1.Medication rules of Astragali Radix in ancient Chinese medical books based on "disease-medicine-dose" pattern.
Jia-Lei CAO ; Lü-Yuan LIANG ; Yi-Hang LIU ; Zi-Ming XU ; Xuan WANG ; Wen-Xi WEI ; He-Jia WAN ; Xing-Hang LYU ; Wei-Xiao LI ; Yu-Xin ZHANG ; Bing-Qi WEI ; Xian-Qing REN
China Journal of Chinese Materia Medica 2025;50(3):798-811
This study employed the "disease-medicine-dose" pattern to mine the medication rules of traditional Chinese medicine(TCM) prescriptions containing Astragali Radix in ancient Chinese medical books, aiming to provide a scientific basis for the clinical application of Astragali Radix and the development of new medicines. The TCM prescriptions containing Astragali Radix were retrieved from databases such as Chinese Medical Dictionary and imported into Excel 2020 to construct the prescription library. Statical analysis were performed for the prescriptions regarding the indications, syndromes, medicine use frequency, herb effects, nature and taste, meridian tropism, dosage forms, and dose. SPSS statistics 26.0 and IBM SPSS Modeler 18.0 were used for association rules analysis and cluster analysis. A total of 2 297 prescriptions containing Astragali Radix were collected, involving 233 indications, among which sore and ulcer, consumptive disease, sweating disorder, and apoplexy had high frequency(>25), and their syndromes were mainly Qi and blood deficiency, Qi and blood deficiency, Yin and Yang deficiency, and Qi deficiency and collateral obstruction, respectively. In the prescriptions, 98 medicines were used with the frequency >25 and they mainly included Qi-tonifying medicines and blood-tonifying medicines. Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Citri Reticulatae Pericarpium were frequently used. The medicines with high frequency mainly have warm or cold nature, and sweet, pungent, or bitter taste, with tropism to spleen, lung, heart, liver, and kidney meridians. In the treatment of sore and ulcer, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to promote granulation and heal up sores. In the treatment of consumptive disease, Astragali Radix was mainly used with the dose of 37.30 g and combined with Ginseng Radix et Rhizoma to tonify deficiency and replenish Qi. In the treatment of sweating disorder, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to consolidate exterior and stop sweating. In the treatment of apoplexy, Astragali Radix was mainly used with the dose of 7.46 g and combined with Glycyrrhizae Radix et Rhizoma to dispell wind and stop convulsions. Astragali Radix can be used in the treatment of multiple system diseases, with the effects of tonifying Qi and ascending Yang, consolidating exterior and stopping sweating, and expressing toxin and promoting granulation. According to the manifestations of different diseases, when combined with other medicines, Astragali Radix was endowed with the effects of promoting granulation and healing up sores, tonifying deficiency and Qi, consolidating exterior and stopping sweating, and dispelling wind and replenishing Qi. The findings provide a theoretical reference and a scientific basis for the clinical application of Astragali Radix and the development of new medicines.
Drugs, Chinese Herbal/history*
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Humans
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Medicine, Chinese Traditional/history*
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History, Ancient
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Astragalus Plant/chemistry*
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China
;
Astragalus propinquus
2.Blood glucose-lowering mechanism of Poria aqueous extract by UPLC-Q-TOF-MS/MS combined with network pharmacology and experimental verification.
Dan-Dan ZHANG ; Wen-Biao WAN ; Qing YAO ; Fang LI ; Zi-Yin YAO ; Xiao-Chuan YE
China Journal of Chinese Materia Medica 2025;50(14):3980-3989
Ultra performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry/mass spectrometry(UPLC-Q-TOF-MS/MS), network pharmacology, and animal experiments were integrated o explore the blood glucose-lowering effects and mechanisms of Poria aqueous extract. Firstly, the active components of Poria aqueous extract were identified by UPLC-Q-TOF-MS/MS. Subsequently, network pharmacology was employed to predict the blood glucose-lowering components and mechanisms of Poria aqueous extract. Finally, a rat model of diabetes mellitus, 16S rDNA sequencing, and Western blot were employed to investigate the blood glucose-lowering effect and mechanism of Poria aqueous extract. A total of 39 triterpenoids were identified in the Poria aqueous extract, among them, 25-hydroxypachymic acid, 25α-hydroxytumulosic acid, 16α-hydroxytrametenolic acid, polyporenic acid C, and tumulosic acid may be the main active ingredients for treating diabetes. The Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis revealed that Poria might exert its therapeutic effects through multiple pathways such as NOD-like receptor signaling pathway, nuclear factor-kappa B(NF-κB) signaling pathway, and tumor necrosis factor(TNF) signaling pathway. The results of animal experiments demonstrated that Poria aqueous extract significantly reduced the levels of blood glucose and lipids and regulated the intestinal flora in diabetic rats. The main affected taxa included g_Escherichia-Shigella, g_Corynebacterium, g_Prevotella_9, g_Prevotellaceae_UCG-001, and g_Bacteroidota_unclassified. In addition, Poria aqueous extract lowered the levels of D-lactic acid and lipopolysaccharide, alleviated colonic mucosal damage, significantly down-regulated the protein levels of NOD-like receptor pyrin domain-containing protein 3(NLRP3), NF-κB, and TNF-α, and significantly up-regulated the protein levels of zonula occludens 1 and occludin in diabetic rates. Poria aqueous extract may play a role in treating diabetes mellitus by repairing the intestinal flora disturbance, protecting the intestinal barrier function, and inhibiting the NF-κB/NLRP3 signaling pathway. The results provide a scientific basis for clinical application and expansion of indications of Poria.
