BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals ; Mice ; Chronic Kidney Disease-Mineral and Bone Disorder/genetics* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Sphingolipids/metabolism* ; Transcriptome/genetics* ; Signal Transduction/genetics* ; X-Ray Microtomography ; Adenine

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Alzheimer's disease (AD), a prototypical neurodegenerative disorder, encompasses multifaceted pathological processes. As pivotal cellular structures within the central nervous system, ion channels play critical roles in regulating neuronal excitability, synaptic transmission, and neurotransmitter release. Extensive research has revealed significant alterations in the expression and function of ion channels in AD, implicating an important role of ion channels in the pathogenesis of abnormal Aβ deposition, neuroinflammation, oxidative stress, and disruptions in calcium homeostasis and neural network functionality. This review systematically summarizes the crucial roles and underlying mechanisms of ion channels in the onset and progression of AD, highlighting how these channel abnormalities contribute to AD pathophysiology. We also discuss the therapeutic potential of ion channel modulation in AD treatment, emphasizing the importance of addressing multifactorial nature and heterogeneity of AD. The development of multi-target drugs and precision therapies is proposed as a future direction of scientific research.
Alzheimer Disease/therapy* ; Humans ; Ion Channels/physiology* ; Oxidative Stress ; Animals ; Amyloid beta-Peptides/metabolism* ; Synaptic Transmission ; Calcium/metabolism*

Objective To specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells(BMSCs)after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase(MetRSL247G)for nascent protein labeling,in order to explore the potential mechanisms of action in BMSCs post-transplantation.Methods Point mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine(ANL)-mediated labeling of nascent proteins in BMSCs.The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging(FUNCAT).Thirty healthy female C57BL/6J mice(8-10 weeks old)were divided into control and experimental groups,with 15 mice in each group.The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group,while control mice underwent only thoracotomy without coronary ligation.After modeling,both groups received intramyocardial injections of MetRSL247G-modified BMSCs(MetRSL247G-BMSCs)at 3 different sites in the peri-infarct ischemic region.Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0,2,and 6(n=5 for each time point)respectively,euthanized 24 h after the last injection,and cardiac tissues were isolated.The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected,using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry(LC-MS)analysis.Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction(PPI)analysis,and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.Results Under fluorescence microscopy,the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals,confirming the successful construction of the MetRSL247G-BMSCs cell line.Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL,validating the sensitivity and specificity of the labeling method.GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation,extracellular matrix organization,and focal adhesion.KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway,actin cytoskeleton regulation pathway,and apoptosis pathway.Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1(P＜0.05),upregulated anti-apoptotic factors,pro-apoptotic factors,and cell adhesion-related factors on day 3(P＜0.05),and upregulated anti-apoptotic factors,cell differentiation-related factors,and cell adhesion-related factors on day 7(P＜0.05)compared with control group.Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7(P＜0.05).On day 3,most differentially expressed proteins,including anti-apoptosis factors(Protein S100-A11,Clusterin,Gelsolin),pro-apoptosis factor(Cathepsin B),cell differentiation-related factor(Transgelin-2),and cell adhesion-related factors(Cofilin-1,Periostin,Fibronectin)were significantly upregulated(P＜0.05).Conclusions The MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins,confirming the feasibility of this nascent protein labeling technique.Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization.BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades,activating inflammatory factors,regulating actin cytoskeleton structure,and modulating apoptosis,thereby maintaining the survival of BMSCs.

This review delves into the pivotal role of necrotic apoptosis in Alzheimer's disease(AD),with a focus on treatment strategies,drug development,prospects,and challenges,highlighting its significance in the progression of the disease.Firstly,necrotic apoptosis plays a crucial role in the pathogenesis of AD,particularly in association with the abnormal metabolism of β-amyloid(Aβ)and Tau proteins.The primary focus of drug design is to regulate the metabolism pathways of these two proteins to slow down or inhibit the progression of necrotic apoptosis.Secondly,the progress in drug development further emphasizes the importance of necrotic apoptosis in treating AD.Current research mainly focuses on drugs that affect the metabolism of Aβ and Tau proteins,such as lecanemab.Still,inconsistent result underscore the necessity for a more comprehensive understanding of the molecular mechanisms of necrotic apoptosis.Finally,the prospects and challenges of necrotic apoptosis research in AD are thoroughly discussed.A deeper understanding of necrotic apoptosis contributes to a better comprehension of the pathological mechanisms of AD but also may reveal new therapeutic targets.However,challenges such as multifactorial influences and the selection of treatment timing necessitate further in-depth research in the future.In conclusion,this review advocates for future research to deepen the understanding of the molecular mechanisms of necrotic apoptosis,enhance research on treatment strategies,gain a deeper understanding of its cross-regulation with other cell death pathways,and promote collaboration between basic research and clinical practice to advance the comprehensive understanding and treatment of Alzheimer's disease and necrotic apoptosis.

