1.Multidimensional analysis of concurrent proximal bronchiolar adenoma and lung carcinoma
Lu-Yao LI ; Gong-Ming DONG ; Yun-Peng ZHANG ; Ting-Ting WANG ; Fu-Quan JIA ; Guan-Jun ZHANG
Journal of Pathology and Translational Medicine 2026;60(3):356-363
Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.
2.Influenza A virus infection activates TLR3-mediated necroptosis
Weijie LI ; Congying HUANG ; Ziling ZENG ; Xiang LI ; Jia XU ; Tian GONG ; Hao ZHANG ; Xinyan ZHANG ; Ping WANG ; Yuanjia HU ; Haiyu XU ; Lijuan SONG
Science of Traditional Chinese Medicine 2026;4(1):40-49
Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 −10; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 −7). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.
3.Pathogenesis and treatment of "inflammation cancer transformation" of ulcerative colitis based on "Kenang" theory.
Jia-Kang XIE ; Xiao-Ning XU ; Feng-Ting AI ; Shao-Xi LI ; Yun AN ; Xuan GONG ; Yong CAO
China Journal of Chinese Materia Medica 2025;50(8):2298-2304
Ulcerative colitis(UC) is a recurrent, chronic, nonspecific inflammatory bowel disease. The longer the course of the disease, the higher the risk of cancerization. In recent years, the incidence and mortality rates of colon cancer in China have been increasing year by year, seriously threatening the life and health of patients. Therefore, studying the mechanism of "inflammation cancer transformation" in UC and conducting early intervention is crucial. The "Kenang" theory is an important component of traditional Chinese medicine(TCM) theory of phlegm and blood stasis. It is based on the coexistence of phlegm and blood stasis in the body and deeply explores the pathogenic syndromes and characteristics of phlegm and blood stasis. Kenang is a pathological product formed when long-term Qi stagnation leads to the internal formation of phlegm and blood stasis, which is hidden deep within the body. It is characterized by being hidden, progressive, and difficult to treat. The etiology and pathogenesis of "inflammation cancer transformation" in UC are consistent with the connotation of the "Kenang" theory. The internal condition for the development of UC "inflammation cancer transformation" is the deficiency of healthy Qi, with Qi stagnation being the key pathological mechanism. Phlegm and blood stasis are the main pathogenic factors. Phlegm and blood stasis accumulate in the body over time and can produce cancer toxins. Due to the depletion of healthy Qi and a weakened constitution, the body is unable to limit the proliferation and invasion of cancer toxins, eventually leading to cancer transformation in UC. In clinical treatment, the focus should be on removing phlegm and blood stasis, with syndrome differentiation and treatment based on three basic principles: supporting healthy Qi to strengthen the body's foundation, resolving phlegm and blood stasis to break up the Kenang, and regulating Qi and blood to smooth the flow of energy and resolve stagnation. This approach helps to dismantle the Kenang, delay, block, or even reverse the cancerization process of UC, reduce the risk of "inflammation cancer transformation", improve the patient's quality of life, and provide new perspectives and strategies for early intervention in the development of colon cancer.
Humans
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Colitis, Ulcerative/immunology*
;
Medicine, Chinese Traditional
;
Drugs, Chinese Herbal/therapeutic use*
;
Cell Transformation, Neoplastic
4.Research progress on biosynthesis and metabolic regulation of flavonoids in Ginkgo biloba.
Yuan-Jia LI ; Jian-Feng GONG ; Bin LI ; Xu LU
China Journal of Chinese Materia Medica 2025;50(15):4201-4208
Ginkgo biloba, an ancient relict plant, holds a lengthy medicinal tradition in China. The leaves and seeds of this remarkable species contain flavonoids, a class of active compounds that offer a multitude of pharmacological advantages. The understanding of the synthesis process of these flavonoids can be deepened substantially by elucidating their biosynthetic pathway and metabolic regulation mechanisms. This can thereby provide a foundation for achieving precise regulation of flavonoid biosynthesis, which is of great significance for improving the production efficiency and quality of flavonoids in G. biloba. This review comprehensively summarizes research advancements in metabolomics, genomics, and transcriptomics of flavonoids in G. biloba, aiming to establish a thorough academic framework. It examines key enzymes in the biosynthetic pathway of flavonoids in G. biloba and their functions, highlighting their crucial roles in flavonoid production. Additionally, it outlines transcriptional regulation mechanisms associated with flavonoid in G. biloba biosynthesis, focusing on transcription factors responsive to environmental cues and their regulatory networks that modulate flavonoid gene expression. These insights offer a theoretical foundation for precise control of G. biloba flavonoid production. By amalgamating these diverse research findings, this review aims to establish a robust theoretical groundwork for future studies on biosynthesis and efficient utilization of flavonoids in G. biloba.
