1.Clinical features and multimodal quantitative radiological features of primary liver cancer patients with different traditional Chinese medicine syndrome types
Feng WU ; Muqing LUO ; Wantingting WEN ; Ziwei CAI ; Yinqi LIU ; Jian XIANG ; Xiaona ZHOU ; Qian GUO ; Kun ZHANG
Journal of Clinical Hepatology 2026;42(5):1093-1100
ObjectiveTo investigate the association of the traditional Chinese medicine (TCM) syndrome types of primary liver cancer (PLC) with clinical features and multimodal quantitative radiological features on computed tomography (CT) and magnetic resonance imaging (MRI), and to provide a reference for the objectification of TCM syndrome differentiation and precise diagnosis and treatment. MethodsA retrospective analysis was performed for the clinical data of 312 patients who were diagnosed with PLC in The First Affiliated Hospital of Hunan University of Chinese Medicine from March 2020 to June 2025, and according to the TCM syndrome type, they were divided into stagnation of liver Qi group with 40 patients, stagnation of liver Qi and spleen deficiency group with 109 patients, Qi stagnation and blood stasis group with 62 patients, dampness-heat toxin amassment group with 81 patients, and liver-kidney Yin deficiency group with 20 patients. Clinical features and multimodal quantitative radiological features were compared between the patients with different TCM syndrome types. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Dunn’s multiple test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups, and the Bonferroni method was used for further comparison between two groups. ResultsThere were significant differences between the patients with different TCM syndrome types in China liver cancer staging (CNLC), Child-Pugh class, alanine aminotransferase, aspartate aminotransferase, albumin, direct bilirubin, total bilirubin, prothrombin time, neutrophil, and albumin-bilirubin score (all P<0.05). In the stagnation of liver Qi group, the patients with Child-Pugh class A accounted for 75.00%; among the patients with CNLC stage I PLC, the patients with stagnation of liver Qi accounted for 60.00%, and those with Qi stagnation and blood stasis syndrome accounted for 59.68%, while among the patients with CNLC stage IV PLC, the distribution proportion of dampness-heat toxin amassment (27.16%) and liver-kidney Yin deficiency (30.00%) was significantly higher than that of stagnation of liver Qi (2.50%) (all P<0.05). Radiological examination showed that there were significant differences between the patients with different TCM syndrome types in the number of tumors, ascites, venous tumor thrombus, maximum tumor diameter, intrahepatic metastasis, and lymph node metastasis in the hepatic hilar and retroperitoneal regions (all P<0.05). Compared with the patients with stagnation of liver Qi, the patients with liver depression and spleen deficiency or liver-kidney Yin deficiency were more likely to develop intrahepatic metastasis; the patients with liver depression and spleen deficiency, dampness-heat toxin amassment, or liver-kidney Yin deficiency were more likely to develop lymph node metastasis in the hepatic hilar and retroperitoneal regions; the patients with liver-kidney Yin deficiency were more likely to experience multiple tumors; the patients with liver depression and spleen deficiency or dampness-heat toxin amassment were more likely to develop ascites (all P<0.05). Compared with the patients with Qi stagnation and blood stasis syndrome, the patients with liver depression and spleen deficiency had a significantly longer maximum tumor diameter and a significantly higher proportion of patients with venous tumor thrombus (both P<0.05). Furthermore, among the 184 patients with MRI diffusion-weighted imaging sequences, the patients with dampness-heat toxin amassment or Qi stagnation and blood stasis syndrome had significantly higher ADC values and relative ADC values than those with stagnation of liver Qi (all P<0.05). ConclusionThere are significant differences in CT/MRI radiological features and clinical features between PLC patients with different TCM syndrome types, among whom the patients with liver depression and spleen deficiency, dampness-heat toxin amassment, and liver-kidney Yin deficiency tend to exhibit progressive radiological features, and those with dampness-heat toxin amassment or Qi stagnation and blood stasis syndrome tend to have higher ADC values. These findings provide an objective basis for TCM syndrome differentiation in PLC.
