1.A Hidden Diagnosis: Disseminated Histoplasmosis Mimicking Tuberculosis in the Elderly
Wan Muhamad Amir Wan Md Zin ; Moon Yan Yap ; Meroshini Sundaran ; Siti Nabilah &lsquo ; Atiqah Othman ; Siti Nabihah Mohamed Hatta ; Maz Anirah Abdul Azis
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):28-
Introduction:
Histoplasmosis is a rare opportunistic, inhalation-acquired
systemic mycosis caused by Histoplasma capsulatum,
endemic to Southeast Asia, including Malaysia. Although
classically seen in immunocompromised hosts, it is
increasingly reported in immunocompetent individuals.
Infection is associated with environmental exposures such
as bat or bird droppings and soil disruption. Histoplasmosis
is a progressive granulomatous disease that can closely
mimic tuberculosis and malignancy, making diagnosis
challenging.
Case:
An 87-year-old Malay male with a history of treated
pulmonary tuberculosis presented with a 6-month history
of intermittent fever, anorexia, weight loss, and hypotension. Initial computed tomography imaging demonstrated bilateral heterogeneous adrenal masses (right: 2.2
× 3.7 × 5.0 cm; left: 2.0 × 3.7 × 5.2 cm) with indeterminate
washout characteristics. Biochemical adrenal evaluation,
including a short Synacthen test, confirmed primary
adrenal insufficiency. Extensive microbiological and
malignancy workup, including bronchoscopy, cultures,
and tumor markers, was non-diagnostic. In view of clinical
deterioration and epidemiological risk, empirical antituberculous therapy was initiated; however, no clinical
improvement was observed after 2 months. PET-FDG revealed intensely hypermetabolic bilateral adrenal masses
(SUVmax right 16.7, left 13.2) with no other abnormal
foci. Non-invasive fungal investigations were negative.
Definitive diagnosis was established via computed
tomography-guided adrenal biopsy, which demonstrated
necrotizing granulomatous inflammation with intracellular
yeasts, subsequently identified as H. capsulatum. The patient
was treated with oral itraconazole and corticosteroid
replacement, resulting in significant clinical improvement
and planned interval radiological reassessment.
Conclusion
Disseminated histoplasmosis is a diagnostic challenge,
particularly in frail elderly patients, where invasive
procedures may be delayed. It can mimic tuberculosis
and malignancy and may lack an identifiable exposure
history. Non-invasive tests may be inconclusive, making
tissue biopsy essential. Adrenal involvement may result
in primary adrenal insufficiency, further complicating
the clinical picture. Early consideration and timely
confirmation are crucial for appropriate management.
Adrenal incidentaloma
;
Lung Neoplasms
2.Hashimoto's Thyroiditis Presenting With Recurrent Massive Pleural Effusion Suggestive of Lymphocytic Interstitial Pneumonitis
Endah Pratamaningtias ; Nyoman Satvika Dharma Yudha
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):106-
Introduction:
Hashimoto's thyroiditis is a common autoimmune thyroid
disease; however, pulmonary involvement is a rare
manifestation. Lymphocytic interstitial pneumonitis is
commonly associated with autoimmune diseases, but its
association with Hashimoto's thyroiditis remains poorly
understood.
Case:
A 63-year-old male with prior diagnosis of Hashimoto's
thyroiditis presented with recurrent massive pleural
effusion and progressive dyspnea. He also experienced
fatigue, cold intolerance, and constipation. Physical
examination revealed facial puffiness, diffuse goiter, and
dry skin. Thyroid function tests performed 6 months before
admission confirmed overt hypothyroidism (thyroidstimulating hormone [TSH] 80.30 µIU/mL, free thyroxine
4 [FT4] 0.46 ng/dL). One month prior to admission,
laboratory findings showed subclinical hypothyroidism
(TSH 9.09 µIU/mL, FT4 1.42 ng/dL). Despite levothyroxine
treatment TSH levels remained elevated at 21.8 µIU/mL
during admission. Anti-thyroid peroxidase antibodies were
positive (13.95 IU/mL). Repeated thoracentesis revealed
exudative pleural effusion with lymphocytic predominance
and no evidence of malignancy in cytological examination.