Objective:To investigate the long-term efficacy, safety and prognostic factors of intraoperative radiotherapy (IORT) for narrow-margin (resection margin < 1 cm) hepatectomy in patients with hepatocellular carcinoma (HCC) during radical surgery.Methods:A retrospective cohort study was conducted. The data of primary HCC patients undergoing radical surgery and narrow-margin hepatectomy IORT in the Cancer Hospital of the Chinese Academy of Medical Sciences from November 2009 to February 2019 were collected. IORT applied 6 MeV or 9 MeV electron beams and a single irradiation was given to the margin. Kaplan-Meier method was used for the overall survival (OS) and disease-free survival (DFS) analysis; log-rank test was used for survival comparison among subgroups. The recurrence patterns and adverse reactions were recorded. Univariate and multivariate Cox proportional hazards models were used to analyze the factors influencing the OS and DFS.Results:A total of 64 patients were enrolled, with the median age [ M ( Q1, Q3)] of 57 years (49, 63) years. All patients included 55 males (85.9%) and 9 females (14.1%). The median dose of IORT was 15 Gy (range: 12-17 Gy). The median follow-up time was 83.3 (64.4, 91.9) months. The 1-year, 3-year, 5-year, 7-year, 10-year OS rates were 90.4%, 80.6%, 75.5%, 71.4% and 47.6%, respectively; the 1-year, 3-year, 5-year, 7-year,10-year DFS rates were 77.8%, 68.1%, 59.6%, 57.6% and 38.4%, respectively. Univariate Cox regression analysis indicated that preoperative serum alpha-fetoprotein (AFP) > 400 ng/ml was an independent risk factor for poor OS (> 400 ng/ml vs. ≤ 400 ng/ml: HR = 6.57, 95% CI: 2.16-19.96, P < 0.001), while not the independent influencing factor of poor DFS ( HR = 1.71, 95% CI: 0.65-4.52, P = 0.277). The age ≤ 60 years or not, gender, viral hepatitis or not, American Joint Committee on Cancer stage, tumor diameter (> 5 cm or not), tumor number, degree of tumor differentiation, microvascular invasion or not, microsatellite nodules or not, anatomical liver resection or not, and the dose of IORT ≤15 Gy or not were not the independent influencing factors of poor OS and DFS (all P > 0.05). Kaplan-Meier method analysis showed that patients with preoperative serum AFP ≤ 400 ng/ml (48 cases) had better OS compared with those with preoperative serum AFP>400 ng/ml (16 cases) (5-year OS rate: 84.8% vs. 44.9%; 7-year OS rate: 79.9% vs.37.4%), and the difference was statistically significant ( P = 0.002). There was no statistically significant difference in the DFS between the 2 groups ( P = 0.134). During the follow-up, 28 patients (43.8%) relapsed, including 17 cases (26.6%) of early recurrence and 11 cases (17.2%) of late recurrence. No marginal recurrence was observed. There were 22 cases (34.4%) of intrahepatic recurrence alone, 2 cases (3.1%) of extrahepatic recurrence and 4 cases (6.3%) of stimutaneous recurrence inside and outside the liver. The 1-, 3-, 5- and 7-year cumulative recurrence rates inside the liver were 19.0%, 27.2%, 37.4% and 39.3% respectively, and the cumulative recurrence rates outside the liver were 6.4%, 8.0%, 9.6% and 9.6% respectively. There were no adverse reactions above grade 3 in the entire group. There were no surgery-related deaths within 30 d after the operation, and no radiation-induced liver disease occurred. Conclusions:Narrow-margin IORT helps HCC patients receiving hepatectomy to achieve favorable long-term survival and adverse reactions are tolerable. It can be used as a safe and effective adjuvant therapy alternative.

