1.Apoptosis Regulation by Buzhong Yiqitang via PERK/eIF2α/ATF4/CHOP Pathway to Enhance Pulmonary Surfactant-associated Protein C Expression and Ameliorate Lung Injury in CIH Mice
Luyao ZHANG ; Yangjing WANG ; Bingbing LIU ; Jieru LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):19-27
ObjectiveTo investigate the effects of Buzhong Yiqitang on the abnormal expression of pulmonary surfactant-associated protein C (SFTPC) and lung injury induced by chronic intermittent hypoxia (CIH) and the mechanism of action. MethodsForty healthy adult male SPF-grade C57BL/6 mice were randomly allocated into five experimental groups: a normoxia group, a CIH group, and low-, medium-, and high-dose Buzhong Yiqitang groups, with eight mice in each group. During the modeling, mice in the normoxia group were housed under standard oxygen concentrations, while the CIH and all Buzhong Yiqitang groups were placed in a hypoxic chamber for 8 h daily over 35 d. Prior to each chamber session, mice in the low-, medium-, and high-dose Buzhong Yiqitang groups were administered decoctions by gavage at corresponding doses (8.1, 16.2, 32.4 g·kg-1·d-1 of crude drug, respectively), while those in normoxia and CIH groups received an equivalent volume of saline by gavage. The general conditions of the mice were recorded before and after the experiment. Pulmonary function was assessed using a non-invasive detection system. Serum SFTPC levels were measured using enzyme-linked immunosorbent assay (ELISA). Histopathological changes in lung tissue were evaluated using hematoxylin-eosin (HE) staining. Apoptosis in lung tissue was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Protein expression of SFTPC, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α (p-eIF2α), activating transcript factor 4 (ATF4), and CCAAT/enhancer-binding protein homologous protein (CHOP) in lung tissue was analyzed by Western blot. Immunofluorescence staining was employed to assess the expression of SFTPC and CHOP proteins in lung tissue. ResultsCompared to those in the normoxia group, mice in the CIH group showed significantly impaired pulmonary function and increased histopathological lung injury scores (P<0.05, P<0.01). Serum SFTPC levels increased, while SFTPC expression in lung tissue was reduced (P<0.05, P<0.01). The rate of apoptotic cells in lung tissue increased, and the expression of endoplasmic reticulum stress markers p-PERK, p-eIF2α, ATF4, and CHOP was upregulated (P<0.05, P<0.01). Compared with the CIH group, Buzhong Yiqitang intervention improved pulmonary function indicators and decreased the histopathological lung injury scores (P<0.05, P<0.01). Serum SFTPC levels were decreased, and lung tissue SFTPC expression was recovered (P<0.05, P<0.01). The apoptotic rate of lung tissue cells was significantly reduced, with downregulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2 expression (P<0.05, P<0.01). Activation and expression of p-PERK, p-eIF2α, ATF4, and CHOP were also decreased (P<0.05, P<0.01). ConclusionBuzhong Yiqitang can alleviate lung injury and improve pulmonary function by reducing lung cell apoptosis and enhancing alveolar surfactant secretion, which may be related to the modulation of the PERK/eIF2α/ATF4/CHOP signaling pathway.