Infectious etiologies and malignancy were ruled out.
Thyroid ultrasonography demonstrated diffuse hypoechoic
enlargement of the thyroid gland. Chest radiography
showed massive unilateral pleural effusion, while thoracic
computed tomography revealed ground-glass opacities
with a reticulogranular pattern and interlobular septal thickening, accompanied by multiple thin-walled cysts,
highly suggestive of lymphocytic interstitial pneumonitis.
Thyroid immunohistochemical analysis was performed
(CD 20, CD 3, CD 10, CD 138, Ki 67, BCL 2, BCL 6,
Thyroglobulin, MUM 1, Cyclin D1), consistent with
lymphocytic thyroiditis. Significant clinical and laboratory
improvement was achieved after combined treatment with
levothyroxine and corticosteroid.
Conclusion
This case underscores the importance of considering
autoimmune-related lymphocytic interstitial pneumonitis
in patients with Hashimoto's thyroiditis who present with
unexplained recurrent pleural effusion after exclusion of
more common etiologies, such as infection and malignancy.
Early recognition may lead to favorable improvement.
Lung Diseases, Interstitial
;
Pleural Effusion
;
Thyroiditis
3.Clinical profile and prescribing patterns of therapy in children with bronchial asthma in a rural site in the Philippines: A retrospective cohort study.
Gayle Therese K. Gonzales-javier ; Leonila F. Dans ; Kristine Tanega-aliling ; Carol Stephanie C. Tan-lim ; Cara Lois T. Galingana ; Mia P. Rey ; Maria Rhodora D. Aquino ; Josephine T. Sanchez ; Antonio L. Dans
Acta Medica Philippina 2025;59(1):84-90
BACKGROUND
Bronchial asthma is one of the most common chronic childhood diseases encountered in the primary care setting. Adherence to recommendations from clinical practice guidelines on asthma can be utilized as an indicator of quality of care when evaluating the implementation of the universal health care in the Philippines.
OBJECTIVESTo determine the clinical profile of pediatric patients with bronchial asthma; and to evaluate the prescription patterns for asthma treatment in a primary care setting.
METHODSThis was a retrospective cohort study that involved review of the electronic medical records in a rural site of the Philippine Primary Care Studies (PPCS). All patients less than 19 years old who were diagnosed with asthma from April 2019 to March 2021 were included. Quality indicators for asthma care were based on adherence to recommendations from the 2019 Global Initiative for Asthma (GINA) Guidelines.
RESULTSThis study included 240 asthmatic children with mean age of 6 years (SD ± 4.9) and a slight male preponderance (55.4%). Majority (138 children or 57.5%) were less than 6 years old. Out of the 240 children, 224 (93.3%) were prescribed inhaled short-acting beta-agonists (SABA) and 66 (27.5%) were prescribed oral SABA. Only 14 children (5.8%) were prescribed inhaled corticosteroids (ICS), with 13 children (5.4%) given ICS with longacting beta-agonists (LABA) preparations, and one child (0.4%) given ICS alone. Quality indicators used in this study revealed underutilization of ICS treatment across all age groups, and an overuse of SABA-only treatment in children 6 years old and above. Moreover, 71.3% of the total patients were prescribed antibiotics despite the current GINA recommendation of prescribing antibiotics only for patients with strong evidence of lung infection, such as fever or radiographic evidence of pneumonia.
CONCLUSIONThere were 240 children diagnosed with asthma over a 2-year period in a rural community, with a mean age of 6 years old and a slight male predominance. This quality-of-care study noted suboptimal adherence of rural health physicians to the treatment recommendations of the GINA guidelines, with overuse of SABA and underuse of ICS for asthma control.
Human ; Male ; Infant Newborn: First 28 Days After Birth ; Infant: 1-23 Months ; Child Preschool: 2-5 Yrs Old ; Child: 6-12 Yrs Old ; Asthma ; Lung
4.Traditional Chinese Exercise Improves Lung Function and Exercise Capacity in Patients with Preserved Ratio Impaired Spirometry.
