Safety and effectiveness of using Disposable Ultrasonic shears to coagulate 5-7 mm blood vessels: protocol for a prospective, multicenter, randomized, parallel controlled, non-inferiority clinical trial.

BACKGROUND: The ultrasonic scalpel is widely used during surgery. It is safe and effective to close the pulmonary artery branch vessels of 7 mm or below with an ultrasonic energy device as reported. However, there have been no multicenter randomized clinical trial to assess the safety and effectiveness of using ultrasonic scalpel to coagulate 5-7 mm blood vessels in thoracic surgery. METHODS: This is a prospective, multicenter, randomized, parallel controlled, non-inferiority clinical trial. A total of 144 eligible patients planning to undergo lung or esophageal surgery will be randomly allocated to the experimental group and the control group. The investigational product (Disposable Ultrasonic Shears manufactured by Reach Surgical, Inc.) and the control product (Harmonic Ace + 7, 5 mm Diameter Shears with Advanced Hemostasis) will be used in each group. The primary endpoint is the success rate of coagulating target blood vessels during surgery. Secondary endpoints include postoperative rebleeding, intraoperative bleeding volume, drainage volume, surgical duration, etc. Postoperative follow-up before and after discharge will be performed. DISCUSSION: This clinical trial aims to evaluate the safety and effectiveness of using the investigational product (Disposable Ultrasonic Shears manufactured by Reach Surgical, Inc.) and that of the control product (Harmonic Ace + 7, 5 mm Diameter Shears with Advanced Hemostasis) to coagulate 5-7 mm blood vessels in thoracic surgery. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06002737. The trial was prospectively registered on 16 August 2023, https://www. CLINICALTRIALS: gov/study/NCT06002737 .

Robotic-assisted Versus Video-assisted Thoracoscopic Lobectomy: Short-term Results of a Randomized Clinical Trial (RVlob Trial).

OBJECTIVE: To determine whether RAL affects perioperative outcomes and long-term efficacy in NSCLC patients, compared with traditional VAL. SUMMARY OF BACKGROUND DATA: RAL is a promising treatment for NSCLC. However, its efficacy has not been fully evaluated. METHODS: A single-center, open-labeled prospective randomized clinical trial was launched in May 2017 to compare the efficacy of RAL and VAL. By May 2020, 320 patients were enrolled. The perioperative results of RAL and VAL were compared. RESULTS: The 320 enrolled patients were randomly assigned to the RAL group (n = 157) and the VAL group (n = 163). Perioperative outcomes were comparable between the 2 groups, including the length of hospital stay (P = 0.76) and the rate of postoperative complications (P = 0.45). No perioperative mortality occurred in either group. The total amount of chest tube drainage {830 mL [interquartile range (IQR), 550-1130 mL] vs 685 mL [IQR, 367.5-1160 mL], P = 0.007} and hospitalization costs [$12821 (IQR, $12145-$13924) vs $8009 (IQR, $7014-$9003), P < 0.001] were significantly higher in the RAL group. RAL group had a significantly higher number of LNs harvested [11 (IQR, 8-15) vs 10 (IQR, 8-13), P = 0.02], higher number of N1 LNs [6 (IQR, 4-8) vs 5 (IQR, 3-7), P = 0.005], and more LN stations examined [6 (IQR, 5-7) vs 5 (IQR, 4-6), P < 0.001]. CONCLUSIONS: Both RAL and VAL are safe and feasible for the treatment of NSCLC. RAL achieved similar perioperative outcomes, together with higher LN yield. Further follow-up investigations are required to evaluate the long-term efficacy of RAL. (ClinicalTrials.gov identifier: NCT03134534).

Effects of pre-operative enteral immunonutrition for esophageal cancer patients treated with neoadjuvant chemoradiotherapy: protocol for a multicenter randomized controlled trial (point trial, pre-operative immunonutrition therapy).