2.Bioinformatic and Mendelian Randomization Analyses of Correlation Between Differentially Expressed Genes and Prognosis of Oral Squamous Cell Carcinoma Patients
Maolin LIU ; Xiaona SONG ; Yaqi LIU ; Shuxuan SHI ; Guohua SONG
Cancer Research on Prevention and Treatment 2025;52(2):133-141
Objective Differentially expressed genes in oral squamous cell carcinoma (OSCC) were subjected to bioinformatic and Mendelian randomization analyses to elucidate their prognostic significance in OSCC. Methods The TCGA database and dataset GSE138206 were used to screen the common differential genes of OSCC, and their relationship was analyzed by using Mendelian randomization. The prognostic value of differential genes was further analyzed by Cox risk regression. The biological function of genes with high prognostic value was further evaluated by single gene differential analysis. Results A total of 147 common differential genes were screened from the two databases. Results of two-sample Mendelian randomization showed that GREM2 was associated with the increased risk of OSCC. In addition, SH3BGRL2 was associated with a decreased risk of OSCC, and DKK1, CCL11, and HOXC6 were considered as independent prognostic markers of OSCC. The predicted results of DKK1 were consistent with the actual results. KEGG enrichment analysis indicated the potential involvement of DKK1 in arachidonic acid and linoleic acid metabolism. Furthermore, DKK1 showed positive correlations with Tgd and Th2 cells, while displaying negative associations with PDC, Cytotoxic cells, Mast cells, CD8 T cells, TFH cells, B cells, T cells, and Th17 cells. Conclusion GREM2 is associated with an increased risk of OSCC. DKK1 is highly expressed in OSCC and associated with poor prognosis, which may be involved in regulating the metabolism of arachidonic acid and linoleic acid and immune cell invasion in OSCC.
3.Oral Herombopag Olamine and subcutaneous recombinant human thrombopoietin after haploidentical hematopoietic stem cell transplantation
Dai KONG ; Xinkai WANG ; Wenhui ZHANG ; Xiaohang PEI ; Cheng LIAN ; Xiaona NIU ; Honggang GUO ; Junwei NIU ; Zunmin ZHU ; Zhongwen LIU
Chinese Journal of Tissue Engineering Research 2025;29(1):1-7
BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.
4.Effect of short-chain fatty acid on perioperative cognitive dysfunction in aged rats through p38 MAPK/NF-κB p65 pathway
Xiang LIU ; Xiaona TAN ; Yaozong YU ; Junfang NIU ; Qiujun WANG ; Lei SHI
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(1):9-15
Objective:To evaluate the effect of short-chain fatty acid(SCFA) on perioperative cognitive dysfunction in aged rats through mitogen-activated protein kinase p38(p38 MAPK)/nuclear factor-κB p65(NF-κB p65) pathway.Methods:According to random number table method, 32 healthy SPF-grade male SD rats, aged 16 months and weighing 520~620 g, were divided into control group, short-chain fatty acid group (SCFA group), perioperative cognitive dysfunction group (PCD group) and perioperative cognitive dysfunction+ short-chain fatty acid group (SCFA+ PCD group), with 8 rats in each group. The perioperative cognitive dysfunction model was established by sevoflurane anesthesia plus internal fixation of tibial fractures. Rats in SCFA group and SCFA+ PCD group freely drank water added with SCFA for 28 days. On the 29th day, rats in SCFA+ FCD group underwent tibial fracture internal fixation surgery. Morris water maze test was performed on the 7th day after surgery to evaluate the cognitive function of rats. The Nissl bodies of hippocampus were observed by Nissl's staining. The hippocampus tissue was collected to analyze the expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), p38 MAPK, phosphorylated p38 MAPK, NF-κB p65 and phosphorylated NF-κB p65 by Western blot.The SPSS 27.0 software was used for statistical analysis. One-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for further pairwise comparison. Results:(1) The results of Morris water maze test showed that the times of crossing the original platform, the escape latency and the residence time in the original platform quadrant were statistically significant among the four groups on the 7th day after surgery ( F=13.80, 47.80, 6.46, all P<0.05). The escape latencies of the SCFA+ PCD group and PCD group were both longer than that in the control group (both P<0.05). The times of crossing the original platform in SCFA+ PCD group and PCD group were less than that of control group (both P<0.05). The residence time in the original platform quadrant in SCFA+ PCD group and PCD group was shorter than that of control group (both P<0.05).Compared with PCD group, the escape latency was shorter, the times of crossing the original platform were more and the residence time in the original platform quadrant was longer in SCFA+ PCD group (all P<0.05). (2) The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were statistically significant among the four groups ( F=184.28, 139.27, 19.40, 58.47, all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were higher in SCFA+ PCD group (0.49±0.10, 0.60±0.05, 0.489±0.012, 0.435±0.005) and PCD group (0.85±0.05, 1.12±0.08, 0.519±0.028, 0.473±0.008) than those in control group (0.13±0.02, 0.42±0.10, 0.437±0.010, 0.362±0.013)(all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were lower in SCFA+ PCD group than PCD group (all P<0.05). (3) The average gray value of Nissl bodies was statistically significant different among the four groups ( F=14.65, P<0.05). The average gray value of Nissl bodies was lower in SCFA+ PCD group (193.2±8.1) and PCD group (160.5±14.1) than that of control group (221.2±14.8) (both P<0.05). The average gray value of Nissl bodies was higher in SCFA+ PCD group than that in PCD group( P<0.05). Conclusion:Short-chain fatty acid attenuates cognitive dysfunction, which may be related with inhibiting p38 MAPK/NF-κB p65 pathway and reducing the neuroinflammation.
