1.FAH promotes glioblastoma progression by activating the PI3K/AKT/mTOR signaling pathway
Shihao LI ; Bing ZHAO ; Tieniu YANG ; Jinliang YANG ; Yongliang ZHANG ; Zhongsen LI ; Shunli LI ; Ning CHEN ; Jianbiao WANG ; Jia LI ; Qingfang MA
Acta Universitatis Medicinalis Anhui 2026;61(4):662-676
ObjectiveTo investigate the functional role and underlying molecular mechanisms of fumarylacetoacetate hydrolase (FAH) in the progression of glioblastoma (GBM). MethodsDifferential expression analysis was performed on the TCGA-GBM, GSE4290, and GSE116520 datasets. Weighted gene co-expression network analysis (WGCNA) was used to identify key modules, and Cox regression and risk modeling were used to screen prognostic genes. Immune infiltration analysis of prognostic genes was carried out by using single-cell RNA sequencing panels. The clinical expression signature of FAH in GBM was analyzed in the TCGA and HPA databases. The functional role of FAH was validated by in vitro and in vivo experiments, and pathway analysis was performed to explore the underlying mechanisms. ResultsA total of 152 overlapping genes were identified across the three GBM datasets (P<0.05). WGCNA revealed that the turquoise module was most strongly associated with tumor purity, stromal score, immune score, and ESTIMATE score (P<0.001). Compared with normal tissues, three prognostic genes (CTSD, FAH, and THBD) were upregulated in GBM and correlated with immune infiltration (P<0.05). FAH mRNA and protein levels were elevated in GBM tissues relative to normal tissues, and its expression was significantly associated with age stratification and TP53 mutation (P<0.05). CCK-8 assay results showed that, compared with the shNC group, the proliferative activity of GBM cells in the shFAH group was reduced (P<0.001). Transwell migration and invasion assays demonstrated that, relative to the shNC group, the numbers of migrated and invaded cells in the shFAH group decreased (P<0.05). Western blot analysis revealed that the protein expression levels of PI3K, p-AKT, and p-mTOR in the shFAH group decreased compared with those in the shNC group (P<0.05). In vivo subcutaneous xenograft experiments further confirmed that tumor volume and weight significantly decreased in the shFAH group compared with the shNC group (P<0.001). ConclusionFAH promotes GBM progression by activating the PI3K/AKT/mTOR signaling pathway and may serve as a potential therapeutic target for GBM.
2.Genomic characterization of Legionella pneumophila isolated from industrial circulating cooling water
Man YU ; Ying TANG ; Xiangjun ZHANG ; Chenyi TAO ; Yong NING ; Yi XU ; Xiaodong JIA ; Xia ZHANG
China Occupational Medicine 2026;53(1):50-57
Objective To analyze the genomic characteristics of Legionella pneumophila (L. pneumophila) isolated from industrial circulating cooling water in workplace. Methods A total of 20 L. pneumophila strains isolated from industrial circulating cooling water collected from eight chemical enterprises were selected as the research subjects. Whole-genome sequencing was performed on the strains, followed by multilocus sequence typing (MLST), whole-genome single nucleotide polymorphism analysis, virulence factor profiling, and antibiotic resistance gene detection. Results The dominant MLST typing among the 20 L. pneumophila strains was ST2. Serogroup 1 (Lp1) strains exhibited high genetic diversity. Strains from different enterprises showed substantial genomic diversity, suggesting possible inter-enterprise dissemination. Each isolate harbored 175-295 virulence genes; among them, virulence genes were identified, and 139 genes were detected in all the 20 strains. These genes primarily included those related to the Dot/Icm type Ⅳ bacterial secretion system, flagellar synthesis and motility, and type Ⅳ pili. The number of virulence genes carried by L. pneumophila strains of different ST types differed (P<0.01), with unidentified sequence types harboring more virulence genes than other STs (P<0.01). A total of four resistance genes were predicted, including aminoglycoside phosphotransferase-encoding gene APH(9)-Ia, carbapenemase-encoding gene OXA-29, and efflux pump genes-encoding genes LpeA and LpeB, with detection rates of 100.00%, 100.00%, 10.00%, and 10.00%, respectively. These genes may confer resistance to cephalosporins, penicillins, and aminoglycosides, and all strains were multidrug resistance. Conclusion L. pneumophila isolated from industrial recirculating cooling water exhibits high genetic diversity, strong pathogenicity, and significant multidrug resistance potential.
