Based on the ultra performance liquid chromatography-quadrupole Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology, combined with related literature, databases, and reference material information, this study qualitatively analyzed the components of Dayuanyin in the tissue of rats after gavage and employed molecular docking technology to predict the rationality of the mechanism behind the antipyretic effect of the in vivo components in Dayuanyin. A total of 21, 26, 20, 21, 14, and 31 prototype components and 3, 16, 3, 7, 5, and 24 metabolites were identified from the heart, liver, spleen, lung, kidney, and hypothalamus of the rats, respectively, and the binding ability of key components and targets was further verified by molecular docking. The results showed that all components had good binding ability with targets. The established UPLC-Q-Exactive Orbitrap-MS could effectively and quickly identify the Dayuanyin components distributed in tissue and preliminarily identify their metabolites. Many components were identified in the hypothalamus, which suggested that the components delivered to the brain should be focused on in the study on Dayuanyin in the treatment of febrile diseases. The molecular docking technology was used to predict the rationality of the mechanism behind its antipyretic effect, which lays the foundation for the clarification of the material basis and action mechanism of Dayuanyin, the development of new preparations, and the prediction of quality markers.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Molecular Docking Simulation ; Male ; Antipyretics/metabolism* ; Rats, Sprague-Dawley ; Tissue Distribution ; Mass Spectrometry ; Chromatography, High Pressure Liquid ; Hypothalamus/metabolism*

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Langerhans cell histiocytosis of bone is a rare tumor disease characterized by the large accumulation of CD1a⁺ and CD207⁺ dendritic cells in tissues of unknown cause.It mainly occurs in children aged 1-4 years old,with incidences of 4-6 per million in children and 1-2 per million in adults.Due to its low incidence,diverse clinical manifestations,and no obvious specificity of imaging manifestations,the definitive diagnosis and early treatment of this type of tumor are challenging.In this paper,we report 8 cases of Langerhans cell histiocytosis of bone and review the relevant literature published in the past five years to summarize the clinical characteristics,pathological features,diagnosis,treatment,and prognosis of this disease.
Humans ; Bone Diseases/therapy* ; Histiocytosis, Langerhans-Cell/therapy*

Objective To explore the distribution and difference of bone thickness in the infrazygomatic crest(IZC)in adolescents at different eruption stages of the maxillary second molar and provide guidance for placement of orthodontic IZC miniscrew.Methods Cone beam CT scans of 110 adolescents with normal occlusion were assessed.According to the eruption stage of the maxillary second molar,the subjects were divided into 3 groups of S1(44 cases),S2(30 cases),and S3(36 cases).The horizontal base plane(HB)in this study was defined as a horizontal axial section with the mesiobuccal cusps of the left maxillary first molar on.Two coronal slices of interest were selected which passing through the apex of mesiobuccal(MB)and distobuccal(DB)roots of the left maxillary first molar respectively.In both of the two coronal slices,the buccal bone thickness was measured at 13(HB13),15(HB15),17(HB17)mm above the HB plane at a gingival inclination of 60°.The measurement differences of bone thickness between MB and DB,and among different heights were evaluated,and the differences among S1,S2,and S3 groups in each simulated paths were compared.Distributions of measurements were reported as colormaps.Results The IZC bone thickness of DB was thicker than MB at HB13 and HB15 in the 3 groups.The higher the insertion height,the smaller the bone thickness(P<0.05).Bone thickness decreased from S1 to S2 to S3 at HB13 and HB15.The maximum bone thickness(5.20 mm)was observed at HB13 in DB,and the minimum bone thicness(1.90 mm)was observed at HB17 in DB.Conclusion The thickest bone in IZC of the three groups located at HB13 in DB of the maxillary first molar,and the bone thickness decreases with the increase of the insertion height.The later the eruption stage of the maxillary second molar,the less bone thickness in the IZC region and the operation difficulty might increase.