5.Linc00426 competitively binds to USP3 with miR-455-5p to promote invasion and metastasis of oral squa-mous cell carcinoma cells
Yanqiao ZHAO ; Lu LIU ; Xiaona WANG ; Chonggao YIN ; Hongli LI
Journal of Practical Stomatology 2025;41(6):774-780
Objective:To study the effects of Linc00426 on the migration,invasion and proliferation of oral squamous carcinoma cells(OSCC).Methods:TCGA database was used to query the differential expression of Linc00426.RT-qPCR was used to detect the expression level of Linc00426 in normal human oral keratinocytes(NHOK)cells and various OSCC cells lines,the knockout effi-ciency of Linc00426 at 3 sites and the expression level of miR-455-5p.Transwell test and EdU test were used to detect the changes of the migration,invasion and proliferation of CAL27 cells.Bioinformatics databases was used to predict subcellular localization and downstream miRNAs and target proteins of Linc00426.Western blot assay was used to detect the changes of USP3 expression levels in CAL27 cells.Results:The expression level of Linc00426 was increased in OSCC tissue(P<0.05),and its expression in CAL27,HN4 and HN30 cells was higher than that in NHOK cells(P<0.05).Knocking out Linc00426 inhibited the migration,invasion,and proliferation ability of CAL27 cells(P<0.05).The bioinformatics database indicates that the subcellular localization of Linc00426 is in the cytoplasm;Linc00426 is negatively correlated with miR-455-5p,and miR-455-5p is negatively correlated with USP3,in which there are targeted binding sites.Knocking out miR-455-5p promoted the migration,invasion and proliferation of CAL27 cells(P<0.05).Knocking out USP3 inhibited the migration,invasion and proliferation of CAL27 cells(P<0.05).Knock out Linc00426 reduced the expression level of USP3,while knocking out miR-455-5p increased the expression level of USP3(P<0.05).Conclusion:Linc00426 plays a role as an oncogene in OSCC cells and could inhibit the migration,invasion and proliferation of the cells by targeting USP3 to regulate miR-455-5p.
6.Effects of fluorine exposure on calcium ion metabolism and the expression of related calcium-regulating proteins in the kidneys of rats
Yuchen ZHANG ; Yanan LIU ; Yuting CHEN ; Yuxi WANG ; Meichen ZHANG ; Yanmei YANG ; Yanhui GAO ; Xiaona LIU ; Yang LIU
Chinese Journal of Endemiology 2025;44(4):279-285
Objective:To analyze the effects of fluorine exposure on calcium ion metabolism and the expression of related calcium-regulating proteins in the kidneys of rats.Methods:Forty-five 5-week-old specific pathogen-free male Wistar rats (weighed 90 - 120 g) were selected and divided into three groups according to the randomized numeric table: 0 (control), 50, and 100 mg/L fluorine exposure groups, with 15 rats in each group. The control group was given deionized water, while the 50 and 100 mg/L fluorine exposure groups were given sodium fluoride solutions containing 50 and 100 mg/L fluorine ions, respectively. After 12 weeks, urine samples were collected, and kidneys and blood were harvested. Urinary fluorine levels were measured using a fluoride ion-selective electrode method. Calcium ion levels in the urine, kidneys, and serum were determinated using the methylthymol blue microplate method. The protein expression levels of transient receptor potential vanilloid receptor 5 (TRPV5), calbindin-D28K (CB-D28K), sodium-calcium exchanger-1 (NCX1), Klotho and plasma membrane calcium ATPase 1b (PMCA1b) in the kidneys were detected by Western blotting and immunohistochemistry.Results:The urinary fluorine levels in the control group and the 50 and 100 mg/L fluorine exposure groups were (0.48 ± 0.09), (20.01 ± 1.68), (37.45 ± 2.45) mg/L, respectively, with statistically significant differences between the groups ( F = 929.58, P < 0.001). Significant differences in calcium ion levels in urine, kidneys, and