1.Effects of different concentrations of alcoholic beverage and doses of al-cohol on a rat model of alcoholic liver disease
Chen WANG ; Jianjiao ZUO ; Yanshan MA ; Yuntong ZHOU ; Zhiwei LI ; Linan ZHANG ; Yinghua XIE
Chinese Journal of Pathophysiology 2025;41(11):2272-2280
AIM:To establish a stable and efficient rat model of alcoholic liver disease(ALD),we investigat-ed the effects of different alcoholic beverage concentrations and alcohol dosing regimens.METHODS:(1)SPF-grade male SD rats were randomized into 5 groups(n=10):blank,ALD1,ALD2,ALD3,and ALD4.Except for the blank group,rats received intragastric administration of 56%alcohol(6 mL/kg twice daily with an 8-hour interval)for 4 weeks,along with free access to 0%,5%,10%,or 15%alcoholic beverage to evaluate concentration-dependent effects.(2)An-other cohort was divided into three groups(n=10):blank,ALD5,and ALD6.Rats(except blank)were gavaged with 56%alcohol twice daily for 9 weeks(8 mL/kg for ALD5;6 mL/kg in week 1,increasing by 0.5 mL/kg weekly for ALD6),with 10%alcoholic beverage available ad libitum to assess dose-dependent effects.Serum biochemical markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglycerides(TG),high-density li-poprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)]and inflammatory cytokines[interleu-kin-6(IL-6),IL-1β and tumor necrosis factor-α(TNF-α)]were analyzed after modeling,complemented by imaging(B-ultrasound,CT,and MRI).Success and survival rates were calculated.RESULTS:(1)ALD1~4 groups exhibited sig-nificantly elevated ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α(P<0.05 or P<0.01)and reduced HDL-C and liver-to-spleen CT density ratio vs blank.ALD3(10%alcoholic beverage)showed the highest modeling success rate with low mortality.(2)ALD5 and ALD6 groups also had siginificant differin terms(P<0.01),with ALD6(gradually increas-ing dose)displaying more severe liver injury,higher success rate,and better survival.CONCLUSION:The optimal ALD model was induced by intragastric administration of 56%alcohol(6 mL/kg twice daily in week 1,increasing by 0.5 mL/kg weekly for 9 weeks)combined with 10%alcoholic beverage.This protocol offers a reliable approach for ALD re-search and drug development.
2.Comparison of the efficacy of anatomical resection versus hepatic parenchymal preservation preference in patients with solitary small hepatocellular carcinoma and cirrhosis: a multicenter retrospective study
Liming HUANG ; Yun YANG ; Yuntong LI ; Xianming WANG ; Siming ZHENG ; Qiang LU ; Zisen LAI ; Yongping LAI ; Zongren DING ; Jiahui LYU ; Jiacheng ZHANG ; Xinfeng QIU ; Weiping ZHOU ; Kongying LIN ; Yongyi ZENG
Chinese Journal of Hepatology 2025;33(4):348-358
Objective:To investigate the efficacy of anatomical resection (AR) in the early stages of treating solitary hepatocellular carcinoma (HCC) combined with liver cirrhosis with a diameter of ≤5 cm in comparison to different surgical methods of preferential hepatic parenchymal preservation (non-anatomical liver resection, NAR).Methods:The clinical data of 1 390 cases with solitary HCC combined with liver cirrhosis at an early stage who underwent liver resection at Mengchao Hepatobiliary Hospital of Fujian Medical University and six other medical centers from September 2013 to May 2019 were retrospectively analyzed. Patients were divided into the AR group (486 cases) and the NAR group (904 cases) and the wide surgical margin (WSM) group (745 cases) and the narrow surgical margin (NSM) group (645 cases) according to whether they received AR and the width of the surgical margin (1 cm). The basic information of the patients, preoperative evaluation index data, and postoperative follow-up (follow-up every 3 months) were collected. The Kaplan-Meier method was used to plot the survival curve.The log-rank test was used to compare the difference in survival between the two groups. The Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. Propensity score matching (PSM) was applied to reduce intergroup bias.Results:The overall survival (OS) rates for all patients at 1, 3, and 5 years were 95.5%, 79.9%, and 