1.ERBB3 blockade sensitizes hepatocellular carcinoma to regorafenib after first-line tyrosine kinase inhibitor resistance by inhibiting HIF1A-ABCB1 signaling
Baorui TAO ; Chenhe YI ; Bo ZHANG ; Yan GENG ; Yinchen GU ; Rongquan SUN ; Xiangyu WANG ; Jing LIN ; Jinhong CHEN
Clinical and Molecular Hepatology 2026;32(2):787-807
Background/Aims:
Regorafenib is recommended by guidelines and trials as a sequential second-line therapy following progression on first-line sorafenib or lenvatinib in hepatocellular carcinoma (HCC). However, efficacy is limited, highlighting the urgent need to screen suitable patients and develop sensitization strategies.
Methods:
Acquired sorafenib- or lenvatinib-resistant (SR or LR) HCC cell lines and organoids were established. Genome-wide CRISPR library screen was performed in SR or LR cell strains to identify synthetic lethal targets of regorafenib. RNA-seq and FITC-regorafenib efflux assay were used to elucidate ERBB3-driven downstream signaling. Preclinical mouse models of cell line- and patient-derived xenografts and clinical cohorts of HCC patients were employed to validate the efficacy of ERBB3-guided patient stratification.
Results:
Screening with CRISPR library, we showed that inhibition of ERBB3 was synthetic lethal with regorafenib in SR or LR cell strains and organoids. Mechanistically, SR or LR triggered feedback activation of ERBB3 signaling and mediated regorafenib efflux via ERBB3-HIF1A-ABCB1 cascade pathway, limiting sensitivity to regorafenib. Moreover, ERBB3-low tumors following SR or LR exhibited significant sensitivity to regorafenib, suggesting its potential as a predictive biomarker to screen optimal candidates for sequential therapy. Seribantumab, an ERBB3-targeting monoclonal antibody, inhibited ERBB3-HIF1A-ABCB1 cascade, and its combination with regorafenib exerted marked synergistic anti-tumor effects on ERBB3-high tumors resistant to sorafenib or lenvatinib both in vitro and in vivo.
Conclusions
This study revealed that ERBB3 was a key resistance factor driving limited efficacy to sequential regorafenib, but also an effective therapeutic target whose inhibition enhanced regorafenib sensitivity after SR or LR.
2.Graphene-mediated Far-infrared Therapy Enhances Anti-non-small Cell Lung Cancer Effects of Panax quinquefolium Saponins via cGAS/STING Signaling Pathway
Huifang ZANG ; Zikai GENG ; Yan GAO ; Lu LIU ; Yifei WANG ; Bonian ZHAO ; Jing LYU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):131-145
ObjectiveTo investigate whether the inhibitory effect of Panax quinquefolium saponins (PQS) on non-small cell lung cancer (NSCLC) is enhanced under graphene-mediated far-infrared therapy (GFIR), and to analyze its relationships with mitochondrial dysfunction, mitochondrial DNA (mtDNA) leakage, and the activation of cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathways. MethodsIn the cell experiments, the cell-counting kit 8 (CCK-8) was employed to assess the inhibitory effects of PQS alone or in combination with GFIR (PQS+GFIR) on A549 cell viability. The scratch assay and the colony formation assay were adopted to evaluate cell migration and colony formation capabilities, respectively. Flow cytometry was employed to assess apoptosis, mitochondrial membrane potential, and reactive oxygen species (ROS) levels. Immunofluorescence (IF) assay was performed to assess mitochondrial localization. Real-time polymerase China reaction(PCR) was used to detect mitochondrial DNA (mtDNA) leakage. A STING knockdown cell model was established by transfecting cells with small interfering RNA (siRNA), and the knockdown efficiency was assessed by Real-time PCR and Western blot. The cell viability and