Yan-Yi LIU ; Gai-Hua HOU ; Kun XIA ; Xiao-Yan YAO ; Yi WANG ; Guang-Xi LI
Chinese journal of integrative medicine 2025;31(12):1113-1118
OBJECTIVE:
To investigate the effect of traditional Chinese Five-body balance exercise on patients with preserved ratio impaired spirometry (PRISm).
METHODS:
Fifteen patients with PRISm and 15 patients diagnosed with chronic obstructive pulmonary disease (COPD) were recruited from the Outpatient Department of Guang'anmen Hospital and Beijing Niujie Health Service Center from April to December, 2023. Participants in both groups attended supervised Five-body balance exercise training twice a week for 12 weeks. Patients with COPD continued their regular medication regimen during the intervention period. The endpoints were mean changes in the 6-min walk test (6MWT), St. George's Respiratory Questionnaire (SGRQ) score, cardiopulmonary exercise testing (CPET), pulmonary function, and scores of COPD assessment test (CAT), modified British Medical Research Council, Self-Rating Anxiety Scale, and Self-Rating Depression Scale from baseline to 12 weeks. Adverse events were monitored throughout the study.
RESULTS:
The PRISm group showed a significant improvement from baseline to week 12 in 6MWT, SGRQ symptom score, and forced vital capacity (FVC) compared to the COPD group (P<0.05). No significant between-group changes were observed in other outcome measurements (P>0.05). In addition, compared with baseline, both groups exhibited improvements in 6MWT, SGRQ score, and CPET at week 12 (P<0.05). The PRISm group also showed a significant increase in forced expiratory volume in 1 s and FVC, as well as a significant decrease in CAT score at week 12 (P<0.05). No adverse events were reported.
CONCLUSION
Patients with PRISm may benefit from Five-body balance exercise training, which can improve the exercise capacity, health-related quality of life, and lung function. (Registration No. ChiCTR2200059290).
Humans
;
Spirometry
;
Male
;
Female
;
Pulmonary Disease, Chronic Obstructive/therapy*
;
Lung/physiopathology*
;
Middle Aged
;
Exercise Tolerance/physiology*
;
Exercise Therapy
;
Aged
;
Medicine, Chinese Traditional
;
Respiratory Function Tests
;
East Asian People
5.Liujunzi Decoction Regulated Intestinal Flora Homeostasis to Relieve Lung-Gut Axis Inflammation in Asthma Flora Disorder Mice: Possibly Related to GATA3/ILC2.
Wen-Ting XU ; Qi WANG ; Xin-Yu WU ; Jing-Han HUANG ; Jing WANG
Chinese journal of integrative medicine 2025;31(11):1001-1010
OBJECTIVE:
To explore the effects and mechanism of Chinese medicine Liujunzi Decoction (LJZD) on regulating microbial flora in mice with asthma flora disorder.
METHODS:
Thirty BALB/c female mice were divided into control, model, LJZD [3.5 g/(kg•d), by gavage], dexamethasone [DXMS, 0.7 mg/(kg•d), intraperitoneal injection], and Clostridium butyricum [CB, 230 mg/(kg•d), by gavage] groups according to a random number table, 6 mice in each group. The asthma flora disorder mice model was induced with ovalbumin (OVA). Lung and gut lesions were analyzed by hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) stainings. The secretory immunoglobulin A (sIgA) protein expression in lung and gut tissues was detected by Western blot. Flow cytometry was used to detect the relative counts of GATA binding protein 3 (GATA3)/type 2 innate lymphoid cells (ILC2) in lung and gut. The levels of inflammatory factors in lung and gut tissues were detected by enzyme-linked immunosorbent assay (ELISA). Chao1 and Shannon index were used to compare microbial abundance and diversity in alveolar lavage fluid and cecal contents. The similarity or difference in the composition of mice microbial communities was analyzed through cluster analysis. The serum short-chain fatty acids (SCFAs) content was detected by ultra performance liquid chromatograph mass spectrometer (LC-MS)/MS.