Ginkgo biloba/chemistry*
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Flavonoids/biosynthesis*
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Gene Expression Regulation, Plant
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Plant Proteins/genetics*
;
Biosynthetic Pathways
5.A study of early graft healing after anterior cruciate ligament reconstruction in over-the-top position.
Jue GONG ; Zhiheng WEI ; Mengyang JIA ; Weiming WANG ; Xianxiang XIANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(3):307-313
OBJECTIVE:
To compare early graft healing between over-the-top (OTT) and anatomic single-bundle (SB) anterior cruciate ligament (ACL) reconstruction.
METHODS:
A clinical data of 40 patients underwent ACL reconstruction, who admitted between June 2021 and October 2022 and met the selective criteria, was retrospectively analyzed. Among them, 20 patients were treated with OTT reconstruction (OTT group) and 20 with SB reconstruction (SB group). There was no significant difference between groups ( P>0.05) in the gender, age, affected side, disease duration, degree of meniscus injury, body mass index, and preoperative International Knee Documentation Committee (IKDC) score, Lysholm score, pain visual analogue scale (VAS) score, and KT-2000 measurement. At 3, 6, and 12 months, MRI was performed to measure the signal noise quotient (SNQ) of the proximal end, middle, and distal end of the graft in the two groups, as well as at the corner of the graft with lateral femoral condyle and 1 cm around the femoral fixation point in the OTT group, to observe the degree of graft healing. Before operation and at 3, 6, and 12 months, the knee function and pain were evaluated by IKDC score, Lysholm score, and VAS score. Before operation and at 12 months after operation, the KT-2000 measurement was taken to evaluation the knee joint stability.
RESULTS:
All operations were successfully completed in both groups and the incisions healed by first intention. All patients were followed up 12-15 months (mean, 12.9 months), with no significant difference in the follow-up time between groups ( P>0.05). After operation, the IKDC score, VAS score, and Lysholm score improved gradually over time in both groups, with significant differences between different time points ( P<0.05). The differences between groups at 3, 6, and 12 months after operation were not significant ( P>0.05). The anterior and posterior stability of the knee joint improved significantly in both groups at 12 months after operation, and the difference in KT-2000 measurements was significant when compared with the preoperative value ( P<0.05), but the difference of pre- and post-operation between groups was not significant ( P>0.05). At 3, 6, and 12 months after operation, MRI showed that the differences in the SNQ of the proximal end and middle of the grafts between the two groups were not significant ( P>0.05), and the SNQ of distal end was significantly higher in the SB group than in the OTT group ( P<0.05). At each time point, grafts in the OTT group had the highest SNQ at the corner and the lowest at the fixation point, and the differences were significant compared to the other sites ( P<0.05). In the two groups, except for the fixation point, the SNQ of the remaining sites were highest at 6 months and lowest at 12 months ( P<0.05). In addition, there were significant differences in SNQ between the different sites of grafts ( P<0.05), and the SNQ was lowest at proximal end and highest at distal end. At last follow-up, the knee grafts in both groups were in good shape and no graft necrosis or loosening of the internal fixation was observed.
CONCLUSION
The knee joint function and graft healing after OTT reconstruction of ACL are similar to those of SB reconstruction, but it should be noted that the healing at the corner of the graft is slower.