Objective To explore the association between psychological resilience and internet addiction among senior primary school students,so as to provide a scientific basis for formulating strategies for preventing internet addiction and enhancing psychological resilience in this group.Methods A stratified cluster sampling method was employed.In May 2021,a total of 1 618 fourth-and fifth-grade students from 5 primary schools in Jiading District,Shanghai were surveyed on psychological resilience and internet addiction through questionnaires.Independent sample t-tests,chi-square tests,and Logistic regression models were used for data analysis.Results Among the 1 618 students,the prevalence rate of internet addiction was 8.8%(142 students).The total score of psychological resilience(t=6.215,P<0.001)and the scores of three dimensions,namely family support(t=3.509,P<0.001),goal focus(t=6.965,P<0.001),and positive perception(t=5.887,P<0.001),of those reported with internet addiction were all significantly lower than those without internet addiction.Multivariate logistic regression analysis showed that compared with individuals with low psychological resilience,those with moderate(aOR=0.395,95%CI:0.267-0.584,P<0.001)and high psychological resilience(aOR=0.167,95%CI:0.077-0.365,P<0.001)had a lower probability of internet addiction.The three sub-dimensions of psychological resilience,namely goal focus,positive perception and family support,also showed a statistically significant negative association with internet addiction in these students.Conclusion Nearly one-tenth senior primary school students in Jiading District self-reported internet addiction.Higher levels of psychological resilience were associated with a lower probability of internet addiction among senior primary school students.Focusing on enhancing the goal focus,positive perception and family support dimensions in psychological resilience may be of great significance for preventing internet addiction among senior primary school students.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:To investigate the clinical characteristics of cervical adenocarcinoma and analyze the survival status and related prognostic factors.Methods:The data of 229 patients with cervical adenocarcinoma who were diagnosed pathologically in the General Hospital of Ningxia Medical University from January 2013 to October 2022 were retrospectively analyzed. Among them, 198 early stage patients were mainly treated with surgery, and 31 locally advanced stage patients were mainly treated with chemoradiotherapy. The overall survival (OS) and progression-free survival (PFS) rates in the whole cohort of patients and different treatment subgroups were calculated. Kaplan‐Meier method and log‐rank test were used for survival analysis, and Cox proportional hazards model was used for univariate and multivariate survival analyses.Results:Among the 229 patients, there were 11 subtypes of pathological classifications, predominantly of the usual‐type. At the end of follow‐up, 57 patients (24.9%) relapsed. The 3‐ and 5‐year OS rates were 86.4% and 79.3%, respectively, and the 3‐ and 5‐year PFS rates were 81.6% and 73.6%, respectively. Multivariate analysis showed that International Federation of Gynecology and Obstetrics (FIGO) staging of stages Ⅲ‐Ⅳ was an independent prognostic factor for OS and PFS ( HR=2.033, 95% CI=1.456‐2.839, P<0.001; HR=1.701, 95% CI=1.251‐2.313, P=0.001). Lymph node metastasis was an independent risk factor for PFS ( HR=1.610,95% CI=1.021‐2.539, P=0.041). Subgroup analysis of 198 patients with surgical treatment: the 3‐ and 5‐year OS rates were 90.0% and 84.9%, and the 3‐ and 5‐year PFS rates were 82.7% and 76.7%, respectively. Multivariate analysis showed that lymph node metastasis and deep invasion depth were the main risk factors for OS ( HR=6.893, 95% CI=2.592‐18.327, P<0.001; HR=1.952, 95% CI=1.164‐3.272, P=0.011) and PFS ( HR=5.507, 95% CI=2.569‐11.805, P<0.001; HR=1.638, 95% CI=1.09‐2.461, P=0.018). Ovarian preservation was an independent risk factor for PFS ( HR=3.364, 95% CI=1.115‐10.151, P=0.031). Conclusions:The pathological types of cervical adenocarcinoma are complex and diverse. Local recurrence and distant metastasis are the main reasons for treatment failure. FIGO stage, lymph node metastasis and postoperative depth of invasion are the main prognostic factors of cervical adenocarcinoma.

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.