Animals
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Rats
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Network Pharmacology
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Tandem Mass Spectrometry
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Male
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Drugs, Chinese Herbal/pharmacology*
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Chromatography, High Pressure Liquid
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Blood Glucose/drug effects*
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Rats, Sprague-Dawley
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Hypoglycemic Agents/administration & dosage*
;
Poria/chemistry*
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Diabetes Mellitus, Experimental/metabolism*
;
NF-kappa B/genetics*
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Gastrointestinal Microbiome/drug effects*
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Humans
3.Complications among patients undergoing orthopedic surgery after infection with the SARS-CoV-2 Omicron strain and a preliminary nomogram for predicting patient outcomes.
Liang ZHANG ; Wen-Long GOU ; Ke-Yu LUO ; Jun ZHU ; Yi-Bo GAN ; Xiang YIN ; Jun-Gang PU ; Huai-Jian JIN ; Xian-Qing ZHANG ; Wan-Fei WU ; Zi-Ming WANG ; Yao-Yao LIU ; Yang LI ; Peng LIU
Chinese Journal of Traumatology 2025;28(6):445-453
PURPOSE:
The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery.
METHODS:
A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications.
RESULTS:
In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram.
CONCLUSION
Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans
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COVID-19/complications*
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Male
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Female
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Middle Aged
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Postoperative Complications/epidemiology*
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SARS-CoV-2
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Orthopedic Procedures/adverse effects*
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Aged
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Nomograms
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Adult
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Retrospective Studies
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Risk Factors
4.Impact of human papillomavirus and coinfection with other sexually transmitted pathogens on male infertility.
Xin FAN ; Ya XU ; Li-Feng XIANG ; Lu-Ping LIU ; Jin-Xiu WAN ; Qiu-Ting DUAN ; Zi-Qin DIAN ; Yi SUN ; Ze WU ; Yun-Hua DONG
Asian Journal of Andrology 2025;27(1):84-89
This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans
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Male
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Infertility, Male/epidemiology*
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Coinfection/microbiology*
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Papillomavirus Infections/virology*
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Adult
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Sexually Transmitted Diseases/complications*
;
China/epidemiology*
;
Staphylococcus aureus/isolation & purification*
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Chlamydia trachomatis/isolation & purification*
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Prevalence
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Mycoplasma genitalium/isolation & purification*
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Ureaplasma urealyticum/isolation & purification*
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Neisseria gonorrhoeae/isolation & purification*
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Enterococcus faecalis/isolation & purification*
;
Streptococcus agalactiae/isolation & purification*
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Herpesvirus 2, Human/genetics*
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Pseudomonas aeruginosa/isolation & purification*
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Semen/virology*
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Sperm Motility
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Spermatozoa/microbiology*
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Human Papillomavirus Viruses
5.A Study of Flow Sorting Lymphocyte Subsets to Detect Epstein-Barr Virus Reactivation in Patients with Hematological Malignancies.
Hui-Ying LI ; Shen-Hao LIU ; Fang-Tong LIU ; Kai-Wen TAN ; Zi-Hao WANG ; Han-Yu CAO ; Si-Man HUANG ; Chao-Ling WAN ; Hai-Ping DAI ; Sheng-Li XUE ; Lian BAI
Journal of Experimental Hematology 2025;33(5):1468-1475
OBJECTIVE:
To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation.
METHODS:
Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0.
RESULTS:
A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×104 copies/ml, significantly higher than that in T cells (4.00×103 copies/ml, P <0.01) and NK cells (2.85×102 copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days).
CONCLUSION
In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans
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Hematologic Neoplasms/virology*
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Herpesvirus 4, Human/physiology*
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Epstein-Barr Virus Infections
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Hematopoietic Stem Cell Transplantation
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Virus Activation
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Lymphocyte Subsets/virology*
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Flow Cytometry
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Killer Cells, Natural/virology*
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Male
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Female
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B-Lymphocytes/virology*
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Viral Load
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Adult
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T-Lymphocytes/virology*
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Middle Aged
6.Association between atherogenic index of plasma trajectory and new-onset coronary heart disease in Chinese elderly people: a prospective cohort study.