BACKGROUND: Neoadjuvant chemoradiation followed by esophagectomy has been established as the first-line treatment for locally advanced esophageal cancer. Postoperative enteral nutrition has been widely used to improve perioperative outcomes. However, whether to implement preoperative nutritional intervention during neoadjuvant therapy is yet to be verified by prospective studies. METHODS: POINT trial is a multicenter, open-labeled, randomized controlled trial. A total of 244 patients with surgically resectable esophageal cancer are randomly assigned to nutritional therapy group (arm A) or control group (arm B) with a 2:1 ratio. Both groups receive neoadjuvant chemotherapy with concurrent radiotherapy based on the CROSS regimen followed by minimally invasive esophagectomy. The primary endpoint is the rate of nutrition and immune-related complications after surgery. Secondary endpoints include completion rate of neoadjuvant chemoradiation and related adverse events, rate of pathological complete response, perioperative outcomes, nutritional status, overall survival, progression-free survival and quality of life. DISCUSSION: This trial aims to verify whether immunonutrition during neoadjuvant chemoradiation can reduce the rate of complications and improve perioperative outcomes. Frequent communication and monitoring are essential for a multicenter investigator-initiated trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04513418. The trial was prospectively registered on 14 August 2020, https://www. CLINICALTRIALS: gov/ct2/show/NCT04513418 .

Beam complexity and monitor unit efficiency comparison in two different volumetric modulated arc therapy delivery systems using automated planning.

BACKGROUND: To investigate the beam complexity and monitor unit (MU) efficiency issues for two different volumetric modulated arc therapy (VMAT) delivery technologies for patients with left-sided breast cancer (BC) and nasopharyngeal carcinoma (NPC). METHODS: Twelve left-sided BC and seven NPC cases were enrolled in this study. Each delivered treatment plan was optimized in the Pinnacle3 treatment planning system with the Auto-Planning module for the Trilogy and Synergy systems. Similar planning dose objectives and beam configurations were used for each site in the two different delivery systems to produce clinically acceptable plans. The beam complexity was evaluated in terms of the segment area (SA), segment width (SW), leaf sequence variability (LSV), aperture area variability (AAV), and modulation complexity score (MCS) based on the multileaf collimator sequence and MU. Plan delivery and a gamma evaluation were performed using a helical diode array. RESULTS: With similar plan quality, the average SAs for the Trilogy plans were smaller than those for the Synergy plans: 55.5 ± 21.3 cm2 vs. 66.3 ± 17.9 cm2 (p < 0.05) for the NPC cases and 100.7 ± 49.2 cm2 vs. 108.5 ± 42.7 cm2 (p < 0.05) for the BC cases, respectively. The SW was statistically significant for the two delivery systems (NPC: 6.87 ± 1.95 cm vs. 6.72 ± 2.71 cm, p < 0.05; BC: 8.84 ± 2.56 cm vs. 8.09 ± 2.63 cm, p < 0.05). The LSV was significantly smaller for Trilogy (NPC: 0.84 ± 0.033 vs. 0.86 ± 0.033, p < 0.05; BC: 0.89 ± 0.026 vs. 0.90 ± 0.26, p < 0.05). The mean AAV was significantly larger for Trilogy than for Synergy (NPC: 0.18 ± 0.064 vs. 0.14 ± 0.037, p < 0.05; BC: 0.46 ± 0.15 vs. 0.33 ± 0.13, p < 0.05). The MCS values for Trilogy were higher than those for Synergy: 0.14 ± 0.016 vs. 0.12 ± 0.017 (p < 0.05) for the NPC cases and 0.42 ± 0.106 vs. 0.30 ± 0.087 (p < 0.05) for the BC cases. Compared with the Synergy plans, the average MUs for the Trilogy plans were larger: 828.6 ± 74.1 MU and 782.9 ± 85.2 MU (p > 0.05) for the NPC cases and 444.8 ± 61.3 MU and 393.8 ± 75.3 MU (p > 0.05) for the BC cases. The gamma index agreement scores were never below 91% using 3 mm/3% (global) distance to agreement and dose difference criteria and a 10% lower dose exclusion threshold. CONCLUSIONS: The Pinnacle3 Auto-Planning system can optimize BC and NPC plans to achieve the same plan quality using both the Trilogy and Synergy systems. We found that these two systems resulted in different SAs, SWs, LSVs, AAVs and MCSs. As a result, we suggested that the beam complexity should be considered in the development of further methodologies while optimizing VMAT autoplanning.

