1.Simvastatin alleviates kidney ischemia reperfusion injury by inhibiting ferroptosis
Zhihui FU ; Zhongzhong LIU ; Qifa YE ; Qi XIAO ; Qin DENG ; Jiansheng XIAO ; Biqi FU
Acta Universitatis Medicinalis Anhui 2026;61(1):45-52
ObjectiveTo investigate the effect and mechanism of simvastatin pretreatment on kidney ischemia reperfusion injury (IRI) in mice. MethodsFifteen male C57BL/6 mice aged 6-8 weeks were divided into three groups: Sham operation group (Sham group), kidney IRI group (IR group), and simvastatin pretreatment+kidney IRI group (SIM group). Hematoxylin-eosin (HE) staining of kidney tissue and detection of serum creatinine (SCr) and lactate dehydrogenase (LDH) were used to evaluate kidney injury. The levels of superoxide dismutase (SOD), reduced glutathione (GSH), malondialdehyde (MDA) and reactive oxygen species (ROS) were detected to evaluate oxidative stress. The contents of ferrous iron (Fe2+) and ferric iron (Fe3+) in kidney tissue were detected, and the morphological changes of mitochondria were observed by transmission electron microscope. The relative expression levels of Kruppel-like factor 2 (KLF2), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-coa synthetase long chain family member 4 (ACSL4) protein in kidney tissue were detected. ResultsCompared with the IR group, the SIM group had significantly reduced renal tubular injury and decreased contents of Scr and LDH in serum (P < 0.001). It also showed increased expression of SOD and GSH and decreased expression of MDA and ROS (P < 0.01). Simvastatin pretreatment reduced the contents of Fe2+ and Fe3+ in the tissues (P < 0.01) and alleviated mitochondrial damage. It also promoted the expression of KLF2 (P < 0.01), up-regulated the expression of ferroptosis-related protective proteins GPX4 and SLC7A11, and down-regulated the expression of ferroptosis-related damage protein ACSL4 (P < 0.05). ConclusionSimvastatin pretreatment may inhibit kidney ferroptosis by promoting the expression of KLF2 to alleviate kidney IRI.
2.Clinical Efficacy of Yishen Jiangtang Decoction Combined with Conventional Western Medicine Treatment for Diabetic Kidney Disease with Pattern of Qi-Yin Deficiency Combined with Dampness-heat and Blood Stasis
Yunjie YANG ; Yasheng DENG ; Kaiying HE ; Qi ZHANG ; Yongxin YU ; Yaqing RUAN ; Zhuang HAN ; Qiwei CHEN ; Yi WEI ; Qiu CHEN ; Jing WU ; Mingqian JIANG ; Shiwei RUAN ; Jianting WANG ; Yuliang QIU ; Lixiang ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):157-167
ObjectiveTo observe the clinical efficacy and safety of Yishen Jiangtang decoction combined with conventional Western medicine treatment in managing stage G3A3 diabetic kidney disease (DKD) in the patients with the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis, and to explore its mechanism of inhibiting the endoplasmic reticulum stress (ERS)-apoptosis axis and delaying renal fibrosis (RF). MethodsA single-center, randomized, parallel-controlled clinical trial was conducted. A total of 78 patients diagnosed with stage G3A3 DKD and traditional Chinese medicine (TCM) pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis and treated in the Department of Nephrology and the Department of Endocrinology of the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine from March 2025 to February 2026 were enrolled. They were randomly assigned at a 1∶1 ratio into a control group (conventional Western medicine treatment) and an experimental group (Yishen Jiangtang decoction combined with conventional Western medicine treatment), with 39 patients in each group. The treatment lasted for 12 weeks. Basic demographic data and medical history were collected before and after treatment. The two groups before and after treatment were compared in terms of the following parameters: Blood urea nitrogen (BUN), serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Enzyme-linked immunosorbent assay (ELISA) kits were used to measure serum glucose-regulated protein 78 (GRP78), serum cysteinyl aspartate-specific protease-3 (Caspase-3), and serum and urinary transforming growth factor-β1 (TGF-β1) levels before and after treatment. TCM symptom scores, TCM syndrome efficacy, and overall clinical efficacy were evaluated before and after treatment. Spearman correlation analysis was performed to explore the correlations of serum levels of GRP78 and Caspase-3, as well as serum and urinary levels of TGF-β1, with renal function, proteinuria, and glucose and lipid metabolism indicators in patients with DKD. In addition, safety indicators were also monitored. ResultsA total of 75 patients completed the study (38 in the control group and 37 in the experimental group). ① Baseline data: The two groups were comparable in terms of sex and age, with no statistically significant difference. ② Efficacy outcomes: Compared with baseline levels, both groups showed reductions in BUN, SCr, UACR, FBG, TG, TC, LDL-C, and TCM symptom scores (P<0.01) and increases in eGFR level (P<0.01). Moreover, the experimental group outperformed the control group in altering the indicators above (P<0.05). Regarding TCM syndrome efficacy, the total response rate in the experimental group was 83.78%, which was higher than that (57.89%) in the control group (P<0.05). Regarding overall clinical efficacy, the total response rate in the experimental group was 78.38%, which was higher than that (50.00%) in the control group (P<0.05). ③ Mechanism outcomes: Compared with baseline levels, both groups showed declined serum levels of GRP78, Caspase-3, and TGF-β1 and urinary level of TGF-β1 after treatment (P<0.01). Moreover, the experimental group showed greater declines than the control group (P<0.05). The serum levels of GRP78, Caspase-3,and TGF-β1 and the urinary level of TGF-β1 in DKD patients showed positive correlations with BUN, SCr, UACR, and FBG and negative correlations with eGFR (P<0.05). ④ Safety outcomes: Neither group showed drug-related adverse reactions, and laboratory safety parameters remained within normal ranges. ConclusionYishen Jiangtang decoction combined with conventional Western medicine treatment may safely and effectively alleviate clinical symptoms, correct glucose and lipid metabolism disorders, and protect the renal function in patients with stage G3A3 DKD and the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis. The mechanism may be associated with inhibition of the ERS-apoptosis axis and delay of the RF process.
3.Clinical Efficacy of Yishen Jiangtang Decoction Combined with Conventional Western Medicine Treatment for Diabetic Kidney Disease with Pattern of Qi-Yin Deficiency Combined with Dampness-heat and Blood Stasis
Yunjie YANG ; Yasheng DENG ; Kaiying HE ; Qi ZHANG ; Yongxin YU ; Yaqing RUAN ; Zhuang HAN ; Qiwei CHEN ; Yi WEI ; Qiu CHEN ; Jing WU ; Mingqian JIANG ; Shiwei RUAN ; Jianting WANG ; Yuliang QIU ; Lixiang ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):157-167
ObjectiveTo observe the clinical efficacy and safety of Yishen Jiangtang decoction combined with conventional Western medicine treatment in managing stage G3A3 diabetic kidney disease (DKD) in the patients with the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis, and to explore its mechanism of inhibiting the endoplasmic reticulum stress (ERS)-apoptosis axis and delaying renal fibrosis (RF). MethodsA single-center, randomized, parallel-controlled clinical trial was conducted. A total of 78 patients diagnosed with stage G3A3 DKD and traditional Chinese medicine (TCM) pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis and treated in the Department of Nephrology and the Department of Endocrinology of the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine from March 2025 to February 2026 were enrolled. They were randomly assigned at a 1∶1 ratio into a control group (conventional Western medicine treatment) and an experimental group (Yishen Jiangtang decoction combined with conventional Western medicine treatment), with 39 patients in each group. The treatment lasted for 12 weeks. Basic demographic data and medical history were collected before and after treatment. The two groups before and after treatment were compared in terms of the following parameters: Blood urea nitrogen (BUN), serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Enzyme-linked immunosorbent assay (ELISA) kits were used to measure serum glucose-regulated protein 78 (GRP78), serum cysteinyl aspartate-specific protease-3 (Caspase-3), and serum and urinary transforming growth factor-β1 (TGF-β1) levels before and after treatment. TCM symptom scores, TCM syndrome efficacy, and overall clinical efficacy were evaluated before and after treatment. Spearman correlation analysis was performed to explore the correlations of serum levels of GRP78 and Caspase-3, as well as serum and urinary levels of TGF-β1, with renal function, proteinuria, and glucose and lipid metabolism indicators in patients with DKD. In addition, safety indicators were also monitored. ResultsA total of 75 patients completed the study (38 in the control group and 37 in the experimental group). ① Baseline data: The two groups were comparable in terms of sex and age, with no statistically significant difference. ② Efficacy outcomes: Compared with baseline levels, both groups showed reductions in BUN, SCr, UACR, FBG, TG, TC, LDL-C, and TCM symptom scores (P<0.01) and increases in eGFR level (P<0.01). Moreover, the experimental group outperformed the control group in altering the indicators above (P<0.05). Regarding TCM syndrome efficacy, the total response rate in the experimental group was 83.78%, which was higher than that (57.89%) in the control group (P<0.05). Regarding overall clinical efficacy, the total response rate in the experimental group was 78.38%, which was higher than that (50.00%) in the control group (P<0.05). ③ Mechanism outcomes: Compared with baseline levels, both groups showed declined serum levels of GRP78, Caspase-3, and TGF-β1 and urinary level of TGF-β1 after treatment (P<0.01). Moreover, the experimental group showed greater declines than the control group (P<0.05). The serum levels of GRP78, Caspase-3,and TGF-β1 and the urinary level of TGF-β1 in DKD patients showed positive correlations with BUN, SCr, UACR, and FBG and negative correlations with eGFR (P<0.05). ④ Safety outcomes: Neither group showed drug-related adverse reactions, and laboratory safety parameters remained within normal ranges. ConclusionYishen Jiangtang decoction combined with conventional Western medicine treatment may safely and effectively alleviate clinical symptoms, correct glucose and lipid metabolism disorders, and protect the renal function in patients with stage G3A3 DKD and the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis. The mechanism may be associated with inhibition of the ERS-apoptosis axis and delay of the RF process.
