1.Mechanism of Paeoniflorin Regulating TLR4/NF-κB-IRS1 Inflammation-insulin Signaling Axis to Improve Metabolic Dysfunction Associated Fatty Liver Disease Combined with Insulin Resistance
Luyu LI ; Yiming FAN ; Wenlong YU ; Yiteng ZHANG ; Yaorui HU ; Huanxin DING ; Chuxuan LIU ; Xin JIN ; Hongyu ZHANG ; Qian XU ; Guangyong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):146-156
ObjectiveTo investigate the therapeutic effect of paeoniflorin on metabolic dysfunction-associated fatty liver disease (MASLD) combined with insulin resistance (IR), and to elucidate its regulatory mechanisms on the Toll-like receptor 4 (TLR4)/nuclear transcription factor (NF)-κB-insulin receptor substrate 1 (IRS1) inflammation-insulin signaling axis. MethodsMASLD mouse model was established using a 60% high-fat diet. Mice were randomly assigned to a normal control group, a MASLD model group, and paeoniflorin groups (low dose: 25 mg·kg-1·d-1, medium dose: 50 mg·kg-1·d-1, high dose: 100 mg·kg-1·d-1), receiving intragastric administration for consecutive 12 weeks. Concurrently, a palmitic acid/oleic acid (PA/OA)-induced lipid deposition model was established in HepG2 cells. Cell counting kit-8 (CCK-8) assay was performed to determine the optimal concentrations of PA/OA and paeoniflorin for intervention. Mice body weight, liver index, and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), and total cholesterol (TC) were measured. Fasting blood glucose (FBG) and fasting insulin (FINS) levels were measured, and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated, while an oral glucose tolerance test (OGTT) was performed to evaluate glucose metabolism. Hematoxylin and eosin (HE) staining was used to observe pathological changes and inflammatory cell infiltration in liver tissue, and oil red O staining was used to evaluate lipid droplet deposition in liver tissue and HepG2 cells. Potential targets were screened using network pharmacology and molecular docking. Western blot analysis was performed to detect the expression of HSP90AA1, TLR4, p-NF-κB p65, p-IRS1, and p-Akt proteins in liver tissue and HepG2 cells. ResultsCompared with the normal control group, mice in the MASLD model group exhibited significantly increased body weight, liver index, and serum levels of ALT, AST, TG, and TC, as well as markedly elevated FBG, FINS, and HOMA-IR, and impaired glucose tolerance (P<0.01). HE staining revealed marked hepatic steatosis and inflammatory cell infiltration, while oil red O staining showed a significant increase in lipid droplet deposition. Compared with the MASLD model group, after intervention with various doses of paeoniflorin, the increase in body weight and liver index was reduced, serum ALT, AST, TG, and TC levels decreased, and FBG, FINS, and HOMA-IR were significantly lowered, with glucose tolerance markedly improved (P<0.05, P<0.01), showing a certain dose-dependent trend. HE and oil red O staining results showed a marked reduction in hepatic steatosis and lipid deposition. In vitro experiments demonstrated that, compared with the control group, PA/OA treatment significantly induced increased lipid deposition in HepG2 cells. Compared with the model group, paeoniflorin intervention significantly reduced intracellular lipid droplets, and lipid deposition showed a dose-dependent decreasing trend. Mechanism studies indicated that, compared with the normal control group, the MASLD model group exhibited significantly elevated expression of TLR4, HSP90AA1, and p-NF-κB p65, while p-IRS1 (Ser307) expression was elevated and p-Akt (Ser473) expression was reduced (P<0.01). Compared with the model group, the expression of the aforementioned proteins was significantly reversed in all treatment groups following intervention (P<0.05, P<0.01). ConclusionPaeoniflorin significantly alleviates lipid deposition and insulin resistance in MASLD mice. Its mechanism of action may involve targeting HSP90AA1, TLR4, and NF-κB1 to regulate the TLR4/NF-κB-IRS1 inflammation-insulin signaling axis. This regulation suppresses inflammatory responses and restores insulin signaling, thereby ameliorating abnormalities in glucose and lipid metabolism.