3.Role of cancer-associated fibroblasts autophagy in papillary thyroid cancer
Xuemei ZHANG ; Danyang SUN ; Ning LI ; Qicheng ZHANG ; Ke XU ; Wei ZHENG ; Qiang JIA ; Jian TAN ; Zhaowei MENG
Chinese Journal of Endocrinology and Metabolism 2025;41(2):135-144
Objective:To investigate the inpact of thyroid cancer-derived cancer-associated fibroblasts(CAF) autophagy on papillary thyroid cancer(PTC).Methods:CAF and normal fibroblasts were isolated from cancerous and adjacent normal thyroid tissues from four PTC patients. Expressions of fibroblast activation protein(FAP) and α-smooth muscle actin in cells were assessed. Conditioned medium of CAF and normal fibroblasts were prepared and used to culture PTC cells. The effects of CAF and normal fibroblasts on survival, proliferation, migration, invasion and iodine uptake of PTC cells were evaluated through cell proliferation assay, cell scratch assay, cell invasion assay, and cell iodine uptake assay. The autophagy level of CAF was also evaluated. Autophagy inhibition and activation were used to regulate the autophagy of CAF, and then their effects on PTC cell proliferation, migration and invasion were further evaluated. The in vivo effect of CAF autophagy on PTC xenograft tumor growth was evaluated.Results:CAF exhibited higher FAP expression and basal autophagy levels. PTC cells co-cultured with CAF-conditioned media showed enhanced proliferation, migration, invasion, and reduced iodine uptake. Autophagy inhibition reduced these effects, while autophagy activation further promoted them. In vivo, inhibiting CAF autophagy suppressed tumor growth.Conclusions:CAF promotes PTC cell malignancy through autophagy activation, enhancing proliferation, migration, and invasion while reducing iodine uptake.
4.Wendantang Regulates Energy Metabolism in Treatment of Myocardial Ischemia via SIRT3/PGC-1α Pathway
Xinjun ZHANG ; Zhiqiang XIAO ; Jia LU ; Wenliang DUN ; Ning GU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):1-8
ObjectiveTo investigate the mechanism by which Wendantang regulates the silent information regulator 3 (SIRT3)/peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) pathway to influence energy metabolism and thereby prevent and treat myocardial ischemia (MI) in a rat model of hyperlipidemia (HL). MethodsThirty SD rats were randomly assigned into five groups: control, model, low-dose (3.702 g·kg-1·d-1) Wendantang, high-dose (7.404 g·kg-1·d-1) Wendantang, and positive control (trimetazidine, 0.006 g·kg-1·d-1), with six rats in each group. The control group was fed normally, while the other groups were fed with a high-fat diet for six weeks for the modeling of HL. Subsequently, the drug intervention groups were administrated with corresponding drugs by gavage, and the control and model groups received an equivalent volume of normal saline for 14 days. One hour after the last gavage, the other groups except the control group were injected intraperitoneally with posterior pituitary hormone (30 U·kg-1) to induce MI. Electrocardiography (ECG) was employed to detect changes in the electrocardiogram. Hematoxylin-eosin staining was performed to observe cardiac pathological changes. Enzyme-linked immunosorbent assay was employed to measure the serum levels of cardiac troponin I(cTnI), myoglobin (MYO), and creatine kinase-MB (CK-MB). Colorimetry was used to determine the levels of total cholesterol (TC) and triglycerides (TG) in the serum and ATP, malondialdehyde (MDA), and superoxide dismutase (SOD) in the myocardial tissue. Western blot was employed to determine the protein levels of SIRT3, PGC-1α, adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated AMPK (p-AMPK) in the myocardial tissue. Real-time PCR was employed to measure the mRNA levels of SIRT3, PGC-1α, and AMPKα in the myocardial tissue. ResultsCompared with the control group, the model group showed significant J-point deviation and elevation in the ECG image, increased heart rate, disarrangement of myocardial fibers with unclear boundaries, elevated levels of CK-MB, cTnI, MYO, TC, and TG (P<0.05, P<0.01), declined levels of SOD and ATP (P<0.01), down-regulated mRNA levels of SIRT3, PGC-1α, and AMPK (P<0.05), and down-regulated protein levels of SIRT3, PGC-1α, and p-AMPK (P<0.05). Compared with the model group, the low-dose and high-dose Wendantang groups and the trimetazidine group showed inhibited J-point deviation and elevation in the ECG image, slowed heart rate, reduced inflammatory cell infiltration, alleviated disarrangement of myocardial fibers, declined levels of CK-MB, cTnI, MYO, TC, and TG (P<0.05, P<0.01), elevated level of SOD (P<0.01), up-regulated mRNA levels of SIRT3, PGC-1α, and AMPK (P<0.05, P<0.01) and up-regulated protein levels of SIRT3, PGC-1α, and p-AMPK (P<0.05, P<0.01). ConclusionWendantang can effectively intervene in HL-associated MI in rats by reducing oxidative stress in myocardial cells, alleviating lipid metabolism disorders, and improving myocardial energy metabolism via the SIRT3/PGC-1α signaling pathway.