4.Traditional Chinese Medicine Intervention in Depression Based on Signaling Pathway Regulation: A Review
Jinjiang XU ; Li WU ; Qi ZHANG ; Yasheng DENG ; Jingjing XIE ; Haobin CHEN ; En ZHAO ; Man ZHANG ; Jianye DAI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):319-328
Depression is a common psychiatric disorder characterized by persistent low mood or mental disorders. Current treatments primarily focus on regulating neurotransmitter levels, but their effectiveness is limited. The mechanisms underlying its onset are complex, and there is no unified consensus. Abnormal signaling pathway transmission plays a crucial role in the development of depression, involving multiple pathways, including Toll-like receptor 4/nucleotide-binding oligomerization domain-like receptor protein 3 (TLR4/NLRP3), nuclear factor-κB (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), brain-derived neurotrophic factor/tyrosine kinase receptor B (BDNF/TrkB), cyclic AMP/protein kinase A/cAMP response element-binding protein (cAMP/PKA/CREB), and others. Traditional Chinese medicine(TCM) is based on a holistic approach and the principle of treatment based on the differentiation of syndromes, regulating the balance of multiple systems and organ functions from a macroscopic perspective. This approach has shown unique advantages in the treatment of depression. TCM attributes the onset of depression to dysfunction of the organ systems, involving liver Qi stagnation, heart spirit deficiency, kidney essence depletion, and spleen dysfunction. TCM compound treatments focus on soothing the liver, strengthening the spleen, calming the heart, and replenishing essence, with formulas such as Xiaoyaosan, Zishui Qinggan Yin, and Chahu Jia Guizhi Longgu Muli Tang. The active components of Chinese herbs mainly aim to tonify and regulate Qi, such as salidroside, ginsenoside Rb1, astragaloside, and muscone. External TCM treatments, primarily acupuncture, aim to open the orifices and invigorate the spirit. Acupoints such as Baihui, Shenting, and Yintang are commonly used. Additionally, massage and moxibustion therapy can intervene in depression by regulating signaling pathways. This article reviews the core role of signaling pathways in the development of depression and the mechanism of TCM regulation of signaling pathways to intervene in depression, aiming to discover new therapeutic approaches that can improve the symptoms of depressed patients.
5.Structure and Function of GPR126/ADGRG6
Ting-Ting WU ; Si-Qi JIA ; Shu-Zhu CAO ; De-Xin ZHU ; Guo-Chao TANG ; Zhi-Hua SUN ; Xing-Mei DENG ; Hui ZHANG
Progress in Biochemistry and Biophysics 2025;52(2):299-309
GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.