2.Mechanism of Paeoniflorin Regulating TLR4/NF-κB-IRS1 Inflammation-insulin Signaling Axis to Improve Metabolic Dysfunction Associated Fatty Liver Disease Combined with Insulin Resistance
Luyu LI ; Yiming FAN ; Wenlong YU ; Yiteng ZHANG ; Yaorui HU ; Huanxin DING ; Chuxuan LIU ; Xin JIN ; Hongyu ZHANG ; Qian XU ; Guangyong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):146-156
ObjectiveTo investigate the therapeutic effect of paeoniflorin on metabolic dysfunction-associated fatty liver disease (MASLD) combined with insulin resistance (IR), and to elucidate its regulatory mechanisms on the Toll-like receptor 4 (TLR4)/nuclear transcription factor (NF)-κB-insulin receptor substrate 1 (IRS1) inflammation-insulin signaling axis. MethodsMASLD mouse model was established using a 60% high-fat diet. Mice were randomly assigned to a normal control group, a MASLD model group, and paeoniflorin groups (low dose: 25 mg·kg-1·d-1, medium dose: 50 mg·kg-1·d-1, high dose: 100 mg·kg-1·d-1), receiving intragastric administration for consecutive 12 weeks. Concurrently, a palmitic acid/oleic acid (PA/OA)-induced lipid deposition model was established in HepG2 cells. Cell counting kit-8 (CCK-8) assay was performed to determine the optimal concentrations of PA/OA and paeoniflorin for intervention. Mice body weight, liver index, and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), and total cholesterol (TC) were measured. Fasting blood glucose (FBG) and fasting insulin (FINS) levels were measured, and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated, while an oral glucose tolerance test (OGTT) was performed to evaluate glucose metabolism. Hematoxylin and eosin (HE) staining was used to observe pathological changes and inflammatory cell infiltration in liver tissue, and oil red O staining was used to evaluate lipid droplet deposition in liver tissue and HepG2 cells. Potential targets were screened using network pharmacology and molecular docking. Western blot analysis was performed to detect the expression of HSP90AA1, TLR4, p-NF-κB p65, p-IRS1, and p-Akt proteins in liver tissue and HepG2 cells. ResultsCompared with the normal control group, mice in the MASLD model group exhibited significantly increased body weight, liver index, and serum levels of ALT, AST, TG, and TC, as well as markedly elevated FBG, FINS, and HOMA-IR, and impaired glucose tolerance (P<0.01). HE staining revealed marked hepatic steatosis and inflammatory cell infiltration, while oil red O staining showed a significant increase in lipid droplet deposition. Compared with the MASLD model group, after intervention with various doses of paeoniflorin, the increase in body weight and liver index was reduced, serum ALT, AST, TG, and TC levels decreased, and FBG, FINS, and HOMA-IR were significantly lowered, with glucose tolerance markedly improved (P<0.05, P<0.01), showing a certain dose-dependent trend. HE and oil red O staining results showed a marked reduction in hepatic steatosis and lipid deposition. In vitro experiments demonstrated that, compared with the control group, PA/OA treatment significantly induced increased lipid deposition in HepG2 cells. Compared with the model group, paeoniflorin intervention significantly reduced intracellular lipid droplets, and lipid deposition showed a dose-dependent decreasing trend. Mechanism studies indicated that, compared with the normal control group, the MASLD model group exhibited significantly elevated expression of TLR4, HSP90AA1, and p-NF-κB p65, while p-IRS1 (Ser307) expression was elevated and p-Akt (Ser473) expression was reduced (P<0.01). Compared with the model group, the expression of the aforementioned proteins was significantly reversed in all treatment groups following intervention (P<0.05, P<0.01). ConclusionPaeoniflorin significantly alleviates lipid deposition and insulin resistance in MASLD mice. Its mechanism of action may involve targeting HSP90AA1, TLR4, and NF-κB1 to regulate the TLR4/NF-κB-IRS1 inflammation-insulin signaling axis. This regulation suppresses inflammatory responses and restores insulin signaling, thereby ameliorating abnormalities in glucose and lipid metabolism.
