[Hepatitis B virus infection status and clinical characteristics in patients with rheumatoid arthritis].

Objective: To investigate the epidemiology of hepatitis B virus (HBV) infection in patients with rheumatoid arthritis (RA) in China and its association with RA disease characteristics. Methods: A cross-sectional study. A retrospective study was conducted on RA patients recruited from January 2001 to February 2023 in the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital. Demographic and clinical data were collected including age, gender, disease duration, active smoking, RA disease activity, physical function, radiographic assessment, serological markers of HBV infection and liver function indicators. According to the status of HBV infection, RA patients were grouped as chronic HBV infection, resolved HBV infection and no HBV infection groups. The distribution of each group and the clinical characteristics of RA patients were analyzed. Results: Among 1 941 RA patients, 1 461 (75.3%) completed HBV screening, including 335 males (22.9%) and 1 126 females (77.1%), with a mean age of (55.4±13.1) years. The prevalence of chronic HBV infection was 10.1%(148/1 461), which was significantly higher in male patients than in females [14.6%(49/335) vs 8.8%(99/1 126), P<0.001], especially among those males born from 1970 to 1979[20.0%(7/35) vs 8.5%(17/201), P=0.037] and 1980-1989 [31.8%(7/22) vs 10.5%(14/133), P=0.007]. Among 148 RA patients with chronic HBV infection, there were 5 cases (3.4%) of chronic hepatitis B, 2 cases (1.4%) of HBV-associated cirrhosis and 1 case (0.7%) of hepatocellular carcinoma. The prevalence of resolved HBV infection was 57.6%(841/1 461). There were 472(32.3%) patients with no HBV infection and 267(56.6%) of them showed negative anti-HBs. Among all RA patients, 15 (1.0%) patients had abnormal liver function, of which 7 cases were drug-induced liver injury, 5 cases were chronic hepatitis B, 2 cases were non-alcoholic fatty liver disease, and 1 case was primary biliary cholangitis. Conclusion: Chronic HBV infection remains a common complication in RA patients in China, the infection rate is 10.1%, and the screening and management of HBV infection should be strengthened in clinical practice.

[Obstructive sleep apnea and central/peripheral chemosensitivity: an essential part of pathophysiological mechanisms].

Unstable ventilatory control is one of the key pathophysiological mechanisms of obstructive sleep apnea (OSA), and the activity of chemoreceptors is an important part of ventilatory control. Chemosensitivity has a significant impact on the severity and prognosis of OSA, and the incidence of comorbidities. The focus on reducing chemosensitivity can be seen as an emerging theme to promote individualized and precise treatment of OSA. Further exploration of chemosensitivity in OSA will be an emerging direction and a major challenge for current and future research in the field of sleep.

Cellular and Molecular Connections Between Bone Fracture Healing and Exosomes.

Fracture healing is a multifaceted process that requires various phases and intercellular interactions. In recent years, investigations have been conducted to assess the feasibility of utilizing exosomes, small extracellular vesicles (EVs), to enhance and accelerate the healing process. Exosomes serve as a cargo transport platform, facilitating intercellular communication, promoting the presentation of antigens to dendritic cells, and stimulating angiogenesis. Exosomes have a special structure that gives them a special function, especially in the healing process of bone injuries. This article provides an overview of cellular and molecular processes associated with bone fracture healing, as well as a survey of existing exosome research in this context. We also discuss the potential use of exosomes in fracture healing, as well as the obstacles that must be overcome to make this a viable clinical practice.

[Spatial distribution of Oncomelania hupensis spread in Hubei Province from 2020 to 2022].