6.A study on the value of thromboelastography-guided antiplatelet therapy in preventing cerebral ischemic events after stent-assisted coil embolization of intracranial aneurysms
Yingqi WANG ; Xiaoming ZHOU ; Qi WU ; An ZHANG ; Hui DING ; Shujuan CHEN ; Jinlong DENG ; Xin ZHANG
Chinese Journal of Cerebrovascular Diseases 2025;22(6):395-402
Objective To investigate the value of adjusting antiplatelet treatment regimens guided by thromboelastography(TEG)in predicting cerebral ischemic events after stent-assisted embolization of intracranial aneurysms.Methods This study retrospectively and consecutively enrolled patients with intracranial aneurysms who underwent stent-assisted coil embolization admitted to the Department of Neurosurgery of the General Hospital of Eastern Theater Command,from March 2022 to May 2024.Baseline and clinical data of the patients,including gender,age,hypertension,diabetes,dyslipidemia,smoking history,drinking history,and intraoperative use of tirofiban were collected.Antiplatelet therapy(conventional dose aspirin[100 mg once daily]+clopidogrel[75 mg once daily])was initiated immediately after the diagnosis of intracranial aneurysm,and TEG was performed 3 days later.According to the platelet inhibition rate in TEG parameters(platelet inhibition rate induced by arachidonic acid[AA]pathway[AA inhibition rate]or adenosine diphosphate[ADP]pathway[ADP inhibition rate],AA inhibition rate ≥ 50%indicated aspirin effectiveness,AA inhibition rate<50%indicated aspirin resistance;ADP inhibition rate ≥ 30%indicated clopidogrel effectiveness,ADP inhibition rate<30%indicated clopidogrel resistance),the patients were divided into the control group(TEG test results met the criteria,i.e.,AA inhibition rate ≥ 50%and ADP inhibition rate ≥ 30%),the conventional dual antiplatelet therapy group(TEG test results did not meet the criteria but were not adjusted for antiplatelet therapy,i.e.,AA inhibition rate<50%and/or ADP inhibition rate<30%,but with complex aneurysm morphology[such as irregular shape,daughter sac formation]or high bleeding risk,continuing conventional dual antiplatelet therapy),and the intensified group(TEG test results did not meet the criteria and the antiplatelet therapy regimen was adjusted,i.e.,AA inhibition rate<50%and/or ADP inhibition rate<30%,adjusting the antiplatelet therapy regimen).All patients underwent stent-assisted coil embolization after TEG testing.From 0 to 3 months after the operation,all three groups maintained the above antiplatelet therapy.At 3 months after the operation,routine head MRI,CT and other examinations were performed.If no cerebral ischemic events occurred and the imaging results were satisfactory(good stent position,no aneurysm occlusion residual or slight residual at the neck[neck width of the aneurysm 2mm]),the treatment could be adjusted to single antiplatelet therapy(aspirin 100 mg once daily).If a patient experienced a cerebral ischemic event during the follow-up period,regardless of the stage after the operation,dual antiplatelet therapy(aspirin[100mg once daily]+clopidogrel[75 mg once daily])was immediately restarted or maintained and continued for at least 6 months.The primary endpoint was intraoperative and 6-months postoperative cerebral ischemic events(including DSA-confirmed intraoperative acute thrombosis and infarction foci confirmed by head CT or MRI).Baseline and clinical data of the three groups were compared.All patients were divided into groups with ischemic stroke event and without according to the primary endpoint,univariate Logistic regression analysis was then performed on both groups.Variables with P<0.1 in the univariate Logistic regression analysis were included in the multivariate Logistic regression analysis to explore the influencing factors of cerebral ischemic events after stent-assisted coil embolization for intracranial aneurysms.Results A total of 499 patients were included,including 178 males and 321 females,with a median age of 59(53,68)years.Among them,there were 341 patients in the control group,42 in the conventional dual antiplatelet therapy group,and 116 in the intensified group.There were 47 cases of cerebral ischemic events and 452 cases without cerebral ischemic events.There was a statistically significant difference in the intraoperative use rate of tirofiban across the control group,the conventional dual antiplatelet therapy group,and the intensified group(20.2%[69/341]vs.26.2%[11/42]vs.42.2%[49/116],P<0.01);no statistically significant differences were observed among the three groups in terms of age,gender composition,the proportion of patients with hypertension,diabetes,dyslipidemia,smoking history,drinking history,and the incidence of cerebral ischemic events(all P>0.05).The results of multivariate Logistic regression analysis showed that hypertension(OR,2.924,95%CI 1.416-6.037,P=0.004)and intraoperative use of tirofiban(OR,3.638,95%CI 1.892-6.996,P<0.01)were independent risk factors for intraoperative and 6-months postoperative cerebral ischemic events after stent-assisted coil embolization in patients with intracranial aneurysms.In comparison with the control group,the intensified group has reduced the risk of cerebral ischemic events(OR,0.238,95%CI 0.088-0.646,P=0.005),while there was no statistically significant difference between the conventional dual antiplatelet therapy group and the control group(OR,0.521,95%CI 0.149-1.826,P=0.308).Conclusions This study demonstrates that adjusting the antiplatelet therapy regimens in patients with intracranial aneurysms who did not meet the platelet inhibition rate based on TEG results can significantly reduce the risk of intraoperative and 6-months postoperative cerebral ischemic events.These finding may require validation through further,large-scaled,prospective studies.
