1.Effects of Tongdu Tiaoshen acupuncture on depression-like behavior and Endophilin A1/ROS pathway in hippocampal tissue of CUMS model rats.
Ling ZOU ; Xiaoge SONG ; Yanbiao ZHAO ; Tingting QIAN ; Yifan CHU ; Wen PAN ; Haoran CHU ; Shaojie YANG ; Meixiang SUN ; Peiyang SUN
Chinese Acupuncture & Moxibustion 2025;45(9):1281-1289
OBJECTIVE:
To observe the effects of Tongdu Tiaoshen acupuncture (for unblocking the obstruction in the governor vessel and regulating the spirit) on depression-like behavior and the hippocampal Endophilin A1/reactive oxygen species (ROS) pathway in the chronic unpredictable mild stress (CUMS) model rats, and explore the mechanism of this therapy for depression.
METHODS:
Forty-eight male SD rats of SPF grade were randomly divided into a normal group (n=12) and a modeling group (n=36). In the modeling group, CUMS was performed to establish depression model. The successfully-modeled rats were randomized into a model group, a Tongdu Tiaoshen acupuncture group (referred to as the acupuncture group), and a fluoxetine group, with 12 rats in each group. In the acupuncture group, "Baihui" (GV20), "Shenting" (GV24), "Shuigou" (GV26) and "Dazhui" (GV14) were stimulated with acupuncture. This intervention measure was delivered once a day, continuously for 6 days; it was discontinued on day 7 and was completed in 28 days. In the fluoxetine group, intragastric administration was done with fluoxetine solution (2.1 mg/kg), once a day, and for 28 consecutive days. Before and after modeling, and after intervention completion, the body mass, sucrose preference rate and the total distance of movement and the boxes of horizontal crossing in the open field experiment were observed in each group. After intervention, using HE staining, the hippocampal neuron morphology was observed; using Nissl staining, the hippocampal Nissl body number was counted. The hippocampal mitochondria was observed under transmission electron microscopy. The average fluorescence intensity of ROS in hippocampal was determined using flow cytometry. With Western blot method, the protein expression of Endophilin A1, growth associated protein 43 (GAP-43), and brain-derived neurotrophic factor (BDNF) in hippocampal was detected; and with RT-qPCR method, the mRNA expression of Endophilin A1, GAP-43, and BDNF was recorded. Using the immunofluorescence, the average fluorescence intensity of Endophilin A1, GAP-43, and BDNF in hippocampal tissue was determined.
RESULTS:
Compared with the normal group, in the model group, the body mass, sucrose preference rate, and the total distance of movement and the boxes of horizontal crossing in the open field experiment decreased (P<0.01); the hippocampal neuronal structure was unclear, the matrix was relatively loose, and the number of Nissl body decreased (P<0.01); mitochondrial structure was disarranged, the outer membrane was ruptured, mitochondrial cristae was irregular or missed; the average fluorescence intensity of ROS in hippocampal tissue, the protein and mRNA expression and the average fluorescence intensity of Endophilin A1 in hippocampal tissue increased (P<0.01), while the protein and mRNA expression of GAP-43 and BDNF and its average fluorescence intensity decreased (P<0.01). Compared with the model group, the acupuncture group and the fluoxetine group showed the increase in body mass, sucrose preference rate, the total distance of movement and the boxes of horizontal crossing in the open field experiment (P<0.05, P<0.01); the hippocampal neuronal structure became relatively clear, the matrix was relatively dense, and the number of Nissl body was elevated (P<0.01); mitochondrial structure got normal and disarranged slightly, the average fluorescence intensity of ROS in hippocampal tissue, the protein and mRNA expression and the average fluorescence intensity of Endophilin A1 in hippocampal tissue were reduced (P<0.01), while the protein and mRNA expression of GAP-43 and BDNF and the average fluorescence intensity rose (P<0.01, P<0.05). Compared with the fluoxetine group, the acupuncture group presented the increase in the average fluorescence intensity of ROS, the protein expression and the average fluorescence intensity of Endophilin A1, the protein expression of GAP-43 and the mRNA expression of BDNF (P<0.01, P<0.05), and the decrease of the protein expression and the average fluorescence intensity of BDNF, the mRNA expression of Endophilin A1, and the average fluorescence intensity of GAP-43 (P<0.01, P<0.05).