63.5%, respectively. The recurrence-free survival (RFS) rates were 81.5%, 59.0%, and 43.7%, respectively. There was a statistically significant difference in RFS rate between the AR group and the NAR group prior to PSM, but no statistically significant difference in OS rate (RFS rate: 47.0% vs. 41.9%, P<0.05; OS rate: 64.4% vs. 62.9%, P>0.05). The postoperative RFS rate and OS rate were significantly superior in the WSM group than those of the NSM group (RFS rate: 47.8% vs. 37.2%, P<0.001; OS rate: 69.0% vs. 57.3%, P<0.001). There was no statistically significant difference in OS rate and RFS rate between the AR group and the NAR group following PSM (RFS: 46.3% vs. 45.1%, P>0.05; OS rate: 64.0% vs. 64.3%, P>0.05).The 5-year OS and RFS rates in the WSM group were 66.8% and 60.2%, respectively. The 5-year OS and RFS rates for the NSM group were 48.7% and 41.4%, respectively, with a statistically significant difference ( P<0.05). Cox multivariate analysis indicated that serum albumin, tumor diameter, microvascular invasion, and surgical margin were independent prognostic factors affecting OS and RFS. The Child-Pugh grade and satellite lesions were independent prognostic factors affecting OS. Conclusion:Anatomical liver resection is not an independent risk factor for prognosis, but the state of the resection margin determines the prognosis of patients with solitary HCC combined with cirrhosis. Therefore, hepatic resection margins should be prioritized in such patients.
3.Clinical Value of Tumor-Stroma Ratio Combined with KRAS/NRAS/BRAF Gene Status in Prognostic Assessment of Patients with Colorectal Cancer
Ziyang ZHANG ; Yuanfei LI ; Yuntong GUO ; Gen ZHU ; Guang YANG ; Yu WANG
Cancer Research on Prevention and Treatment 2025;52(8):676-681
Objective To investigate the clinical value of tumor-stroma ratio (TSR) in combination with KRAS, BRAF, NRAS, and microsatellite status for prognostic assessment of patients with colorectal cancer. Methods A total of 51 colorectal cancer cases meeting the inclusion and exclusion criteria were enrolled in this study. TSR levels were evaluated through optical microscopy. The KRAS/NRAS/BRAF mutation profiles and microsatellite status were determined in accordance with genetic testing results. Clinical data, pathological characteristics, and survival outcomes were systematically recorded. Results Among the 51 patients with colorectal cancer, 19 (37.3%) were categorized into the low stromal group and 32 (62.7%) into the high stromal group. Statistically significant differences were observed between the two groups in drug resistance, M stage, TNM stage, neural invasion, and microsatellite status (P<0.05). Compared with patients exhibiting high TSR, those with low TSR demonstrated significantly increased recurrence rates (5 vs. 21 cases, P=0.007), shortened disease-free survival (34.21 vs. 14.34 months, P=0.001), and reduced overall survival (38.79 vs. 23.09 months, P=0.021). Multivariate Cox regression analysis identified N stage, M stage, TNM stage, neural invasion, lymphovascular invasion, and TSR as independent risk factors for disease-free survival. N stage, M stage, neural invasion, lymphovascular invasion, and TSR emerged as independent prognostic factors for overall survival (P<0.05). Although the combined models of TSR with KRAS, NRAS, BRAF, and microsatellite status, respectively, demonstrated overall statistical significance (P<0.05), none of the dummy variables in these models reached individually statistical significance (P>0.05), and therefore cannot be considered independent prognostic factors. Conclusion TSR serves as an independent predictor of poor prognosis in advanced colorectal cancer, with patients exhibiting low TSR demonstrating a significantly higher risk of recurrence and metastasis than those with high TSR. For patients with colon cancer undergoing first-line palliative chemotherapy after postoperative recurrence, histopathological assessment of TSR in primary tumor sites holds prognostic value and may serve as a relevant factor for evaluating treatment resistance in clinical management.