3.Impact and predictive value of subclinical hypothyroidism on metabolic associated fatty liver disease
Huanxin LIU ; Zhong LI ; Qian NIE ; Cuiqiao MENG
Chinese Journal of Health Management 2025;19(7):500-506
Objective:To explore the impact and predictive value of subclinical hypothyroidism on metabolic associated fatty liver disease (MAFLD).Methods:The study adopted a cross-sectional design. A total of 6 597 adults with subclinical hypothyroidism who received health check-ups in the Health Examination Center of Hebei General Hospital from 2018 to 2022 were selected as subjects. The participants were randomly divided into a modeling group (4 617) and a validation group (1 980) in a 7∶3 ratio. The basic information and serological indicators were collected in those subjects. The general clinical characteristics of the MAFLD and non-MAFLD participants were compared in the modeling group. Multivariate logistic regression analysis was used to explore the impact of thyroid hormone on MAFLD. The R language was applied to construct a nomogram prediction model, and internal validation and external validation of the model were performed to evaluate the prediction performance of the model.Results:Of the 6 597 study subjects, the prevalence of MAFLD was 31.14% (2 054/6 597). After preliminary comparison of baseline data from the modeling group, multivariate analysis showed that free triiodothyronine/free thyroxine (FT3/FT4) ( OR=20.945,95% CI: 5.862-74.838), male ( OR=1.394,95% CI: 1.109-1.752), age ( OR=1.017,95% CI: 1.009-1.025), diastolic blood pressure ( OR=1.017,95% CI: 1.004-1.021), waist circumference ( OR=1.049,95% CI:1.031-1.067), body mass index ( OR=1.236,95% CI:1.175-1.299), triglyceride ( OR=1.525,95% CI: 1.379-1.687), low density lipoprotein cholesterol ( OR=1.493,95% CI: 1.313-1.698), fasting glucose ( OR=1.173,95% CI:1.101-1.249) were risk factors for MAFLD, and high density lipoprotein cholesterol ( OR=0.243,95% CI: 0.163-0.363), aspartate aminotransferase/alanine aminotransferase ( OR=0.242,95% CI: 0.183-0.320) were protective factors for MAFLD (all P<0.05). The results showed that the two groups of calibration curves showed the consistency between MAFLD occurrence risk and actual occurrence risk. The AUCs of internal and external validation was 0.897 and 0.907, respectively. This nomogram model had a high predictive value. Conclusion:FT3/FT4 is an independent risk factor for MAFLD in the population with subclinical hypothyroidism. The prediction model incorporating thyroid function and metabolic parameters may provide clinical value for early identification of MAFLD.