serum were observed among the three groups ( F = 14.66, 11.09, 10.31, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group exhibited higher levels of calcium ion in the urine and kidneys, and lower serum calcium ion levels ( P < 0.05). The results of Western blotting analysis revealed that the protein expression levels of TRPV5 and CB-D28K in the kidneys increased with the increase of fluorine exposure level ( Z = 2.11, 2.11, P = 0.035). The protein expression level of NCX1 in the kidneys showed a decreasing trend with increasing fluorine exposure level ( Z = - 2.11, P = 0.035). Significant differences were also observed in the protein expression levels of Klotho and PMCA1b among the three groups ( F = 8.93, 7.08, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group showed higher level of Klotho protein expression and lower level of PMCA1b protein expression in the kidneys ( P < 0.05). Immunohistochemical results indicated significant differences in the protein expression levels of TRPV5, CB-D28K, NCX1, and Klotho in the kidneys of the three groups ( F = 27.56, 24.94, 16.05, 32.72, P < 0.05). Compared with the control group, the protein expression levels of TRPV5, CB-D28K, and Klotho in kidneys of 50 and 100 mg/L fluorine exposure groups were higher, while the protein expression levels of NCX1 were lower ( P < 0.05). Conclusion:Fluorine exposure may cause calcium ion metabolism disorders by regulating the expression levels of Klotho and other calcium-regulating proteins in the kidneys.
7.Placenta derived mesenchymal stem cells inhibit the activation of rat astrocytes via TGF-β/Smad pathway
Ningmei LIU ; Taojuan WU ; Dongmei CHEN ; Ting LIU ; Xiaona MA ; Haibin MA ; Xueyun LIANG
Chinese Journal of Neuroanatomy 2025;41(2):187-193
Objective:To investigate the effects and its related mechanism of placenta-derived mesenchymal stem cells(PMSCs)on the lipopolysaccharides(LPS)damaged astrocytes.Methods:Primary astrocytes were isolated from the cerebral cortex of neonatal rats.The expression of glial fibrillary acidic protein(GFAP)was identified using immu-nofluorescence staining to evaluate the purity of the primary astrocytes.PMSCs were cocultured with LPS-treated astro-cytes.The expression levels of factors related to inflammation including interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),arginase-1(Arg-1),S100 calcium-bind-ing protein A10(S100A10),and TGF-β/Smad signaling pathway-related proteins such as transforming growth factor beta 1(TGF-β1),transforming growth factor beta type I receptor(TβRⅠ),transforming growth factor beta type II re-ceptor(TβRⅡ),phospho-Smad2 and phospho-Smad3(p-Smad2,p-Smad3)in astrocytes from each group were detec-ted using real time RT-PCR or Western blot techniques.Results:Astrocytes at the third passage exhibited an 80%pos-itivity rate for GFAP.After treated with 10 μg/ml LPS,the astrocytes expression levels of pro-inflammatory factors IL-1β,iNOS,IL-6,and TNF-α were significantly increased(P<0.05),while their expression levels of the anti-inflam-matory factors of Arg-1 and S100A10 were significantly decreased(P<0.05).Meanwhile,their expression levels of TGF-β/Smad signaling pathway related proteins of TGF-β1,TβRⅠ,TβRⅡ,p-Smad2 and Smad3 were increased(P<0.05).After the LPS damaged astrocytes were cocultured with PMSCs,their expression levels of pro-inflammatory factors IL-1β,iNOS,IL-6,and TNF-α were significantly decreased(P<0.05),while their expression levels of the anti-inflammatory factors of Arg-1 and S100A10 were significantly increased(P<0.05).Also,their expression levels of TGF-β/Smad signaling pathway related proteins of TGF-β1,TβRⅠ,TβRⅡ,p-Smad2,and Smad3 were decreased(P<0.05).Conclusion:PMSCs may inhibit the activation of A1 astrocytes through the TGF-β/Smad signaling path-way,by which reducing the astrocytic activation.