OBJECTIVE: To identify the spatial distribution pattern of Oncomelania hupensis spread in Hubei Province, so as to provide insights into precision O. hupensis snail control in the province. METHODS: Data pertaining to emerging and reemerging snails were collected from Hubei Province from 2020 to 2022 to build a spatial database of O. hupensis snail spread. The spatial clustering of O. hupensis snail spread was identified using global and local spatial autocorrelation analyses, and the hot spots of snail spread were identified using kernel density estimation. In addition, the correlation between environments with snail spread and the distance from the Yangtze River was evaluated using nearest-neighbor analysis and Spearman correlation analysis. RESULTS: O. hupensis snail spread mainly occurred along the Yangtze River and Jianghan Plain in Hubei Province from 2020 to 2022, with a total spread area of 4 320.63 hm2, including 1 230.77 hm2 emerging snail habitats and 3 089.87 hm2 reemerging snail habitats. Global spatial autocorrelation analysis showed spatial autocorrelation in the O. hupensis snail spread in Hubei Province in 2020 and 2021, appearing a spatial clustering pattern (Moran's I = 0.003 593 and 0.060 973, both P values < 0.05), and the mean density of spread snails showed spatial aggregation in Hubei Province in 2020 (Moran's I = 0.512 856, P < 0.05). Local spatial autocorrelation analysis showed that the high-high clustering areas of spread snails were mainly distributed in 50 settings of 10 counties (districts) in Hubei Province from 2020 to 2022, and the high-high clustering areas of the mean density of spread snails were predominantly found in 219 snail habitats in four counties of Jiangling, Honghu, Yangxin and Gong'an. Kernel density estimation showed that there were high-, secondary high- and medium-density hot spots in snail spread areas in Hubei Province from 2020 to 2022, which were distributed in Jingzhou District, Wuxue District, Honghu County and Huangzhou District, respectively. There were high- and medium-density hot spots in the mean density of spread snails, which were located in Jiangling County, Honghu County and Yangxin County, respectively. In addition, the snail spread areas negatively correlated with the distance from the Yangtze River (r = -0.108 9, P < 0.05). CONCLUSIONS: There was spatial clustering of O. hupensis snail spread in Hubei Province from 2020 to 2022. The monitoring and control of O. hupensis snails require to be reinforced in the clustering areas, notably in inner embankments to prevent reemerging schistosomiasis.

[Risk factors for pulmonary atelectasis in adults with tracheobronchial tuberculosis].

Objective: To investigate the risk factors for pulmonary atelectasis in adults with tracheobronchial tuberculosis(TBTB). Methods: Clinical data of adult patients (≥18 years old) with TBTB from February 2018 to December 2021 in Public Health Clinical Center of Chengdu were retrospectively analyzed. A total of 258 patients were included, with a male to female ratio of 1∶1.43. The median age was 31(24, 48) years. Clinical data including clinical characteristics, previous misdiagnoses/missed diagnoses before admission, pulmonary atelectasis, the time from symptom onset to atelectasis and bronchoscopy, bronchoscopy and interventional treatment were collected according to the inclusion and exclusion criteria. Patients were divided into two groups according to whether they had pulmonary atelectasis. Differences between the two groups were compared. Binary logistic regression was used to analyze the risk factors for pulmonary atelectasis. Results: The prevalence of pulmonary atelectasis was 14.7%, which was most common in the left upper lobe (26.3%). The median time from symptom onset to atelectasis was 130.50(29.75,358.50)d, and the median time from atelectasis to bronchoscopy was 5(3,7)d. The median age, the proportion of misdiagnosis of TBTB before admission, and the time from symptom onset to bronchoscopy in the atelectasis group were higher than those without atelectasis, and the proportion of receiving bronchoscopy examination and interventional therapy previously, and the proportion of pulmonary cavities were lower than those without atelectasis (all P<0.05). The proportions of cicatrices stricture type and lumen occlusion type in the atelectasis group were higher than those without atelectasis, while the proportions of inflammatory infiltration type and ulceration necrosis type were lower than those without atelectasis (all P<0.05). Older age (OR=1.036, 95%CI: 1.012-1.061), previous misdiagnosis(OR=2.759, 95%CI: 1.100-6.922), longer time from symptom onset to bronchoscopy examination (OR=1.002, 95%CI: 1.000-1.005) and cicatrices stricture type (OR=2.989, 95%CI: 1.279-6.985) were independent risk factors for pulmonary atelectasis in adults with TBTB (all P<0.05). Of the patients with atelectasis who underwent bronchoscopy interventional therapy, 86.7% had lung reexpansion or partial reexpansion. Conclusions: The prevalence of pulmonary atelectasis is 14.7% in adult patients with TBTB. The most common site of atelectasis is left upper lobe. The TBTB type of lumen occlusion is complicated by pulmonary atelectasis in 100% of cases. Being older, misdiagnosed as other diseases, longer time from onset of symptoms to bronchoscopy examination, and being the cicatrices stricture type are factors for developing pulmonary atelectasis. Early diagnosis and treatment are needed to reduce the incidence of pulmonary atelectasis and increase the rate of pulmonary reexpansion.