4.Relationship between RB1 gene deletion and prognosis of multiple myeloma and effect of renal insufficiency on it
Xinyue LANG ; Guihua ZHANG ; Huanxin ZHANG ; Kaige LIU ; Zhengxia SONG ; Kailin XU ; Jinge XU ; Qiurong ZHANG
Cancer Research and Clinic 2025;37(2):124-131
Objective:To investigate the relationship between retinoblastoma binding protein 1 (RB1) gene deletion and the prognosis of multiple myeloma (MM) patients, and the possible effect of renal insufficiency on it.Methods:A retrospective cohort study was conducted. The clinical data and follow-up information of MM patients who were treated in the Second Affiliated Hospital of Xuzhou Medical University and the Affiliated Hospital of Xuzhou Medical University from December 2020 to November 2023 were collected. According to the presence of RB1 gene deletion in bone marrow samples detected by fluorescence in situ hybridization (FISH), the patients were divided into the RB1 gene deletion group and the RB1 gene non-deletion group, and the clinicopathological characteristics and hematological index levels were compared between the two groups. Renal insufficiency was determined by renal function assessment indicator serum creatinine (Scr) >177 μmol/L. The Spearman test was used to analyze the relationship between the number of RB1 gene deletion positive cells and levels of Scr, hemoglobin and serum calcium in MM patients. The Kaplan-Meier method was used to analyze progression-free survival (PFS), and the Cox proportional hazards model was used to determine the influencing factors of PFS in all MM patients and RB1 gene deletion and non-deletion MM patients.Results:A total of 75 MM patients were enrolled, of whom 24 (32.0%) had RB1 gene deletion. There were no significant differences in gender, age ≥65 years old, bone destruction and lactate dehydrogenase level between the RB1 gene deletion and non-deletion groups (all P > 0.05). There were significant differences in the distributions of patients in each stage of MM International Staging System (ISS) and revised International Staging System (R-ISS) between the two groups, as well as in hemoglobin, serum calcium, Scr, β 2-microglobulin, serum albumin levels, and the proportion of bone marrow plasma cells (all P < 0.05). The number of RB1 gene deletion positive cells was positively correlated with Scr level ( r = 0.863, P = 0.016), but not with hemoglobin and serum calcium levels (both P > 0.05). The PFS of the RB1 gene non-deletion group was better than that of the RB1 gene deletion group (1-year PFS rate: 83.5% vs. 71.7%, 2-year PFS rate: 56.3% vs. 26.3%), and the difference was statistically significant ( P = 0.012). PFS in the non-renal insufficiency group was better than that in the renal insufficiency group (1-year PFS rate: 85.6% vs. 61.9%, 2-year PFS rate: 58.0% vs. 13.5%), and the difference was statistically significant ( P = 0.001). The PFS of patients without renal insufficiency in both the RB1 gene deletion and non-deletion groups was better than that in patients with renal insufficiency, and the differences were statistically significant (both P < 0.05). Multivariate Cox regression analysis showed that ISS stage Ⅲ was an independent risk factor for poor PFS in MM patients (stage Ⅲ vs. stage Ⅰ, HR = 11.317, 95% CI: 1.220-104.979, P = 0.033). Multivariate Cox regression analysis in RB1 gene deletion and non-deletion groups showed that ISS stage Ⅲ (stage Ⅲ vs. stageⅠ, HR = 4.166, 95% CI: 1.419-12.225, P = 0.009), R-ISS stage Ⅲ (stage Ⅲ vs. stage Ⅰ, HR = 3.800, 95% CI: 1.005-14.367, P = 0.049), serum calcium > 2.52 mmol/L (> 2.52 mmol/L vs. ≤2.52 mmol/L, HR = 2.398, 95% CI: 1.037-5.546, P = 0.041) and renal insufficiency (yes vs. no, HR = 2.363, 95% CI: 1.021-5.472, P = 0.045) were independent risk factors for poor PFS in RB1 gene non-deletion MM patients, and serum calcium >2.52 mmol/L (>2.52 mmol/L vs. ≤ 2.52 mmol/L, HR = 3.673, 95% CI: 1.160-11.627, P = 0.027) and renal insufficiency (yes vs. no, HR = 3.985, 95% CI: 1.220-13.016, P = 0.022) were independent risk factors for poor PFS in RB1 gene deletion MM patients. Conclusions:The PFS of MM patients with RB1 gene deletion is worse than that of patients without RB1 gene deletion, RB1 gene deletion may be related to renal insufficiency in MM patients, and the prognosis of MM patients with RB1 gene deletion and renal insufficiency may be worse.