RESULTS:
The asthma flora disorder model mice showed obvious asthma-related symptoms, but LJZD treatment effectively alleviated these symptoms. LJZD restored alveolar wall thickening, airway inflammatory cell infiltration, gut tissue structure destruction, and inflammatory cell infiltration in asthma flora disorder mice. LJZD downregulated the sIgA protein expression in mice (P<0.05). Moreover, LJZD decreased the activation of GATA3/ILC2s in lung and gut tissue (P<0.01), and reduced the levels of interleukin (IL)-5, IL-33, IL-25, IL-9 and IL-13 (P<0.01). LJZD treatment returned the abundance of microbial species and the microbial community structure of alveolar lavage fluid and cecal content in asthma flora disorder mice to the normal state. The SCFAs content and body metabolism were also improved.
CONCLUSION
LJZD exerted anti-asthmatic effects by improving the microbial balance of lung-gut axis and affecting systemic metabolism, consequently regulating the GATA3/ILC2s axis to impact the lung inflammatory response.
Animals
;
Asthma/pathology*
;
GATA3 Transcription Factor/metabolism*
;
Drugs, Chinese Herbal/therapeutic use*
;
Gastrointestinal Microbiome/drug effects*
;
Mice, Inbred BALB C
;
Female
;
Lung/drug effects*
;
Homeostasis/drug effects*
;
Inflammation/pathology*
;
Lymphocytes/drug effects*
;
Mice
6.Triptolide Ameliorates Collagen-Induced Arthritis and Bleomycin-Induced Pulmonary Fibrosis in Rats by Suppressing IGF1-Mediated Epithelial Mesenchymal Transition.
Pei-Pei LU ; Lan YAN ; Qi GENG ; Lin LIN ; Lu-Lu ZHANG ; Chang-Qi SHI ; Peng-Cheng ZHAO ; Xiao-Meng ZHANG ; Jian-Yu SHI ; Cheng LYU
Chinese journal of integrative medicine 2025;31(12):1069-1077
OBJECTIVE:
To investigate the common mechanisms among collagen-induced arthritis (CIA), bleomycin (BLM)-induced pulmonary fibrosis, and CIA+BLM to evaluate the therapeutic effect of triptolide (TP) on CIA+BLM.
METHODS:
Thirty-six male Sprague-Dawley rats were randomly assigned to 6 groups according to a random number table (n=6 per group): normal control (NC), CIA, BLM, combined CIA+BLM model, TP low-dose (TP-L, 0.0931 mg/kg), and TP high-dose (TP-H, 0.1862 mg/kg) groups. The CIA model was induced by intradermal injection at the base of the tail with emulsion of bovine type II collagen and incomplete Freund's adjuvant (1:1), with 200 µL administered on day 0 and a booster of 100 µL on day 7. Pulmonary fibrosis was induced via a single intratracheal injection of BLM (5 mg/kg). The CIA+BLM model combined both protocols, and TP was administered orally from day 14 to 35. After successful modeling, arthritis scores were recorded every 3 days, and pulmonary function was assessed once at the end of the treatment period. Lung tissues were collected for histological analysis (hematoxylin eosin and Masson staining), immunohistochemistry, measurement of hydroxyproline (HYP) content, and calculation of lung coefficient. In addition, HE staining was performed on the ankle joint. Total RNA was extracted from lung tissues for transcriptomic analysis. Differentially expressed genes (DEGs) were compared with those from the RA-associated interstitial lung diseases patient dataset GSE199152 to identify overlapping genes, which were then used to construct a protein-protein interaction network. Hub genes were identified using multiple topological algorithms.
RESULTS:
The successfully established CIA+BLM rat model exhibited significantly increased arthritis scores and severe pulmonary fibrosis (P<0.01). By intersecting the DEGs obtained from transcriptomic analysis of lung tissues in CIA, BLM, and CIA+BLM rats with DEGs from rheumatoid arthritis-interstitial lung disease patients (GSE199152 dataset), 50 upregulated and 44 downregulated genes were identified. Through integrated PPI network analysis using multiple topological algorithms, IGF1 was identified as a central hub gene. TP intervention significantly improved pulmonary function by increasing peak inspiratory flow (P<0.01), and reduced lung index and HYP content (P<0.01). Histopathological analysis showed that TP alleviated alveolar collapse, interstitial thickening, and collagen deposition in the lung tissues (P<0.01). Moreover, TP treatment reduced the expression of collagen type I and α-SMA and increased E-cadherin levels (P<0.01). TP also significantly reduced arthritis scores and ameliorated synovial inflammation (P<0.05). Both transcriptomic and immunohistochemical analyses confirmed that IGF1 expression was elevated in the CIA+BLM group and downregulated following TP treatment (P<0.05).