Robotic sleeve resection for pulmonary disease.

BACKGROUND: Few studies have described robotic sleeve resection with pulmonary resection. Here, we report the successful implementation of a completely portal robotic sleeve resection with or without pulmonary resection using a modified suture mode. METHODS: In total, 339 patients underwent curative robotic pulmonary surgery at Ruijin Hospital between May 2015 and September 2017. Three of these patients underwent robotic sleeve resection (right upper lobe, one; left upper lobe, one; and lingular segmental bronchus, one). Five port incisions were utilized, and a simple continuous running suture combined with two interrupted sutures of the membranous and cartilaginous junction portion was preferred for the anastomosis. RESULTS: The postoperative course was uneventful for two patients with squamous cell carcinoma. The lingular segmental bronchus patient without pulmonary resection (a salivary gland tumor) underwent short-term atelectasis. The median operation time was 155 (range 132-230) minutes. The median anastomosis time was 25 (range 23-32) minutes. The median length of postoperative hospital stay was 7 (range 6-10) days. There was no mortality or conversion to thoracotomy for any of the patients. All patients were followed for 3-6 months, and there is no tumour recurrence. CONCLUSIONS: Our limited experience suggested that robotic sleeve resection for pulmonary disease with or without pulmonary resection may be safe and effective. The anastomosis time can be shortened with more robotic surgery experiences and the modified suture mode.

[Anti-oxidantive effect of methylene blue on acute lung injury induced by paraquat in rat].

OBJECTIVE: To study the protection effects of methylene blue on acute lung injury that induced by paraquat in rats. METHODS: 24 male SD rats were randomly distributed into four groups of 6 rats each group including control group, methylene blue group, paraquat group and paraquat plus methylene blue group. The rats were challenged acutely with paraquat( 25 mg/kg, i. p. ). After two hours treatment, the rats in paraquat plus methylene group were treated by methylene blue( 2 mg/kg, i. p. ) or vehicle treatment for 24 hours. Then, lung specimens were collected for pathological examinations and biochemical analysis including content of malondialdehyde( MDA) and activity of lactate dehydrogenase( LDH) and superoxide dismutase( SOD). The bronchoalveolar lavage fluids were also collected for the analysis of myeloperoxidase( MPO) activity. RESULTS: Compared to control group, the rats treated with paraquat induced acute lunginjury which was reflected by the increase of pathological score( P < 0. 05) and wet/dry ratio of lung tissue( P < 0. 05). Moreover, the content of MDA and LDH were increased, but the activity of SOD was decreased in lung tissues, and the activity of MPO were increased in bronchoalveolar lavage fluid in rats treated with paraquat. Compared to the rats with paraquat exposure, the pathological score( P < 0. 05) and wet/dry ratio( P <0. 05) in the rats treated with paraquat plus methylene blue were decreased. The content of MDA( P < 0. 05) and LDH( P < 0. 05) were also decreased, but the activity of SOD was increased( P < 0. 05). Moreover, the activity of MPO in bronchoalveolar lavage fluid was decreased in paraquat exposure rats with methylene blue treatment. CONCLUSION: Acute lung injury that induced by paraquat in rats is protected by methylene blue. The result may provide a new way to treat patients with acute paraquat poisoning.

[Effect of respiratory movement on cone beam computed tomography images].

To investigate the impact of respiratory movement to determine the target volume on cone beam CT (CBCT) for lung tumor, we used CIRS dynamic thorax phantom (Model-CIRS008) to simulate the sinusoidal motion of lung tumor. With a constant amplitude, the ratio of the time of near-end-expiratory and near-end-inspiratory (E/I) changed when it was scanned with CBCT. We analyzed the contrast changes of target by extracting the CT value of each pixel on the center line of the target movement direction. The targets were contoured with region growing method and compared with the motion volume generated by the tumor trajectory method. The result showed that the contrast of near-end-expiratory increased and the contrast of near-end-inspiratory decreased with increasing E/I. The contoured volume generated by region growing method decreased with increasing E/I. When E/I = 4, the amplitude A = 1 cm, diameter of 1 cm and 3 cm target volumes were reduced by 48.2% and 22.7%. The study showed that CBCT was not suitable to be used to accurately determine the range of lung tumor movement. The internal target volume (ITV) may be underestimated in CBCT images.