5.The comparative study of TyG and TyG-BMI index with occurrence of hyperuricemia in physical examina-tion population
Qian NIE ; Xuemei ZHANG ; Zhihua HAO ; Ruolin XIE ; Huanxin LIU ; Xiaoqian WU ; Luping REN
The Journal of Practical Medicine 2025;41(8):1192-1198
Objective To investigate the predictive capacity of the Triglyceride-Glucose(TyG)index and the Triglyceride-Glucose-Body Mass Index(TyG-BMI)for the development of hyperuricemia(HUA)in a health examination population,and to identify suitable indicators as risk assessment tools for HUA.Methods This study ultimately included 12 004 participants from a health examination cohort.According to SUA levels,the partici-pants were categorized into a normal group(n=9 952)and a hyperuricemia(HUA)group(n=2 052).The TyG index and TyG-BMI index were calculated,and participants were further stratified into four groups(Q1—Q4)based on the quartiles of these indices.Binary logistic regression analysis was performed to assess the association between TyG,TyG-BMI,and HUA.The predictive value of TyG,TyG-BMI,and their combination for HUA was evaluated using Receiver Operating Characteristic(ROC)curves and the Area Under the Curve(AUC).Subgroup analyses were carried out by gender and age.Results The TyG and TyG-BMI indices were significantly elevated in the HUA group compared to the normal group.The prevalence of HUA was markedly higher in the TyG-Q4 and TyG-BMI-Q4 groups than in the other three corresponding quartile groups.Binary logistic regression analysis revealed a positive association between TyG,TyG-BMI levels,and the risk of HUA.The AUC values for predicting HUA using TyG,TyG-BMI,and their combination were 0.700,0.747,and 0.822,respectively.Specifically,for males,the AUC values were 0.641,0.674,and 0.709,respectively,whereas for females,they were 0.742,0.776,and 0.829,respectively.Among individuals younger than 60 years old,the AUC values were 0.716,0.759,and 0.835,respectively,while for those aged 60 years or older,the values were 0.614,0.645,and 0.731,respectively.Conclusions TyG and TyG-BMI are significantly associated with the risk of HUA.Specifically,TyG-BMI demon-strates superior predictive performance compared to TyG alone.Moreover,the combination of TyG and TyG-BMI further improves predictive accuracy,particularly among female and middle-aged or younger populations.
6.One case of eustachian tube hairy polyp was removed by microscope combined with endoscope.
Jiahui JIN ; Bo CAO ; Huanxin YU ; Feifan QI ; Guangping LIU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(6):578-581
This paper reports the diagnosis and treatment of a child with eustachian hairy polyp. The patient was a female, aged 1 year and 4 months, and visited our clinic due to "intermittent purulent discharge of the left ear, nasal congestion and sleep snoring for 1 year". Preoperative endoscopic examination found white masses at the posterior part of the nasal cavity on both sides. The imaging findings showed masses with streaks and circular-like mixed signal accompanied by slightly uneven enhancement at the left eustachian duct and the posterior wall of the nasopharyngeal cavity, and soft tissue density in the left tympanic antrum. Left modified radical mastoidectomy and radical endoscopic resection surgery for nasopharyngeal tumors was performed under general anesthesia. Histopathological examination revealed polyp of the left eustachian tube hair. The patient's symptoms improved after surgery, and no tumor recurrence was found after 3 months of follow-up.