CONCLUSION
Tongdu tiaoshen acupuncture alleviates depression-like behaviors in CUMS model rats and protects hippocampal neurons, which may be related to suppressing Endophilin A1/ROS signaling pathway and attenuating oxidative stress reactions.
Animals
;
Male
;
Hippocampus/metabolism*
;
Acupuncture Therapy
;
Rats, Sprague-Dawley
;
Rats
;
Depression/psychology*
;
Humans
;
Reactive Oxygen Species/metabolism*
;
Disease Models, Animal
;
Acupuncture Points
2.Regulatory mechanism of electroacupuncture on hypothalamic-pituitary-testicular axis in oligospermic rats
Zhenning ZHAO ; Kaiying LI ; Nan YANG ; Wenjing SUN ; Xiaoge WEI ; Jing MU ; Huisheng MA
Chinese Journal of Tissue Engineering Research 2025;29(26):5563-5571
BACKGROUND:Electroacupuncture can treat oligoasthenospermia by stimulating hormone synthesis and release in the hypothalamus,pituitary gland and testis,but its mechanism is complex,and the efficacy of electroacupuncture is closely related to the idea of acupoint compatibility.OBJECTIVE:To explore whether electroacupuncture therapy can improve the function status of hypothalamic-pituitary-testicular axis by adjusting the level of serum related sex hormones in rats,so as to treat adenine-induced oligoasthenospermia in rats.METHODS:Fifty adult male Sprague-Dawley rats were randomly divided into blank,model,electroacupuncture,L-carnitine,and non-meridian and non-acupuncture point groups,with 10 rats in each group.Except for the blank group,the rats in the other four groups were given 200 mg/(kg·d)adenine via intragastric administration for 28 days to establish oligoasthenospermia models.After modeling,the rats in the electroacupuncture group were given electroacupuncture treatment at Zhongji,Guanyuan,Zusanli and Sanyinjiao acupoints,the non-acupoint group was selected for electroacupuncture treatment at three non-acupoint points,and the rats in the L-carnitine group were given oral infusion of L-carnitine,once daily,for 28 continuous days.After treatment,the kidney and testicular organ coefficients were calculated.Sperm count,survival rate and motility rate were determined.Pathological morphological changes of kidney and testicular tissues were observed.Serum sex hormones testosterone,gonadotropin releasing hormone,follicle stimulating hormone,luteinizing hormone,estradiol,statin B and prolactin levels were detected in rats of each group.RESULTS AND CONCLUSION:(1)The renal organ coefficient in the model group was higher than that in the blank,electroacupuncture and L-carnitine groups(P<0.05),the renal organ coefficient in the non-acupoint group was higher than that in the electroacupuncture group(P<0.05),and there was no significant difference in the testicular organ coefficient among all groups(P>0.05).(2)Compared with the blank group,sperm count,survival rate and motility rate were decreased in the model group(P<0.05);compared with the model group,sperm count,survival rate and motility rate were increased in the electroacupuncture group and L-carnitine group(P<0.05);compared with the non-acupoint group,sperm count,survival rate and motility rate were higher in the electroacupuncture group(P<0.05).(3)Hematoxylin-eosin staining results indicated that the kidney and testicular tissues of rats in the model group were severely damaged,while damage to kidney and testicular tissues was less in the electroacupuncture group and L-carnitine group compared with the model group,but severer in the non-acupoint group than the electroacupuncture group.(4)Compared with the blank group,the levels of testosterone,gonadotropin releasing hormone,and inhibin B in the serum of rats in the model group were decreased(P<0.05),and the levels of follicle-stimulating hormone,luteinizing hormone,estradiol,and prolactin were increased(P<0.05).Compared with the model group,the levels of testosterone,gonadotropin-releasing hormone,and inhibin B in the serum of rats in the electroacupuncture group and L-carnitine group were increased(P<0.05),and the levels of follicle-stimulating hormone,luteinizing hormone,estradiol,and prolactin were decreased(P<0.05).Compared with the non-acupoint group,the levels of testosterone,gonadotropin-releasing hormone,and inhibin Bin the serum of the rats in electroacupuncture group were increased(P<0.05),and the levels of follicle-stimulating hormone,luteinizing hormone,estradiol,and prolactin were decreased(P<0.05).To conclude,electroacupuncture at Zhongji,Guanyuan,Zusanli,and Sanyinjiao acupoints can effectively treat oligoasthenospermia by regulating the functional state of the hypothalamic-pituitary-testicular axis in rats.
