ObjectiveTo investigate the effects of Xijiao Dihuangtang （XJDHT） on mice with sepsis and cellular models of sepsis and explore its molecular mechanism in alleviating sepsis-induced inflammatory responses via regulating pyruvate kinase M2 （PKM2）-mediated one-carbon metabolism pathway. MethodsForty C57BL/6N mice were randomly divided into four groups： normal group， model group， low-dose XJDHT group （7.7 g·kg^-1）， and high-dose XJDHT group （15.4 g·kg^-1）. After one week of continuous gavage， sepsis was induced using cecal ligation and puncture （CLP） in groups except the normal group. 24 h after the surgery， mortality rates in all groups were recorded， and serum cytokines were measured by enzyme linked immunosorbent assay （ELISA）. Lung histopathology was examined by hematoxylin-eosin （HE） staining. During the in vitro experiment， the human monocytic leukemia cell line （THP-1） was exposed to various concentrations of XJDHT and treated with lipopolysaccharide （LPS） at a final concentration of 2 mg·L^-1 for 24 h. Cell apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay. Protein levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， B-cell lymphoma 2 （Bcl-2）， and Bcl-2-associated X protein （Bax） were measured by Western blot. Transcriptome sequencing was performed to analyze differentially expressed genes in all groups and conduct gene ontology （GO） enrichment. Key genes in the one-carbon metabolism pathway， including pyruvate kinase M2 （PKM2）， 5-methyltetrahydrofolate-homocysteine methyltransferase （MTR）， and phosphoglycerate dehydrogenase （PHGDH）， were verified by Western blot. A PKM2 inhibition model was established using shikonin for further protein expression analysis. ResultsAnimal experiments showed that compared with the normal group， the model group exhibited significantly elevated body temperature and lung pathology （P<0.01） and increased serum TNF-α and IL-1β levels （P<0.01）. High-dose XJDHT reduced body temperature and lung tissue damage （P<0.01） and significantly decreased serum TNF-α and IL-1β levels （P<0.01）. Low-dose XJDHT treatment showed no significant temperature change （P<0.01） but reduced serum TNF-α and IL-1β levels （P<0.01）. Transcriptome sequencing and Western blot revealed significant differences in the expression of TNF-α， IL-1β， and one-carbon metabolism genes （PKM2， MTR， and PHGDH） （P<0.01）. Cell experiments demonstrated that compared to the normal group， the model group showed elevated protein expressions of TNF-α and IL-1β in THP-1 cells （P<0.01）， decreased Bcl-2/Bax ratio， and increased apoptosis （P<0.01）. Transcriptome sequencing and Western blot revealed significant differences in the expression of TNF-α， IL-1β， and one-carbon metabolism genes （PKM2， MTR， and PHGDH） （P<0.01）. Compared to the model group， high-dose XJDHT significantly increased Bax/Bcl-2 ratio and PHGDH protein expression （P<0.01） and effectively reduced cell apoptosis （P<0.01） while down-regulating protein expressions of TNF-α， IL-1β， PKM2， and MTR （P<0.01）. Low-dose XJDHT moderately increased Bax/Bcl-2 ratio and PHGDH protein expression （P<0.05）， reduced apoptosis （P<0.05）， and decreased IL-1β and MTR protein levels （P<0.05， P<0.01）， but there were no significant changes in TNF-α and PKM2 expression. After PKM2 inhibition by shikonin in THP-1 cells， the expression of protein related to one-carbon metabolism was detected. Compared with the blank group， the LPS-induced model group showed significantly upregulated PKM2 and MTR protein expression （P<0.01） and downregulated PHGDH expression （P<0.01）. Compared with the model group， shikonin treatment significantly reduced PKM2 expression （P<0.05）， increased PHGDH expression （P<0.01）， and decreased MTR expression （P<0.05）. ConclusionXJDHT can inhibit the release of inflammatory factors in sepsis， and its mechanism is related to the intervention of the PKM2-regulated one-carbon metabolism pathway in macrophages.