5.Comparison of chemical constituents in traditional decoction and formula granule decoction of Wendan Decoction
Tan XUE ; Man-wen XU ; Xue-hua FAN ; Feng-yu DONG ; Yan MIAO ; Jia-ning SUN ; Jun-han SHI ; Lu ZHANG ; Jing YAO ; Rui-xin LIU
Chinese Traditional Patent Medicine 2025;47(2):384-394
AIM To compare the chemical constituents in traditional decoction and formula granule decoction of classical famous prescription Wendan Decoction.METHODS The HPLC fingerprints were established,after which the contents of adenosine,synephrine,liquiritin,naringin,hesperidin,6-gingerol and adenosine cyclophosphate were determined,cluster analysis,principal component analysis and multidimensional scaling analysis were adopted in the investigation of component differences,and the equivalent of formula granules was adjusted.RESULTS The similarities of HPLC fingerprints for 10 batches of traditional decoctions were higher than those of HPLC fingerprints for 9 batches of formula granule decoctions(P<0.01).Adenosine,synephrine,liquiritin,hesperidin and cyclic adenosine monophosphate demonstrated higher contents in traditional decoctions than those in formula granule decoctions(P<0.05),6-gingerol displayed lower content than that in the latter produced by manufacturers A,C(P<0.05),which was higher than that in the latter produced by manufacturer B(P<0.01).Various batches of traditional decoctions and formula granule decoctions could be obviously distinguished,adenosine,synephrine and hesperidin exhibited great influences on the classification of principal component analysis,and the quality of formula granule decoctions produced by manufacturer C was closer to that of traditional decoctions.After equivalent correction,the contents of various constituents in formula granule decoctions produced by manufacturers A,C showed no significant differences as compared with those in traditional decoction(P>0.05).CONCLUSION The formula granules of Wendan Decoction from different manufacturers exist quality differences,so the preparation process and extraction process of this preparation should be optimized to improve quality,and equivalent ratio should be adjusted according to actual requirements to ensure its scientific and rational clinical application.
6.Analysis and prevention of influencing factors for work-related musculoskeletal disorders among bus drivers
Yaling ZOU ; Jie ZHANG ; Wenyan HUANG ; Shiqi QIU ; Jintong HE ; Ning JIA ; Zhongxu WANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(4):269-274
Objective:To investigate the occurrence of work-related musculoskeletal disorders (WMSDs) in bus drivers in Zhuhai City, analyze the ergonomic factors, and explore the prevention and control measures of WMSDs.Methods:From March to May 2023, 1675 active bus drivers from 5 branches of a bus group in Zhuhai were selected by stratified sampling method. The incidence of WMSDs among bus drivers in the past 12 months was investigated by using the modified Chinese Version of Musculoskeletal Disorders Questionnaire. The influencing factors of WMSDs were analyzed by χ2 test and generalized linear model. Results:The total incidence of WMSDs in bus drivers in the past 12 months was 47.2% (790/1675) , and the incidence of WMSDs in neck and shoulder and lower back was 36.9% (618/1675) and 31.7% (531/1675) , respectively. The χ2 test showed that there were statistically significant differences in the incidence of WMSDs among bus drivers with different individual factors such as body mass index (BMI) , physical exercise and looking down at mobile phones ( P<0.05) . There were significant differences in the incidence of WMSDs in the neck and shoulder of bus drivers with different years of service and number of stops on their routes ( P<0.05) . There were statistically significant differences in the incidence of WMSDs in the lower back of bus drivers with different one-way driving time, shift patterns, and rest breaks during work ( P<0.05) . Abnormal BMI, professional working years >12 years, uncomfortable working posture, frequent turning, slightly forward neck posture, large forward neck posture and long shoulder posture were the risk factors for WMSDs of bus drivers ( P<0.05) , and comfortable seat was the protective factor ( P<0.05) . One-way driving time >70 min, shift work schedules, uncomfortable working posture, slightly forward back posture, and frequent turning were the risk factors leading to lower back WMSDs ( P<0.05) , and physical exercise, comfortable driving cabin space, and seat comfort were the protective factors ( P<0.05) . Conclusion:The total incidence of WMSDs in bus drivers is higher, and ergonomic factors are related to the occurrence of WMSDs. In the implementation of bus driving space comfort, human-computer interaction interface friendliness and seat comfort, employers should be reasonable allocation of fitness facilities, regular training, reasonable shift organization and other measures to prevent and control the occurrence of bus drivers WMSDs.