apoptosis following gene knockdown were assessed through the CCK-8 assay and flow cytometry. In the animal experiments, an allogeneic xenograft mouse model was established with Lewis lung cancer cells. Mice were randomized into a control group, a model group, a cisplatin group, a low-dose PQS (PQS-Low, 90 mg·kg-1) group, a high-dose PQS (PQS-High, 180 mg·kg-1) group, a low-dose PQS combined with GFIR (PQS-Low+GFIR, 90 mg·kg-1) group, and a high-dose PQS combined with GFIR (PQS-High+GFIR, 180 mg·kg-1) group. Treatment lasted for 14 days, and the fluorescence intensity was monitored at the tumor site by small-animal in vivo imaging during the treatment period. Flow cytometry was utilized to determine the proportions of T-lymphocyte subsets, B-lymphocyte levels, and peripheral blood NK cell levels in the spleens of mice. Immunohistochemical (IHC) staining was performed to assess the infiltration of CD3+, CD4+, and CD8+ T-lymphocytes in the tumor tissue. Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the levels of interferon-α (IFN-α), interferon-β (IFN-β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in mouse tumors. The mRNA levels of cGAS, STING, TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), interferon beta 1 (IFNB1), and nuclear factor κB p65 (NF-κB p65) were determined by Real-time PCR. The protein levels of cGAS, STING, p-STING, TBK1, p-TBK1, IRF3, p-IRF3, NF-κB p65, and p-NF-κB p65 were quantified via Western blot. ResultsThe cell experiment results showed that compared with the control group, PQS inhibited the viability and migration of A549 cells, promoted apoptosis, affected mitochondrial localization, reduced mitochondrial membrane potential, increased the ROS level, and promoted mtDNA leakage. Following STING knockdown, the reductions in cell viability and the apoptosis-inducing effects caused by PQS were partially reversed (P<0.05, P<0.01). Compared with the PQS group, the PQS+GFIR group showed inhibited A549 cell migration and colony formation, exacerbated apoptosis, downregulated mitochondrial membrane potential, elevated ROS levels, and promoted mtDNA leakage. After STING knockdown, the reduced A549 cell viability and abnormal apoptosis phenotype were further reversed (P<0.05, P<0.01). The animal experiment results showed that compared with the control group, the model group mice exhibited reduced proportions of T-lymphocyte subsets, CD19+ B-lymphocyte levels, and peripheral blood NK1.1+ cell levels in the spleen (P<0.01). Compared with the model group, the PQS group showed increased immune cell parameters in mice (P<0.05, P<0.01). Compared with the PQS group, the PQS+GFIR group exhibited enhanced levels of the aforementioned indicators (P<0.01). Compared with the model group, the PQS group showed significantly reduced fluorescence intensity in transplanted tumors, significantly upregulated expression of CD3 and CD4 in the tumor tissue, elevated levels of IFN-α and IL-6 in tumors, and upregulated mRNA levels of cGAS, STING, TBK1, IRF3, IFNB1, and NF-κB p65 as well as upregulated protein level of cGAS and phosphorylation level of STING in tumors (P<0.05, P<0.01). Compared with the PQS group, the PQS+GFIR group demonstrated further reduced tumor fluorescence intensity, elevated levels of CD3, CD4, and CD8 as well as cytokine levels in tumor tissue, and upregulated mRNA levels of genes related to the cGAS/STING pathway as well as upregulated protein level of cGAS and phosphorylation levels of STING, TBK1, IRF3, and NF-κB p65 (P<0.05, P<0.01) ConclusionGFIR enhances the inhibitory effect of PQS on NSCLC, potentially through mitochondrial dysfunction, mtDNA leakage, and activation of the cGAS/STING signaling pathway.