4.Effects of different concentrations of alcoholic beverage and doses of al-cohol on a rat model of alcoholic liver disease
Chen WANG ; Jianjiao ZUO ; Yanshan MA ; Yuntong ZHOU ; Zhiwei LI ; Linan ZHANG ; Yinghua XIE
Chinese Journal of Pathophysiology 2025;41(11):2272-2280
AIM:To establish a stable and efficient rat model of alcoholic liver disease(ALD),we investigat-ed the effects of different alcoholic beverage concentrations and alcohol dosing regimens.METHODS:(1)SPF-grade male SD rats were randomized into 5 groups(n=10):blank,ALD1,ALD2,ALD3,and ALD4.Except for the blank group,rats received intragastric administration of 56%alcohol(6 mL/kg twice daily with an 8-hour interval)for 4 weeks,along with free access to 0%,5%,10%,or 15%alcoholic beverage to evaluate concentration-dependent effects.(2)An-other cohort was divided into three groups(n=10):blank,ALD5,and ALD6.Rats(except blank)were gavaged with 56%alcohol twice daily for 9 weeks(8 mL/kg for ALD5;6 mL/kg in week 1,increasing by 0.5 mL/kg weekly for ALD6),with 10%alcoholic beverage available ad libitum to assess dose-dependent effects.Serum biochemical markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglycerides(TG),high-density li-poprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)]and inflammatory cytokines[interleu-kin-6(IL-6),IL-1β and tumor necrosis factor-α(TNF-α)]were analyzed after modeling,complemented by imaging(B-ultrasound,CT,and MRI).Success and survival rates were calculated.RESULTS:(1)ALD1~4 groups exhibited sig-nificantly elevated ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α(P<0.05 or P<0.01)and reduced HDL-C and liver-to-spleen CT density ratio vs blank.ALD3(10%alcoholic beverage)showed the highest modeling success rate with low mortality.(2)ALD5 and ALD6 groups also had siginificant differin terms(P<0.01),with ALD6(gradually increas-ing dose)displaying more severe liver injury,higher success rate,and better survival.CONCLUSION:The optimal ALD model was induced by intragastric administration of 56%alcohol(6 mL/kg twice daily in week 1,increasing by 0.5 mL/kg weekly for 9 weeks)combined with 10%alcoholic beverage.This protocol offers a reliable approach for ALD re-search and drug development.
5.Comparison of the efficacy of anatomical resection versus hepatic parenchymal preservation preference in patients with solitary small hepatocellular carcinoma and cirrhosis: a multicenter retrospective study
Liming HUANG ; Yun YANG ; Yuntong LI ; Xianming WANG ; Siming ZHENG ; Qiang LU ; Zisen LAI ; Yongping LAI ; Zongren DING ; Jiahui LYU ; Jiacheng ZHANG ; Xinfeng QIU ; Weiping ZHOU ; Kongying LIN ; Yongyi ZENG
Chinese Journal of Hepatology 2025;33(4):348-358
Objective:To investigate the efficacy of anatomical resection (AR) in the early stages of treating solitary hepatocellular carcinoma (HCC) combined with liver cirrhosis with a diameter of ≤5 cm in comparison to different surgical methods of preferential hepatic parenchymal preservation (non-anatomical liver resection, NAR).Methods:The clinical data of 1 390 cases with solitary HCC combined with liver cirrhosis at an early stage who underwent liver resection at Mengchao Hepatobiliary Hospital of Fujian Medical University and six other medical centers from September 2013 to May 2019 were retrospectively analyzed. Patients were divided into the AR group (486 cases) and the NAR group (904 cases) and the wide surgical margin (WSM) group (745 cases) and the narrow surgical margin (NSM) group (645 cases) according to whether they received AR and the width of the surgical margin (1 cm). The