Humans
;
Female
;
Eustachian Tube/surgery*
;
Polyps/surgery*
;
Infant
;
Endoscopy
7.The comparative study of TyG and TyG-BMI index with occurrence of hyperuricemia in physical examina-tion population
Qian NIE ; Xuemei ZHANG ; Zhihua HAO ; Ruolin XIE ; Huanxin LIU ; Xiaoqian WU ; Luping REN
The Journal of Practical Medicine 2025;41(8):1192-1198
Objective To investigate the predictive capacity of the Triglyceride-Glucose(TyG)index and the Triglyceride-Glucose-Body Mass Index(TyG-BMI)for the development of hyperuricemia(HUA)in a health examination population,and to identify suitable indicators as risk assessment tools for HUA.Methods This study ultimately included 12 004 participants from a health examination cohort.According to SUA levels,the partici-pants were categorized into a normal group(n=9 952)and a hyperuricemia(HUA)group(n=2 052).The TyG index and TyG-BMI index were calculated,and participants were further stratified into four groups(Q1—Q4)based on the quartiles of these indices.Binary logistic regression analysis was performed to assess the association between TyG,TyG-BMI,and HUA.The predictive value of TyG,TyG-BMI,and their combination for HUA was evaluated using Receiver Operating Characteristic(ROC)curves and the Area Under the Curve(AUC).Subgroup analyses were carried out by gender and age.Results The TyG and TyG-BMI indices were significantly elevated in the HUA group compared to the normal group.The prevalence of HUA was markedly higher in the TyG-Q4 and TyG-BMI-Q4 groups than in the other three corresponding quartile groups.Binary logistic regression analysis revealed a positive association between TyG,TyG-BMI levels,and the risk of HUA.The AUC values for predicting HUA using TyG,TyG-BMI,and their combination were 0.700,0.747,and 0.822,respectively.Specifically,for males,the AUC values were 0.641,0.674,and 0.709,respectively,whereas for females,they were 0.742,0.776,and 0.829,respectively.Among individuals younger than 60 years old,the AUC values were 0.716,0.759,and 0.835,respectively,while for those aged 60 years or older,the values were 0.614,0.645,and 0.731,respectively.Conclusions TyG and TyG-BMI are significantly associated with the risk of HUA.Specifically,TyG-BMI demon-strates superior predictive performance compared to TyG alone.Moreover,the combination of TyG and TyG-BMI further improves predictive accuracy,particularly among female and middle-aged or younger populations.
8.Impact and predictive value of subclinical hypothyroidism on metabolic associated fatty liver disease
Huanxin LIU ; Zhong LI ; Qian NIE ; Cuiqiao MENG
Chinese Journal of Health Management 2025;19(7):500-506
Objective:To explore the impact and predictive value of subclinical hypothyroidism on metabolic associated fatty liver disease (MAFLD).Methods:The study adopted a cross-sectional design. A total of 6 597 adults with subclinical hypothyroidism who received health check-ups in the Health Examination Center of Hebei General Hospital from 2018 to 2022 were selected as subjects. The participants were randomly divided into a modeling group (4 617) and a validation group (1 980) in a 7∶3 ratio. The basic information and serological indicators were collected in those subjects. The general clinical characteristics of the MAFLD and non-MAFLD participants were compared in the modeling group. Multivariate logistic regression analysis was used to explore the impact of thyroid hormone on MAFLD. The R language was applied to construct a nomogram prediction model, and internal validation and external validation of the model were performed to evaluate the prediction performance of the model.Results:Of the 6 597 study subjects, the prevalence of MAFLD was 31.14% (2 054/6 597). After preliminary comparison of baseline data from the modeling group, multivariate analysis showed that free triiodothyronine/free thyroxine (FT3/FT4) ( OR=20.945,95% CI: 5.862-74.838), male ( OR=1.394,95% CI: 1.109-1.752), age ( OR=1.017,95% CI: 1.009-1.025), diastolic blood pressure ( OR=1.017,95% CI: 1.004-1.021), waist circumference ( OR=1.049,95% CI:1.031-1.067), body mass index ( OR=1.236,95% CI:1.175-1.299), triglyceride ( OR=1.525,95% CI: 1.379-1.687), low density lipoprotein cholesterol ( OR=1.493,95% CI: 1.313-1.698), fasting glucose ( OR=1.173,95% CI:1.101-1.249) were risk factors for MAFLD, and high density lipoprotein cholesterol ( OR=0.243,95% CI: 0.163-0.363), aspartate aminotransferase/alanine aminotransferase ( OR=0.242,95% CI: 0.183-0.320) were protective factors for MAFLD (all P<0.05). The results showed that the two groups of calibration curves showed the consistency between MAFLD occurrence risk and actual occurrence risk. The AUCs of internal and external validation was 0.897 and 0.907, respectively. This nomogram model had a high predictive value. Conclusion:FT3/FT4 is an independent risk factor for MAFLD in the population with subclinical hypothyroidism. The prediction model incorporating thyroid function and metabolic parameters may provide clinical value for early identification of MAFLD.