2.Cancer-associated fibroblasts mediate migration of myeloid-derived suppressor cells in pancreatic ductal adenocarcinoma through SDF-1/CXCR4 pathway
Bingbing ZHANG ; Hao HU ; Yuchuan SHI ; Xuefei LIU ; Zhi ZHU ; Jing ZHANG
Academic Journal of Naval Medical University 2025;46(7):838-846
Objective To explore the mechanism by which cancer-associated fibroblasts(CAFs)regulate CD13-high expression neutrophil-like myeloid-derived suppressor cell(CD13hi-nMDSC)migration in pancreatic ductal adenocarcinoma(PDAC),so as to provide potential molecular targets and experimental evidences for immunotherapy in patients.Methods CAFs were isolated and purified from pancreatic cancer tissues of 5 PDAC patients.The phenotype and purity of CAFs were identified by immunofluorescence and flow cytometry.The expression of related factors in CAF was detected by quantitative polymerase chain reaction(qPCR)and enzyme-linked immunosorbent assay(ELISA).CAF conditioned medium and myeloid-derived suppressor cell(MDSC)migration system were constructed by Transwell to observe the migration of MDSCs and to study the specific mechanisms by which the aforementioned cytokines participate in regulating the migration of MDSCs.Results The isolated primary CAFs expressed activation biomarkers fibroblast activation protein(FAP)and α-smooth muscle actin(α-SMA),while the human foreskin fibroblasts(HFFs)of control cells did not express FAP and α-SMA.qPCR results showed that the mRNA expression levels of interleukin 6(IL-6),monocyte chemotactic protein 1(MCP-1),and stromal cell-derived factor 1(SDF-1)in CAFs were higher than those in HFFs(all P<0.01).The contents of IL-6,MCP-1,and SDF-1 in the CAF culture supernatant were significantly higher than those in the HFF culture supernatant(all P<0.01),and the secretion content increased with the prolongation of culture time.Compared with HFF conditioned medium and regular medium(RPMI 1640),CAF conditioned medium could recruit more total MDSCs and CD13hi-nMDSCs(all P<0.01).The addition of SDF-1 recombinant protein alone in the culture system could induce the migration of total MDSCs and CD13hi-nMDSCs,and the addition of SDF-1 neutralizing antibodies or C-X-C motif chemokine receptor 4(CXCR4)blocking antibodies could significantly reduce the migration of CD13hi-nMDSCs induced by CAF conditioned medium(all P<0.01).Although MCP-1 alone could also induce the migration of total MDSCs and CD13hi-nMDSCs,the number of CD13hi-nMDSCs migrating was significantly less than that of the SDF-1 experimental group.The IL-6 recombinant protein did not induce the migration of total MDSCs or CD13hi-nMDSCs.Conclusion CAFs can mediate the migration of total MDSCs and CD13hi-nMDSCs in PDAC through SDF-1/CXCR4 pathway.
3.The diagnostic value of CT imaging evaluation for lymph node metastasis in gallbladder cancer and its correlation with prognosis
Sen YANG ; Shuai YAN ; Feilong TAN ; Yihan WANG ; Bingbing LIU ; Xueliang YUE ; Hongshan LIU
Chinese Journal of General Surgery 2025;40(4):290-294
Objective:To assess the accuracy of preoperative enhanced CT in evaluating the degree of lymph node metastasis in gallbladder cancer.Methods:A retrospective analysis was performed on the enhanced CT imaging data of 124 gallbladder cancer patients who underwent surgical treatment at Henan Provincial People's Hospital from Jan 2017 to Dec 2018. Imaging staging was used to classify lymph node metastasis. Pathological and imaging data of 70 patients with confirmed postoperative lymph node pathology were compared to evaluate the accuracy of imaging methods in detecting lymph node involvement.Results:Lymph node metastasis in the 124 surgical patients was categorized into three groups using imaging evaluation methods. The overall accuracy of determining lymph node positivity and negativity was 63%, with a sensitivity of 64% and specificity of 62%. The accuracy of detecting lymph node metastasis in gallbladder cancer was higher when lymph node fusion and internal necrosis were observed. The overall survival rate differed significantly among gallbladder cancer patients at different lymph node imaging stages ( P<0.05). Conclusion:CT imaging evaluation has diagnostic value for lymph node metastasis in gallbladder cancer and has a certain predictive effect on the prognosis of patients.