3.A systematic review of validation studies on the performance of GLIM criteria for malnutrition assessment
Yongshuai MENG ; Yanjuan LU ; Chunlei LIU ; Huilin JIA ; Mengying SUN ; Xiaoge HE ; Xiaoya SHENG ; Linna ZHANG ; Yinan MA ; Sangsang KE ; Lichuan ZHANG ; Qian LU
Chinese Journal of Clinical Nutrition 2025;33(4):290-298
Objective:To systematically evaluate studies validating the performance of the Global Leadership Initiative on Malnutrition (GLIM) in diagnosing malnutrition.Methods:Seven Chinese and English databases including Embase, Web of Science (WOS), PubMed, CINAHL, Cochrane Library, SinoMed, CNKI, Wanfang Data, and VIP Database were searched for articles on the validation of GLIM criteria published between September 2018 and September 2024. Two researchers independently performed literature screening and data extraction. The concurrent and predictive validity of the criteria was analyzed.Results:A total of 136 papers were included for analysis. The GLIM criteria for diagnosing malnutrition had a sensitivity of 77%, a specificity of 87%, and an area under the curve (AUC) of 0.90. Malnutrition diagnosed by the GLIM criteria predicted prolonged hospital and intensive care unit (ICU) stays, increased readmission and complication rates (both overall and infectious), reduced survivals (median, overall, and disease-free), and increased in-hospital and follow-up mortalities. Both moderate and severe malnutrition predicted decreased overall survival. However, only three studies analyzed the impact of nutritional therapy on the clinical outcomes of malnourished patients.Conclusions:The GLIM criteria accurately differentiate malnutrition and are a valid predictive tool of clinical outcomes. However, the validity criteria in these validation studies were questionable, along with high methodological heterogeneity. Furthermore, there is a lack of studies validating the role of nutritional therapy in improving the clinical outcomes of malnourished patients.
4.A real-world study of radiotherapy sequential immunotherapy for stage III non-small cell lung cancer
Congxiu HUANG ; Shaojun WANG ; Yu LIN ; Xiaoge SUN ; Zhilong YU ; Hao YANG ; Zhanbiao HE
Chinese Journal of Radiation Oncology 2025;34(1):57-64
Objective:To evaluate the effects of sequential immunotherapy with radiotherapy on survival time and immune function in patients with unresectable stage III non-small cell lung cancer (NSCLC) in a real-world study.Methods:Data of 84 patients with unresectable stage III NSCLC who were treated at the Affiliated Hospital of Inner Mongolia Medical University from January 2021 to December 2022 (retrospective cohort) and from January 2023 to December 2023 (prospective cohort) were collected. The patients were divided into the combination group ( n=40) and radiotherapy group ( n=44) based on whether they received sequential immunotherapy or not. The progression-free survival (PFS) and overall survival (OS) between two groups were compared using standardized mortality ratio weighting (SMRW). Univariate Cox proportional hazards model, multivariate regression analysis, multi-model comparison of propensity score matching and subgroup analysis were emploed to analyze the robustness of clinical efficacy between two groups. E-value analysis was used to analyze the sensitivity of unmeasured confounding factors in observational studies. Additionally, the percentage of CD4 +T cells, CD8 +T cells and natural killer (NK) cells, and CD4 +/CD8 + T cell ratio before and after treatment between two groups were compared using analysis of covariance. Results:Among 84 patients, 77 (92%) cases were male and 7 (8%) were female. Among them, 42 (50%) were aged 65 years or older. The variables showed high homogeneity after SMRW, with a standardized mean difference of less than 0.1. In the combination group, the median PFS [17.0 months vs. 7.0 months, HR=0.260, 95% CI: 0.130-0.490, P<0.001] and OS [not reached vs. 24.0 months, HR=0.210, 95% CI: 0.070-0.590, P=0.002] were significantly longer compared to that in the radiotherapy group, with statistically significant differences. The study results were confirmed by robustness and sensitivity analyses. After treatment, patients in the combination group showed a statistically significant increase in the percentage of CD4 + T cells and NK cells, and CD4 +/CD8 + T cell ratio, as well as a decrease in the percentage of CD8 + T cells compared to those in the radiotherapy group (all P<0.05). Conclusions:Sequential immunotherapy following radiotherapy can significantly improve survival and prognosis of unresectable stage III NSCLC patients. The survival benefit is even greater when combined with chemotherapy. The main mechanism of the survival benefit may be the improvement of anti-tumor immune function.