CONCLUSION
TP exerts protective effects in the CIA+BLM model by alleviating arthritis and pulmonary fibrosis through the inhibition of IGF1-mediated EMT.
Animals
;
Pulmonary Fibrosis/complications*
;
Bleomycin/adverse effects*
;
Phenanthrenes/pharmacology*
;
Male
;
Rats, Sprague-Dawley
;
Diterpenes/pharmacology*
;
Epoxy Compounds/therapeutic use*
;
Arthritis, Experimental/complications*
;
Insulin-Like Growth Factor I/metabolism*
;
Rats
;
Lung/physiopathology*
7.Quercetin Confers Protection against Sepsis-Related Acute Respiratory Distress Syndrome by Suppressing ROS/p38 MAPK Pathway.
Wei-Chao DING ; Juan CHEN ; Quan LI ; Yi REN ; Meng-Meng WANG ; Wei ZHANG ; Xiao-Hang JI ; Xin-Yao WU ; Shi-Nan NIE ; Chang-Bao HUANG ; Zhao-Rui SUN
Chinese journal of integrative medicine 2025;31(11):1011-1020
OBJECTIVE:
To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS).
METHODS:
In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro.
RESULTS:
Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01).
CONCLUSION
Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals
;
Sepsis/drug therapy*
;
Quercetin/therapeutic use*
;
Respiratory Distress Syndrome/enzymology*
;
p38 Mitogen-Activated Protein Kinases/metabolism*
;
Mice, Inbred C57BL
;
Reactive Oxygen Species/metabolism*
;
Apoptosis/drug effects*
;
Male
;
Oxidative Stress/drug effects*
;
MAP Kinase Signaling System/drug effects*
;
Lung/drug effects*
;
Mice
;
Lipopolysaccharides
;
Macrophages, Alveolar/pathology*
;
Inflammation/pathology*
;
Protective Agents/therapeutic use*
8.Lu'e Biyan Formula for Treatment of Allergic Rhinitis Patients with Fei (Lung)-Qi Deficiency-Coldness Syndrome: A Randomized, Double Blind, and Placebo-Controlled Trial.
Ming-Yue JIA ; Mei-Yi ZHANG ; Si-Yao XIAO ; Yang YU ; Xiang SHAO ; Chun-Sheng HAN ; Gui-Ling HAN
Chinese journal of integrative medicine 2025;31(11):1029-1036
OBJECTIVE:
To observe the clinical effect and safety of Lu'e Biyan Formula (LBF) combined with loratadine in the treatment of moderate to severe allergic rhinitis (AR) patients with Fei (Lung)-qi deficiency-coldness (FQDC) syndrome.
METHODS:
From September 2023 to December 2024, moderate to severe AR patients with FQDC syndrome were recruited from the Outpatient Department of Integrated Traditional Chinese and Western Medicine for Pulmonary Diseases Part 1, China-Japan Friendship Hospital. Participants were randomly assigned to a test group and a control group by using a random number table at a ratio of 1:1. Both groups received oral loratadine tablets (10 mg, once daily) for 2 weeks. In addition, the test group received oral LBF (30 mL, twice daily), and the control group received a placebo of LBF. Changes in the Total Nasal Symptom Score (TNSS), Total Non-nasal Symptom Score (TNNSS), Visual Analog Scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Chinese medicine (CM) syndrome scores before and after treatment were compared between groups. Moreover, the total effective rates and disease recurrence rates were compared. Adverse events (AEs) during the study period were also recorded.