ObjectiveThis study aims to reveal the mechanism of liver and kidney injuries caused by Dictamni Cortex and its interrelationship by metabonomics analysis of liver and kidney via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS）. MethodsThe content of the marker compounds of Dictamni Cortex was measured by high-performance liquid chromatography （HPLC） to carry out quality control. Sprague Dawley （SD） rats were randomly divided into a blank group （normal saline）， an administration group （0.9， 2.7， 8.1 g·kg^-1）， and a high-dose withdrawal control group， with eight rats in each group. Continuous administration was performed once daily for 28 days. The liver and kidney injuries caused by each administration group were assessed by organ indices， pathological observations， and serum and plasma biochemical indices measured by enzyme-linked immunosorbent assay （ELISA）. The potential biomarkers of liver and kidney injuries caused by Dictamni Cortex were screened， and pathway enrichment analysis and correlation analysis were performed based on UPLC-Q-TOF-MS. ResultsCompared with the blank group， both the medium- and low-dose groups showed insignificant damage to the liver and kidney of rats. The high-dose group exhibited the most serious damage， and the level of liver and kidney function indices ［alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， creatinine （Cr）， and blood urea nitrogen （BUN）］ and serum inflammatory indices （［interleukin 1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α）］ in the serum were significantly changed （P<0.01）. The liver and kidney metabolism pathways and differential metabolites were quite different. Among them， phenylalanine metabolism， niacin and nicotinamide metabolism， and glycerophospholipid metabolism were common pathways. Correlation analysis of differential metabolites showed that there were significant correlations among disorders of 4′-Phosphopantothenoylcysteine， PC （16∶0/15∶0）， phenylethylamine， arachidonic acid， and linoleic acid in liver and kidney tissue. ConclusionThe decoction of Dictamni Cortex can cause liver and kidney injuries， and its mechanism may be related to oxidative stress and lipid metabolism disorders. The correlation of differential metabolites indicates the interaction between liver and kidney injuries.

ObjectiveTo explore the mechanism of the immunotoxicity induced by dictamnine （DIC） in rats and the recovery effect after drug withdrawal by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry， thereby providing a theoretical basis for elucidating the toxic mechanism of DIC. MethodsSD rats were randomized into blank （normal saline）， DIC （10 mg·kg^-1）， and DIC withdrawal （recovery period） groups （n=8）. The rats were continuously treated for 7 days， once a day， and the body weight and organ weight were recorded. The levels of interleukin-1 （IL-1）， IL-6， and tumor necrosis factor-α （TNF-α） in the serum and immunoglobulin A （IgA）， immunoglobulin G （IgG）， and immunoglobulin M （IgM） in the spleen were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to observe the pathological changes in the spleen. ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was employed to screen the potential biomarkers of immune inflammation caused by DIC， and pathway enrichment analysis and correlation analysis were performed. The mRNA levels of IL-1β， TNF-α， lysophosphatidylcholine acyltransferase 2 （LPCAT2）， and farnesoid X receptor （FXR） in the serum were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， the DIC group showed elevated levels of IL-1β， IL-6， and TNF-α in the serum （P<0.01）， and the DIC withdrawal group showcased lowered levels of IL-1β， IL-6， and TNF-α in the serum （P<0.01）. The levels of IgA， IgG， and IgM in the spleen of rats in the DIC group were decreased （P<0.01）， while those in the DIC withdrawal group were recovered （P<0.05， P<0.01）. Untargeted metabolomics of the serum and spleen screened out 14 common differential metabolites and 14 common metabolic pathways. The Spearman correlation analysis between differential metabolites and inflammatory factors identified PC （32∶0）， LysoPC （20∶4/0∶0）， LysoPC （P-18∶0/0∶0）， taurochenodeoxycholic acid， taurocholic acid， LysoPC ［20∶5（5Z，8Z，11Z，14Z，17Z）/0∶0］， chenodeoxycholic acid， arachidonic acid， LysoPC （18∶0/0∶0）， LysoPC （15∶0/0∶0）， LysoPC （16∶0/0∶0）， and LysoPC （17∶0/0∶0） as the biomarkers of immunotoxicity induced by DIC in SD rats. In the process of immunotoxicity caused by DIC， lipid metabolism disorders such as glycerophospholipid metabolism， primary bile acid metabolism， and arachidonic acid metabolism were enriched， which was consistent with the DIC-induced inflammatory factors and pathological characteristics of the spleen. Compared with the blank group， the DIC group exhibited up-regulated mRNA levels of IL-1β， TNF-α， LPCAT2， and FXR （P<0.01）， and the up-regulation was decreased in the withdrawal group （P<0.01）. ConclusionDIC can lead to immune and inflammatory disorders. DIC withdrawal can regulate the expression of biomarkers related to serum and spleen metabolites， regulate the inflammatory metabolic pathway， reduce the inflammation level， and alleviate the metabolic disorders， thus attenuating the potential toxicity induced by DIC.

