Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Retrieving keyframes most relevant to text from small intestine videos with given labels can efficiently and accurately locate pathological regions. However, training directly on raw video data is extremely slow, while learning visual representations from image-text datasets leads to computational inconsistency. To tackle this challenge, a small bowel video keyframe retrieval based on multi-modal contrastive learning (KRCL) is proposed. This framework fully utilizes textual information from video category labels to learn video features closely related to text, while modeling temporal information within a pretrained image-text model. It transfers knowledge learned from image-text multimodal models to the video domain, enabling interaction among medical videos, images, and text data. Experimental results on the hyper-spectral and Kvasir dataset for gastrointestinal disease detection (Hyper-Kvasir) and the Microsoft Research video-to-text (MSR-VTT) retrieval dataset demonstrate the effectiveness and robustness of KRCL, with the proposed method achieving state-of-the-art performance across nearly all evaluation metrics.
Humans ; Video Recording ; Intestine, Small/diagnostic imaging* ; Machine Learning ; Image Processing, Computer-Assisted/methods* ; Algorithms

OBJECTIVE: Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer treatment through combining the benefits of various mechanisms. METHODS: In this study, we developed a synergistic strategy for chemo-photothermal therapy by constructing nanocomposites using gold nanorods (GNRs) and tetrahedral framework nucleic acids (tFNA) loaded with the anti-tumor drug doxorubicin (DOX). RESULTS: Our in vitro studies have systematically clarified the anti-cancer behaviors of tFNA-DOX@GNR nanocomposites, characterized by their enhanced cellular uptake and proficient lysosomal escape capabilities. It was found that the key role of tFNA-DOX@GNR nanocomposites in tumor ablation is primarily due to their capacity to induce cytotoxicity in tumor cells via a photothermal effect, which generates instantaneous high temperatures. This mechanism introduces various responses in tumor cells, facilitated by the thermal effect and the integrated chemotherapeutic action of DOX. These reactions include the induction of endoplasmic reticulum stress, characterized by elevated reactive oxygen species levels, the promotion of apoptotic cell death, and the suppression of tumor cell proliferation. CONCLUSION This work exhibits the potential of synergistic therapy utilizing nanocomposites for cancer treatment and offers a promising avenue for future therapeutic strategies.
Doxorubicin/chemistry* ; Gold/chemistry* ; Nanotubes/chemistry* ; Humans ; Nanocomposites/chemistry* ; Cell Line, Tumor ; Nucleic Acids/chemistry* ; Antibiotics, Antineoplastic/pharmacology* ; Antineoplastic Agents/administration & dosage*

Objective:To explore the clinical application value of transoral robotic surgery (TORS) in the treatment of tonsil squamous cell carcinoma (TSCC).Methods:A retrospective analysis was conducted. The clinical data of 157 TSCC patients were collected who received TORS at five medical centers, namely, the Sun Yat-sen University Cancer Center, Sun Yat-sen Memorial Hospital, Eye Ear Nose and Throat Hospital of Fudan University, the First Affiliated Hospital of China Medical University, and Tongji Hospital of Tongji Medical College, from January 1 2017 to July 31 2022. There were 130 males and 27 females, aged 24-85 years. All patients were followed-up at least for 2 years (2-year group), among them, 99 patients had a follow-up of 3 years (3-year group). The overall survival (OS), progression-free survival (PFS), clinical stage, human papillomavirus (HPV) infection status were analyzed. SPSS 25.0 and SAS 9.4 were used for statistical analysis.Results:The OS and PFS of the 2-year group were 91.7% and 87.9%, respectively. The OS and PFS of the 3-year group were 85.9% and 82.8%, respectively. The prognosis of patients with locally early-stage was better than that of locally advanced patients, with the OS of 94.4% for T1-2 vs. 78.0% for T3 ( P=0.005) and the PFS of 91.2% for T1-2 vs. 75.0% for T3 ( P=0.011) in the 2-year group; the OS of 91.1% for T1-2 vs. 65.0% for T3 ( P=0.004) and the PFS of 88.6% for T1-2 vs. 60.0% for T3 ( P=0.002) in the 3-year group; and also, the OS of 90.0% for stage Ⅰ-Ⅱ vs. 79.5% for stage Ⅲ-Ⅳ ( P=0.204) and the PFS of 86.7% for stage Ⅰ-Ⅱ vs. 76.9% for stage Ⅲ-Ⅳ ( P=0.188) in the 3-year group. The prognosis of HPV-positive TSCC patients was better than that of HPV-negative patients in the 3-year group, with the OS of 90.9% for HPV-positive vs. 80.5% for HPV-negative ( P=0.045) and the PFS of 90.9% for HPV-positive vs. 75.6% for HPV-negative ( P=0.047). The average time of postoperative tracheal cannula indwelling was 25.1 days. The indwelling rate and average indwelling time of the postoperative nasogastric tube were 94.3% (148/157) and 8.5 days, respectively. Conclusion:TORS has outstanding survival benefits for TSCC patients. HPV-positive TSCC patients have a better prognosis than HPV-negative patients. TORS treatment of TSCC patients has advantages in postoperative recovery and quality of life.