9.Relationship between RB1 gene deletion and prognosis of multiple myeloma and effect of renal insufficiency on it
Xinyue LANG ; Guihua ZHANG ; Huanxin ZHANG ; Kaige LIU ; Zhengxia SONG ; Kailin XU ; Jinge XU ; Qiurong ZHANG
Cancer Research and Clinic 2025;37(2):124-131
Objective:To investigate the relationship between retinoblastoma binding protein 1 (RB1) gene deletion and the prognosis of multiple myeloma (MM) patients, and the possible effect of renal insufficiency on it.Methods:A retrospective cohort study was conducted. The clinical data and follow-up information of MM patients who were treated in the Second Affiliated Hospital of Xuzhou Medical University and the Affiliated Hospital of Xuzhou Medical University from December 2020 to November 2023 were collected. According to the presence of RB1 gene deletion in bone marrow samples detected by fluorescence in situ hybridization (FISH), the patients were divided into the RB1 gene deletion group and the RB1 gene non-deletion group, and the clinicopathological characteristics and hematological index levels were compared between the two groups. Renal insufficiency was determined by renal function assessment indicator serum creatinine (Scr) >177 μmol/L. The Spearman test was used to analyze the relationship between the number of RB1 gene deletion positive cells and levels of Scr, hemoglobin and serum calcium in MM patients. The Kaplan-Meier method was used to analyze progression-free survival (PFS), and the Cox proportional hazards model was used to determine the influencing factors of PFS in all MM patients and RB1 gene deletion and non-deletion MM patients.Results:A total of 75 MM patients were enrolled, of whom 24 (32.0%) had RB1 gene deletion. There were no significant differences in gender, age ≥65 years old, bone destruction and lactate dehydrogenase level between the RB1 gene deletion and non-deletion groups (all P > 0.05). There were significant differences in the distributions of patients in each stage of MM International Staging System (ISS) and revised International Staging System (R-ISS) between the two groups, as well as in hemoglobin, serum calcium, Scr, β 2-microglobulin, serum albumin levels, and the proportion of bone marrow plasma cells (all P < 0.05). The number of RB1 gene deletion positive cells was positively correlated with Scr level ( r = 0.863, P = 0.016), but not with hemoglobin and serum calcium levels (both P > 0.05). The PFS of the RB1 gene non-deletion group was better than that of the RB1 gene deletion group (1-year PFS rate: 83.5% vs. 71.7%, 2-year PFS rate: 56.3% vs. 26.3%), and the difference was statistically significant ( P = 0.012). PFS in the non-renal insufficiency group was better than that in the renal insufficiency group (1-year PFS rate: 85.6% vs. 61.9%, 2-year PFS rate: 58.0% vs. 13.5%), and the difference was statistically significant ( P = 0.001). The PFS of patients without renal insufficiency in both the RB1 gene deletion and non-deletion groups was better than that in patients with renal insufficiency, and the differences were statistically significant (both P < 0.05). Multivariate Cox regression analysis showed that ISS stage Ⅲ was an independent risk factor for poor PFS in MM patients (stage Ⅲ vs. stage Ⅰ, HR = 11.317, 95% CI: 1.220-104.979, P = 0.033). Multivariate Cox regression analysis in RB1 gene deletion and non-deletion groups showed that ISS stage Ⅲ (stage Ⅲ vs. stageⅠ, HR = 4.166, 95% CI: 1.419-12.225, P = 0.009), R-ISS stage Ⅲ (stage Ⅲ vs. stage Ⅰ, HR = 3.800, 95% CI: 1.005-14.367, P = 0.049), serum calcium > 2.52 mmol/L (> 2.52 mmol/L vs. ≤2.52 mmol/L, HR = 2.398, 95% CI: 1.037-5.546, P = 0.041) and renal insufficiency (yes vs. no, HR = 2.363, 95% CI: 1.021-5.472, P = 0.045) were independent risk factors for poor PFS in RB1 gene non-deletion MM patients, and serum calcium >2.52 mmol/L (>2.52 mmol/L vs. ≤ 2.52 mmol/L, HR = 3.673, 95% CI: 1.160-11.627, P = 0.027) and renal insufficiency (yes vs. no, HR = 3.985, 95% CI: 1.220-13.016, P = 0.022) were independent risk factors for poor PFS in RB1 gene deletion MM patients. Conclusions:The PFS of MM patients with RB1 gene deletion is worse than that of patients without RB1 gene deletion, RB1 gene deletion may be related to renal insufficiency in MM patients, and the prognosis of MM patients with RB1 gene deletion and renal insufficiency may be worse.