7.Work Memory Impairment in Patients with Chronic Fatigue Syndrome and Spleen Deficiency
Tian ZHOU ; Yunhe ZHANG ; Ziyao WU ; Sitong FENG ; Yanzhe NING ; Hongxiao JIA
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(11):3148-3156
Objective To characterize working memory performance in patients with chronic fatigue syndrome(CFS)and spleen-deficiency syndrome and to examine its associations with clinical symptoms by Sternberg working memory task(SWMT).Methods 31 CFS patients meeting both CDC-1994 criteria and consensus criteria for spleen-deficiency pattern were recruited from outpatient clinics and universities from September 2022 and June 2025.31 healthy controls were also recruited based on age,sex,and education.All subjects completed the SWMT.Group differences were analyzed.Within the CFS cohort,reaction time(RT)was correlated with scores on the checklist individual strength(CIS),36-item short-form health survey(sf-36),and fatigue scale-14(FS-14).Mediation was examined.Results RT lengthened with increasing memory load in both groups.CFS patients displayed slower RTs than controls in the baseline and 6-digit set(P<0.05).The 3-digit RT difference,though not significant(P>0.05),yielded a medium effect size(r=0.36).Accuracy did not differ between two groups.Among CFS patients,3-digit RT correlated positively with CIS total and the 4 sub-scale scores.6-digit RT correlated with the SF-36 health-transition dimension(r=0.396,P=0.027).CIS and FS-14 scores directly impaired SF-36 social functioning without working-memory mediating.Conclusion CFS patients with spleen-deficiency exhibit slowed processing speed rather than capacity loss.The close link between working-memory slowing and fatigue suggests a distinct neural basis.These results support the traditional concept"the spleen stores Yi"and integrate TCM pattern differentiation with modern cognitive neuroscience in CFS.
8.Relationship Between Cognitive Function and Cardio-Electroencephalographic Coupling in Coronary Heart Disease Patients with Heart-Qi Deficiency Pattern
Bixiu HUO ; Bin WANG ; Yunhe ZHANG ; Sitong FENG ; Yanzhe NING ; Hongxiao JIA
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(11):3108-3118
Objective To explore their inter-relationship,cognitive performance and cardio-electroencephalographic coupling in coronary heart disease(CHD)patients with heart-qi deficiency pattern were characterized.Methods Thirty CHD patients who met the diagnostic criteria for heart-qi deficiency were enrolled.Thirty healthy volunteers without heart-qi deficiency or CHD served as controls.Cognitive function was assessed with the repeatable battery for the assessment of neuropsychological status(RBANS).Simultaneous resting-state electrocardiogram and electroencephalogram were recorded,and the strength of heart-brain coupling was quantified by calculating the maximal information coefficient(MIC)between heart-rate variability(HRV)and EEG signals.Results Compared with controls,heart-qi deficiency CHD patients showed lower RBANS total scores and reduced performance in immediate memory,visuospatial/constructional ability,and attention.Significant between-group differences in HRV-EEG MIC values were observed at several channels(P<0.05).In patients,the MIC values for HRV-Beta(channel FC1)and HRV-Delta(channel F2)were positively correlated with RBANS total score(P<0.05).Conclusion CHD patients with heart-qi deficiency exhibit impaired cognition and altered cardio-electroencephalographic coupling.These findings suggest that heart-brain interactions may contribute to the pathophysiological mechanisms underlying cognitive decline in this population.