Characterization of a GH20 ß-N-Acetylhexosaminidase from Flavobacterium algicola Suitable to Synthesize Lacto-N-triose II.

ß-N-Acetylhexosaminidases have attracted much attention in the enzymatic synthesis of lacto-N-triose II (LNT2) as a backbone precursor of human milk oligosaccharides (HMOs). In this study, a novel glycoside hydrolase (GH) 20 family ß-N-acetylhexosaminidase, FlaNag2353, from Flavobacterium algicola was biochemically characterized and applied to synthesize LNT2. FlaNag2353 displayed optimal activity to p-nitrophenyl N-acetyl-ß-d-glucosaminide (pNP-GlcNAc) at 40 °C and pH 8.0. In addition to its excellent hydrolysis activity toward pNP-GlcNAc and chitooligosaccharides, FlaNag2353 showed trans-glycosylation activity. Under conditions of pH 9.0 and 55 °C for 2 h and utilizing 200 mM lactose and 10 mM pNP-GlcNAc, FlaNag2353 synthesized LNT2 with a conversion ratio of 4.15% calculated from pNP-GlcNAc. Moreover, when applied to LNT2 synthesis with 10 mM pNP-GlcNAc and 9.7% (w/v) industrial waste whey powder, FlaNag2353 achieved a conversion ratio of 2.39%. This study has significant implications for broadening the applications of GH20 ß-N-acetylhexosaminidases and promoting the high-value utilization of whey powder.

Margin quality analysis for wedge resection of lung cancer and construction of a predictive model.

Background: Insufficient pulmonary wedge resection margin is associated with malignant positive margins and high local recurrence risk for lung cancer. This study aimed to identify the risk factors of insufficient or guideline discordant resection margin distance and establish a predictive model to preoperatively estimate the risk of discordant margin for individual patient. Methods: Guideline discordant resection margin was defined as ratio of resection margin distance to tumor size less than one. Patients who had pulmonary malignancies and underwent wedge resection between April 2014 and February 2023 were enrolled and stratified by quality of resection margin. Multivariable logistic regression analysis was employed to identify risk factors of guideline discordant margin and a predictive model was developed. Data from March 2023 to January 2024 were collected for internal validation. Results: A total of 530 patients were included. The incidence of guideline discordant wedge resection margin was 37.2%. Longer tumor's max distance to pleura and larger tumor size were variables associated with increased risk and included in the final model. Preoperative localization and right-side surgery were protective variables in the predictive model. A nomogram was built based on the predictive model. The model showed satisfying predictive performance with a concordance index of 0.720 for the predictive model, and 0.761 for internal validation. The goodness-if-fit tests were non-significant for both model development and internal validation data set. Conclusions: The preoperative predictive model and nomogram show good predictive performance to estimate the risk of guideline discordant wedge resection margin. Individualized surgical plans or preoperative nodule localization can be made for high-risk patients.

Ultra-short-period perioperative pulmonary rehabilitation on short-term outcomes after surgery in smoking patients with lung cancer: A randomized clinical trial.