Objective:To explore the clinical application value of transoral robotic surgery (TORS) in the treatment of tonsil squamous cell carcinoma (TSCC).Methods:A retrospective analysis was conducted. The clinical data of 157 TSCC patients were collected who received TORS at five medical centers, namely, the Sun Yat-sen University Cancer Center, Sun Yat-sen Memorial Hospital, Eye Ear Nose and Throat Hospital of Fudan University, the First Affiliated Hospital of China Medical University, and Tongji Hospital of Tongji Medical College, from January 1 2017 to July 31 2022. There were 130 males and 27 females, aged 24-85 years. All patients were followed-up at least for 2 years (2-year group), among them, 99 patients had a follow-up of 3 years (3-year group). The overall survival (OS), progression-free survival (PFS), clinical stage, human papillomavirus (HPV) infection status were analyzed. SPSS 25.0 and SAS 9.4 were used for statistical analysis.Results:The OS and PFS of the 2-year group were 91.7% and 87.9%, respectively. The OS and PFS of the 3-year group were 85.9% and 82.8%, respectively. The prognosis of patients with locally early-stage was better than that of locally advanced patients, with the OS of 94.4% for T1-2 vs. 78.0% for T3 ( P=0.005) and the PFS of 91.2% for T1-2 vs. 75.0% for T3 ( P=0.011) in the 2-year group; the OS of 91.1% for T1-2 vs. 65.0% for T3 ( P=0.004) and the PFS of 88.6% for T1-2 vs. 60.0% for T3 ( P=0.002) in the 3-year group; and also, the OS of 90.0% for stage Ⅰ-Ⅱ vs. 79.5% for stage Ⅲ-Ⅳ ( P=0.204) and the PFS of 86.7% for stage Ⅰ-Ⅱ vs. 76.9% for stage Ⅲ-Ⅳ ( P=0.188) in the 3-year group. The prognosis of HPV-positive TSCC patients was better than that of HPV-negative patients in the 3-year group, with the OS of 90.9% for HPV-positive vs. 80.5% for HPV-negative ( P=0.045) and the PFS of 90.9% for HPV-positive vs. 75.6% for HPV-negative ( P=0.047). The average time of postoperative tracheal cannula indwelling was 25.1 days. The indwelling rate and average indwelling time of the postoperative nasogastric tube were 94.3% (148/157) and 8.5 days, respectively. Conclusion:TORS has outstanding survival benefits for TSCC patients. HPV-positive TSCC patients have a better prognosis than HPV-negative patients. TORS treatment of TSCC patients has advantages in postoperative recovery and quality of life.

Objective:To evaluate the efficacy of acute T-cell lymphoblastic leukemia(T-ALL)in children and explore the prognostic risk factors.Methods:The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed,and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia(B-ALL)in the same period.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and event-free survival(EFS),and COX proportional hazard regression model was used to evaluate the prognostic factors.Among 116 children with T-ALL who received standard treatment,78 cases received the Chinese Childhood Leukemia Collaborative Group(CCLG)-ALL 2008 protocol(CCLG-ALL 2008 group),and 38 cases received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 protocol(CCCG-ALL 2015 group).The efficacy and serious adverse event(SAE)incidence of the two groups were compared.Results:Proportion of male,age ≥ 10 years old,white blood cell count(WBC)≥ 50 × 109/L,central nervous system leukemia,minimal residual disease(MRD)≥ 1％during induction therapy,and MRD ≥ 0.01％at the end of induction in T-ALL children were significantly higher than those in B-ALL children(P＜0.05).The expected 10-year EFS and OS of T-ALL were 59.7％and 66.0％,respectively,which were significantly lower than those of B-ALL(P＜0.001).COX analysis showed that WBC ≥ 100 x 109/L at initial diagnosis and failure to achieve complete remission(CR)after induction were independent risk factors for poor prognosis.Compared with CCLG-ALL 2008 group,CCCG-ALL 2015 group had lower incidence of infection-related SAE(15.8％vs 34.6％,P=0.042),but higher EFS and OS(73.9％vs 57.2％,PEFS=0.090;86.5％vs 62.3％,PoS=0.023).Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL.WBC ≥ 100 × 109/L at initial diagnosis and non-CR after induction(especially mediastinal mass has not disappeared)are the risk factors for poor prognosis.CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