Objective To investigate the relationship between Helicobacter pylori (Hp) infection and disease severity and pathological type of intestinal polyps in inpatients. Methods The data of 303 inpatients with intestinal polyps in the hospital from August 2022 to February 2025 were collected and analyzed. The clinical characteristics of patients were analyzed, and the influencing factors of pathological types of polyps were explored. Results Among the 303 inpatients with intestinal polyps, there were 135 Hp positive cases and 168 Hp negative cases. The number of polyps, maximum polyp diameter, number of ileocecus/ascending colon/transverse colon polyps, number of descending colon/sigmoid colon/rectal polyps and adenomatous polyps in the Hp-positive group were higher than those in the Hp-negative group (P<0.05). Multivariate logistic regression analysis indicated that age [OR (95%CI)=1.03 (1.01-1.05)] and positive Hp[OR (95%CI)=2.61 (1.62-4.20)] were independent risk factors of occurrence of adenomatous polyps (P<0.05). ROC curve results revealed that the AUCs of age, positive HP and combination in the diagnosis of adenomatous polyps were 0.574, 0.608 and 0.646, and the 95%CI values were 0.509-0.638, 0.545-0.672 and 0.584-0.708 respectively. The efficiency of combination of the two indexes was higher than that of single diagnosis. Conclusion Hp infection is associated with disease severity in inpatients with intestinal polyps, and it may be involved in the occurrence and development of adenomatous polyps.

Mental state is an important part of the normal life activities of the human body, and it is also the most external expression and the most easily obtained information of the physical condition. The normal activities of the mind depend on the normal operation of the viscera, qi, and blood, and are a unified whole that prospers together and suffers together. The theory of the five-spirit-viscera in the Yellow Emperor’s Inner Classic revealed that the normal mental activities of the human body were dominated by the five internal organs, that is, the five internal organs were the body and the five spirits were the function. And it highlighted the viewpoint that the five internal organs store the spirits and are actually one. The heart governs the spirit and belongs to the four internal organs. On this basis, Synopsis of Golden Chamber used the internal organs to diagnose and treat mental diseases, integrating the theory of the five spirits into it, forming a unique method of diagnosis and treatment with the heart as the leading factor and regulating the qi and blood of the four internal organs. It identified the pathogenesis of diseases such as pathogenic crying, lily disease, and hysteria from five levels: heart deficiency and weak qi, heart-lung disharmony, heart-liver disharmony, the heart of the loss of the spleen nourishment, and disharmony between heart and kidney. The treatment was mainly to replenish the deficiency of the viscera and eliminate the pathogens, reflecting the characteristics of regulating the mind and calming the four internal organs. This unique view on diagnosis and treatment has profoundly influenced the diagnosis and treatment theories of mental illnesses by later doctors, and is of great significance to the current clinical treatment of such illnesses.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