BACKGROUND: Pulmonary rehabilitation is essential for airway management after thoracic surgery. Most current pulmonary rehabilitations are composed of 2-4-week exercises, which require significant consumption of medical resources and concerns about disease progression. MATERIALS AND METHODS: This single-center, prospective, randomized controlled trial enrolled smoking patients with pulmonary masses or nodules suitable for lobectomy, aged 18-80, with smoking history (≥20 pack-years). Eligible patients were randomized in a 1:1 ratio into two groups. Patients in the intervention group underwent perioperative breathing exercises based on positive pressure vibration expectoration and three-day preoperative lower limb endurance training. Patients in the control group received routine perioperative care. The primary outcome was in-hospital incidence of postoperative pulmonary complications. Secondary outcomes included postoperative hospital stay, total hospitalization cost, postoperative drainage time, drainage volume, semiquantitative cough strength score, pain score, Borg scale-assessed fatigue, and walking distance on postoperative days 1 and 2. RESULTS: A total of 194 patients were included in the study with 94 in the intervention group and 100 in the control group. Our ultrashort pulmonary rehabilitation program potentially reduced pulmonary complications incidence (24.5% vs. 33.0%), but without statistical significance (P=0.190). No significant differences were found in other perioperative outcomes, except for postoperative semiquantitative cough strength score (3 [interquartile range, 3-3.75] vs. 3 [interquartile range, 2-3], P<0.001) and change in walking distance from postoperative days 1 to 2 (60 [interquartile range, 40-82.5] vs. 30 [interquartile range, 10-60], P=0.003). CONCLUSION: There were no significant differences in postoperative complications and other hospitalizations, but our ultrashort rehabilitation program improved patients' semiquantitative cough strength score and walking distance, indicating potential for better outcomes. This treatment is a safe and effective means of airway management for thoracic surgery in the era of enhanced recovery. (ClinicalTrials.gov Identifier: XXX).

Lymph node metastasis in early invasive lung adenocarcinoma: Prediction model establishment and validation based on genomic profiling and clinicopathologic characteristics.

BACKGROUND: The presence of lymph node (LN) metastasis directly affects the treatment strategy for lung adenocarcinoma (LUAD). Next-generation sequencing (NGS) has been widely used in patients with advanced LUAD to identify targeted genes, while early detection of pathologic LN metastasis using NGS has not been assessed. METHODS: Clinicopathologic features and molecular characteristics of 224 patients from Ruijin Hospital were analyzed to detect factors associated with LN metastases. Another 140 patients from Huashan Hospital were set as a test cohort. RESULTS: Twenty-four out of 224 patients were found to have lymph node metastases (10.7%). Pathologic LN-positive tumors showed higher mutant allele tumor heterogeneity (p < 0.05), higher tumor mutation burden (p < 0.001), as well as more frequent KEAP1 (p = 0.001), STK11 (p = 0.004), KRAS (p = 0.007), CTNNB1 (p = 0.017), TP53, and ARID2 mutations (both p = 0.02); whereas low frequency of EGFR mutation (p = 0.005). A predictive nomogram involving male sex, solid tumor morphology, higher T stage, EGFR wild-type, and TP53, STK11, CDKN2A, KEAP1, ARID2, KRAS, SDHA, SPEN, CTNNB1, DICER1 mutations showed outstanding efficiency in both the training cohort (AUC = 0.819) and the test cohort (AUC = 0.780). CONCLUSION: This study suggests that the integration of genomic profiling and clinical features identifies early-invasive LUAD patients at higher risk of LN metastasis. Improved identification of LN metastasis is beneficial for the optimization of the patient's therapy decisions.

Online tools to predict individualised survival for primary oesophageal cancer patients with and without pathological complete response after neoadjuvant therapy followed by oesophagectomy: development and external validation of two independent nomograms.

OBJECTIVE: This study aimed to develop and validate robust predictive models for patients with oesophageal cancer who achieved a pathological complete response (pCR) and those who did not (non-pCR) after neoadjuvant therapy and oesophagectomy. DESIGN: Clinicopathological data of 6517 primary oesophageal cancer patients who underwent neoadjuvant therapy and oesophagectomy were obtained from the National Cancer Database for the training cohort. An independent cohort of 444 Chinese patients served as the validation set. Two distinct multivariable Cox models of overall survival (OS) were constructed for pCR and non-pCR patients, respectively, and were presented using web-based dynamic nomograms (graphical representation of predicted OS based on the clinical characteristics that a patient could input into the website). The calibration plot, concordance index and decision curve analysis were employed to assess calibration, discrimination and clinical usefulness of the predictive models. RESULTS: In total, 13 and 15 variables were used to predict OS for pCR and non-pCR patients undergoing neoadjuvant therapy followed by oesophagectomy, respectively. Key predictors included demographic characteristics, pretreatment clinical stage, surgical approach, pathological information and postoperative treatments. The predictive models for pCR and non-pCR patients demonstrated good calibration and clinical utility, with acceptable discrimination that surpassed that of the current tumour, node, metastases staging system. CONCLUSIONS: The web-based dynamic nomograms for pCR (https://predict-survival.shinyapps.io/pCR-eso/) and non-pCR patients (https://predict-survival.shinyapps.io/non-pCR-eso/) developed in this study can facilitate the calculation of OS probability for individual patients undergoing neoadjuvant therapy and radical oesophagectomy, aiding clinicians and patients in making personalised treatment decisions.