5.Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: the initial results of a randomized controlled clinical trial (STELLAR II)
Haoyue LI ; Haitao ZHOU ; Lichun WEI ; Yinggang CHEN ; Wenjue ZHANG ; Feiyan DENG ; Ning LI ; Zheng JIANG ; Zheng LIU ; Jianwei LIANG ; Zhaoxu ZHENG ; Xianyu MENG ; Yufei LU ; Zifa LEI ; Xiaoge SUN ; Gong LI ; Yingjie WANG ; Yongwen SONG ; Shunan QI ; Hao JING ; Yirui ZHAI ; Shulian WANG ; Yexiong LI ; Yuan TANG ; Jing JIN
Chinese Journal of Oncology 2025;47(9):913-921
Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.
6.Regulatory mechanism of electroacupuncture on hypothalamic-pituitary-testicular axis in oligospermic rats
Zhenning ZHAO ; Kaiying LI ; Nan YANG ; Wenjing SUN ; Xiaoge WEI ; Jing MU ; Huisheng MA
Chinese Journal of Tissue Engineering Research 2025;29(26):5563-5571
BACKGROUND:Electroacupuncture can treat oligoasthenospermia by stimulating hormone synthesis and release in the hypothalamus,pituitary gland and testis,but its mechanism is complex,and the efficacy of electroacupuncture is closely related to the idea of acupoint compatibility.OBJECTIVE:To explore whether electroacupuncture therapy can improve the function status of hypothalamic-pituitary-testicular axis by adjusting the level of serum related sex hormones in rats,so as to treat adenine-induced oligoasthenospermia in rats.METHODS:Fifty adult male Sprague-Dawley rats were randomly divided into blank,model,electroacupuncture,L-carnitine,and non-meridian and non-acupuncture point groups,with 10 rats in each group.Except for the blank group,the rats in the other four groups were given 200 mg/(kg·d)adenine via intragastric administration for 28 days to establish oligoasthenospermia models.After modeling,the rats in the electroacupuncture group were given electroacupuncture treatment at Zhongji,Guanyuan,Zusanli and Sanyinjiao acupoints,the non-acupoint group was selected for electroacupuncture treatment at three non-acupoint points,and the rats in the L-carnitine group were given oral infusion of L-carnitine,once daily,for 28 continuous days.After treatment,the kidney and testicular organ coefficients were calculated.Sperm count,survival rate and motility rate were determined.Pathological morphological changes of kidney and testicular tissues were observed.Serum sex hormones testosterone,gonadotropin releasing hormone,follicle stimulating hormone,luteinizing hormone,estradiol,statin B and prolactin levels were detected in rats of each group.RESULTS AND CONCLUSION:(1)The renal organ coefficient in the model group was higher than that in the blank,electroacupuncture and L-carnitine groups(P<0.05),the renal organ coefficient in the non-acupoint group was higher than that in the electroacupuncture group(P<0.05),and there was no significant difference in the testicular organ coefficient among all groups(P>0.05).(2)Compared with the blank group,sperm count,survival rate and motility rate were decreased in the model group(P<0.05);compared with the model group,sperm count,survival rate and motility rate were increased in the electroacupuncture group and L-carnitine group(P<0.05);compared with the non-acupoint group,sperm count,survival rate and motility rate were higher in the electroacupuncture group(P<0.05).(3)Hematoxylin-eosin staining results indicated that the kidney and testicular tissues of rats in the model group were severely damaged,while damage to kidney and testicular tissues was less in the electroacupuncture group and L-carnitine group compared with the model group,but severer in the non-acupoint group than the electroacupuncture group.(4)Compared with the blank group,the levels of testosterone,gonadotropin releasing hormone,and inhibin B in the serum of rats in the model group were decreased(P<0.05),and the levels of follicle-stimulating hormone,luteinizing hormone,estradiol,and prolactin were increased(P<0.05).Compared with the model group,the levels of testosterone,gonadotropin-releasing hormone,and inhibin B in the serum of rats in the electroacupuncture group and L-carnitine group were increased(P<0.05),and the levels of follicle-stimulating hormone,luteinizing hormone,estradiol,and prolactin were decreased(P<0.05).Compared with the non-acupoint group,the levels of testosterone,gonadotropin-releasing hormone,and inhibin Bin the serum of the rats in electroacupuncture group were increased(P<0.05),and the levels of follicle-stimulating hormone,luteinizing hormone,estradiol,and prolactin were decreased(P<0.05).To conclude,electroacupuncture at Zhongji,Guanyuan,Zusanli,and Sanyinjiao acupoints can effectively treat oligoasthenospermia by regulating the functional state of the hypothalamic-pituitary-testicular axis in rats.