3.Graphene-mediated Far-infrared Therapy Enhances Anti-non-small Cell Lung Cancer Effects of Panax quinquefolium Saponins via cGAS/STING Signaling Pathway
Huifang ZANG ; Zikai GENG ; Yan GAO ; Lu LIU ; Yifei WANG ; Bonian ZHAO ; Jing LYU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):131-145
ObjectiveTo investigate whether the inhibitory effect of Panax quinquefolium saponins (PQS) on non-small cell lung cancer (NSCLC) is enhanced under graphene-mediated far-infrared therapy (GFIR), and to analyze its relationships with mitochondrial dysfunction, mitochondrial DNA (mtDNA) leakage, and the activation of cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathways. MethodsIn the cell experiments, the cell-counting kit 8 (CCK-8) was employed to assess the inhibitory effects of PQS alone or in combination with GFIR (PQS+GFIR) on A549 cell viability. The scratch assay and the colony formation assay were adopted to evaluate cell migration and colony formation capabilities, respectively. Flow cytometry was employed to assess apoptosis, mitochondrial membrane potential, and reactive oxygen species (ROS) levels. Immunofluorescence (IF) assay was performed to assess mitochondrial localization. Real-time polymerase China reaction(PCR) was used to detect mitochondrial DNA (mtDNA) leakage. A STING knockdown cell model was established by transfecting cells with small interfering RNA (siRNA), and the knockdown efficiency was assessed by Real-time PCR and Western blot. The cell viability and apoptosis following gene knockdown were assessed through the CCK-8 assay and flow cytometry. In the animal experiments, an allogeneic xenograft mouse model was established with Lewis lung cancer cells. Mice were randomized into a control group, a model group, a cisplatin group, a low-dose PQS (PQS-Low, 90 mg·kg-1) group, a high-dose PQS (PQS-High, 180 mg·kg-1) group, a low-dose PQS combined with GFIR (PQS-Low+GFIR, 90 mg·kg-1) group, and a high-dose PQS combined with GFIR (PQS-High+GFIR, 180 mg·kg-1) group. Treatment lasted for 14 days, and the fluorescence intensity was monitored at the tumor site by small-animal in vivo imaging during the treatment period. Flow cytometry was utilized to determine the proportions of T-lymphocyte subsets, B-lymphocyte levels, and peripheral blood NK cell levels in the spleens of mice. Immunohistochemical (IHC) staining was performed to assess the infiltration of CD3+, CD4+, and CD8+ T-lymphocytes in the tumor tissue. Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the levels of interferon-α (IFN-α), interferon-β (IFN-β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in mouse tumors. The mRNA levels of cGAS, STING, TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), interferon beta 1 (IFNB1), and nuclear factor κB p65 (NF-κB p65) were determined by Real-time PCR. The protein levels of cGAS, STING, p-STING, TBK1, p-TBK1, IRF3, p-IRF3, NF-κB p65, and p-NF-κB p65 were quantified via Western blot. ResultsThe cell experiment results showed that compared with the control group, PQS inhibited the viability and migration of A549 cells, promoted apoptosis, affected mitochondrial localization, reduced mitochondrial membrane potential, increased the ROS level, and promoted mtDNA leakage. Following STING knockdown, the reductions in cell viability and the apoptosis-inducing effects caused by PQS were partially reversed (P<0.05, P<0.01). Compared with the PQS group, the PQS+GFIR group showed inhibited A549 cell migration and colony formation, exacerbated apoptosis, downregulated mitochondrial membrane potential, elevated ROS levels, and promoted mtDNA leakage. After STING knockdown, the reduced A549 cell viability and abnormal apoptosis phenotype were further reversed (P<0.05, P<0.01). The animal experiment results showed that compared with the control group, the model group mice exhibited reduced proportions of T-lymphocyte subsets, CD19+ B-lymphocyte levels, and peripheral blood NK1.1+ cell levels in the spleen (P<0.01). Compared with the model group, the PQS group showed increased immune cell parameters in mice (P<0.05, P<0.01). Compared with the PQS group, the PQS+GFIR group exhibited enhanced levels of the aforementioned indicators (P<0.01). Compared with the model group, the PQS group showed significantly reduced fluorescence intensity in transplanted tumors, significantly upregulated expression of CD3 and CD4 in the tumor tissue, elevated levels of IFN-α and IL-6 in tumors, and upregulated mRNA levels of cGAS, STING, TBK1, IRF3, IFNB1, and NF-κB p65 as well as upregulated protein level of cGAS and phosphorylation level of STING in tumors (P<0.05, P<0.01). Compared with the PQS group, the PQS+GFIR group demonstrated further reduced tumor fluorescence intensity, elevated levels of CD3, CD4, and CD8 as well as cytokine levels in tumor tissue, and upregulated mRNA levels of genes related to the cGAS/STING pathway as well as upregulated protein level of cGAS and phosphorylation levels of STING, TBK1, IRF3, and NF-κB p65 (P<0.05, P<0.01) ConclusionGFIR enhances the inhibitory effect of PQS on NSCLC, potentially through mitochondrial dysfunction, mtDNA leakage, and activation of the cGAS/STING signaling pathway.