Objective:To analyze the clinical characteristics and prognosis of children with hypodiploid B-cell precursor acute lymphoblastic leukemia(BCP-ALL).Methods:The clinical data of 1 287 children with BCP-ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed.According to the results of chromosome karyotype,all the patients were grouped into hypodiploid subgroup and non-hypodiploid subgroup.The clinical characteristics,early treatment response[minimal residual disease(MRD)on middle stage of induction chemotherapy and end of induction chemotherapy]and long-term efficacy[overall survival(OS)and event-free survival(EFS)]were compared.The prognostic factors of hypodiploid BCP-ALL were further explored.Results:Among 1 287 BCP-ALL patients,28 patients(2.2％)were hypodiploid BCP-ALL.The proportion of patients with white blood cell count(WBC)≥50 x 109/L in the hypodiploid subgroup was significantly higher than that in the non-hypodiploid subgroup(P=0.004),while there was no statistically significant difference in gender ratio,age group at initial diagnosis,and early treatment response between the two groups(all P＞0.05).The 5-year EFS and OS rate of the hypodiploid subgroup were 75.0％(95％CI:66.8％-83.2％)and 77.8％(95％CI:69.8％-85.8％),respectively,which were lower than those of non-hypodiploid subgroup[EFS:79.6％(95％CI:78.4％-80.8％);OS:86.4％(95％CI:85.4％-87.5％)],but the difference was not statistically significant(all P＞0.05).Further subgroup analysis by risk stratification showed that the 5-year EFS and OS rates of the hypodiploid subgroup were significantly lower than those in the low-risk(LR)group[LR group EFS:91.4％(95％CI:88.4％-93.6％),P＜0.001;OS:94.7％(95％CI:92.1％-96.4％),P＜0.001];it was similar to that of BCP-ALL children stratified into intermediate-risk(IR)excluding hypodiploid[IR group EFS:79.4％(95％CI:74.9％-83.2％),P=0.343;OS:87.3％(95％CI:83.6％-90.2％),P=0.111];while was higher than that of EFS in HR group,but the difference was not statistically significant[HR group EFS:58.7％(95％CI:52.6％-64.8％),P=0.178.OS:69.9％(95％CI:63.5％-75.4％),P=0.417].Univariate analysis showed that gender,age,white blood cell count,and MRD on middle stage of induction chemotherapy had no significant impact on OS and EFS;chromosome count＜40 was a risk factor for lower OS(P=0.026),but has no significant effect on EFS;MRD≥0.01％after induction therapy was a risk factor for lower OS and EFS(P=0.002,and 0.001,respectively).Conclusion:Children with hypodiploid BCP-ALL have an intermediate prognosis,and MRD ≥0.01％after induction chemotherapy may be a risk factors for poor prognosis.

Objective:To analyze the related factors of treatment failure in children with acute lymphoblastic leukemia (ALL)in real-world.Methods:The clinical data of 1414 newly diagnosed children with ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed.Treatment failure was defined as relapse,non-relapse death,and secondary tumor.Results:Following-up for median time 49.7 (0.1-136. 9)months,there were 269 cases (19.0％)treatment failure,including 140 cases (52.0％)relapse,and 129 cases (48.0％)non-relapse death.Cox univariate and multivariate analysis showed that white WBC≥50 ×109/L at newly diagnosis,acute T-cell lymphoblastic leukemia (T-ALL),BCR-ABL1,KMT2A-rearrangement and poor early treatment response were independent risk factor for treatment failure (all HR>1.000,P<0.05).The 5-year OS of 140 relapsed ALL patients was only 23.8％,with a significantly worse prognosis for very early relapse (relapse time within 18 months of diagnosis).Among 129 patients died from non-relapse death,71 cases (26.4％)were died from treatment-related complications,56 cases (20.8％)died from treatment abandonment,and 2 cases (0.7％)died from disease progression.Among them,treatment-related death were significantly correlated with chemotherapy intensity,while treatment abandonment were mainly related to economic factors.Conclusion:The treatment failure of children with ALL in our province is still relatively high,with relapse being the main cause of treatment failure,while treatment related death and treatment abandonment caused by economic factors are the main causes of non-relapse related death.