[Efficacy of arteriovenous argatroban versus heparin flush anticoagulation after cardiovascular surgery].

Objective: To compare the effects of arteriovenous argatroban and heparin flushes on platelet count and assess the occurrence of heparin-induced thrombocytopenia (HIT) and other complications in patients undergoing cardiovascular surgeries. Methods: A single-center, prospective randomized control study was conducted. Patients who underwent cardiovascular surgery at Fuwai Hospital, Chinese Academy of Medical Sciences from March to December 2019 were randomly divided into the argatroban group (250 ml normal saline plus 2.5 mg of argatroban) and the heparin group (250 ml normal saline plus 10 mg of heparin). Platelet count, hemorrhage, and thrombosis were assessed. The 4T scores of HIT, the incidences of HIT and other complications were also evaluated. Results: A total of 491 patients (307 males and 184 females) were included in the study, with a mean age of (52.3±13.7) years. There were 245 cases in the argatroban group and 246 cases in the heparin group, respectively. There was no statistically significant difference in the preoperative platelet count between the argatroban and heparin groups [198.0 (161.0, 248.0)×109/L vs 194.0 (157.2, 243.8)×109/L, P=0.498]. Likewise, there were no statistically significant differences in the platelet count between the argatroban and heparin groups at 12 h, 1 day, and 5 days after operation [127.0 (100.0, 154.0)×109/L vs 121.5 (90.2, 149.0)×109/L, 126.0 (97.0, 162.0)×109/L vs 123.5 (88.0, 151.0)×109/L, 168.0 (130.0, 215.0) ×109/L vs 161.0 (101.0, 210.5)×109/L] (repeated measures ANOVA between groups: F=3.327, P=0.069; time comparison: F=532.523, P<0.001; time interaction between groups: F=0.675, P=0.512). The proportion of 4T scores of medium and high scores (≥4)[9.8% (24/245) vs 10.6% (26/246), P=0.777] and incidence of HIT antibody positive [1.63% (4/245) vs 1.63% (4/246), P=0.726] were similar between argatroban group and the heparin group. Mechanical ventilation time was shorter in the argatroban group than that in the heparin group [13.0 (11.0, 21.0) vs 15.5 (12.0, 21.0) h, P=0.020]. Conclusion: Compared with heparin, routine management with argatroban for arteriovenous flush in patients undergoing cardiovascular surgery does not affect the HIT incidence.

Using Proteome Microarray and Gene Expression Omnibus Database to Screen Tumour-Associated Antigens to Construct the Optimal Diagnostic Model of Oesophageal Squamous Cell Carcinoma.

AIMS: Autoantibodies against tumour-associated antigens (TAAs) are promising biomarkers for early immunodiagnosis of cancers. This study was designed to screen and verify autoantibodies against TAAs in sera as diagnostic biomarkers for oesophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: The customised proteome microarray based on cancer driver genes and the Gene Expression Omnibus database were used to identify potential TAAs. The expression levels of the corresponding autoantibodies in serum samples obtained from 243 ESCC patients and 243 healthy controls were investigated by enzyme-linked immunosorbent assay (ELISA). In total, 486 serum samples were randomly divided into the training set and the validation set in the ratio of 2:1. Logistic regression analysis, recursive partition analysis and support vector machine were performed to establish different diagnostic models. RESULTS: Five and nine candidate TAAs were screened out by proteome microarray and bioinformatics analysis, respectively. Among these 14 anti-TAAs autoantibodies, the expression level of nine (p53, PTEN, GNA11, SRSF2, CXCL8, MMP1, MSH6, LAMC2 and SLC2A1) anti-TAAs autoantibodies in the cancer patient group was higher than that in the healthy control group based on the results from ELISA. In the three constructed models, a logistic regression model including four anti-TAA autoantibodies (p53, SLC2A1, GNA11 and MMP1) was considered to be the optimal diagnosis model. The sensitivity and specificity of the model in the training set and the validation set were 70.4%, 72.8% and 67.9%, 67.9%, respectively. The area under the receiver operating characteristic curve for detecting early patients in the training set and the validation set were 0.84 and 0.85, respectively. CONCLUSIONS: This approach to screen novel TAAs is feasible, and the model including four autoantibodies could pave the way for the diagnosis of ESCC.