RESULTS:
Totally 109 participants were recruited, and the full analysis set included 105 cases, 54 in the test group and 51 in the control group. Compared with the pre-treatment values, the scores of sneezing, runny nose, nasal obstruction, nasal itching, TNSS, TNNSS, VAS, RQLQ, and CM syndrome were significantly reduced in both groups at 1 and 2 weeks post-treatment and 12 weeks post-drug withdrawal (P<0.01). After treatment, the aforementioned scores in the test group were all markedly lower than those in the control group (P<0.01). Moreover, the total effective rate in the test group was higher than that in the control group (98.15% vs. 70.59%, P<0.01). After 12 weeks of drug withdrawal, there was no significant difference in the recurrence rate between groups (13.21% vs. 22.22%, P>0.05). No obvious AEs were observed in either group following treatment.
CONCLUSIONS
The combination of LBF with loratadine can effectively alleviate the symptoms of moderate to severe AR patients with FQDC syndrome, thereby improving their quality of life. This therapy demonstrated both precise effect and high safety. (Trial registration No. ITMCTR2025000589).
Humans
;
Drugs, Chinese Herbal/therapeutic use*
;
Male
;
Rhinitis, Allergic/drug therapy*
;
Female
;
Adult
;
Double-Blind Method
;
Quality of Life
;
Qi
;
Middle Aged
;
Loratadine/therapeutic use*
;
Medicine, Chinese Traditional
;
Syndrome
;
Lung/drug effects*
;
Young Adult
;
Treatment Outcome
9.Resveratrol Attenuates Inflammation in Acute Lung Injury through ROS-Triggered TXNIP/NLRP3 Pathway.
Wen-Han HUANG ; Kai-Ying FAN ; Yi-Ting SHENG ; Wan-Ru CAI
Chinese journal of integrative medicine 2025;31(12):1078-1086
OBJECTIVE:
To evaluate the protective effects of resveratrol against acute lung injury (ALI) and investigate the potential mechanisms underlying the reactive oxygen species (ROS)-triggered thioredoxin-interacting protein (TXNIP)/NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) pathway.
METHODS:
C57BL/6 mice and J774A.1 cells were selected as the research subjects. Thirty Mice were randomly divided into 5 groups of 6 in each group: control with 0.9% saline, 5 mg/kg lipopolysaccharide (LPS) 24 h, 25 mg/kg resveratrol + 5 mg/kg LPS, 100 mg/kg resveratrol + 5 mg/kg LPS, and 4 mg/kg NLRP3 inhibitor CY-09 + 5 mg/kg LPS. For cell stimulation, cells were pretreated with 5 and 20 µmol/L resveratrol for 2 h, and stimulated with or without 1 µg/mL LPS and 3 mmol/L ATP for 2 h. The antioxidant N-acetyl-L-cysteine (NAC, 2 µmol/L) was used as the positive control group. Hematoxylin and eosin staining was used to evaluate the degree of lung LPS-induced tissue damage, and enzyme-linked immunosorbent assay was used to evaluate the contents of interleukin-1 β (IL-1 β) and IL-18 in the serum and cell supernatant. ROS and malondialdehyde (MDA) levels in the lung tissue were detected using the corresponding kits. Western blotting was used to detect the expressions of TXNIP, high-mobility group box 1 (HMGB1), NLRP3, as well as cysteine-aspartic acid protease 1 (caspase-1) and gasdermin D (GSDMD) along with their cleaved forms in lung tissue. Additionally, reverse transcription quantitative polymerase chain reaction was performed to analyze the expression of related inflammatory cytokines. ROS content was detected using flow cytometry and confocal laser microscopy. Mitochondrial morphological changes were observed using transmission electron microscopy, and HMGB1 expression was detected using immunofluorescence.