OBJECTIVE: To investigate the relationship between serum levels of fibroblast growth factor-23 (FGF-23), heparanase (HPSE) and early renal impairment (RI) in patients with multiple myeloma (MM). METHODS: A retrospective analysis was conducted on the clinical data of 125 MM patients who were initially diagnosed in the Department of Hematology of the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology from June 2020 to June 2023. The patients were divided into RI group (>176.80 μmol/L) and non-RI group (≤176.80 μmol/L) based on their serum creatinine levels when diagnosed. The baseline data and laboratory indexes of the two groups were compared. The relationship between serum FGF-23, HPSE and early RI in MM patients was analyzed. RESULTS: Among 125 newly diagnosed MM patients, 33 cases developed early RI, accounting for 26.40%. The proportion of light chain type, blood urea nitrogen (BUN), blood uric acid, lactate dehydrogenase, FGF-23, and HPSE levels in RI group were higher than those in non-RI group (all P <0.05). There was no statistical significant difference in other data between the two groups (P >0.05). Multivariate logistic regression analysis showed that BUN, FGF-23 and HPSE were associated with early RI in MM patients (all P <0.05). The serum FGF-23 level was divided into Q1-Q4 groups by quartile, and the serum HPSE level was divided into q1-q4 groups. The correlation analysis showed that with the increase of serum FGF-23 and HPSE levels, the incidence of early RI increased (r =0.668, 0.592). Furthermore, logistic regression analysis showed that after controlling for confounding factors, elevated levels of serum FGF-23 and HPSE were still influencing factors for early RI in MM patients (OR>1, P <0.05). According to Pearson's linear correlation test, there was a positive correlation between serum FGF-23 level and HPSE level (r =0.373). CONCLUSION There is a certain correlation between serum levels of FGF-23, HPSE and early RI in MM patients, and the incidence of early RI is higher in patients with abnormally high levels of both.
Humans ; Multiple Myeloma/complications* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/blood* ; Glucuronidase/blood* ; Male ; Female ; Middle Aged ; Renal Insufficiency/blood* ; Aged

OBJECTIVE: To investigate the correlation between platelet alloantibodies and CD8⁺ T cell with platelet desialylation and apoptosis in platelet transfusion refractoriness(PTR). METHODS: The expression of RCA-1, CD62P and Neu1 on platelets were detected in 135 PTR patients and 260 healthy controls. The ability of PTR patients' sera with anti-HLA antibody, anti-CD36 antibody and antibody-negative groups to induce platelet desialylation and apoptosis, and the potential effect of FcγR inhibitors on desialylation and apoptosis were evaluated. Additionally, the association between CD8⁺ T cells and platelet desialylation in patients was analyzed. RESULTS: The expression of RCA-1 and Neu1 on platelets in PTR patients were significantly higher than those in healthy donors（P < 0.05）, but were not related to platelet alloantibody (P >0.05). The sera of PTR patients generally induced platelet desialylation in vitro （P < 0.05）, with no significant differences among the groups（P >0.05）. However, the sera with anti-CD36 antibodies could induce platelet apoptosis significantly higher than that in the anti-HLA antibody group and antibody-negative group in vitro (P < 0.05). In PTR patients with anti-CD36 antibodies, platelet apoptosis was dependent on FcγR signaling, while desialylation is not. Moreover, CD8⁺ T cells in PTR patients were significantly associated with platelet desialylation (P < 0.05). CONCLUSION Platelet desialylation is a common pathological phenomenon in PTR patients， which involves the participation of CD8⁺ T cell, but isn't associated with platelet alloantibody; while anti-CD36 antibodies have potential clinical significance in predicting platelet apoptosis in PTR patients.
Humans ; Apoptosis ; CD8-Positive T-Lymphocytes/immunology* ; Blood Platelets/metabolism* ; Platelet Transfusion ; Isoantibodies ; Male ; Female ; Middle Aged