9.Effect of PSMA gene expression on the biological behavior of prostate cancer cells and its mechanism
Ru-meng WANG ; Ning ZHANG ; Yang LIU ; Chao WANG ; Jia-qi JIA ; Wen-hao QU ; Li-zhou JIA
Journal of Regional Anatomy and Operative Surgery 2025;34(11):943-949
Objective To explore the effect of PSMA gene on the biological behavior of prostate cancer cells and its molecular mechanism.Methods The expression of PSMA in prostate cancer and its relationship with prognosis were analyzed based on the GEPIA database.The mRNA and protein expression levels of PSMA in normal prostate epithelial cell RWPE-2 and prostate cancer cells DU145 and PC-3 were detected by RT-qPCR and Western blot,respectively.DU145 cells were used to construct knockdown cell lines,which were transfected with PSMA lentiviral knockdown plasmid and its negative control,serving as the sh PSMA group and the sh NC group,respectively;PC-3 cells were used to construct overexpression cell lines,which were transfected with PSMA lentiviral overexpression plasmid and its negative control,serving as the OE PSMA group and the OE NC group.CCK-8 assay and clone formation assay were used to detect the cell proliferation ability,wound healing assay and Transwell assay were used to detect the cell migration and invasion abilities,flow cytometry was used to detect the cell apoptosis,and Western blot was used to detect the expression of PI3K,Akt,BAX and Bcl-2 proteins.Prostate cancer cells of DU145 cell line were inoculated into the left armpit of BALB/c nude mice to form tumors,the tumor size was observed,and the tumor weight was measured;HE staining was used to evaluate the degree of damage;and the expression of PSMA was detected by immunohistochemistry.Results GEPIA database analysis showed that PSMA gene was highly expressed in prostate cancer and was related to the prognosis of prostate cancer.The results of RT-qPCR and Western blot showed that the mRNA and protein expression levels of PSMA in PC-3 and DU145 cells were higher than those in RWPE-2 cell(P<0.01).Compared with the sh NC group,the sh PSMA group showed decreased cell proliferation,migration and invasion abilities(P<0.05),and increased cell apoptosis rate(P<0.05).Compared with the OE NC group,the OE PSMA group demonstrated increased cell proliferation,migration and invasion abilities(P<0.05),and decreased apoptosis rate(P<0.05).Compared with the sh NC group,the protein expression of PI3K,Akt and Bcl-2 in the sh PSMA group decreased(P<0.05),and the protein expression of BAX increased(P<0.05).Compared with the OE NC group,the protein expression of PI3K,Akt and Bcl-2 in the OE PSMA group increased(P<0.05),and the protein expression of BAX decreased(P<0.05).Results of subcutaneous transplantation of prostate cancer in nude mice showed that the tumor weight of nude mice decreased(P<0.05),tumor cells exhibited irregular shapes,nuclei were deeply stained,and PSMA expression was weakly positive,after knocking down the PSMA.Conclusion PSMA gene may participate in regulating the proliferation,invasion,migration,and apoptosis of prostate cancer cells through the PI3K/Akt signaling pathway.
10.Comparison of chemical constituents in traditional decoction and formula granule decoction of Wendan Decoction
Tan XUE ; Man-wen XU ; Xue-hua FAN ; Feng-yu DONG ; Yan MIAO ; Jia-ning SUN ; Jun-han SHI ; Lu ZHANG ; Jing YAO ; Rui-xin LIU
Chinese Traditional Patent Medicine 2025;47(2):384-394
AIM To compare the chemical constituents in traditional decoction and formula granule decoction of classical famous prescription Wendan Decoction.METHODS The HPLC fingerprints were established,after which the contents of adenosine,synephrine,liquiritin,naringin,hesperidin,6-gingerol and adenosine cyclophosphate were determined,cluster analysis,principal component analysis and multidimensional scaling analysis were adopted in the investigation of component differences,and the equivalent of formula granules was adjusted.RESULTS The similarities of HPLC fingerprints for 10 batches of traditional decoctions were higher than those of HPLC fingerprints for 9 batches of formula granule decoctions(P<0.01).Adenosine,synephrine,liquiritin,hesperidin and cyclic adenosine monophosphate demonstrated higher contents in traditional decoctions than those in formula granule decoctions(P<0.05),6-gingerol displayed lower content than that in the latter produced by manufacturers A,C(P<0.05),which was higher than that in the latter produced by manufacturer B(P<0.01).Various batches of traditional decoctions and formula granule decoctions could be obviously distinguished,adenosine,synephrine and hesperidin exhibited great influences on the classification of principal component analysis,and the quality of formula granule decoctions produced by manufacturer C was closer to that of traditional decoctions.After equivalent correction,the contents of various constituents in formula granule decoctions produced by manufacturers A,C showed no significant differences as compared with those in traditional decoction(P>0.05).CONCLUSION The formula granules of Wendan Decoction from different manufacturers exist quality differences,so the preparation process and extraction process of this preparation should be optimized to improve quality,and equivalent ratio should be adjusted according to actual requirements to ensure its scientific and rational clinical application.

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