Objective:To explore the effect of timely induction intervention on postpartum urination in primipara during vaginal delivery, so as to provide the evidence for preventing the occurrence of postpartum urinary retention and relieving the pain of primipara.Methods:This study adopted a randomized controlled trial design, and selected 400 cases of primipara who were hospitalized for vaginal delivery in the Obstetric Department of Dalian Women and Children's Medical Group Sports New Town Hospital from June 2021 to September 2022 as the study objects by convenience sampling method. They were divided into the intervention group and the control group with 200 cases each by random number table method, and the control group received routine postpartum care. Instruct active urination within 6 hours after delivery. The intervention received timely induction urination intervention. The general condition and bladder urine volume of the women in the intervention group were evaluated at 2, 4, 6 h after delivery, respectively, and personalized guidance was implemented, including the frequency of massage of the bottom of the uterus, the control of water intake, the selection of methods and timing of inducing urination, etc., and routine postpartum care was given when the women completed their first urination and had no complaints of discomfort. The first urination time, first urination volume, first bladder irritation during the first urination and the incidence of postpartum urinary retention in different periods were compared between the two groups.Results:The patients in the control group were (29.60 ± 3.20) years old, while the patients in the intervention group were (28.81 ± 3.42) years old. The first urination time in the intervention group was (6.89 ± 2.18) h, which was shorter than that in the control group (9.11 ± 3.86) h, and the difference was statistically significant ( t=-2.49, P<0.01). The first urination volume in the intervention group was (322.36 ± 120.15) ml, which was higher than that in the control group (262.93 ± 105.68) ml, and the difference was statistically significant ( t=3.39, P<0.05). The incidence of the first bladder irritation in the intervention group was 22.0%(44/200), which was lower than that in the control group 33.5%(67/200), and the difference was statistically significant ( χ2=6.60, P<0.05). The incidence of postpartum urinary retention within 24 h in the intervention group was 5.5%(11/200), which was lower than that in the control group 11.5%(23/200), and the difference was statistically significant ( χ2=4.63, P<0.05). The incidence of postpartum urinary retention within 1 week in the intervention group was 9.5%(19/200), which was lower than that in the control group 16.5%(33/200), and the difference was statistically significant ( χ2=4.33, P<0.05). There was no significant difference in the incidence of postpartum urinary retention within 24 to 72 h between the two groups ( P>0.05). Conclusions:Timely induction intervention can reduce the incidence of postpartum urinary retention, shorten the time of first urination, increase the volume of first urination and improve the comfort of first urination, which is worthy of clinical application.

OBJECTIVE: Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and hydrogen nuclear magnetic resonance spectroscopy (¹H NMR), the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma (RhRR, Dahuang in Chinese), Eupolyphaga Steleophaga (EuS, Tubiechong in Chinese) combined with RhRR acting on acute liver injury were explored. METHODS: Models of acute liver injury were established, and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS. The liver tissues of different groups of mice were analyzed by ¹H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR. RESULTS: Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups, and the absorption of free anthraquinone in RhRR increased after compatibility with EuS. In addition, the pathological state of acute liver injury in rats can selectively promote the absorption of emodin, chrysophanol, physcion and aloe emodin. Through 15 differential metabolites in the liver tissue of acute liver injury mice, it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid, alanine, aspartic acid and glutamic acid, and phosphoinositide. However, the regulation of RhRR was weaker than that of RhRR-EuS. CONCLUSION For the first time, we studied the pharmacokinetics and metabolomics differences of RhRR-EuS and RhRR in rats and mice with acute liver injury, in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China. Methods This study included individuals aged 28 days-85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA. Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0-1 year,and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains. Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Humans ; Pyrazinamide/therapeutic use* ; Isoniazid/therapeutic use* ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/microbiology* ; Mycobacterium tuberculosis/genetics* ; Tuberculosis/drug therapy* ; Rifampin/therapeutic use* ; Mutation ; Drug Resistance, Multiple, Bacterial/genetics*