4.Comparative efficacy of robot-assisted balloon tibioplasty and traditional open reduction and internal fixation in the treatment of AO/OTA type 41B2 tibial plateau fracture
Jialang HU ; Jing JIAO ; Yucheng HUANG ; Wen XIONG ; Jinyi WU ; Hai DENG ; Zhihua GENG ; Xuan MA ; Ming CHEN
Chinese Journal of Trauma 2025;41(4):369-376
Objective:To compare the clinical efficacy of robot-assisted balloon tibioplasty and traditional open reduction and internal fixation in the treatment of AO/OTA type 41B2 tibial plateau fracture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 70 patients with AO/OTA type 41B2 tibial plateau fracture who were admitted to Wuhan Fourth Hospital from September 2019 to October 2022, including 35 males and 35 females, aged 24-62 years [(44.9±9.5)years]. Among them, 41 patients underwent traditional open reduction and internal fixation (open reduction group), while 29 patients underwent robot-assisted balloon tibioplasty (balloon group). The following parameters were compared between the two groups: incision length, operative blood loss, number of intraoperative fluoroscopies, operation duration, and length of hospital stay; Rasmussen radiological scores at 3 days, 3 months postoperatively, and at the last follow-up and the fracture healing time; pain visual analogue scale (VAS) scores preoperatively, and at 2 days and 3 months postoperatively; knee joint range of motion at 5 days, 3 months postoperatively, and at the last follow-up; Hospital for Special Surgery (HSS) knee function scores at 3, 6 months postoperatively, and at the last follow-up; incidence rate of complications at 15 days postoperatively.Results:All the patients were followed for 12-24 months [18(17, 20)months]. The incision length, operative blood loss and length of hospital stay in the balloon group were 1.6(1.5, 3.0)cm, 5.0(5.0, 5.0)ml and 11.0(9.0, 14.0)days, less than those in the open reduction group [12.0(11.0, 12.0)cm, 100.0(50.0, 120.0)ml and 15.0(13.0, 20.0)days] ( P<0.01). The number of intraoperative fluoroscopies and operation duration in the open reduction group were 9.0(7.0, 10.0)times and 75.0(60.0, 90.0)minutes, less than those in the balloon group [336.0(335.0, 340.0)times and [90.0(70.0, 105.0)minutes] ( P<0.05). There were no significant differences in the Rasmussen radiological scores between the two groups at 3 days, 3 months postoperatively, or at the last follow-up ( P>0.05). The fracture healing time in the balloon group was 3.0(3.0, 3.0)months, shorter than 3.0(3.0, 3.5)months in the open reduction group ( P<0.05). No significant differences were observed between the two groups in VAS scores before operation or at 3 months postoperatively ( P>0.05). However, the VAS score was 2.0(2.0, 3.0)points at 2 days postoperatively in the balloon group, lower than 5.0(5.0, 6.0)points in the open reduction group ( P<0.01). The knee joint range of motion at 5 days, 3 months postoperatively and at the last follow-up were 90.0(85.0, 90.0)°, 135.0(130.0, 135.0)° and 140.0(135.0, 140.0)° in the balloon group, better than 65.0(60.0, 70.0)°, 125.0(120.0, 130.0)°, 130.0(130.0, 140.0)° in the open reduction group ( P<0.01). Similarly, the HSS knee function scores at 3, 6 months postoperatively and at the last follow-up were 80.0(80.0, 81.0)points, 91.0(90.0, 92.0)points, and 95.0(93.0, 96.0)points in the balloon group, better than 71.0(70.0, 72.0)points, 83.0(81.0, 84.0)points, and 86.0(84.0, 88.0)points in the open reduction group ( P<0.01). The incidence rate of complications in the balloon group was 0, comparable to 12% (5/41) in the open reduction group ( P>0.05). Conclusion:Compared with traditional open reduction and internal fixation surgery, robot-assisted balloon tibioplasty in the treatment of AO/OTA type 41B2 tibial plateau fracture significantly reduces surgical trauma, alleviates postoperative pain, promotes fracture healing, and accelerates functional recovery of the affected limbs.