4.Advances in conversion therapy for unresectable hepatocellular carcinoma
Ke YU ; Jiajia JIA ; Ying SHA ; Yufan TANG ; Baiquan ZHOU ; Bingbing WEN ; Luyao LI ; Jixiang LIU ; Ruifang FAN
Chinese Journal of Hepatobiliary Surgery 2025;31(9):706-711
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Surgical resection remains the preferred treatment modality, offering the potential for cure. However, over half of HCC patients present as intermediate to advanced stages at diagnosis, with multiple factors precluding surgical resection. Conversion therapy represents an important treatment strategy by enabling tumor downstaging, offering future resectability for patients with intermediate-to-advanced HCC who are initially unresectable. This article reviews the relevant concepts and research progress in conversion therapy for HCC.
5.Development of DUS Test Guidelines for New Pinellia ternata
Xinyao LI ; Mingxing WANG ; Bingbing LIAO ; Changjie CHEN ; Xiufu WAN ; Lanping GUO ; Yuhuan MIAO ; Dahui LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):225-233
Pinellia ternata, belonging to the Pinellia genus within the Araceae family, is a medicinal plant due to its tubers. There are severe issues with unclear germplasm and mixed varieties in its cultivation, necessitating urgent new variety protection efforts. The distinctness, uniformity, and stability (DUS) testing of the plant variety is the basis for protecting new plant varieties, and the DUS test guidelines are the technical basis for DUS testing. To develop the DUS test guidelines for P. ternata, agronomic traits of 229 germplasm of P. ternata were observed and measured during its two growth stages over the years, and each character was graded and described. A total of 38 traits were selected as the test traits of the DUS test guideline for P. ternata. There were three plant traits, 19 leaf traits, six flower traits, two fruit traits, two tuber traits, five bulbil traits, and one ploidy trait. These traits could be divided into 22 quality characters, 12 quantitative characters, and four pseudo-quantitative characters, as well as seven groups, including plants, leaves, flowers, fruit, tubers, bulbils, and ploidy. By searching for standard traits, 10 standard varieties were ultimately determined. Preparing these guidelines will have great significance for reviewing and protecting P. ternata varieties, safeguarding breeders' rights, and promoting the development of the P. ternata industry.
6.Effect of stress-induced hyperglycemia on new-onset atrial fibrillation in patients with acute myocardial infarction
Hongkai DONG ; Xuan XUE ; Bingbing PENG ; Meiling LIU ; Liuyi HAO
Journal of Public Health and Preventive Medicine 2025;36(6):114-118
Objective To explore the effect of stress hyperglycemia (SHG) on new-onset atrial fibrillation (NOAF) in patients with acute myocardial infarction (AMI). Methods A total of 1 321 patients with non-diabetic AMI who were admitted to the hospital from February 2024 to February 2025 were retrospectively selected. The occurrence of SHG was assessed according to the blood glucose level at admission. All patients received standard treatment after admission. The occurrence of NOAF during hospitalization was recorded. According to the presence or absence of NOAF occurrence, the patients were classified into NOAF group (n=118) and no-NOAF group (n=1,203). The clinical data of the two groups were collected and compared. Multivariate logistic regression analysis was applied to analyze the factors influencing the occurrence of NOAF in AMI patients. Results Among the 1 321 patients, 369 cases (27.93%) had SHG according to their blood glucose test at admission. After the completion of hospitalization, 118 of the 1321 patients developed NOAF, with an incidence rate of 8.93%. Multivariate logistic regression analysis revealed that SHG (OR=2.776, 95%CI: 1.384-5.567), smoking history (OR=2.680, 95%CI: 1.457-4.931), Killip grading at admission (OR=2.779, 95%CI: 1.361-5.671), Gensini score (OR=1.119, 95%CI: 1.038-1.205), time from onset to revascularization (OR=1.114, 95%CI: 0.973-1.275), and NT-proBNP (OR=1.123, 95%CI: 1.049-1.203) were independent influencing factors of NOAF in patients with AMI (P<0.05). Conclusion SHG, smoking history, Killip grading at admission, Gensini score, NT-proBNP, and time from onset to revascularization may influence the occurrence of NOAF in AMI patients during hospitalization, which should be given high attention.