[Clinical characteristics and short-term prognosis of 22 cases with SARS-CoV-2 infection associated acute encephalopathy].

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.

[Efficacy and safety of low-dose rasburicase for refractory chronic gouty arthritis].

Objective: To explore the efficacy and safety of low-dose rasburicase for refractory chronic gouty arthritis. Methods: A cohort study. The clinical data of patients with refractory chronic gouty arthritis who were treated with rasburicase at Sun Yat-sen Memorial Hospital, Sun Yat-sen University between January 2021 and July 2022 were retrospectively analyzed. Refractory chronic gouty arthritis was defined as serum uric acid (sUA)>360 µmol/L and urate volume>10 cm3 under dual-energy computed tomography after tolerable maximal oral urate-lowering therapy for at least 3 months. The administration of low-dose rasburicase was applied intravenously with total dosage ranging from 4.5 to 7.5 mg each dose, at 4-week intervals for a maximum of three doses. Efficacy was evaluated by the changes of sUA level, tophus and urate volume. Results: A total of 22 patients were included for analysis, with 95.4% (21/22) male, the mean age was (44±15) years, and the median duration of gout was 11 (6-15) years. The mean sUA at baseline was (667±112) µmol/L. The levels of sUA significantly decreased after each dose of rasburicase (P<0.001), and the median reduction of sUA after each dose of rasburicase was 568 (471-635), 187 (66-335) and 123 (49-207) µmol/L, respectively. At week 12, nine patients (40.9%) exhibited sUA<360 µmol/L and tophus disappeared in one patient. The urate volume significantly decreased at week 12 when compared with that before the first dose of rasburicase in all the patients [40 (16-172) cm3 vs 17 (7-134) cm3, P<0.001], with a median reduction rate of 41.6% (22.9%-58.5%). The everall safety of rasburicase was good, and no serious adverse reactions occurred. Conclusions: Low-dose rasburicase is well-tolerated and effective for decreasing the urate burden in patients with refractory chronic gouty arthritis. Further prospective randomized controlled trials are needed to validate these findings.

[Two cases of airway dysfunction related to diacetyl exposure].

Occupational exposure to diacetyl can lead to bronchiolitis obliterans. In this paper, two patients with severe obstructive ventilation disorder who were exposed to diacetyl at a fragrance and flavours factory were analyzed. The clinical manifestations were cough and shortness of breath. One of them showed Mosaic shadows and uneven perfusion in both lungs on CT, while the other was normal. Field investigation found that 4 of the 8 workers in the factory were found to have obstructive ventilation disorder, and 2 had small airway dysfunction. This paper summarizes the diagnostic process of patients in order to improve the understanding of airway dysfunction caused by occupational exposure to diacetyl and promote the development of relevant standards.

[Association of lean tissue index with arteriovenous fistula dysfunction in maintenance hemodialysis patients].

The clinical data of maintenance hemodialysis (MHD) patients from twenty hemodialysis centers in Guizhou province from June to September 2020 were collected by cross-sectional study. The patients were divided into AFD group and non-AFD group according to whether AFD had occurred. LTI was measured by body composition monitor. The results showed that the incidence of AFD in 2 781 MHD patients was 30.0% (835/2 781). Median LTI level was 15.2 (13.2, 17.5) kg/m2. The LTI level in the AFD group was higher than that in the non-AFD group (P < 0.05). According to the tertiles of LTI, low LTI group (LTI ≤ 13.9 kg/m2) had the highest incidence of AFD (35.5%, 334/940), and the high LTI group had the lowest incidence of AFD (26.3%, 241/916), and the difference among the three groups was statistically significant (χ2=20.182,P < 0.001). Multivariate logistic regression analysis showed that low LTI group as the reference, the risk of AFD in moderate LTI group (13.9 kg/m2 < LTI ≤ 16.6 kg/m2) and high LTI group were associated with the 20.0% (OR=0.800, 95% CI 0.650-0.986, P=0.036) and 22.8% (OR=0.772, 95% CI 0.616-0.966, P=0.024) decrease, respectively. These results suggest that low LTI level is independently associated with an increased risk of AFD in MHD patients.

[Immune checkpoint inhibitor-induced eosinophilic fasciitis: a case report and literature review].