RESULTS:
Resveratrol significantly alleviated LPS-induced lung damage with reduced inflammation, interstitial edema, and leukocyte infiltration (P<0.01). It also decreased serum levels of IL-1 β and IL-18 (P<0.05), while downregulating the expressions of NLRP3, IL-6, and other inflammatory markers at both the protein and mRNA levels (P<0.05). Notably, the higher dose (100 mg/kg) demonstrated a better effect than the lower dose (25 mg/kg). In macrophages, resveratrol reduced IL-1 β and IL-18 following LPS and ATP stimulation, suppressed HMGB1 translocation, and inhibited formation and activation of the NLRP3 inflammasome (P<0.05 or P<0.01). These anti-inflammatory effects were mediated through the suppression ROS accumulation (P<0.01) and mitochondrial dysfunction. Transmission electron microscopy revealed that resveratrol preserved mitochondrial structure, preventing the mitochondrial damage seen in LPS-treated groups (P<0.01). The expressions of cleaved caspase-1, cleaved GSDMD, and cytoplasmic HMGB1 were all reduced following resveratrol treatment (P<0.01). Moreover, resveratrol inhibited dissociation of TXNIP from thioredoxin, blocking subsequent activation of NLRP3 and downstream inflammatory cytokines (P<0.01). Similarly, the higher concentration of resveratrol (20 µ mol/L) exhibited superior efficacy in vitro.
CONCLUSION
Resveratrol can reduce the inflammatory response following ALI and inhibit the activation of NLRP3 inflammasome and the level of HMGB1 in the cytoplasm by inhibiting ROS overproduction.
Acute Lung Injury/metabolism*
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Animals
;
Resveratrol/pharmacology*
;
Reactive Oxygen Species/metabolism*
;
Inflammation/complications*
;
Mice, Inbred C57BL
;
Carrier Proteins/metabolism*
;
Signal Transduction/drug effects*
;
Lipopolysaccharides
;
Thioredoxins/metabolism*
;
Mice
;
Lung/drug effects*
;
Male
;
Cell Line
;
Interleukin-1beta/metabolism*
;
Cell Cycle Proteins
;
Stilbenes/therapeutic use*
10.Radiogenomics-based prediction of KRAS and EGFR gene mutation in non-small cell lung cancer patients.
Jianing LIN ; Zhihang YAN ; Longyu HE ; Hao ZHANG ; Mingxuan XIE
Journal of Central South University(Medical Sciences) 2025;50(5):805-814
OBJECTIVES:
Non-small cell lung cancer (NSCLC) is associated with poor prognosis, with 30% of patients diagnosed at an advanced stage. Mutations in the EGFR and KRAS genes are important prognostic factors for NSCLC, and targeted therapies can significantly improve survival in these patients. Although tissue biopsy remains the gold standard for detecting gene mutations, it has limitations, including invasiveness, sampling errors due to tumor heterogeneity, and poor reproducibility. This study aims to develop machine learning models based on radiomic features to predict EGFR and KRAS gene mutation status in NSCLC patients, thereby providing a reference for precision oncology.
METHODS:
Imaging and mutation data from eligible NSCLC patients were obtained from the publicly available Lung-PET-CT-Dx dataset in The Cancer Imaging Archive (TCIA). A three-dimensional-convolutional neural network (3D-CNN) was used to extract imaging features from the regions of interest (ROI). The LightGBM algorithm was employed to build classification models for predicting EGFR and KRAS gene mutation status. Model performance was evaluated using 5-fold cross-validation, with receiver operator characteristic (ROC) curves, area under the curve (AUC), accuracy, sensitivity, and specificity used for validation.
RESULTS:
The models effectively predicted EGFR and KRAS mutations in NSCLC patients, achieving an AUC of 0.95 for EGFR mutations and 0.90 for KRAS. The models also demonstrated high accuracy (EGFR 89.66%; KRAS 87.10%), sensitivity (EGFR 93.33%; KRAS 87.50%), and specificity (EGFR 85.71%; KRAS 86.67%).
CONCLUSIONS
A radiogenomics-machine learning predictive model can serve as a non-invasive tool for anticipating EGFR and KRAS gene mutation status in NSCLC patients.
Humans
;
Carcinoma, Non-Small-Cell Lung/diagnostic imaging*
;
Lung Neoplasms/diagnostic imaging*
;
Mutation
;
Proto-Oncogene Proteins p21(ras)/genetics*
;
ErbB Receptors/genetics*
;
Machine Learning
;
Positron Emission Tomography Computed Tomography
;
Female
;
Male
;
Neural Networks, Computer
;
Middle Aged
;
Aged


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