7.Mechanism of "olfactory three needles" in regulating microglia and promoting remyelination in vascular dementia rats.
Le LI ; Qiang WANG ; Junyang LIU ; Weijia ZHAO ; Jiawei ZENG ; Bingbing ZHANG ; Ruirui MAO ; Weixing FENG ; Jie LI
Chinese Acupuncture & Moxibustion 2025;45(4):473-481
OBJECTIVE:
To observe the effects of "olfactory three needles" on cognition, learning and memory abilities, as well as hippocampal microglia (MG) phagocytic activity in vascular dementia (VD) rats, and explore the mechanisms of acupuncture in regulating MG activation and improving remyelination, so as to ameliorate VD.
METHODS:
Among 38 SD rats meeting experimental requirements, 9 rats were randomly assigned to a sham-operation group, and the remaining rats underwent permanent bilateral common carotid artery ligation to establish VD model. Eighteen successfully modeled rats were randomly divided into a model group and an electroacupuncture (EA) group, with 9 rats in each one. In the EA group, EA was performed at "olfactory three needles" ("Yintang" [GV24+] and bilateral "Yingxiang" [LI20]), at disperse-dense wave, the frequency of 2 Hz/15 Hz and the current intensity of 1 mA, for 15 min per intervention, once daily. One course was composed of 7 days, and 2 courses were required, with the interval of 2 days. The novel object recognition test was employed to assess the cognition of rats, and the Morris water maze was adopted to observe learning and memory abilities. Luxol fast blue (LFB) staining was performed to evaluate myelin sheath loss in the hippocampus, the Western blot was used to detect the protein expression of triggering receptor expressed on myeloid cells-2 (TREM2) and proteolipid protein (PLP) in the hippocampus; and the immunofluorescence staining was used to detect the positive expression of PLP, sex determining region Y-box 10 (SOX10), ionized calcium binding adaptor molecule 1 (Iba1)+ TREM2+ and Iba1+ lysosome-associated membrane protein 1 (LAMP1)+ in the hippocampus.
RESULTS:
Compared with the sham-operation group, the rats in the model group exhibited the prolonged escape latency on day 3 and 4 (P<0.05, P<0.01), the increase of the total distance traveling (P<0.01) and the decrease of the recognition index (RI) and platform crossing frequency (P<0.01). Compared with the model group, the rats in the EA group showed the shortened escape latency on day 3 and 4 (P<0.05), the decrease of total distance traveling (P<0.01) and the increase of RI and platform crossing frequency (P<0.05, P<0.01). When compared with the sham-operation group, the rats of the model group presented uneven staining, sparse arrangement of myelin sheath fibers, unclear contours, and prominent vacuole-like changes in the hippocampal CA1 region. When compared with the model group, the EA group showed more dense staining, the increase of myelin sheath fibers with more orderly alignment, and fewer vacuolar changes in the hippocampal CA1 region. Compared with the sham-operation group, the model group exhibited the increase of TREM2 protein expression and the decrease of PLP protein expression in the hippocampus (P<0.01), whereas the EA group showed the up-regulation of TREM2 and PLP protein expression when compared with the model group (P<0.01, P<0.05). The positive expression of the hippocampal PLP, SOX10, and Iba1+LAMP1+ in the model group was reduced in comparison with the sham-operation group (P<0.05, P<0.01), and the positive expression of Iba1+ TREM2+ was elevated (P<0.05). In the EA group, the positive expression of PLP, SOX10, Iba1+TREM2+, and Iba1+ LAMP1+ was higher compared with that in the model group (P<0.05, P<0.01).
CONCLUSION
"Olfactory three needles" can improve the learning and memory, and cognitive functions of VD rats, and its mechanism may be associated with the up-regulation of TREM2 and LAMP1 to adjust MG phagocytic activity and intracellular degradation, and promote remyelination.