7.Machine learning-based prediction of accelerated corneal collagen cross-linking surgery outcomes
Qi WAN ; Li CHEN ; Ran WEI ; Hongbo YIN ; Jing TANG ; Yingping DENG ; Ke MA
Chinese Journal of Experimental Ophthalmology 2025;43(4):323-334
Objective:To use machine learning to predict the efficacy of accelerated corneal collagen cross-linking (A-CXL) surgery, identify prognostic factors, and construct models to predict postoperative disease progression.Methods:A single-center retrospective study was conducted.A total of 82 keratoconus patients (112 eyes) who underwent A-CXL surgery at the West China Hospital of Sichuan University between March and December 2021 were enrolled.Preoperative and follow-up examinations included anterior segment evaluation by slit-lamp microscopy, corneal topography using Pentacam, and corneal biomechanical indices using Corvis ST.Disease progression was defined as an increase in maximum keratometry (Kmax) of ≥1 D from the preoperative level at the last follow-up.Various machine learning algorithms were employed to analyze corneal topography, biomechanical parameters and corneal densitometry values to identify prognostic factors and construct models for predicting postoperative disease progression.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of West China Hospital, Sichuan University (No.2023496).Written informed consent was obtained from each subject.Results:During follow-up, 15.1% (17/112) of the eyes showed progression after A-CXL.The preoperative astigmatism and stress-strain index (SSI) in the progression group were (-5.41±2.72)D and 1.41±0.78, respectively, which were significantly higher than (-3.30±2.54)D and 0.95±0.98 in the non-progression group ( t=2.80, 2.03; both P<0.05).Cox regression analysis identified preoperative astigmatism (hazard ratio [HR]=1.20), SSI (HR=1.10), and anterior corneal densitometry of 2-6 mm (CDA6) (HR=2.10) as significant risk factors for post-A-CXL progression.Among various machine learning models developed and validated, the area under the curve (AUC) values for logistic regression, multilayer perceptron (MLP) model, and random forest (RF) exceeded 0.700.For F1-score, the AUC values for logistic regression, MLP, and RF were 0.870, 0.880, and 0.880, respectively.The network structure of the visualized MLP was a single-layer, 24-neurons neural network with 80% accuracy in predicting whether progression occurred after A-CXL.The clinical nomogram developed in conjunction with astigmatism, SSI, and CDA6 predicted the cumulative probability of progression at 0.5, 1, and 2 years postoperatively based on the sum of the specified values for each variable, and based on the optimal cutoff value, keratoconus corneas could be classified into high-, intermediate-, and low-risk groups, respectively.The time-dependent subject operating characteristic curves of the nomogram showed AUCs of 0.734, 0.685, and 0.935 at 0.5, 1, and 2 years postoperatively, respectively, all of which performed well in predicting progression. Conclusions:Preoperative astigmatism, SSI, and CDA6 are significant risk factors for post-A-CXL progression in keratoconus.The MLP model can accurately predict postoperative disease progression, and the clinical nomogram combining preoperative astigmatism, SSI, and CDA6 can effectively differentiate between low-, medium-, and high-risk postoperative progression outcomes.
8.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.