Wan-Li HU ; Yv-Lin CHENG ; Dong-Hai SU ; Yv-Fang CUI ; Zi-Hao LI ; Ge-Fei LI ; Hai-Yun GAO ; Da-Tian GAO ; Xiao-Ke ZHANG ; Song-He SHI
Journal of Geriatric Cardiology 2025;22(10):835-843
BACKGROUND:
The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people.
METHODS:
19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log10 (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023.
RESULTS:
Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses.
CONCLUSIONS
There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.
7.Progress in Clinical Research and Experimental Study of Danggui Shaoyao Powder in the Treatment of Chronic Pelvic Inflammatory Disease
Zi-Yi FENG ; Jia-Jun LIU ; Lan WANG ; Wan-Ying CHEN ; Jie-Ming HUANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):1091-1096
Chronic pelvic inflammatory disease(CPID)is a common chronic inflammatory disease in women,and has a long course and is easy to relapse.Danggui Shaoyao Powder is from Jin Gui Yao Lve(Synopsis of the Golden Chamber),which was a commonly-used formula for the treatment of women's abdominal pain in ancient medical records.It is now often used in the treatment of CPID and has achieved satisfactory therapeutic effect.The article summarizes and analyzes the achievements in the clinical research and experimental study of Danggui Shaoyao Powder in the treatment of CPID over the past 10 years,and invesigates the clinical efficacy of Danggui Shaoyao Powder in the treatment of CPID and its therapeutic mechanism.In the field of clinical studies,Danggui Shaoyao Powder for the treatment of CPID was used by modification,or alone,or in combination with antibiotics and Chinese medicine external treatment,and its combined use was effective on significantly improving the indicators of inflammatory response and immune function,alleviating the clinical signs and symptoms such as pain,and did not increase the incidence of adverse reactions compared with the application of western medicines alone.In the field of experimental studies,Danggui Shaoyao Powder played the therapeutic role in CPID by decreasing the adhesion of endothelial cells,regulating the degradation of extracellular matrix,improving the level of inflammatory factors,and down-regulating the expression of proteins related to the nuclear factor κB(NF-κB)pathway.
8.iTRAQ-based proteomics reveals the mechanism of action of Yinlai decoction in treating pneumonia in mice consuming a high-calorie diet
Qianqian Li ; Tiegang Liu ; Chen Bai ; Xueyan Ma ; Hui Liu ; Zi ; an Zheng ; Yuxiang Wan ; He Yu ; Yuling Ma ; Xiaohong Gu
Journal of Traditional Chinese Medical Sciences 2024;11(1):21-32
Objective:
To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie diet-induced pneumonia through proteomics analysis.
Methods:
Based on the Gene Expression Omnibus (GEO) database, lung tissue samples from normal and high-fat diet (HFD) fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses. In the animal experiments, mice were randomly divided into the control (N), high-calorie diet pneumonia (M), and Yinlai decoction treatment (Y) groups. Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d. The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d. Pathological evaluation of the lung tissue was performed. Differentially expressed proteins (DEPs) in the lung tissue were identified using quantitative proteomics and bioinformatics analyses. The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory (MGL) Tools. DEPs were verified by western blot.
Results:
GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue. The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet. A total of 47 DEPs were identified between the Y and M groups. Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle (TCA) and oxidative phosphorylation. The protein-protein interaction network revealed that Atp5a1, Pdha1, and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction. Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide, praeruptorin B, chrysoeriol, and other components in Yinlai decoction to Atp5a1.
Conclusion
The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation. Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.