8.Effect of short-chain fatty acid on perioperative cognitive dysfunction in aged rats through p38 MAPK/NF-κB p65 pathway
Xiang LIU ; Xiaona TAN ; Yaozong YU ; Junfang NIU ; Qiujun WANG ; Lei SHI
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(1):9-15
Objective:To evaluate the effect of short-chain fatty acid(SCFA) on perioperative cognitive dysfunction in aged rats through mitogen-activated protein kinase p38(p38 MAPK)/nuclear factor-κB p65(NF-κB p65) pathway.Methods:According to random number table method, 32 healthy SPF-grade male SD rats, aged 16 months and weighing 520~620 g, were divided into control group, short-chain fatty acid group (SCFA group), perioperative cognitive dysfunction group (PCD group) and perioperative cognitive dysfunction+ short-chain fatty acid group (SCFA+ PCD group), with 8 rats in each group. The perioperative cognitive dysfunction model was established by sevoflurane anesthesia plus internal fixation of tibial fractures. Rats in SCFA group and SCFA+ PCD group freely drank water added with SCFA for 28 days. On the 29th day, rats in SCFA+ FCD group underwent tibial fracture internal fixation surgery. Morris water maze test was performed on the 7th day after surgery to evaluate the cognitive function of rats. The Nissl bodies of hippocampus were observed by Nissl's staining. The hippocampus tissue was collected to analyze the expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), p38 MAPK, phosphorylated p38 MAPK, NF-κB p65 and phosphorylated NF-κB p65 by Western blot.The SPSS 27.0 software was used for statistical analysis. One-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for further pairwise comparison. Results:(1) The results of Morris water maze test showed that the times of crossing the original platform, the escape latency and the residence time in the original platform quadrant were statistically significant among the four groups on the 7th day after surgery ( F=13.80, 47.80, 6.46, all P<0.05). The escape latencies of the SCFA+ PCD group and PCD group were both longer than that in the control group (both P<0.05). The times of crossing the original platform in SCFA+ PCD group and PCD group were less than that of control group (both P<0.05). The residence time in the original platform quadrant in SCFA+ PCD group and PCD group was shorter than that of control group (both P<0.05).Compared with PCD group, the escape latency was shorter, the times of crossing the original platform were more and the residence time in the original platform quadrant was longer in SCFA+ PCD group (all P<0.05). (2) The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were statistically significant among the four groups ( F=184.28, 139.27, 19.40, 58.47, all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were higher in SCFA+ PCD group (0.49±0.10, 0.60±0.05, 0.489±0.012, 0.435±0.005) and PCD group (0.85±0.05, 1.12±0.08, 0.519±0.028, 0.473±0.008) than those in control group (0.13±0.02, 0.42±0.10, 0.437±0.010, 0.362±0.013)(all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were lower in SCFA+ PCD group than PCD group (all P<0.05). (3) The average gray value of Nissl bodies was statistically significant different among the four groups ( F=14.65, P<0.05). The average gray value of Nissl bodies was lower in SCFA+ PCD group (193.2±8.1) and PCD group (160.5±14.1) than that of control group (221.2±14.8) (both P<0.05). The average gray value of Nissl bodies was higher in SCFA+ PCD group than that in PCD group( P<0.05). Conclusion:Short-chain fatty acid attenuates cognitive dysfunction, which may be related with inhibiting p38 MAPK/NF-κB p65 pathway and reducing the neuroinflammation.