Retrospective Studies
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Treatment Outcome
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Anterior Cruciate Ligament Reconstruction/rehabilitation*
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Follow-Up Studies
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Tibial Meniscus Injuries/surgery*
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Patient Positioning/methods*
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Recovery of Function
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Pain Measurement
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Knee Joint/surgery*
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Humans
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Male
;
Female
;
Adult
;
Wound Healing
6.Glucocorticoid Discontinuation in Patients with Rheumatoid Arthritis under Background of Chinese Medicine: Challenges and Potentials Coexist.
Chuan-Hui YAO ; Chi ZHANG ; Meng-Ge SONG ; Cong-Min XIA ; Tian CHANG ; Xie-Li MA ; Wei-Xiang LIU ; Zi-Xia LIU ; Jia-Meng LIU ; Xiao-Po TANG ; Ying LIU ; Jian LIU ; Jiang-Yun PENG ; Dong-Yi HE ; Qing-Chun HUANG ; Ming-Li GAO ; Jian-Ping YU ; Wei LIU ; Jian-Yong ZHANG ; Yue-Lan ZHU ; Xiu-Juan HOU ; Hai-Dong WANG ; Yong-Fei FANG ; Yue WANG ; Yin SU ; Xin-Ping TIAN ; Ai-Ping LYU ; Xun GONG ; Quan JIANG
Chinese journal of integrative medicine 2025;31(7):581-589
OBJECTIVE:
To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM).
METHODS:
This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis.
RESULTS:
Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings.
CONCLUSIONS
RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult
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Aged
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Female
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Humans
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Male
;
Middle Aged
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Arthritis, Rheumatoid/drug therapy*
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Glucocorticoids/therapeutic use*
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Medicine, Chinese Traditional
;
Retrospective Studies
7.Surveillance report of data of nosocomial infections in a three-A general hospital of Jiangsu Province from 2014 to 2023
Hao GONG ; Shufang JIANG ; Chengyi FENG ; Jia DI
Chinese Journal of Nosocomiology 2025;35(6):939-944
OBJECTIVE To explore the current status of surveillance data of nosocomial infections in a three-A hos-pital of Jiangsu Province and find out the problems in prevention and control of the nosocomial infection so as to provide scientific bases for formulating targeted prevention strategies.METHODS The related data of all infection cases from Changzhou First People's Hospital between 2014 and 2023 were exported from information real-time surveillance system and were analyzed by using Excel 2021 and R 4.3.2 software.RESULTS The average incidence rate of hospital-associated infection was 1.32%from 2014 to 2023,declining from 2.11%in 2014 to 0.97%in 2023,and it showed a downward trend(Z=-30.010,P<0.001).The incidence rate of hospital-associated infec-tion was 19.86%in neurosurgery department(Z=-3.041,P=0.002),10.27%in hematology department(Z=5990,P<0.001),8.85%in neurology department(Z=-1.437,P=0.151),7.00%in critical care medicine de-partment(Z=5.907,P<0.001),6.28%in gastrointestinal surgery department(Z=-4.435,P<0.001),thorac-ic surgery department(Z=1.696,P=0.090),4.52%in cardiothoracic surgery department(Z=13.218,P<0.001),2.95%in oncology department(Z=9.064,P<0.001).Among the patients with hospital-associated infec-tions,the patients with lower respiratory tract infection accounted for 46.71%(the highest),increasing from 34.94%to 51.67%(Z=12.532,P<0.001),the patients with upper respiratory tract infection 10.37%(Z=-10.229,P<0.001),the patients with urinary tract infection 6.92%(Z=1.489,P=0.137),the patients with urinary catheter-related infection 3.71%(Z=13.218,P=0.317).Totally 13,593 strains of pathogens were isola-ted,65.26%of which were gram-negative bacteria and did not show a significant changing trend,24.62%were gram-positive bacteria,and 10.12%were fungi;Klebsiella pneumoniae(15.76%)and Acinetobacter baumannii(15.34%)were the predominant species of the gram-negative bacteria;Staphylococcus aureus(8.37%)and Corynebacterium striatum(3.60%)were dominant among the gram-positive bacteria;Candida albicans(5.13%)and Candida tropicalis(0.96%)were the major species of the fungi.The percentage of central venous catheteriza-tion was the highest(27.04%)among the risk factors for the hospital-associated infection,increasing from 14.87%to 21.75%(Z=17.482,P<0.001).CONCLUSIONS The control of hospital-associated infection has been made remarkable achievement.It is necessary to strengthen the construction of infection control team,push for-ward the whole process and delicacy management,normalize the use of antibiotics,reduce the unnecessary inva-sive procedures and shorten the duration of invasive operations so as to further improve the medical quality.