9.GPR120 mediates mechanism of protective effect of NF-κB and MAPK in regula-ting LTA-induced Mac-T cells
Siqi WANG ; Peiyao ZHOU ; Quanzhou MOU ; Lin WAN ; Xinli LI ; Yang LI ; Xingli HE ; Zhaoyuan WANG ; Zi WANG ; Ziqiang GAO ; Zhihui ZHAO ; Binglei SHEN
Chinese Journal of Veterinary Science 2024;44(10):2165-2171
Lipophosphatidic acid(LTA)was used to stimulate Mac-T cells,and the expression lev-els and phosphorylation levels of key proteins of nuclear factor-κB(NF-κB)and mitogen-activated protein kinase(MAPK)signaling pathway and the expression levels of upstream key action factors TLR4 and MyD88 proteins were detected by Western blot,and EDU assay was used to detect cell proliferation levels and flow cytometry was used to detect apoptosis.The results showed that acti-vation of GPR120 significantly decreased the phosphorylation levels of LTA-induced NF-κB(P65 and IκBα)(P<0.01)and MAPK(JNK,ERK,p38)(P<0.01)in Mac-T cells;inhibition of GPR120 was able to upregulate LTA-induced NF-κB(p65 and IκBα)in Mac-T cells(P<0.01)and MAPK(JNK,ERK,p38)phosphorylation levels(P<0.01);and activation of GPR120 significantly allevia-ted LTA-induced upregulation of TLR4 and MyD88(P<0.01);inhibition of GPR120 significantly exacerbated LTA-induced upregulation of TLR4 and MyD88(P<0.05);LTA stimulation led to a trend of diminished Mac-T cell proliferation and significantly increased apoptosis,whereas activa-tion of the GPR120 gene significantly increased cell activity(P<0.01),promoted cell proliferation and significantly reduced apoptosis(P<0.05)thereby alleviating the damage to Mac-T cells by LTA;LTA stimulation led to a highly significant increase in apoptosis(P<0.01).In contrast,acti-vation of the GPR120 gene significantly reversed the increase in the apoptosis rate of Mac-T cells induced by LTA(P<0.01),while inhibition of the GPR120 gene enhanced the apoptosis-promo-ting effect of LTA(P<0.05),indicating that activation of the GPR120 gene attenuated the in-crease of apoptosis rate caused by LTA-induced inflammatory Mac-T cells.The results suggest that GPR120 can regulate inflammation by mediating TLR4 and MyD88 expression to inhibit NF-κB/MAPK inflammatory pathway activation and can promote cell proliferation.
10.Effect of Plasma Epstein-Barr Virus Nucleic Acid Loads on the Clinical Features and Prognosis in Adult Secondary Hemopha-gocytic Lymphohistiocytosis
Li-Min DUAN ; Guang-Li YIN ; Tian TIAN ; Ju-Juan WANG ; Xin GAO ; Wan-Ying CHENG ; Zi-Wei FANG ; Hong-Xia QIU ; Ji XU
Journal of Experimental Hematology 2024;32(4):1238-1247
Objective:To investigate the effect of pre-treatment plasma Epstein-Barr virus(EBV)DNA copy number on the clinical features and prognosis of patients with adult secondary hemophagocytic lymphohistiocytosis(sHLH).Methods:The clinical characteristics,survival rate,and prognostic factors of 171 patients with adult sHLH treated at Jiangsu Province Hospital from June 2017 to January 2022 were retrospectively analyzed in this study.Patients were divided into three groups,including the EBV DNA-negative group(<5.0 × 102 copies/ml),lower EBV-DNA loads group(5.0 × 102-8.51 × 104 copies/ml),and higher EBV-DNA loads group(>8.51 × 104 copies/ml),according to pre-treatment plasma EBV-DNA copy number.Cox regression model was established for screening prognostic factors.Adult sHLH survival prediction model was constructed and realized through the nomogram based on EBV-DNA load after adjusted the factors affecting survival of etiology and treatment strategy.Concordance index(C-index)and calibration curves were calculated to verify model predictive and discriminatory capacity.Results:Among 171 adult sHLH patients,84 patients were not infected with EBV(EBV DNA-negative group),and 87 with EBV(EBV DNA-positive group,48 lower EBV-DNA loads group and 39 higher EBV-DNA loads group).Consistent elevations in the levels of liver enzymes(ALT and AST),LDH,TG,β2-microglobulin and ferritin across the increasing of EBV-DNA load(all P<0.05),while the levels of fibrinogen decrease(P<0.001).The median follow-up time was 52 days(range 20-230 days),and 123 patients died.The overall survival(OS)rate of patients in EBV DNA-positive group was lower than that in EBV DNA-negative group(median OS:40 days vs 118 days,P<0.001).Higher EBV-DNA loads had worse OS(median OS:24 days vs 45 days vs 118 days,P<0.0001 for trend)compared to lower EBV-DNA loads and EBV DNA-negative group.Multivariate Cox analysis revealed that higher EBV-DNA loads(P=0.005),fibrinogen≤ 1.5 g/L(P=0.012),ferritin(P=0.041),associated lymphoma(P=0.002),and anti-tumor based strategy(P=0.001)were independent prognostic factors for OS.The C-indexes of 30 day,90 days,365 days survival rate were all greater than 0.8 of the nomogram model and calibration curves provided credibility to their predictive capability.Subgroup analysis showed that patients with higher EBV-DNA loads had a significantly worse prognosis in adult sHLH who were women,ferritin>5 000 μg/L,β2-microglobulin>7.4 mmol/L and regardless of age,etiologies,HScore points.Conclusion:The EBV-DNA load is a strong and independent predictor for survival in patients with sHLH.The prognostic nomogram based on EBV-DNA loads was dependable and provides a visual tool for evaluating the survival of adult sHLH.


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