an increase in liver weight and index, resulting in hepatic inflammatory cell infiltration and hepatic steatosis. In addition, this group showed elevated levels of MDA, cytochrome P450(CYP) 3A1, interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α), as well as lower levels of alanine transaminase(ALT) and GSH. A total of 76 differential metabolites were screened from the blank and high-dose ADC groups, which were mainly involved in the pentose phosphate pathway, tryptophan metabolism, purine metabolism, pentose and glucuronic acid interconversion, galactose metabolism, glutathione metabolism, and other pathways. The Mantel test identified biomarkers of hepatotoxicity induced by ADC in SD rats, including glycineamideribotide, dIDP, and galactosylglycerol. In summary, ADC induced hepatotoxicity by disrupting glucose metabolism, ferroptosis, purine metabolism, and other pathways in rats, and glycineamideribotide, dIDP, and galactosylglycerol could be employed as the biomarkers of its toxicity.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Biomarkers/metabolism* ; Liver/metabolism* ; Drugs, Chinese Herbal/adverse effects* ; Female ; Chemical and Drug Induced Liver Injury/metabolism* ; Glutathione/metabolism* ; Humans

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective To explore the mechanism of'homotherapy for heteropathy'Zhigancao Decoction in the treatment of coronary heart disease arrhythmia and pulmonary fibrosis by network pharmacology and molecular docking technology.Methods All the active components of Zhigancao Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Herbal Compendium(HERB).The SwissTargetPrediction database was used to predict the targets.Cytoscape software was used to construct the drugs-targets network diagram and network topology analysis was performed to obtain the core drug targets.The disease targets of coronary heart disease,arrhythmia and pulmonary fibrosis were obtained in GeneCards and OMIM databases,and the intersection targets of Chinese medicine and disease were obtained by Venny software.The intersection targets were imported into the STRING online database to construct a protein-protein interaction network,and the data were imported into Cytoscape software for visualization and screening of core targets.Gene ontology(GO)function enrichment analysis and kyto encyclo-pedia of genes and genomes(KEGG)pathway enrichment analysis were performed on the intersection targets using the Metascape database.Molecular docking verification and heat map visualization were performed on the core intersection target and the core drug target through the CB-DOCK2 online platform.Results A total of 137 active components of Zhigancao Decoction were screened out,and 848 corresponding drug targets were obtained by removing repeated values.A total of 9 962 targets of coronary heart disease,5 735 targets of arrhythmia and 7 722 targets of pulmonary fibrosis were obtained.A total of 362 drug-disease intersection targets were obtained by Venny platform processing.The potential core targets with higher degree values were GAPDH,IL-6,ALB,STAT3,TNF,MMP-9 and so on by network topology analysis.GO functional enrichment analysis showed that the main biological processes(BP)involved in Zhigancao Decoction'homotherapy for heteropathy'were the response to hormones,the positive regulation of circulatory system process,phosphorus metabolism process,the response to exogenous stimulation,and the response to organic matter,the main cellular components(CC)include lipid rafts,receptor complexes,cytoplasmic perinuclear regions,dendrites,membrane sides,etc.,the main molecular functions(MF)include protein kinase activity,kinase binding,protein homopolymerization activity,nuclear receptor activity,heme binding,etc..KEGG pathway enrichment analysis showed that the main signaling pathways involved in Zhigancao Decoction'homotherapy for heteropathy'were lipid and atherosclerosis,calcium signaling pathway,cAMP signaling pathway,insulin resistance,cGMP-PKG signaling pathway,JAK-STAT signaling pathway,NF-κB signaling pathway,etc..The results of molecular docking suggested that there was a good binding activity between the main active component targets of Zhigancao Decoction and the core targets of'homotherapy for heteropathy'.Conclusion Zhigancao Decoction mainly regulates JAK-STAT,NF-κB,cAMP and other signaling pathways,acts on IL-6,STAT3,TNF,MMP-9 and other gene targets,and exerts the effect of'homotherapy for heteropathy'on coronary heart disease arrhythmia and pulmonary fibrosis.

Objective To analyze the changes of liver and kidney function, blood glucose and lipid metabolism at different follow-up time points of different treatment regimens, and to provide reference for clinical optimization and adjustment of medication in HIV/AIDS patients. Methods The changes of liver and kidney function, blood glucose and lipid metabolism at seven follow-up time points were analyzed retrospectively. The baseline blood collection time of HIV /AIDS patients was set as the starting point, and the final follow-up time was set as the end point. The seven follow-up points were 0, 3, 6, 9, 12, 18 and 24 months respectively. Results There were statistically significant differences in the distribution of sex, age, education, marital status, WHO staging, infection route, and baseline CD4+T lymphocyte count among 605 enrolled patients based on different treatment regimens. Liver function: The level of T-Bil in group E was higher than that of baseline at 9M, 12M, 18M and 24M after treatment (P<0.01); In group F, the level of T-Bil was higher than that of baseline at 9M after treatment (P=0.001); The levels of ALT in group C at the six follow-up points after treatment were higher than the baseline (P<0.001); The level of AST in group C was higher than that of baseline after 3M and 6M treatment (P<0.05). Renal function: The level of UREA in group C was higher than that in baseline after 6M treatment (P=0.007); The level of UREA in group F was higher than that in the baseline after 12M treatment (P<0.001); The level of UA in group F was higher than that of baseline after 3M, 6M and 12M treatment (P<0.05). Blood lipid and blood glucose: The levels of Glu at some follow-up points after ART treatment in group A and group C were higher than that at baseline (P<0.05); The levels of TG at some follow-up points in group A, group E and group F after ART treatment were higher than those at baseline (P<0.05); The levels of TC at some follow-up points in group A, group B, group C, group E and group F after ART treatment were all higher than the baseline (P<0.05). Conclusion Regular monitoring of changes in laboratory indicators of different treatment regimens during ART is of great importance to the prognosis of patients. Different laboratory indicators should be monitored according to different treatment regimens to effectively prevent adverse reactions caused by different treatment regimens.