9.Retrospective study on misidentification of bone injuries
Tinghong WANG ; Lirong QIU ; Qi LENG ; Yisi HUANG ; Wei ZHANG ; Lixia ZHANG ; Xiaodong DENG ; Zhenhua DENG ; Yun LIU
Chinese Journal of Forensic Medicine 2025;40(2):142-149
Objective This study aims to investigate controversial cases of forensic clinical re-identification of fractures,exploring the characteristics,causes,and countermeasures related to identification errors in primary bone injuries,complications,and subsequent changes.The goal is to provide identification strategies for similar cases regarding the collection of identification materials,timing,and examination method selection,ultimately establishing a paradigm for such identifications.Methods A total of 103 cases of clinical re-identification of fractures accepted by the West China Forensic Identification Center from 2020 to 2024 were collected,and the data from initial identifications and re-identifications were retrospectively analyzed.Results Male cases accounted for 69.90%of the re-identifications,with disability grade(67.96%)and injury degree(30.10%)being the primary concerns.Individual requests represented a high proportion(92.86%)in the initial assessment of disability levels,while unit or joint requests dominated the re-assessment(92.86%).The agreement rates for disability grade and injury degree were 55.26%and 59.38%,respectively.The reassessment of disability grades primarily involved fractures of limb long bones,spine,and ribs,with 75.53%of opinions resulting in downgraded disability levels.Rib,orbital,and nasal bone fractures were the main focus in injury degree reassessments,with 84.62%of opinions indicating aggravated injuries.The consistency rates for fracture identification in disability grade assessments was 92.21%,while rates for injury degree and sequelae were 65.63%and 48.94%,respectively.Inconsistencies in identifying damage facts—including the presence of fractures,distinguishing between fresh and old fractures,and determining the nature of fractures and sequelae—were primarily noted in rib,orbital,and nasal bone fractures.The utilization rate of CT metadata in initial evaluations(25.00%)was significantly lower than in re-evaluations(95.00%).The identification time for joint mobility dysfunction after fracture in re-identifications was significantly longer than in initial identifications(P=0.0002),and the identification time for cases with agreement was significantly shorter than for cases with disagreement(P=0.036).Conclusion Image data type and identification timing are critical factors that may influence the accuracy and consistency of forensic clinical identification of bone injuries.When necessary,dynamic CT metadata in conjunction with image post-processing technology can be routinely employed to identify fractures of the ribs,orbital bones,or nasal bones,thereby reducing the risk of misidentification.
10.Outcome of endovascular treatment in patients with large vessel occlusive stroke within late window selected by noncontrast CT: comparison with non-endovascular treatment
Zhongwen HU ; Yongliang TANG ; Peng WANG ; Qi DENG
International Journal of Cerebrovascular Diseases 2025;33(2):81-86
Objective:To investigate the efficacy and safety of endovascular therapy (EVT) guided by noncontrast CT (NCCT) in patients with large vessel occlusive stroke within a late window (6-24 hours after onset).Methods:Consecutive patients with acute large vessel occlusive stroke within a late window admitted to the General Hospital of Wanbei Coal-electricity Group Co., Ltd from July 1, 2023 to September 30, 2024 were included retrospectively. All patients completed CT angiography or magnetic resonance angiography to confirm the presence of anterior circulation large vessel occlusion and rule out intracranial hemorrhage (ICH). The Alberta Stroke Program Early CT Score (ASPECTS) ≥4 as assessed by NCCT images was used as the EVT screening criteria. The main outcome measure was the functional outcome assessed by the modified Rankin Scale at 90 days after onset, 0-2 was defined as good outcome. The secondary outcome measures were symptomatic ICH (sICH) and death within 90 days. Multivariate logistic regression analysis was used to determine the independent influencing factors of functional outcome. Results:A total of 74 patients with large vessel occlusive stroke within the late window were enrolled, including 42 males (56.8%), aged 68.69±11.62 years (range, 47-89 years), with a baseline National Institutes of Health Stroke Scale score 11.20±5.12 and a median baseline ASPECTS 7 (interquartile range, 6-8). Ten (13.5%) and 7 patients (9.5%) respectively experienced any ICH and sICH, and 7 (9.5%) died within 90 days after onset. Twenty-seven patients (36.5%) received EVT, 47 (63.5%) only received conventional drug treatment; 20 (27.0%) had good outcome, and 54 (73.0%) had poor outcome. Univariate analysis showed that the good outcome rate in the EVT group at 90 days was significantly higher than that in the non-EVT group (40.7% vs. 19.1%; χ2=4.054, P=0.044), and there was no significant difference in the proportion of patients in sICH (11.1% vs. 8.5%; χ2=0.701, P=0.505) and who died within 90 days (7.4% vs. 10.6%; χ2=1.000, P=0.495) compared to the non-EVT group. The proportion of patients receiving EVT in the good outcome group was significantly higher than that in the poor outcome group (60.0% vs. 27.8%; χ2=6.539, P=0.011). Multivariate logistic regression analysis showed that EVT was an independent influencing factor of good outcome (odds ratio 0.440, 95% confidence interval 0.144-0.987; P=0.041). Conclusion:Compared with the conventional drug treatment alone, EVT guided by NCCT evaluation can achieve better outcome in patients with large vessel occlusion stroke within late window, and does not increase the risk of sICH and death within 90 days.

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