8.Association of RIPK3 with disease severity and lung function in children with MPP
Wenbin LI ; Jia YANG ; Liang GONG
Clinical Medicine of China 2025;41(5):328-332
Objective:To investigate the relationship between serum interacting protein kinase (RIPK)-3 levels and mycoplasma pneumoniae pneumonia (MPP) correlation between disease severity and lung function in children.Methods:A case-control study was conducted. A total of 147 children with MPP admitted to the Children's Hospital Affiliated to Xuzhou Medical University from April 2023 to March 2024 were selected, including 76 cases of mild MPP (mild MPP group) and 71 cases of severe MPP (severe MPP group). Additionally, 36 healthy children who underwent physical examinations during the same period were selected as the healthy control group. The levels of serum RIPK3, C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer of each group were compared, and the correlations between each index and the severity of MPP in children were analyzed. The lung function indicators, including the percentage of peak expiratory flow (PEF% pred) and the percentage of forced expiratory volume in one second (FEV1% pred), were compared between groups, and the correlations between these indicators and the serum RIPK3 levels in children with MPP were analyzed. Measurement data with normal distribution was expressed as " xˉ±s", one-way ANOVA was used on comparison between groups, LSD-t test was used on pairwise comparison.Measurement data with skewed distribution were expressed as M( Q1, Q3). The Kruskal-Wallis H test was used for comparisons among multiple groups, and the Dunn test was used for pairwise comparisons. Counting data was expressed as case(%), χ2 test was used on comparison between groups. The relationships between serum RIPK3, CRP, LDH, D-dimer and the severity of MPP in children were analyzed by Spearman correlation analysis. The relationships between serum RIPK3 levels and PEF% pred, FEV1% pred were analyzed by Pearson correlation analysis. Results:The levels of serum RIPK3, CRP, LDH and D-dimer in children with mild MPP and severe MPP were all higher than those in the healthy control group [(329.67±59.69), (406.77±47.47) ng/L vs. (103.16±15.93) ng/L, (13.49±4.76), (37.76±18.94) mg/L vs. (1.59±0.81) mg/L, (253.12±50.96), (501.96±167.55) U/L vs. (186.06±45.49) U/L, (0.90±0.19), (3.01±1.46) mg/L vs. (0.29±0.12) mg/L], and the levels in the severe MPP group were all higher than those in the mild MPP group (all P < 0.05). The levels of serum RIPK3, CRP, LDH and D-dimer in children with MPP were positively correlated with the severity of the disease (r values were 0.59, 0.76, 0.83, 0.67, all P < 0.001). The levels of PEF% pred and FEV1% pred in children with mild MPP and severe MPP were all lower than those in the healthy control group [(72.65±7.67)%, (59.93±10.17)% vs. (98.54±4.81)%, (73.79±6.56)%, (60.56±10.54)% vs. (98.08±4.65)%], and the levels in the severe MPP group were all lower than those in the mild MPP group (all P < 0.05). The level of serum RIPK3 in children with MPP was negatively correlated with the lung function indicators PEF% pred and FEV1% pred (r values were -0.78, -0.77, all P < 0.001). Conclusions:The serum RIPK3 level in children with MPP is positively correlated with the severity of their condition and negatively correlated with the lung function indicators PEF% pred and FEV1% pred.