Electrochemiluminescence detection of diazinon in vegetables based on the synergistic interaction of WO3-x dots with Au@SiO2 nanocapsules.

In this work, a simple synthesis of low-toxicity transition metal material of WO3-x dots was used as a co-reactant with Au@SiO2 as a core-shell material and a signal amplification factor to collaboratively promote Ru(bpy)32+ electrochemiluminescence (ECL) for the construction of a highly sensitive aptasensor for the detection of diazinon (DZN) in vegetables. Electrodes modified with multi-walled carbon nanotubes-chitosan composite membranes (MWCNTs-CS) were used to load and immobilize more Ru(bpy)32+.can load more Ru(bpy)32+. WO3-x dots synthesized by a simple method showed excellent ECL efficiency as a novel co-reactant for Ru(bpy)32+. Under optimized conditions, this aptasensor for DZN has a wide detection range (10 pg mL-1 - 1 µg mL-1.) and a low detection limit (0.0197 ng L-1). The aptasensor has shown good results in the analysis of real samples in the experiment. This work provides a new approach to the construction of a novel electrochemiluminescence sensor for the detection of pesticides.

Metal-organic framework-based aptasensor utilizing a novel electrochemiluminescence system for detecting acetamiprid residues in vegetables.

The work was based on N-(4-Aminobutyl)-N-ethylisoluminol (ABEI)-functionalized Fe-MIL-101 and gold nanoparticles (AuNPs) as sensing materials, and an electrochemiluminescence (ECL) aptasensor was constructed for detecting acetamiprid. As a metal-organic framework (MOF) material, Fe-MIL-101, was renowned for its unique three-dimensional network structure and efficient catalytic capability. ABEI, a common ECL reagent, was widely applied. ABEI was introduced into the Fe-MIL-101 structure as a luminescence functionalization reagent to form Fe-MIL-101@ABEI. This approach avoided limitations on the loading capacity of luminescent reagents imposed by modification and encapsulation methods. With character of excellent catalytic activity and ease of bioconjugation, AuNPs offered significant advantages in biosensing. Leveraging the reductive properties of ABEI, AuNPs were reduced around Fe-MIL-101@ABEI, resulting in the modified luminescent functionalized material denoted as Fe-MIL-101@ABEI@AuNPs. An aptamer was employed as a recognition element and was modified accordingly. The aptamer was immobilized on Fe-MIL-101@ABEI@AuNPs through gold-sulfur (Au-S) bonds. After capturing acetamiprid, the aptamer induced a decrease in the ECL signal intensity within the ABEI-hydrogen peroxide (H2O2) system, enabling the quantitative detection of acetamiprid. The aptasensor displayed remarkable stability and repeatability, featured a detection range of 1×10-3-1×102 nM, and had a limit of detection (LOD) of 0.3 pM (S/N=3), which underscored its substantial practical application potential.

Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial.

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7-18.1, P = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 .

A feasible technique for distinguishing the intersegmental plane by transbronchial injection of iron sucrose.