7.A real-world study of radiotherapy sequential immunotherapy for stage III non-small cell lung cancer
Congxiu HUANG ; Shaojun WANG ; Yu LIN ; Xiaoge SUN ; Zhilong YU ; Hao YANG ; Zhanbiao HE
Chinese Journal of Radiation Oncology 2025;34(1):57-64
Objective:To evaluate the effects of sequential immunotherapy with radiotherapy on survival time and immune function in patients with unresectable stage III non-small cell lung cancer (NSCLC) in a real-world study.Methods:Data of 84 patients with unresectable stage III NSCLC who were treated at the Affiliated Hospital of Inner Mongolia Medical University from January 2021 to December 2022 (retrospective cohort) and from January 2023 to December 2023 (prospective cohort) were collected. The patients were divided into the combination group ( n=40) and radiotherapy group ( n=44) based on whether they received sequential immunotherapy or not. The progression-free survival (PFS) and overall survival (OS) between two groups were compared using standardized mortality ratio weighting (SMRW). Univariate Cox proportional hazards model, multivariate regression analysis, multi-model comparison of propensity score matching and subgroup analysis were emploed to analyze the robustness of clinical efficacy between two groups. E-value analysis was used to analyze the sensitivity of unmeasured confounding factors in observational studies. Additionally, the percentage of CD4 +T cells, CD8 +T cells and natural killer (NK) cells, and CD4 +/CD8 + T cell ratio before and after treatment between two groups were compared using analysis of covariance. Results:Among 84 patients, 77 (92%) cases were male and 7 (8%) were female. Among them, 42 (50%) were aged 65 years or older. The variables showed high homogeneity after SMRW, with a standardized mean difference of less than 0.1. In the combination group, the median PFS [17.0 months vs. 7.0 months, HR=0.260, 95% CI: 0.130-0.490, P<0.001] and OS [not reached vs. 24.0 months, HR=0.210, 95% CI: 0.070-0.590, P=0.002] were significantly longer compared to that in the radiotherapy group, with statistically significant differences. The study results were confirmed by robustness and sensitivity analyses. After treatment, patients in the combination group showed a statistically significant increase in the percentage of CD4 + T cells and NK cells, and CD4 +/CD8 + T cell ratio, as well as a decrease in the percentage of CD8 + T cells compared to those in the radiotherapy group (all P<0.05). Conclusions:Sequential immunotherapy following radiotherapy can significantly improve survival and prognosis of unresectable stage III NSCLC patients. The survival benefit is even greater when combined with chemotherapy. The main mechanism of the survival benefit may be the improvement of anti-tumor immune function.