9.Construction and performance evaluation of a prediction model for postoperative poor in-hospital prognosis in patients with traumatic brain injury
Tao MEI ; Zheyong JIA ; Lie CHEN ; Peng CAO ; Wei XIAO ; Weiqiang MAO ; Jianwu GONG ; Lixin XU
Chinese Journal of Trauma 2025;41(11):1048-1058
Objective:To construct a prediction model for postoperative poor in-hospital prognosis in patients with traumatic brain injury (TBI) and evaluate its predictive performance.Methods:A retrospective case control study was conducted to analyze the clinical data of 1 120 TBI patients admitted to Changde Hospital Affiliated to Xiangya Medical College of Central South University from May 2019 to December 2024. The patients were divided into the training set ( n=784) and verification set ( n=336) at a ratio of 7∶3. Based on the Glasgow outcome scale-extended (GOS-E) at discharge, the training set was stratified into favorable prognosis group ( n=335, GOS-E 5-8 points) and poor prognosis group ( n=449, GOS-E 1-4 points). The two groups in the training set were compared in terms of general baseline indicators, TBI-related clinical indicators, and admission laboratory blood test results. Univariate analysis and Lasso regression analysis were employed to screen risk factors associated with postoperative poor in-hospital prognosis in TBI patients. Multivariate Logistic regression analysis was used to determine independent risk factors and construct a regression equation. The regression equation was presented using R language to create a visual nomogram for predicting postoperative poor in-hospital prognosis in TBI patients. In both the training set and verification set, the predictive performance of the model was evaluated by calculating the area under the receiver operating characteristic (ROC) curve (AUC), plotting calibration curves, and performing decision curve analysis (DCA). Results:The results of the univariate analysis indicated that the age, Charlson complication index (CCI), time from trauma to admission, time from trauma to operation, cause of injury, abbreviated injury scale (AIS) (head and neck), injury severity score (ISS), admission Glasgow coma scale (GCS), admission pupil responsiveness, multiple craniocerebral injuries, subdural hematoma, intracerebral hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, decompressive craniotomy, intraoperative blood loss, intraoperative blood transfusion, traumatic cerebral infarction, postoperative delayed bleeding, epilepsy seizures, as well as the following admission tested results including red blood cell count, white blood cell count, platelet count, neutrophil percentage, percentage of lymphocytes, albumin, total bilirubin, urea nitrogen, thrombin time (TT), prothrombin time (PT), international standardized ratio (INR), glutamic aminotransferase, alanine aminotransferase, creatinine, and blood glucose were statistically different between the two groups in the training set ( P<0.05). Lasso regression analysis suggested 14 risk factors of age, CCI, cause of injury, head and neck AIS, ISS, admission GCS, admission pupil responsiveness, multiple craniocerebral injuries, subdural hematoma, intracerebral hematoma, intraoperative blood loss, admission platelet count, admission albumin, admission blood glucose for postoperative poor in-hospital prognosis. The results of the multivariate Logistic regression analysis showed that age ( OR=1.02, 95% CI 1.00, 1.03, P<0.01), CCI ( OR=1.46, 95% CI 1.02, 2.09, P<0.05), head and neck AIS ( OR=1.43, 95% CI 1.11, 1.85, P<0.01), ISS ( OR=2.16, 95% CI 1.39, 3.35, P<0.01), admission GCS ( OR=1.59, 95% CI 1.19, 2.13, P<0.01), intracerebral hematoma ( OR=4.41, 95% CI 2.15, 9.44, P<0.01), intraoperative blood loss ( OR=1.05, 95% CI 1.00, 1.09, P<0.05), admission platelet count ( OR=0.98, 95% CI 0.97, 0.99, P<0.01), admission blood glucose ( OR=1.08, 95% CI 1.02, 1.15, P<0.05) could be the main risk factors to construct a prediction model for postoperative poor in-hospital prognosis in TBI patients. Meanwhile, a regression equation was constructed: Logit[ P/(1- P)]=-2.4+ 0.02×"age"+0.38×"CCI"+0.36×"head and neck AIS"+0.77×"ISS"+0.47×"admission GCS"+1.48×"intracerebral hematoma"+0.05×intraoperative blood loss-0.02×admission platelet count+0.08×admission blood glucose. In the training set, the predictive model for poor postoperative in-hospital prognosis in TBI patients achieved an AUC of 0.87 (95% CI 0.84, 0.89), with a Youden′s index of 0.57, sensitivity of 73.70%, and specificity of 83.00%. In the verification set, the model showed an AUC of 0.80 (95% CI 0.76, 0.85), with a Youden′s index of 0.63, sensitivity of 65.20%, and specificity of 77.90%. In the training set, the Brier score for the calibration curve was 0.14 (95% CI 0.13, 0.16). In the verification set, the Brier score for the calibration curve was 0.18 (95% CI 0.15, 0.20). The DCA diagram indicated that the nomogram prediction model provided high clinical net benefit for predicting postoperative poor in-hospital prognosis in TBI patients. Conclusion:The prediction model for postoperative poor in-hospital prognosis in TBI patients, constructed based on age, CCI, head and neck AIS, ISS, admission GCS, intracerebral hematoma, intraoperative blood loss, admission platelet count, and admission blood glucose, exhibits good predictive performance.