Objectives: Pulmonary segmentectomy should be the standard surgical procedure for patients in certain clinical scenarios. However, detecting the intersegmental planes both on the pleural surface and within the lung parenchyma remains a challenge. We developed an intraoperative novel method for distinguishing intersegmental planes of the lung via transbronchial injection of iron sucrose (ClinicalTrials.gov number, NCT03516500). Methods: We first performed a bronchial injection of iron sucrose to identify the intersegmental plane of the porcine lung. Then, we conducted a prospective study to evaluate the safety and feasibility of the technique in 20 patients who underwent anatomic segmentectomy. Iron sucrose was injected into the bronchus of target pulmonary segments, and the intersegmental planes were divided with electrocautery or stapler. Results: The median injection of iron sucrose was 90 mL (range, 70-120 mL), and the median time from injection of iron sucrose to demarcation of intersegmental plane was 8 minutes (range, 3-25 minutes). Qualified identification of the intersegmental plane was observed in 17 cases (85%). The intersegmental plane could not be recognized in 3 cases. All patients experienced no complications related to iron sucrose injection or complications of Clavien-Dindo grade 3 or more. Conclusions: Transbronchial injection of iron sucrose is a simple, safe, and feasible approach to identify the intersegmental plane (NCT03516500).

Electrochemiluminescence Sensor Based on CTS-MoS2 and AB@CTS with Functionalized Luminol for Detection of Malathion Pesticide Residues.

The accumulation of pesticide residues poses a significant threat to the health of people and the surrounding ecological systems. However, traditional methods are not only costly but require expertise in analysis. An electrochemiluminescence (ECL) aptasensor was developed using chitosan and molybdenum disulfide (CTS-MoS2), along with acetylene black (AB@CTS) for the rapid detection of malathion residues. Due to the weak interaction force, simple composite may lead to uneven dispersion; MoS2 and AB were dissolved in CTS solution, respectively, and utilized the biocompatibility of CTS to interact with each other on the electrode. The MoS2 nanosheets provided a large specific surface area, enhancing the utilization rate of catalytic materials, while AB exhibited excellent conductivity. Additionally, the dendritic polylysine (PLL) contained numerous amino groups to load abundant luminol to catalyze hydrogen peroxide (H2O2) and generate reactive oxygen species (ROS). The proposed ECL aptasensor obtained a low detection limit of 2.75 × 10-3 ng/mL (S/N = 3) with a good detection range from 1.0 × 10-2 ng/mL to 1.0 × 103 ng/mL, demonstrating excellent specificity, repeatability, and stability. Moreover, the ECL aptasensor was successfully applied for detecting malathion pesticide residues in authentic samples with recovery rates ranging from 94.21% to 99.63% (RSD < 2.52%). This work offers valuable insights for advancing ECL sensor technology in future applications.

Chronic obstructive pulmonary disease alters the genetic landscape and tumor immune microenvironment in lung cancer patients.

Background: Chronic obstructive pulmonary disease (COPD) and lung cancer are leading causes of morbidity and mortality worldwide. Studies have reported molecular alterations in patients with lung cancer and in patients with COPD. However, few investigation has been conducted on the molecular characteristics of lung cancer patients with COPD. Materials and methods: We performed a retrospective cohort study that included 435 patients with pathologically confirmed lung cancer at the Ruijin Hospital. For patients with documented spirometry, Global Initiative for Chronic Obstructive Lung Disease criteria were used to define COPD. For patients without documented spirometry, chest computed tomography and other clinical information were used to define COPD. Tumor tissue DNA was extracted from formalin-fixed paraffin-embedded samples. DNA mutation analysis, multiplex immunohistochemistry (mIHC), calculation of tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and predication of neoantigens were performed. Results: Although SNV mutations in lung cancer patients with COPD (G1 group) were generally higher than those in lung cancer patients without COPD (G2 group), the difference in the number of mutations was insignificant between the two groups. Of the 35 mutated genes, the number of them was higher in G1 than in G2, except that of EGFR. PI3K-Akt signaling pathway was enriched from significantly different genes. While TMB and MATH levels were not significantly different, the tumor neoantigen burdenwas markedly higher in G1 than that in G2. The level of CD68+ macrophages was significant higher in the stroma and total areas in the G1 group than in G2 group. The level of CD8+ lymphocytes was markedly higher in the stroma and showed a clear tendency forhigher expression in the G1 group than inthe G2 group. No significant differences were observed for the level of programmed death-ligand 1+ (PD-L1+), programmed death 1+ (PD-1+), and CD68PD-L1 in the stroma, tumor and total areas. Conclusion: Our study revealed different genetic aberrations and pathways, higher neoantigen burden, and higher level of CD68+ macrophages and CD8+ T lymphocytes in lung cancer patients with COPD. Our investigation implies that the existence of COPD should be considered and immunotherapy is a potential choice when treating lung cancer patients with COPD.