8.A systematic review of validation studies on the performance of GLIM criteria for malnutrition assessment
Yongshuai MENG ; Yanjuan LU ; Chunlei LIU ; Huilin JIA ; Mengying SUN ; Xiaoge HE ; Xiaoya SHENG ; Linna ZHANG ; Yinan MA ; Sangsang KE ; Lichuan ZHANG ; Qian LU
Chinese Journal of Clinical Nutrition 2025;33(4):290-298
Objective:To systematically evaluate studies validating the performance of the Global Leadership Initiative on Malnutrition (GLIM) in diagnosing malnutrition.Methods:Seven Chinese and English databases including Embase, Web of Science (WOS), PubMed, CINAHL, Cochrane Library, SinoMed, CNKI, Wanfang Data, and VIP Database were searched for articles on the validation of GLIM criteria published between September 2018 and September 2024. Two researchers independently performed literature screening and data extraction. The concurrent and predictive validity of the criteria was analyzed.Results:A total of 136 papers were included for analysis. The GLIM criteria for diagnosing malnutrition had a sensitivity of 77%, a specificity of 87%, and an area under the curve (AUC) of 0.90. Malnutrition diagnosed by the GLIM criteria predicted prolonged hospital and intensive care unit (ICU) stays, increased readmission and complication rates (both overall and infectious), reduced survivals (median, overall, and disease-free), and increased in-hospital and follow-up mortalities. Both moderate and severe malnutrition predicted decreased overall survival. However, only three studies analyzed the impact of nutritional therapy on the clinical outcomes of malnourished patients.Conclusions:The GLIM criteria accurately differentiate malnutrition and are a valid predictive tool of clinical outcomes. However, the validity criteria in these validation studies were questionable, along with high methodological heterogeneity. Furthermore, there is a lack of studies validating the role of nutritional therapy in improving the clinical outcomes of malnourished patients.
9.Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: the initial results of a randomized controlled clinical trial (STELLAR II)
Haoyue LI ; Haitao ZHOU ; Lichun WEI ; Yinggang CHEN ; Wenjue ZHANG ; Feiyan DENG ; Ning LI ; Zheng JIANG ; Zheng LIU ; Jianwei LIANG ; Zhaoxu ZHENG ; Xianyu MENG ; Yufei LU ; Zifa LEI ; Xiaoge SUN ; Gong LI ; Yingjie WANG ; Yongwen SONG ; Shunan QI ; Hao JING ; Yirui ZHAI ; Shulian WANG ; Yexiong LI ; Yuan TANG ; Jing JIN
Chinese Journal of Oncology 2025;47(9):913-921
Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.
10.CMPK2 promotes CD4+T cell pyroptosis via NLRP3 in systemic lupus erythematosus
Yanan Tan ; Gege Jiang ; Li Jin ; Nan Xiang ; Xiaoge Sun ; Xiaoyi Jia ; Min Zhang
Acta Universitatis Medicinalis Anhui 2024;59(12):2215-2221
Objective:
To investigate the levels of cytidine/uridine monophosphate kinase 2(CMPK2) expression in CD4+T cells of systemic lupus erythematosus(SLE) patients and its correlation with clinical indicators. Additionally, to explore whether CMPK2 can induce pyroptosis in CD4+T cells of SLE patients through NLRP3, potentially providing a new target for the diagnosis and treatment of SLE.
Methods:
RT-qPCR and Western blot analyses were used to assess the gene and protein expression levels of CMPK2 in SLE CD4+T cells and healthy controls(HC). Pearson or Spearman correlation analysis was performed to evaluate the relationship between CMPK2 mRNA expression levels and clinical indicators. Subsequently, the expression levels of pyroptosis-related proteins, including NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), caspase-1, gasdermin D(GSDMD), and the N-terminal domain of GSDMD(GSDMD-N), were examined in SLE CD4+T cells and HC. Furthermore, the protein expression levels of NLRP3, ASC, caspase-1, GSDMD, and GSDMD-N were detected after silencingCMPK2in SLE CD4+T cells.
Results:
CMPK2 expression was significantly elevated in SLE CD4+T cells, exhibiting a positive correlation with SLE disease activity index(SLEDAI), anti-dsDNA antibody, anti-nucleosome antibody, anti-C1q antibody, and a negative correlation with complement C3 and C4 levels. Additionally, the expression levels of pyroptosis-related proteins, including NLRP3, ASC, caspase-1, GSDMD, and GSDMD-N significantly increased in SLE CD4+T cells(P<0.05), Moreover, the levels of cytokines IL-1β and IL-18 in the cell culture supernatants were elevated, and there was a notable increase in the rate of cellular pyroptosis(P<0.05). Silencing CMPK2 led to a reduction in the levels of these markers(P<0.05).
Conclusion
CMPK2 is highly expressed in SLE CD4+T cells and may serve as a diagnostic marker for SLE. Moreover, it is likely involved in the pathogenesis of SLE by promoting CD4+T cell pyroptosis through NLRP3.


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