5.The application value of digital PCR and next-generation sequencing technology in the etiological diagnosis of sepsis patients
Jian SHI ; Jing LEI ; Zeshi LIU ; Chaoliang XIONG ; Tian LI ; Yan GENG
Chinese Journal of Microbiology and Immunology 2025;45(3):256-263
Objective:To explore the value of droplet digital PCR (ddPCR) and next-generation sequencing (NGS) technology in the pathogenetic diagnosis of sepsis patients, and to provide a reference basis for the early diagnosis of sepsis.Methods:A retrospective analysis was used to collect the clinical data of 53 patients with suspected sepsis admitted to the intensive care unit (ICU) of the Second Affiliated Hospital of Xi'an Jiaotong University from February to August 2023, and the blood was collected for blood culture, ddPCR and NGS detection simultaneously.Results:After excluding viral infections, the blood culture positive rate was 18.87%(10/53), the ddPCR positive rate was 47.17% (25/53), and the NGS positive rate was 41.51%(22/53). When using the ddPCR detection range as a reference, the ddPCR positivity rate was 98.11% (52/53), while the NGS positivity rate was 84.91%(45/53). There was a statistically significant difference in the positivity rate between the two groups ( P<0.05). Using blood culture as a reference, the sensitivity (60.00% vs 70.00%) and specificity (65.11% vs 69.77%) of ddPCR and NGS were in good agreement. In terms of pathogen detection, NGS had a wider detection range than ddPCR (34 species vs 21 species), and the difference was statistically significant (χ 2=55.000, P<0.001). In terms of time-consumption, blood culture took 66.93 h on average, while ddPCR was faster than NGS (about 4 h vs 20 h ). In terms of antimicrobial resistance (AMR) gene detection, five resistant strains were detected by both ddPCR and NGS, ddPCR detected two AMR genes, namely blaKPC and mecA, while NGS detected five AMR genes. Among them, except for blaKPC which was detected outside the target range in ddPCR, the other four AMR genes were also detected by ddPCR. Conclusions:Compared with blood culture, ddPCR and NGS have good application value in the etiological diagnosis of sepsis. Specifically, ddPCR has a higher detection rate of pathogens and takes less time. On the other hand, NGS has a wider detection range, especially for the discovery of some rare bacteria or pathogens that are difficult to be cultured routinely.
6.Case 06 (2025): A case of pregnancy complicated by type 1 diabetes with severe diabetic nephropathy and retinopathy
Hongli HUANG ; Huixia YANG ; Geng SONG ; Shuxian WANG ; Ye FENG ; Yumei WEI ; Yu SUN ; Sufang SHI ; Xiaoyong YUAN ; Jing ZHANG
Chinese Journal of Perinatal Medicine 2025;28(1):51-56
This paper reported a type 1 diabetes patient who had severe diabetic nephropathy, retinopathy, hypertension, and hypothyroidism before pregnancy. The patient's blood glucose control was poor before pregnancy, and the complications were not properly treated. This was an unintended pregnancy, with a pre-pregnancy glycated hemoglobin A1c of 7.8% and early pregnancy urine protein of 3.81-4.53 g/24 h. Considering the patient's poor blood glucose control before pregnancy and the lack of proper treatment for multiple complications including nephropathy, a multidisciplinary consultation at an external hospital recommended termination of the pregnancy. However, the patient was determined to continue the pregnancy and was referred to Peking University First Hospital. Through strict blood glucose control, monitoring and evaluation of complications, and comprehensive management, the patient's blood glucose and blood pressure were well controlled during pregnancy. Regular monitoring of urine protein, renal function, and ocular fundus was conducted. At 31 weeks and 4 days of gestation, the patient's 24-hour urine protein significantly increased. After promoting fetal lung maturity, a cesarean section was performed at 34 weeks and 1 day of gestation, resulting in a successful delivery with good maternal and neonatal outcomes. At the 42-day postpartum follow-up, the patient's blood glucose and blood pressure were stable, urine protein returned to pre-pregnancy levels, and the infant was in good general condition.