Animals
;
Dementia, Vascular/metabolism*
;
Rats
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Rats, Sprague-Dawley
;
Microglia/metabolism*
;
Male
;
Acupuncture Therapy/instrumentation*
;
Acupuncture Points
;
Humans
;
Remyelination
;
Memory
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Hippocampus/cytology*
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Cognition
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Electroacupuncture
;
Needles
8.Protective effect of polydatin and its mechanism on liver injury in silicosis rat model
Shuaihui ZHANG ; Dongmin ZHOU ; Bingbing WU ; Jinchao LIU ; Yan YU ; Fuhai SHEN
China Occupational Medicine 2025;52(6):601-611
Objective To explore the protective effect of polydatin and its mechanism on secondary liver injury in silicosis rats based on network pharmacology and animal experiments. Methods i) Network pharmacology study. Based on multiple databases, the targets of polydatin effect related to silicosis and liver injury were collected, and the common targets of polydatin-silicosis-liver injury were screened to construct a protein-protein interaction network. Enrichment analyses were performed to identify core targets involved in the effects of polydatin on silicosis-associated secondary liver injury. The mechanism of action of polydatin in relieving silicosis and silicosis-associated secondary liver injury was investigated, in which polydatin served as molecular docking ligand. ii) Animal experimental validation. Specific pathogen free male SD rats were randomly divided into three groups, with 10 rats per group. Rats in the model and intervention groups received 1 mL of a silica suspension at a mass concentration of 50 g/L for modeling using a one-time non-tracheal exposure method. Then rats in the intervention group were injected intraperitoneally with polydatin solution at 30 mg/kg body weight, once daily starting from the first day after silica exposure, whereas rats in the control group received no treatment. Lung and liver histopathology of rats, which were randomly sacrificed on days 28 and 56 post-exposure in both groups, were examined. Biomarkers of liver injury and hepatic oxidative stress were measured, and hepatic expression of nuclear factor erythroid 2-related factor 2 (NRF2) related proteins was detected by Western blotting. Results i) Network pharmacology study results. A total of 137 polydatin-related targets, 14 812 silicosis-related targets, and 3 038 liver injury-related targets were identified, among which 69 were common targets and 28 were key targets. Gene Ontology analysis indicated that the key targets were involved in 1 883 pathways. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified 137 pathways related to the targets. Molecular docking showed good binding affinities between polydatin and B-cell lymphoma 2 (BCL2), interleukin 6 (IL-6), tumor necrosis factor (TNF), and NRF2. ii) Animal experimental validation results. Compared with the control group, rats in the model group showed increased collagen deposition in both lung and liver tissues, with hepatic degeneration, necrosis, and inflammatory cell infiltration on days 28 and 56 after silica exposure. The collagen in lung and liver tissues of rats on days 28 and 56 after silica exposure increased in the model group compared with the control group (all P<0.05). Meanwhile, serum alanine aminotransferase and aspartate aminotransferase activities, hepatic lactate dehydrogenase 5 activities and NADPH: quinone oxidoreductase 1 (NQO1) expression in liver tissue increased (all P<0.05), whereas hepatic superoxide dismutase activity and NRF2 expression were decreased (all P<0.05). The level of malondialdehyde and the relative expression of heme oxygenase-1 (HO-1) protein in liver tissue in rat of model group were higher than those in the control group (all P<0.05). These alterations were ameliorated in rats of the intervention group compared with the model group (all P<0.05). Conclusion Polydatin exerts protective effects against secondary liver injury in rats with silicosis. These effects may be mediated by regulation of core targets such as BCL2, IL6, TNF, and NRF2, modulation of inflammatory pathways including TNF and IL17 signaling, and activation of the NRF2/HO-1 pathway, thereby exerting synergistic anti-inflammatory, antioxidant, and antifibrotic effects via the "lung-liver axis".
9.Research progress on predicting radiation pneumonia based on four-dimensional computed tomography ventilation imaging in lung cancer radiotherapy.