OBJECTIVES: To explore the effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome (IBS-D) based on 16S rDNA technique. METHODS: Ten rats were randomized from 58 SPF-grade male SD rats to be the blank group. The remained 48 rats were prepared to be IBS-D models by the modified method of acetic acid enema combined with binding tail-clip stress. Forty successfully-modeled rats were randomly divided into a model group, an acupuncture group, a moxibustion group and a western medication group, with 10 rats in each one. In the acupuncture group, the needle was inserted at bilateral "Zusanli" (ST 36) and remained for 15 min in each rat. In the moxibustion group, the suspending moxibustion was delivered at bilateral "Zusanli" (ST 36) for 15 min. The rats in the western medication group were given pinaverium bromide suspension (10 mL/kg) by intragastric administration. The above interventions were performed once daily for consecutive 14 days. The body mass and the score of fecal trait were compared before and after modeling, as well as after intervention in each group. Fecal water content, diarrhea index and colon transit time (CTT) were measured after modeling and intervention in the rats of each group separately. After intervention, the colonic morphology of rats in each group was observed, and using 16S rDNA technique, the intestinal flora was detected. RESULTS: After modeling, compared with the blank group, the body mass and CTT were reduced (P<0.01); fecal trait scores, fecal water contents and diarrhea index increased (P<0.01) in the other 4 groups. After intervention, the body mass and CTT of the rats decreased (P<0.01), and fecal trait score, fecal water content and diarrhea index increased (P<0.01) in the model group compared with those in the blank group. In the acupuncture group, the moxibustion group and the western medication group, when compared with the model group, the body mass and CTT were elevated (P<0.01), while fecal trait scores, fecal water contents and diarrhea index declined (P<0.01). Compared with the western medication group, fecal water content decreased in the acupuncture group and the moxibustion group (P<0.05), while CTT increased in the acupuncture group (P<0.01), the body mass increased and fecal trait score was dropped in the moxibustion group (P<0.05). The colonic mucosa structure was clear and complete, and there was no obvious inflammatory cell infiltration in the blank group. The mild interstitial edema of intestinal mucosa was presented with the infiltration of few inflammatory cells in the model group. There was the infiltration of few inflammatory cells in the mucosa of the acupuncture group, the moxibustion group and the western medication group. Compared with the blank group, the indexes of Richness, Chao1, ACE and Shannon decreased in the model group (P<0.05). Indexes of Richness, Chao1 and ACE increased in the acupuncture group and the moxibustion group (P<0.05), and the Richness index in the western medication group increased (P<0.05) when compared with those in the model group. The relative abundance of Bacteroidetes, Proteobacteria and Prevotella increased (P<0.05), and that of Firmicutes and Muribaculaceae decreased (P<0.05) in the model group compared with those in the blank group. When compared with the model group, the relative abundance of Bacteroidetes, Proteobacteria and Prevotella was reduced (P<0.05), while that of Firmicutes and Muribaculaceae increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group; and that of Actinobacteria and Bifidobacterium increased in the acupuncture group and the moxibustion group (P<0.05). Compared with the blank group, the relative abundance of lipopolysaccharide (LPS) biosynthesis was elevated (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis decreased (P<0.05) in the model group. The relative abundance of LPS biosynthesis was dropped (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group compared with those of the model group. CONCLUSIONS Either acupuncture or moxibustion can relieve the symptoms of IBS-D and protect intestinal mucosa, which may be associated with regulating the structure of intestinal flora and promoting nutrient metabolism and biosynthesis.
Rats ; Male ; Animals ; Irritable Bowel Syndrome/therapy* ; Moxibustion/methods* ; Rats, Sprague-Dawley ; Gastrointestinal Microbiome ; Lipopolysaccharides ; Thioctic Acid ; Ubiquinone ; Zeatin ; Acupuncture Therapy ; Diarrhea/therapy* ; Terpenes ; Water ; Folic Acid ; Acupuncture Points