Sodium glucose cotransporter-2-inhibitor dapagliflozin improves nonalcoholic fatty liver disease by ameliorating dipeptidyl-peptidase-4 protein expression in diabetic mice.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. It can progress from simple steatosis to nonalcoholic steatohepatitis and may even develop into liver fibrosis, hepatocirrhosis, or hepatocellular carcinoma, but there is no effective treatment. MATERIAL AND METHODS: Wild-type (wt) and diabetic (db/db) mouse NAFLD-induced models were used to investigate the hepatoprotective effects and potential mechanisms of dapagliflozin (a new oral hypoglycaemic drug) on type 2 diabetes mellitus (T2DM) complicated with NAFLD, and to establish wt and db/db mouse NAFLD-induced and dapagliflozin treatment models. RESULTS: Dapagliflozin reduces blood glucose, glycosylated haemoglobin, blood lipids, and serum transaminase levels in db/db mice and improves T2DM-related liver injury accompanied by NAFLD; the mechanism may be related to the decrease in dipeptidyl-peptidase-4 (DPP4) protein expression and improvement in liver enzymes. Further mechanism-related studies by our team revealed that dapagliflozin can also downregulate the expression of DPP4 proteins in the liver and reduce serum soluble DPP4 enzyme levels, thereby improving the hepatic steatosis and insulin resistance of NAFLD. CONCLUSION: Dapagliflozin may be an effective drug for the treatment of T2DM-induced NAFLD and NAFLD, providing a reliable laboratory basis and new treatment methods for the clinical treatment of NAFLD.

Pretreatment absolute lymphocyte count is an independent predictor for survival outcomes for esophageal squamous cell carcinoma patients treated with neoadjuvant chemoradiotherapy and pembrolizumab: An analysis from a prospective cohort.

BACKGROUND: The aim of the study was to analyze the relationship between pretreatment inflammatory biomarkers (IBs) and survival outcomes for patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (neo-CRT) and pembrolizumab. METHODS: Clinical variables and IBs (absolute monocyte count [AMC], absolute lymphocyte count [ALC], platelet count [PLT], neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], pan-immune inflammation value [PIV], systemic immunoinflammatory index [SII], systemic immunoreactivity index [SIRI] and prognostic nutritional index [PNI]) were collected. Univariate and multivariate analysis were performed to identify the independent factors for outcomes of ESCC. RESULTS: A total of 51 patients were included. Of these, 35 patients achieved pathological complete response (pCR) after neo-CRT and pembrolizumab (pCR: 68.6%). With a median follow-up of 20 months, the two-year PFS and OS of the cohort was 64% and 91%, respectively. Multivariate logistic regression analysis indicated that ALC (overall response [OR] 4.4, p = 0.051) and PLT (OR 6.7, p = 0.023) were two independent predictors for achieving pCR among ESCC treated with neo-CRT and pembrolizumab. Multivariate Cox regression analysis showed that ALC (HR 0.27, p = 0.028) and SIRI (HR 3.13, p = 0.048) were two independent predictors associated with PFS. Kaplan Meier analysis demonstrated that the PFS of ESCC with high baseline ALC was significantly better than those with low ALC (2-year PFS: 77% vs. 47%, p = 0.027), but not for overall survival (2-year OS: 96% vs. 87%, p = 0.46). CONCLUSIONS: This retrospective analysis based on a prospective cohort for the first time demonstrates that pretreatment ALC is an independent predictor for achieving pCR and favorable outcomes of ESCC treated with neo-CRT and pembrolizumab.