7.Effects of Inhibiting the NKCC1/AQP4 Pathway on Neurological Injury Improvement in a Rat Model of High-Altitude Cerebral Edema
Huali GENG ; Baichuan LI ; Xu SONG ; Yilin XIA ; Xiangyang ZHOU ; Jing GAO ; Lei CHEN
Journal of Sichuan University (Medical Sciences) 2025;56(1):156-165
Objective To investigate the pathogenesis of high-altitude cerebral edema(HACE)and develop new therapeutic strategies.Methods Male Sprague-Dawley(SD)rats of 6 weeks old were selected and placed in a hypobaric chamber.The rats were exposed to the high-altitude environment of 7000 m above sea level for 3 days for HACE modeling.Whether the HACE model was successfully established in the rats was evaluated by measuring brain water content,the degree of disruption to the blood-brain barrier(BBB),and brain tissue Nissl staining.The experimental animals were divided into four groups,with 28 rats in each group.The blank control group was exposed to a normobaric and normoxic environment simulating the conditions at 500 m above sea level for 3 d.The other groups,including a model group(the HACE group),a bumetanide group(the positive control group),and a XH-6003 treatment group,were placed at an altitude of 7 000 m above sea level and were injected with normal saline,bumetanide,and XH-6003,a new type of Na-K-2C1 cotransporter 1(NKCC1)inhibitor,via the tail vein,respectively,twice daily for 3 d.The experimental animals were taken out of the hypobaric chamber for testing after 3 d.The primary outcome measures included brain water content,BBB permeability,changes in brain tissue morphology,and the expression levels of aquaporin-4(AQP4)and NKCC1.The secondary outcome measures included behavioral changes,apoptosis,and oxidative stress markers.Results The HACE rat model was successfully established.The model group exhibited increased brain water content(P<0.0001),BBB disruption(P<0.0001),impairment in learning skills and memory(P<0.001),and anxiety/depression-like behaviors(P<0.01).qPCR results showed significantly increased expression of NKCC1 and AQP4 in the brain tissue of the model group(P<0.01).Pathology examination revealed neuronal and glial cell damage in the hippocampus of the model group(P<0.01).Treatment with XH-6003,the NKCC1 inhibitor,reversed brain water content,BBB disruption,and neuronal and glial cell damage to a certain degree(P<0.05),decreased the expression of NKCC1 and AQP4 in the brain tissue(P<0.01),and inhibited apoptosis-related proteins.Among the oxidative stress indices,only glutathione(GSH)showed improvement(P<0.001).Rats treated with XH-6003 showed functional improvement only in the time spent exploring novel objects,while other behavioral outcomes remained unchanged.Conclusion HACE is associated with the activation of the NKCC1/AQP4 pathway.Inhibition of this pathway alleviates brain edema,BBB disruption,and neuronal and glial cell damage.These findings suggest that XH-6003 holds potential as a therapeutic strategy for HACE at the cellular and molecular levels,but its effects in improving HACE-related behavioral disorders warrant further investigation.
8.Expression and diagnostic value of CYBB and CSF1R in chronic rhinosinusitis with nasal polyps
Yu-Long MA ; Geng LI ; Jing-Fang WU ; Gang XUE ; Xu LIN
Medical Journal of Chinese People's Liberation Army 2025;50(1):35-43
Objective To analyze the gene expression characteristics of chronic rhinosinusitis with nasal polyps(CRSwNP)using bioinformatics methods,aim to investigate the potential biomarkers and their diagnostic value of CRSwNP.Methods(1)The CRSwNP Gene expression data set was downloaded from the American Gene Expression Omnibus(GEO)database.The differentially expressed genes(DEGs)between CRSwNP patients and healthy controls were screened through data analysis.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed on the identified DEGs.Protein-protein interaction(PPI)networks were constructed utilizing the STRING database,and the key genes were identified by using the cytoHubba plugin.The"Cibersort"package was used to analyze the influence of key genes on common immune cells.(2)Thirty-two patients diagnosed with CRSwNP in the First Affiliated Hospital of Hebei North University from June 2022 to June 2023 were selected as the CRSwNP group,and 21 patients with simple deviation of nasal septum without a history of sinusitis during the same period were selected as control group.The pathological characteristics of specimens in the two groups were examined using hematoxylin-eosin(HE)staining.Immunohistochemistry and Western blotting were used to detect the expression levels of key genes in CRSwNP.The levels of key proteins in plasma were detected using ELISA,and ROC curve was used to analyze its efficacy in diagnosing CRSwNP.Results(1)Analysis of three gene expression database sets(GSE36830,GSE23552,and GSE194282)showed that there were 156 DEGs in CRSwNP.GO functional enrichment and KEGG pathway analysis indicated that the functions of the above DEGs were mostly related to immune functions.Key genes such as cytochrome b-245 β chain(CYBB)and colony-stimulating factor 1 receptor(CSF1R)were identified.(2)The results of HE staining revealed that the epithelial of CRSwNP tissue was metaplastic into stratified squamous epithelium with interstitial edema.Both immunohistochemistry and Western blotting analyses indicated that the expression levels of CYBB and CSF1R in the CRSwNP group were significantly increased compared to control group(P<0.05).ELISA results demonstrated that CYBB[(21.20±3.00)μg/ml vs.(17.66±1.66)μg/ml,P<0.05]and CSF1[(477.37±86.63)pg/ml vs.(370.71±66.24)pg/ml,P<0.05]in CRSwNP group were significantly increased compare to control group.ROC curve analysis showed that plasma concentrations of CYBB and CSF1 had AUCs of 0.888(95%CI 0.802-0.974)and 0.821(95%CI 0.711-0.931)for diagnosing of CRSwNP,respectively;their combined AUC was 0.927(95%CI 0.851-1.000).Conclusions CYBB and CSF1R may be involved in the occurrence and development of CRSwNP.Plasma CYBB and CSF1 have high diagnostic value for CRSwNP.