10.Design and clinical application of intracavitary-interstitial brachytherapy applicator template in locally advanced cervical cancer
Yi OUYANG ; Xiaodan HUANG ; Foping CHEN ; Haiying WU ; Weijun YE ; Kai CHEN ; Junyun LI ; Hongying LIU ; Miaoqing MAI ; Huikuan GU ; Huanxin LIN ; Xinping CAO
Chinese Journal of Radiation Oncology 2024;33(2):137-144
Objective:To design and evaluate the application value of intracavitary-interstitial brachytherapy (IC-ISBT) applicator template for locally advanced cervical cancer.Methods:MRI data of 100 patients with ⅡB-ⅣA stage cervical cancer (International Federation of Gynecology and Obstetrics 2018 staging system) before and after external beam radiation therapy (EBRT) admitted to Sun Yat-sen University Cancer Center from March 2019 to September 2020 were collected. The range of primary cervical lesions was retrospectively analyzed and compared. Based on the residual mass of patients, the corresponding high-risk clinical target volume (HR-CTV) was delineated, and the IC-ISBT applicator template was designed and initially applied to cervical cancer patients. Dosimetry analysis and efficacy evaluation were compared between the applicator template-guided ( n=37) and free-hand implantation groups ( n=63). Chi-square test or Fisher exact test was performed for categorical variables, and t-test or U-test for continuous variables. Results:The median distance between the residual tumor margin (clockwise 3, 6, 9, 12 o'clock) and the center of 100 patients with ⅡB-ⅣA stage cervical cancer after EBRT was 16.5, 14.0, 17.0 and 13.0 mm, respectively. The corresponding HR-CTV was superimposed to reconstruct the three-dimensional diagram, and the cylindrical IC-ISBT applicator template with mushroom-like head was designed and manufactured: the longest and shortest diameter of the head was 35 and 20 mm, respectively; the central channel was adapted to the uterine tube, the C1-C12 channels was arranged in inner circle, and the peripheral B1-B5 and A1-A4 pin channels were expanded bilaterally. In terms of dose coverage, there was no significant difference between the HR-CTV D 90% [(635.12±22.65) vs. (635.80±25.84) cGy], bladder D 2 cm3 [(473.79±44.78) vs. (463.55±66.43) cGy)], rectum D 2 cm3 [(396.99±73.54) vs. (408.00±73.94) cGy] and sigmoid colon D 2 cm3 [(293.07±152.72) vs. (311.31±135.77) cGy] between the template-guided and free-hand implantation groups (all P>0.05), but the HR-CTV D 98% was significantly higher [(544.78±32.07) vs. (536.78±32.04) cGy, P=0.007] and the rectum D 1 cm3 and D 0.1 cm3 were significantly lower [(438.62±69.65) vs. (453.97±67.89) cGy, P=0.016; (519.46±70.67) vs. (543.82±81.24) cGy, P=0.001] in the template-guided implantation group. In addition, there was no significant difference in the complete response rate between two groups (86% vs. 83%, P>0.05). Conclusions:This IC-ISBT applicator template is reasonably designed, and the therapeutic efficacy of the template-guided implantation is equivalent to that of free-hand implantation. The dose coverage of the target area meets the clinical demand with a better protection of the organs at risk. The applicator template has the potential to be widely used as a conventional template in clinical practice as the applicator-guided implantation is convenient to operate and repeat.

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