Yuyu LIU ; Li WANG ; Yanping GAO ; Xiang PAN ; Meifang YUAN ; Bingbing HE ; Han BAI ; Wenbing LYU
Journal of Biomedical Engineering 2025;42(4):863-870
Lung cancer is the leading cause of cancer-related deaths worldwide. Radiation pneumonitis is a major complication in lung cancer radiotherapy. Four-dimensional computed tomography (4DCT) imaging provides dynamic ventilation information, which is valuable for lung function assessment and radiation pneumonitis prevention. Many methods have been developed to calculate lung ventilation from 4DCT, but a systematic comparison is lacking. Prediction of radiation pneumonitis using 4DCT-based ventilation is still in an early stage, and no comprehensive review exists. This paper presented the first systematic comparison of functional lung ventilation algorithms based on 4DCT over the past 15 years, highlighting their clinical value and limitations. It then reviewed multimodal approaches combining 4DCT ventilation imaging, dose metrics, and clinical data for radiation pneumonitis prediction. Finally, it summarized current research and future directions of 4DCT in lung cancer radiotherapy, offering insights for clinical practice and further studies.
Humans
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Lung Neoplasms/diagnostic imaging*
;
Four-Dimensional Computed Tomography/methods*
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Radiation Pneumonitis/etiology*
;
Algorithms
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Lung/radiation effects*
;
Pulmonary Ventilation
10.Drug resistance and genomic characteristics of clinically isolated hypermu-coviscous Klebsiella pneumoniae
Bingbing LI ; Dawei CHEN ; Liang LIU ; Min SUN ; Shuangshu LI ; Jie LI ; Pengfei YANG ; Yadong XING
Chinese Journal of Infection Control 2025;24(1):113-120
Objective To analyze the drug resistance and genomic characteristics of clinically isolated hypermuco-viscous Klebsiella pneumoniae(hmKp).Methods Klebsiella pneumoniae isolated from clinical specimens from the sentinel hospitals of National Pathogen Identification Network in Huai'an City from 2019 to 2023 were collected,strains were identified by VITEK 2 Compact,mucus phenotype was determined by string test,resistance of hmKp was determined by microbroth dilution method.Molecular typing was conducted by whole-genome sequencing tech-nology,annotation of virulence and resistance genes carried by strains was performed.Results A total of 60 strains of hmKp were collected,mainly isolated from sputum specimens(33.33%)and blood specimens(28.33%).The average genome size of 60 strains was 5.6 Mb,with an average GC content of 57.09%.Multilocus sequence typing(MLST)showed that there were 28 ST types,with the dominant ST types being ST1 1(11.67%),ST15(11.67%),and ST412(10.00%).Core genome MLST(cgMLST)analysis revealed that some strains were highly homologous,and no outbreak strains were found.Multidrug-resistant strains accounted for 60.00%,while imipe-nem-resistant strains accounted for 28.33%.64 types of resistance genes were carried,84.38%of which were loca-ted on mobile element.The carriage rates of fosfomycin-related resistance genes and extended-spectrum β-lactam an-tibiotic-related resistance genes were relatively high in the strains,at 100%and 98.33%,respectively.Among car-bapenem-resistance gene blaKPC-2,21.67%was carried by ST11,ST1,and ST15 strains,among bla NDM-5 gene,3.33%was carried by ST76 strain.A total of 101 virulence genes were carried,most were Colibactin and type Ⅵsecretion system-related virulence genes.All strains carried capsule synthesis regulation-related genes(rcsA,rcsB),efflux pump-related genes(acrA,acrB),and enterobacterin-related genes(entABCEF,fepABCDFG,fes).Conclusion Clinically isolated hmKp in Huai'an exhibits multidrug resistance,with dominant ST types ST11,ST15,and ST412,carrying multiple horizontally transferable resistance and virulence genes,prevention and control measures should be strengthened.


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