basic information of the patients, preoperative evaluation index data, and postoperative follow-up (follow-up every 3 months) were collected. The Kaplan-Meier method was used to plot the survival curve.The log-rank test was used to compare the difference in survival between the two groups. The Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. Propensity score matching (PSM) was applied to reduce intergroup bias.Results:The overall survival (OS) rates for all patients at 1, 3, and 5 years were 95.5%, 79.9%, and 63.5%, respectively. The recurrence-free survival (RFS) rates were 81.5%, 59.0%, and 43.7%, respectively. There was a statistically significant difference in RFS rate between the AR group and the NAR group prior to PSM, but no statistically significant difference in OS rate (RFS rate: 47.0% vs. 41.9%, P<0.05; OS rate: 64.4% vs. 62.9%, P>0.05). The postoperative RFS rate and OS rate were significantly superior in the WSM group than those of the NSM group (RFS rate: 47.8% vs. 37.2%, P<0.001; OS rate: 69.0% vs. 57.3%, P<0.001). There was no statistically significant difference in OS rate and RFS rate between the AR group and the NAR group following PSM (RFS: 46.3% vs. 45.1%, P>0.05; OS rate: 64.0% vs. 64.3%, P>0.05).The 5-year OS and RFS rates in the WSM group were 66.8% and 60.2%, respectively. The 5-year OS and RFS rates for the NSM group were 48.7% and 41.4%, respectively, with a statistically significant difference ( P<0.05). Cox multivariate analysis indicated that serum albumin, tumor diameter, microvascular invasion, and surgical margin were independent prognostic factors affecting OS and RFS. The Child-Pugh grade and satellite lesions were independent prognostic factors affecting OS. Conclusion:Anatomical liver resection is not an independent risk factor for prognosis, but the state of the resection margin determines the prognosis of patients with solitary HCC combined with cirrhosis. Therefore, hepatic resection margins should be prioritized in such patients.
6.The evaluation of alpha-fetoprotein response on efficacy and prognosis in targeted therapy combined with immunotherapy for intermediate-to-advanced hepatocellular carcinoma: a multicenter clinical study
Kongying LIN ; Qingjing CHEN ; Luobin GUO ; Yun YANG ; Yufeng CHEN ; Jianxi ZHANG ; Fuqun WEI ; Hui ZHANG ; Zhiqing CHENG ; Yuntong LI ; Congren WANG ; Yabin JIANG ; Kecan LIN ; Weiping ZHOU ; Yongyi ZENG
Chinese Journal of Digestive Surgery 2024;23(2):248-256
Objective:To investigate the evaluation efficacy and predictive prognostic value of alpha-fetoprotein (AFP) response in tyrosine kinase inhibitors (TKIs) in combination with PD-1 inhibitors (α-PD-1) for intermediate-to-advanced hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 205 patients with intermediate-to-advanced HCC who were admitted to 9 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from March 2020 to July 2022 were collected. There were 178 males and 27 females, aged (52±12)years. Based on AFP response at 6-8 weeks after treatment, patients were divided into the AFP response group (AFP level decreased by ≥50% compared to baseline) and the AFP no response group (AFP level decreased by <50% compared to baseline). Observation indicators: (1) AFP response evaluation of anti-tumor efficacy; (2) comparison of patient prognosis; (3) analysis of factors affecting patient prognosis. Measurement data with normal distrubution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) and M( Q1, Q3). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional risk model was used for univariate analysis and the COX stepwise regression model was used for multivariate analysis. Results:(1) AFP response evaluation of anti-tumor efficacy. Before treatment, all 205 patients were positive of AFP, with a baseline AFP level of 1 560(219,3 400)μg/L. All 205 patients were treated with TKIs in combination with α-PD-1, and the AFP level was 776(66,2 000)μg/L after 6 to 8 weeks of treatment. Of the 205 patients, 88 cases were classified as AFP response and 117 cases were classified as AFP no response. According to the response evaluation criteria in solid tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were 42.05%(37/88) and 94.32%(83/88) in patients of the AFP response group and 16.24% (19/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=16.846, 25.950, P<0.05). According to the modified response evaluation criteria in solid tumors, the ORR and DCR were 69.32% (61/88) and 94.32% (83/88) in patients of the AFP response group and 33.33% (39/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=26.030, 25.950, P<0.05). (2) Comparison of patient prognosis. All 205 patients were followed up for 12.4(range, 2.4-34.0)months after treatment. The median progression free survival time and total survival time were 5.5 months and 17.8 months, respectively. The 1-year, 2-year progression free survival rates were 20.8% and 7.2%, and the 1-year, 2-year overall survival rates were 68.7% and 31.5%, respectively. The median progression free survival time, 1-year and 2-year progression free survival rates were 9.7 months, 39.6% and 14.2% in patients of the AFP response group and 3.7 months, 7.8% and 2.0% in patients of the AFP no response group, showing a significant difference in progression free survival between them ( χ2=43.154, P<0.05). The median overall survival time, 1-year and 2-year overall survival rates were not reached, 85.2% and 56.3% in patients of the AFP response group and 14.6 months, 56.3% and 14.5% in patients of the AFP no response group, showing a significant difference in overall survival between them ( χ2=33.899, P<0.05). (3) Analysis of factors affecting patient prognosis. Results of multivariate analysis showed that invasion of large blood vessels, extrahepatic metastasis, combined hepatic artery intervention therapy, and AFP response were independent factors influencing progression free survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio=1.474, 1.584, 0.631, 0.367, 95% confidence interval as 1.069-2.033, 1.159-2.167, 0.446-0.893, 0.261-0.516, P<0.05), and Eastern Cooperative Oncology Group score, invasion of large blood vessels, extrahepatic metastasis, and AFP response were independent factors influencing overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio= 1.347, 1.914, 1.673, 0.312, 95% confidence interval as 1.041-1.742, 1.293-2.833, 1.141-2.454, 0.197-0.492, P<0.05). Conclusions:AFP response at 6-8 weeks after treatment can effectively evaluate anti-tumor efficacy of TKIs in combination with α-PD-1 for intermediate-to-advanced HCC. AFP response is the independent factor influencing progression free survival and overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1.
7.Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus
ZHANG HAO ; WANG XINSHU ; HU BO ; LI PEICHENG ; ABUDUAINI YIERFAN ; ZHAO HONGMEI ; JIEENSIHAN AYINAER ; CHEN XISHUANG ; WANG SHIYU ; GUO NUOJIN ; YUAN JIAN ; LI YUNHUI ; LI LEI ; YANG YUNTONG ; LIU ZHONGMIN ; TANG ZHAOSHENG ; WANG HUA
Journal of Zhejiang University. Science. B 2024;25(7):568-580,中插1-中插3
Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.