A 58-year-old male patient with angioimmunoblastic T-cell lymphoma developed a rash and skin tightness on the face, limbs, and trunk together with joint stiffness and dysfunction after 6 months of treatment with the programmed cell death protein-1 inhibitor camrelizumab. Laboratory tests revealed progressive eosinophilia over 6 months, with the eosinophil count increasing from 0.07×109/L to 3.3×109/L. Magnetic resonance imaging showed thickened skin of both forearms, while T2-weighted imaging showed markedly increased signal intensity within the myofascia. Skin biopsy of the right forearm showed thickened and fibrosed fascia and infiltration of inflammatory cells, including lymphocytes, plasma cells, and eosinophils. The patient was diagnosed with immune checkpoint inhibitor (ICI)-induced eosinophilic fasciitis (EF). After beginning treatment with methylprednisolone (40 mg daily), methotrexate (10 mg/week), and baricitinib (4 mg daily), his symptoms of skin tightness and joint dysfunction significantly improved within 1 month, and his peripheral blood eosinophil count decreased to 0.17×109/L. ICI-induced EF is a rare immune-related adverse reaction. To date, only 20 cases have been reported in published foreign literature, and their clinical characteristics are summarized here. The time from ICI treatment to EF was 12 (8,15) months, and the main clinical manifestations included skin involvement (n=19), joint dysfunction (n=11), myalgia/muscle weakness (n=9), and peripheral eosinophilia (n=16). After treatment, the clinical symptoms of EF improved in 17 patients, and eosinophil counts returned to normal after 3 (1,8) months. EF is a dysfunctional adverse response to ICI therapy. Tumor patients undergoing immunotherapy should be monitored for symptoms of EF. Early treatment is essential for preventing complications.

[Efficacy of sacubitril/valsartan in peritoneal dialysis patients with HFpEF and its effect on residual renal function].

Objective: To investigate the efficacy of sacubitril/valsartan in peritoneal dialysis (PD) patients with heart failure with preserved ejection fraction (HFpEF) and its effect on residual renal function. Methods: PD patients with HFpEF in Ningbo First Hospital from March 2018 to August 2021 were retrospectively enrolled and divided into study group with sacubitril/valsartan and control group with valsartan. The clinical baseline data before treatment and clinical indicators during follow-up (6 and 12 months after treatment) were collected and compared between the two groups, and the adverse reactions were also recorded. Results: A total of 99 patients were included in the study. There were 61 patients in the study group, including 44 males and 17 females, with a mean age of (52±13) years. Meanwhile, there were 38 patients in the control group, including 23 males and 15 females, with a mean age of (57±14) years. There was no statistically significant difference in clinical baseline data between the two groups (e.g., age, sex, body mass index, duration of dialysis) (all P>0.05). The N-terminal pro-B-type natriuretic peptide (NT-proBNP) and left ventricular end-systolic dimension (LVDs) were lower, but the left ventricular ejection fraction (LVEF) was higher in the study group than those in the control group at 6 and 12 months after treatment (all P<0.05). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the two groups were lower than baseline values at 6 and 12 months after treatment respectively, with statistically significant differences (all P<0.05). However, there were no statistically significant differences in the decreases of SBP and DBP between the two groups at 6 and 12 months after treatment (all P>0.05). The decrease extents in residual estimated glomerular filtration rate (eGFR) [0.52 (-0.05, 1.19) vs 1.72 (0.97, 2.39) ml·min-1·(1.73 m2)-1, P<0.001]and 24-h residual urine volume [200 (-100, 300) vs 300 (137, 400) ml, P=0.018] at 12 months after treatment were lower in the study group than those in the control group. During the follow-up period, hyperkalemia occurred in 16 cases (26.2%) and 13 cases (34.2%) in the study group and the control group, and hypotension occurred in 3 cases (4.9%) and 1 case (2.6%) in the study group and the control group, respectively. There were no adverse reactions such as cough and angioneurotic edema in the two groups. Conclusions: Sacubitril/valsartan can safely and effectively improve cardiac function and lower blood pressure in PD patients with HFpEF. Compared with valsartan, sacubitril/valsartan may be more beneficial to delay the loss of residual renal function in PD patients with HFpEF.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial.

BACKGROUND: Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). RESULTS: A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802). CONCLUSIONS: NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.