9.Safety analysis of blinatumomab in the treatment of pediatric B-cell acute lymphoblastic leukemia
Danni LI ; Wenwen DING ; Xiaona LIU ; Pingping WEI ; Lei ZHANG ; Hui LIANG
Adverse Drug Reactions Journal 2025;27(9):545-551
Objective:To analyze the safety profile of blinatumomab in children with B-cell acute lymphoblastic leukemia (ALL).Methods:Demographic and clinical data of 33 pediatric B-cell ALL patients treated with blinatumomab in the Women and Children′s Hospital, Qingdao University from January 2022 to November 2024 were retrospectively collected. Demographic data included gender and age, while clinical data comprised leukemia risk stratification, minimal residual disease (MRD) status before blinatumomab use, treatment duration (14-day or 28-day courses), and safety outcomes included drug-related fever, cytokine release syndrome (CRS), tachycardia, blood pressure abnormalities, elevated transaminases, immune effector cell-associated neurotoxicity syndrome (ICANS), oral mucositis, rash, and infections. Patients were stratified by CRS occurrence and transaminase elevation for comparative analysis of demographic/clinical characteristics.Results:A total of 33 children with B-cell type ALL who received blinatumomab treatment were included. Among them, 21 were male and 12 were female; the age was 5.2 (4.7, 7.0) years, ranging from 1.7 to 10.0 years. Risk stratification included low (2 cases), intermediate (23 cases), and high (8 cases) risk. Pre-treatment MRD was negative in 16 and positive in 17 patients. Eight patients received a 14-day blinatumomab course, while 25 cases received a 28-day course. The overall adverse events (AEs) rate was 81.8% (27/33). Among the 27 patients who experienced AEs, there were 5 cases (18.5%) of severe adverse events (all grade 3). The specific adverse events that occurred in the 33 patients included drug-related fever in 21 cases (63.6%) [including 16 cases (48.5%) of CRS], elevated transaminases in 10 cases (30.3%), infectious symptoms in 5 cases (15.2%), rash in 4 cases (12.1%), tachycardia in 3 cases (9.1%), ICANS in 2 cases (6.1%), and oral mucositis in 1 case (3.0%). No statistically significant differences were observed in gender, age, risk stratification, pretreatment MRD status, and treatment duration between the CRS and non-CRS groups, transaminase-elevated and normal groups (all P>0.05). Conclusions:In pediatric B-cell ALL, the most common AEs related to blinatumomab are CRS and elevated transaminases, but most reactions are mild, with rapid recovery and favorable tolerability.
10.Role of meningeal γδ T cell-derived IL-17A in postoperative cognitive dysfunction in aged mice
Xiang LIU ; Xiaona TAN ; Yaozong YU ; Xuechong ZHAO ; Qiujun WANG ; Bo ZHAO
Chinese Journal of Anesthesiology 2025;45(11):1439-1444
Objective:To evaluate the role of meningeal γδ T cell-derived interleukin-17A (IL-17A) in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Forty healthy male C57BL/6N mice, aged 18 months, weighing 30-40 g, were divided into 4 groups ( n=10 each) using a table of random numbers: control group (group C), anti-γδ T cell receptor antibody (Anti-TCR γδ) group, POCD group (group P), and POCD+ Anti-TCR γδ group (group P+ Anti-TCR γδ). Anesthesia was induced with 8% sevoflurane and maintained with 3% sevoflurane, and the internal fixation for tibial fracture was performed to establish the mouse model of POCD in P and P+ Anti-TCR γδ groups. Anti-TCR γδ antibody 2.5 μg was infused into the occipital cistern on postoperative day 4 in P+ Anti-TCR γδ and Anti-TCR γδ groups. The open field test, novel object recognition test and Y-maze test were conducted sequentially at 7th day after surgery. The total distance traveled in the open field and the number of entries into the central area were recorded, and the novel object recognition index and preference index for exploring the novel arm were calculated. The mice were sacrificed at the end of the behavioral testing, the meninges were obtained for detection of the expression of IL-17A in γδ T cells by flow cytometry, and the hippocampal tissues were harvested for determination of the expression of vesicular glutamate transporter1 (VGLUT1), glutamate receptor 1 (GluR1), and IL-17A receptor (IL-17AR) (by Western blot). Results:There was no statistically significant difference in the total distance traveled in the open field test or the number of entries into the central area among the four groups ( P>0.05). Compared with group C, the novel object recognition index and preference index for novel arm exploration were significantly decreased, the expression of meningeal γδ T cells and IL-17AR in hippocampal tissues was up-regulated, and the expression of VGLUT1 and GluR1 was down-regulated in group P and group P+ Anti-TCR γδ ( P<0.05), and no significant change was found in the aforementioned parameters in group Anti-TCR γδ ( P>0.05). Compared with group P, the novel object recognition index and preference index for novel arm exploration were significantly increased, the expression of meningeal γδ T cells and IL-17AR was down-regulated, and the expression of VGLUT1 and GluR1 was up-regulated in group P+ Anti-TCR γδ ( P<0.05). Conclusions:Increased meningeal γδ T cell-derived IL-17A can up-regulate the expression of IL17AR in the hippocampus and down-regulate the expression of VGLUT1 and GluR1, thus involving in the development of POCD in aged mice.

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