8.Predictive efficacy of miR-27b-3p combined with miR-215 in the recurrence of early gastric cancer after endoscopic submucosal dissection
Jin LI ; Fuying ZHU ; Ya XU ; Yuntong LAN
Journal of Clinical Surgery 2024;32(8):830-834
Objective To investigate the efficacy of micrornas(miR)-27B-3P combined with miR-215 in predicting the recurrence of early gastric cancer after endoscopic submucosal dissection(ESD).Methods A total of 122 patients with early gastric cancer admitted to the hospital from January 2021 to February 2022 were selected.All patients received ESD surgery and were followed up for 10~15 months,average(12.57±1.83)months.Patients with early gastric cancer were divided into recurrence group and non-recurrence group according to whether they had recurrence after ESD surgery.The relative expression levels of miR-27b-3p and miR-215 and clinical data of the two groups were compared to analyze the factors affecting the recurrence of early gastric cancer patients after ESD surgery,and analyze the relative expression levels of miR-27b-3p and miR-215 and the predictive value of their combination for the recurrence of early gastric cancer patients after ESD surgery.Results After 10~15 months,average(12.57±1.83)months of follow-up,3 cases of 122 patients were lost to follow-up,the follow-up rate was 97.54%,of which 12 cases relapsed,and the remaining 107 cases did not relapse.The miR-27b-3p in the relapsed group was lower than that in the non-relapsed group(P<0.05),and the relative expression of miR-215 in the relapsed group was higher than that in the non-relapsed group(P<0.05).The proportion of patients with lesion size ≥3 cm and infiltration depth of SM2-SM3 in recurrence group was higher than that in non-recurrence group(P<0.05),and the proportion of patients with R0 resection in recurrence group was lower than that in non-recurrence group(P<0.05).Logistic multivariate regression analysis showed that the lesion size was ≥3 cm and the depth of invasion was SM2-SM3,the relative expression level of miR-27b-3p,the relative expression level of miR-215 were the influential factors for recurrence of early gastric cancer patients after ESD operation(P<0.05).The relative expression levels of miR-27b-3p and miR-215 and their combined prediction of the area under the curve(AUC)of ESD postoperative recurrence in early gastric cancer patients were 0.783,0.845 and 0.935,respectively.Conclusion miR-27b-3p and miR-215 can be used to predict the recurrence risk of early gastric cancer patients after ESD surgery,and the combination of Mir-27B-3P and Mir-215 has higher predictive value.
9.Efficacy observation of combination therapy containing venetoclax for t(11; 14) plasma cell disorders
Yuntong LIU ; Jingyu XU ; Lingna LI ; Lugui QIU ; Gang AN
Journal of Leukemia & Lymphoma 2024;33(12):712-718
Objective:To investigate the efficacy and adverse effects of combination therapy containing venetoclax in the treatment of t(11; 14) plasma cell disorders.Methods:A retrospective case series study was conducted. The clinical data of plasma cell disorders patients with t(11; 14) treated with combination therapy containing venetoclax in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 2020 to September 2023 were collected. The general data included baseline clinical characteristics, treatment regimens, treatment responses, survival, and adverse events. The duration of orally administered venetoclax-based treatment regimen was 28 d, and the dose of venetoclax was appropriately adjusted according to the tumor burden and general conditions of patients. Patients were grouped according to drug dosage and treatment regimen. The overall survival (OS) analysis was performed by using Kaplan-Meier method and log-rank test was used for comparison among groups.Results:Among the 14 plasma cell disorders patients with t(11;14), 13 had multiple myeloma (MM) and 1 had primary plasma cell leukemia (pPCL). The median time [ M ( Q1, Q3)] from initial diagnosis to venetoclax treatment was 21 months (8 months, 39 months). The median number of therapy lines was 2 (1, 4); 7 patients had drug resistance to both proteasome inhibitors (PI) and immunomodulators (IMiD), and 5 patients had drug resistance to PI, IMiD and anti-CD38 monoclonal antibodies; 2 patients died after 1 uncompleted course of treatment and they were not enrolled into efficacy evaluation and survival analysis. Among the 11 MM patients evaluable for treatment response, 6 achieved at least partial remission (PR). Of the 4 patients who received the first-line or second-line therapy containing venetoclax, 2 achieved strict complete remission (sCR), 1 achieved very good partial remission (VGPR), and 1 achieved PR. The median course number of therapy lines with venetoclax was 2 (2, 6), and the median acting time was 