Objective Cognitive impairment(CI)in older individuals has a high morbidity rate worldwide,with poor diagnostic methods and susceptible population identification.This study aimed to investigate the relationship between different retinal metrics and CI in a particular population,emphasizing polyvascular status. Methods We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers,retinal nerve fiber layer(RNFL)thickness,and cognitive function of 3,785 participants,aged 40 years or older.Logistic regression was used to analyze the relationship between retinal metrics and cognitive function.Subgroups stratified by different vascular statuses were also analyzed. Results RNFL thickness was significantly thinner in the CI group(odds ratio:0.973,95%confidence interval:0.953-0.994).In the subgroup analysis,the difference still existed in the non-intracranial arterial stenosis,non-extracranial carotid arterial stenosis,and peripheral arterial disease subgroups(P<0.05). Conclusion A thin RNFL is associated with CI,especially in people with non-large vessel stenosis.The underlying small vessel change in RNFL and CI should be investigated in the future.

Objective To observe the cage subsidence after oblique lateral interbody fusion(OLIF)for lumbar spondylo-sis,summarize the characteristics of the cage subsidence,analyze causes,and propose preventive measures.Methods The data of 144 patients of lumbar spine lesions admitted to our hospital from October 2015 to December 2018 were retrospectively ana-lyzed.There were 43 males and 101 females,and the age ranged from 20 to 81 years old,with an average of(60.90±10.06)years old.Disease types:17 patients of lumbar intervertebral disc degenerative disease,12 patients of giant lumbar disc hernia-tion,5 patients of discogenic low back pain,33 patients of lumbar spinal stenosis,26 patients of lumbar degenerative spondy-lolisthesis,28 patients of lumbar spondylolisthesis with spondylolisthesis,11 patients of adjacent vertebral disease after lumbar internal fixation,7 patients of primary spondylitis in the inflammatory outcome stage,and 5 patients of lumbar degenerative scoliosis.Preoperative dual-energy X-ray bone mineral density examination showed 57 patients of osteopenia or osteoporosis,and 87 patients of normal bone density.The number of fusion segments:124 patients of single-segment,11 patients of two-seg-ment,8 patients of three-segment,four-segment 1 patient.There were 40 patients treated by stand-alone OLIF,and 104 patients by OLIF combined with posterior pedicle screw.Observed the occurrence of fusion cage settlement after operation,conducted monofactor analysis on possible risk factors,and observed the influence of fusion cage settlement on clinical results.Results All operations were successfully completed,the median operation time was 99 min,and the median intraoperative blood loss was 106 ml.Intraoperative endplate injury occurred in 30 patients and vertebral fracture occurred in 5 patients.The mean follow-up was(14.57±7.14)months from 6 to 30 months.During the follow-up,except for the patients of primary lumbar interstitial in-flammation and some patients of lumbar spondylolisthesis with spondylolisthesis,the others all had different degrees of cage subsidence.Cage subsidence classification:119 patients were normal subsidence,and 25 patients were abnormal subsidence(23 patients were grade Ⅰ,and 2 patients were grade Ⅱ).There was no loosening or rupture of the pedicle screw system.The height of the intervertebral space recovered from the preoperative average(9.48±1.84)mm to the postoperative average(12.65±2.03)mm,and the average(10.51±1.81)mm at the last follow-up.There were statistical differences between postop-erative and preoperative,and between the last follow-up and postoperative.The interbody fusion rate was 94.4％.The low back pain VAS decreased from the preoperative average(6.55±2.2 9)to the last follow-up(1.40±0.82),and there was statistically significant different.The leg pain VAS decreased from the preoperative average(4.72±1.49)to the final follow-up(0.60± 0.03),and the difference was statistically significant(t=9.13,P＜0.000 1).The ODI index recovered from the preoperative av-erage(38.50±6.98)％to the latest follow-up(11.30±3.27)％,and there was statistically significant different.The complication rate was 31.3％(45/144),and the reoperation rate was 9.72％(14/144).Among them,8 patients were reoperated due to fusion cage subsidence or displacement,accounting for 57.14％(8/14)of reoperation.The fusion cage subsidence in this group had obvious characteristics.The monofactor analysis showed that the number of abnormal subsidence patients in the osteopenia or osteoporosis group,Stand-alone OLIF group,2 or more segments fusion group,and endplate injury group was higher than that in the normal bone mass group,OLIF combined with pedicle screw fixation group,single segment fusion group,and no endplate injury group,and the comparison had statistical differences.Conclusion Cage subsidence is a common phenomenon after 0-LIF surgery.Preoperative osteopenia or osteoporosis,Stand-alone OLIF,2 or more segments of fusion and intraoperative end-plate injury may be important factors for postoperative fusion cage subsidence.Although there is no significant correlation be-tween the degree of cage subsidence and clinical symptoms,there is a risk of cage migration,and prevention needs to be strengthened to reduce serious complications caused by fusion of cage subsidence,including reoperation.