10.Clinical and molecular characteristics of myeloproliferative neoplasms patients with NFE2 gene mutations
Songyang ZHAO ; Bing LI ; Zefeng XU ; Tiejun QIN ; Shiqiang QU ; Lijuan PAN ; Meng JIAO ; Qingyan GAO ; Huijun WANG ; Qi SUN ; Yujiao JIA ; Yiru YAN ; Jingye GONG ; Fuhui LI ; Xin WANG ; Zhijian XIAO
Chinese Journal of Hematology 2025;46(10):943-951
Objective:To explore the clinical features and molecular characteristics of myeloproliferative neoplasms (MPNs) patients with NFE2 gene mutations.Methods:Gene targeted sequencing was used to detect NFE2 gene mutation in 723 patients diagnosed with MPNs who were admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between April 2021 and June 2023. The association between NFE2 gene mutations and clinical features and molecular characteristics of MPNs patients were retrospectively analyzed.Results:Among 723 patients with MPNs, NFE2 gene mutations were found in 41 cases (5.7%) . NFE2 gene mutations were predominantly frameshift mutations (44.4%) , followed by nonsense mutations (33.3%) . The median number of mutations in patients with NFE2 gene mutations (4 [2,5]) was higher compared to the group without NFE2 gene mutations (2, [1,3]) ( P<0.001) . NFE2 gene mutations frequently co-occurred with mutations in MPL, ATM, PPM1D, and TET1. NFE2 gene mutations were mostly sub-clonal events, with 80.5% occurring after MPNs driver mutations (JAK2, CALR, or MPL) . NFE2 mutations were correlated with older age [median age: 60 (54, 67) years vs 54 (41, 63) years, P=0.001]. Patients with NFE2 gene mutations had a higher incidence of pre-diagnosis thrombosis (39.0% vs 22.0%, P=0.012) and pre-diagnosis arterial thrombosis (36.6% vs 20.4%, P=0.014) . Using a logistic regression analysis model adjusting for age and comorbidities (including chronic infections, malignancies, and autoimmune diseases) , NFE2 gene mutation was identified as an independent determinant of elevated tumor necrosis factor-alpha (TNF-α) ( OR=2.747, 95% CI: 1.143-6.605, P=0.024) , interferon-gamma (IFN-γ) ( OR=2.689, 95% CI: 1.191-6.076, P=0.017) , IL-10 ( OR=3.219, 95% CI: 1.343-7.717, P=0.009) , IL-12P70 ( OR=3.397, 95% CI:1.003-11.508, P=0.049) , IL-17 ( OR=2.284, 95% CI: 1.017-5.127, P=0.045) . In polycythaemia vera (PV) patients with the NFE2 gene mutation, the proportion of those classified as high-risk is notably higher in both the IWG-PV and mutation-enhanced international prognostic systems for PV (MIPSS-PV) (66.7% vs 25.3% for IWG-PV, P=0.033; 22.2% vs 2.0% for MIPSS-PV, P=0.013) . Similarly, for essential thrombocythaemia (ET) patients, the proportion in the high-risk group of the mutation-enhanced international prognostic systems for ET (MIPSS-ET) is significantly higher (15.4% vs 6.1%, P=0.021) . No statistically significant differences were observed in overall survival or cumulative incidence of thrombosis between NFE2-mutated (38 cases) and non-mutated MPNs patients (671 cases, P>0.05) . Conclusion:NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.

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