9.Research Progress on Serological Markers and Prediction Models for Early Diagnosis of Sepsis
Jian SHI ; Chaoliang XIONG ; Jing LEI ; Zeshi LIU ; Yan GENG
Journal of Modern Laboratory Medicine 2025;40(2):214-220
Sepsis constitutes a predominant cause of mortality in critically ill patients,and early determination of the type of infection is crucial for influencing patient management and forecasting outcomes.Currently,blood culture serves as the gold standard for diagnosing sepsis.Yet,its limitations,such as a lengthy culture period and low positivity rate,hinder its ability to provide a microbiological basis for early initiation of antimicrobial therapy in clinical practice.Serological markers have engendered significant interest due to their convenience and rapid detection in vitro,emerging as indispensable laboratory indices for early inference of infection.In recent years,with extensive research on sepsis across diverse academic domains,numerous novel serological markers exhibit promise in diagnosing sepsis.Therefore,this review explores the characteristics and applicatron value of new serological markers for early diagnosis of sepsis,and reviews them in combination with relevant predictive models,bringing new ideas for early clinical diagnosis of sepsis.
10.Clinical characteristics and prognosis of Pseudomonas aeruginosa perito-neal dialysis-associated peritonitis
Zhigang WANG ; Yingzhou GENG ; Xiaopei WANG ; Zhao LI ; Changna LIANG ; Wan-hong LU ; Jing LYU
Chinese Journal of Infection Control 2025;24(3):381-387
Objective To analyze the clinical characteristics and prognosis of Pseudomonas aeruginosa peritoneal dialysis-associated peritonitis(PaeP).Methods Peritoneal dialysis-associated peritonitis(PDAP)patients who were followed up in the nephrology outpatient department of a hospital from January 2019 to December 2020 were analyzed retrospectively.According to bacterial culture results,patients were divided into the PaeP group and non-PaeP group.Clinical characteristics of PaeP patients and antimicrobial susceptibility testing results of Pseudomonas aeruginosa were analyzed,clinical manifestations,laboratory test results,and prognosis of two groups of patients were compared.Results A total of 124 peritoneal dialysis patients were included in analysis,164 cases of peritoni-tis occurred,16 cases were in the PaeP group and 148 in the non-PaeP group.11 patients developed 16 episodes of Pseudomonas aeruginosa infection,accounting for 8.9%of PDAP patients.Among them,4 patients had peritoneal dialysis catheter exit-site infection,with 5 recurrence cases,1 case cured,1 case died,and 9 cases were extubated.Among the extubated patients,1 withdrew dialysis,3 were recovered to peritoneal dialysis after hemodialysis,5 changed to permanently hemodialysis,with a technical failure rate of 54.5%.Compared with the non-PaeP group,patients in the PaeP group had a shorter dialysis time(13.83±4.92 vs 38.53±35.77 months).During the infection period,C-reactive protein levels were higher(96.61±6.17 vs 45.87±44.65 mg/L),while albumin levels were lower(25.62±4.42 vs 29.46±8.25 g/L).At the onset of infection,the proportion of polymorphonuclear cells in perito-neal dialysis fluid was relatively higher.On the 5th day of treatment,the negative conversion rate of white blood cell count in peritoneal dialysis fluid was relatively low.Differences were all statistically significant(all P<0.05).The cure rate of patients in the PaeP group was lower than that in the non-PaeP group,the technical failure rate was higher than that in the non-PaeP group,both with statistically significant differences(both P<0.05).There was no statistically significant difference in the mortality between two groups of patients(P>0.05).Conclusion PaeP patients have severe clinical manifestations,poor clinical treatment prognosis,high recurrence and extubation rates.For patients with repeated episodes,resetting and replacing the tunnel after extubation is an effective means to re-duce technical failures.

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