1.1 months (0.75 months, 1.75 months). Until the last follow-up in May 2024, the median duration of remission of 11 MM patients was 3.3 months (95% CI: 0-7.1 months), and the median OS time was 22.7 months (95% CI: 0-52.5 months). The median OS time was 9.6 months, 31.2 months, respectively in venetoclax combined with PI group (6 cases) and venetoclax combined with daratumumab (Dara) group (4 cases), and the difference in OS between the 2 groups was statistically significant ( P = 0.093); the median duration of remission was 1.7 months and 9.8 months, respectively in venetoclax combined with PI group and venetoclax combined with Dara group, and the difference was statistically significant between the 2 groups ( P = 0.025). The median OS time in high-dose group (maximum dose of venetoclax ≥300 mg, 6 cases) and low-dose group (maximum dose of venetoclax < 300 mg, 5 cases) was 31.2 and 7.5 months, respectively, and the difference in OS was statistically significant ( P = 0.013). The median duration of remission was 9.8 months, 1.6 months, respectively, and the difference was statistically significant ( P = 0.048). Grade ≥3 adverse events of 11 MM patients included neutropenia, lymphopenia, infection, thrombocytopenia, and hypokalemia; 6 patients experienced grade ≥3 adverse events, 2 patients discontinued treatment due to adverse events, and no treatment-related deaths occurred. The pPCL patient received 5 courses of treatment with venetoclax plus DECP (cisplatinum + etoposide + cyclophosphamide + dexamethasone) induction therapy followed by chimeric antigen receptor T cell therapy and then continued venetoclax maintenance, achieving sCR with the duration remission of 18.7 months. During induction, the patient experienced grade 3 neutropenia and infection. Conclusions:The combination therapy containing venetoclax is safe and manageable in MM patients with t(11; 14) and pPCL. The patients receiving early, regular, and adequate-dose treatment with venetoclax have better therapeutic efficacy.
10.X-ray imaging characteristics of calcaneus in adult patients with osteoarticular diseases and its impact on disease diagnosis
Yuntong MA ; Dongyu HU ; Shengfeng SUN ; Qingquan WU ; Guangxiang LI
Chinese Journal of Endemiology 2024;43(8):666-669
Objective:To analyze the X-ray imaging characteristics of calcaneus in adult patients with osteoarticular diseases and its impact on disease diagnosis.Methods:Totally 78 patients (156 ankle joints) with osteoarticular diseases admitted to the Affiliated Hospital of Jining Medical University from June 2019 to June 2022 were selected as research subjects, including 72 cases of osteoarthritis and 6 cases of Kashin-Beck disease. Another 50 volunteers who underwent health examination in this hospital during the same period were selected as control group, all of them underwent calcaneal X-ray examination. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of calcaneal X-ray parameters in predicting adult osteoarticular diseases.Results:Among 72 patients with osteoarthritis, 63 cases (87.50%) showed joint surface sclerosis in the calcaneal X-ray changes. Forty-seven cases (65.28%) had narrowing of the subtalar joint space; 14 cases showed disappearance of the subtalar joint space, accounting for 19.44%. Among the 6 patients with Kashin-Beck disease, the X-ray changes of the calcaneus showed joint surface sclerosis in 6 cases, narrowing of the subtalar joint space in 4 cases, and disappearance of the subtalar joint space in 2 cases. The length, height, Bohler angle, Gissane angle, and inclination angle of the calcaneus in patients with Kashin-Beck disease were all smaller than those in the osteoarthritis group and the control group, the height to length ratio of the calcaneus was higher than that in the osteoarthritis group and the control group, and the difference was statistically significant ( P < 0.05). The length, height, Bohler angle, Gissane angle, and inclination angle of the calcaneus in patients of the osteoarthritis group were all smaller than those in the control group, and the height to length ratio of the calcaneus was higher than that in control group, and the difference was statistically significant ( P < 0.05). ROC curve analysis showed that the sensitivity of Bohler angle, Gissane angle, and the height to length ratio of the calcaneus in predicting osteoarticular diseases (72 patients with osteoarthritis) were 92.5%, 87.6% and 80.4%, respectively, with specificity of 73.0%, 68.8% and 63.1%, respectively. Conclusion:The calcaneal X-ray manifestations of adult patients with osteoarticular diseases vary greatly, among which Bohler angle, Gissane angle, and height to length ratio of the calcaneus have certain accuracy in diagnosis of osteoarthritis.

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