AIM To study the chemical constituents from salt-processed Citri Reticulatae Semen and their antioxidant activities.METHODS The 85% ethanol extract from salt-processed Citri Reticulatae Semen was isolated and purified by silica gel,D101 macroporous resins,MCI,ODS,Sephadex LH-20 and semi-prepative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their antioxidant activities in vitro of the ethanol extract of Citri Reticulatae Semen,salt-processed Citri Reticulatae Semen and all the obtained compounds were evaluated by DPPH and ABTS+assay.RESULTS Sixteen compounds were isolated and identified as limonin(1),obacunone(2),nomilin(3),deacetyl nomilin(4),kaempferol(5),nobiletin(6),diosmetin(7),isosakuranetin(8),hesperetin(9),epicatechin(10),trans-p-menthane-1α,2β,8-triol(11),byakangelicin(12),vanillin(13),p-coumaric acid(14),4-[(1-ethoxy-2-hydroxy)ethyl]phenol(15),catechol(16).Compound 10 showed strong DPPH free radical scavenging activity,with an IC50 value of(0.015±0.001)μmol/mL,and strong ABTS+radical scavenging activity,with an IC50 value of(0.010±0.005)μmol/mL.CONCLUSION Compounds 8,11,15-16 are isolated from genus Citrus for the first time,5,12,14 are obtained from Citri Reticulatae Semen for the first time.Compound 10 shows obvious antioxidant activities.After salt roasting,the antioxidant activity of the ethanol extract of Citri Reticulatae Semen is enhanced.

AIM To study the chemical constituents from the leaves of Citrus reticulata Blanco and their anti-inflammatory activities.METHODS The 85%ethanol extract from the leaves of C.reticulata was isolated and purified by silica gel,D101 macroporous resin,MCI,ODS and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The Griess method was used to determine their inhibitory activities on lipopolysaccharide-induced NO production in macrophages RAW 264.7 cells.The mice foot swelling inflammation model induced by carrageenan was established,and the levels of IL-1β,TNF-α were detected.RESULTS Twelve compounds were isolated and identified as nobiletin(1),tangeretin(2),5-demethylinoblitin(3),5,4'-dihydroxy-6,7,8,3'-tetramethoxy flavone(4),5-hydroxy-7,8,3',4'-trimethoxyflavanone(5),3,5,6,7,8,3',4'-heptamethoxyflavanone(6),hesperetin(7),5-hydroxy-6,7,3',4'-tetramethoxyphenone(8),β-balsam alcohol(9),stigmaster-5-en-3β-alcohol(10),p-hydroxybenzaldehyde(11),vanillin(12).Compounds 1,4,6,7,10 and 12 had strong inhibitory activites on NO release in LPS-induced RAW 264.7 cells,and the IC50 values were(25.21±2.10),(37.77±0.50),(38.19±1.58),(21.89±1.73),(43.81±1.18),(47.98±2.55),(41.23±1.11),(43.80±1.43)μmol/mL,respectively.Compounds 2-3 reduced IL-1β and TNF-α levels(P＜0.05,P＜0.01).CONCLUSION Compounds 6-7,9 are isolated from this plant for the first time.Compounds 1-4,8 exhibit strong in vitro anti-inflammatory activities,and compounds 2-3 exhibit significant in vivo anti-inflammatory activities.

Abstract: Objective　To analyze the distribution characteristics of the main pathogens of HIV/AIDS patients with wound infections and provide basis for clinical diagnosis and treatment. Methods　The clinical data of 294 patients with positive secretions or pus specimens from 2016 to 2020 were analyzed retrospectively. Results　A total of 357 strains of pathogenic bacteria were isolated from 294 cases, of which 123 strains of Gram-negative bacilli (G-b), accounting for 34.5%, were mainly Escherichia coli (15.4%), Klebsiella pneumoniae (3.9%), and Pseudomonas aeruginosa (3.6%); Gram-positive bacilli (G+b) 14 strains, accounting for 3.9%; 108 Gram-positive cocci (G+c), accounting for 30.3%, of which 44 strains were coagulase-positive Staphylococcus aureus (12.3%), Coagulase-negative staphylococci were mainly Staphylococcus epidermidis (4.2%) and Staphylococcus hemolyticus (2.8%); 37 strains of fungi, accounting for 10.4%, were mainly Candida albicans (5.9%); 75 strains of Mycobacterium, accounting for 21.0%, including 41 strains of Mycobacterium tuberculosis (11.5%) and 34 strains of non-tuberculosis mycobacteria (9.5%). 52 of the 294 HIV/AIDS patients had mixed infections, accounting for 17.7%. There was significant difference in the distribution of G+c, G-b, mycobacteria and mixed infection among different specimen sources (P<0.05), and there was significant difference in the distribution of mycobacteria among different CD4+T lymphocyte counts (P<0.05). There was significant difference in the level of CD4+T lymphocytes between patients of different ages (P<0.05), and there was significant difference in the level of CD4+T lymphocytes from postoperative incision and other parts (P<0.05). Conclusions　Patients with HIV/AIDS are prone to combined wound infections with various pathogenic bacteria. We should strengthen the research on wound infection in HIV/AIDS patients, and timely send patients with a low number of CD4+T lymphocytes for secretion or pus culture, so as to carry out targeted treatment and improve the prognosis of patients.