Thickness measurements of graphene oxide flakes using atomic force microscopy: results of an international interlaboratory comparison.

Flake thickness is one of the defining properties of graphene-related 2D materials (GR2Ms), and therefore requires reliable, accurate, and reproducible measurements with well-understood uncertainties. This is needed regardless of the production method or manufacturer because it is important for all GR2M products to be globally comparable. An international interlaboratory comparison on thickness measurements of graphene oxide flakes using atomic force microscopy has been completed in technical working area 41 of versailles project on advanced materials and standards. Twelve laboratories participated in the comparison project, led by NIM, China, to improve the equivalence of thickness measurement for two-dimensional flakes. The measurement methods, uncertainty evaluation and a comparison of the results and analysis are reported in this manuscript. The data and results of this project will be directly used to support the development of an ISO standard.

Prediction of pulmonary metastasis in esophageal carcinoma patients with indeterminate pulmonary nodules.

BACKGROUND: Indeterminate pulmonary nodules (IPNs) are common after surgery for esophageal cancer. The paucity of data on postoperative IPNs for esophageal cancer causes a clinical dilemma. OBJECTIVE: The aim of this study was to identify the characteristics and clinical significance of IPNs after radical esophagectomy for metastatic esophageal cancer, determine the risk factors for pulmonary metastasis, and construct a risk score model to standardize the appropriate time to either follow up or treat the patient. METHODS: All consecutive patients with esophageal squamous cell carcinoma (ESCC) who underwent radical surgery between 2013 and 2016 were included in this retrospective study. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors and develop risk score models. RESULTS: A total of 816 patients were enrolled in the study. During a median follow-up period of 45 months, IPNs were detected in 221 (27.1%) patients, of whom 66 (29.9%) were diagnosed with pulmonary metastases. The following five variables maintained prognostic significance after multivariate analyses: the pathologic N category, number of IPNs, shape of IPNs, time of detection of IPNs, and size of IPNs. The Pulmonary Metastasis Prediction Model (PMPM) scale ranges from 0 to 15 points, and patients with higher scores have a higher probability of pulmonary metastases. The Hosmer-Lemeshow test showed a good calibration performance of the clinical prediction model (χ2 = 8.573, P = 0.380). After validation, the PMPM scale showed good discrimination with an AUC of 0.939. CONCLUSION: A PMPM scale for IPNs in patients who underwent esophagectomy for ESCC may be clinically useful for diagnostic and therapeutic decision-making.

Prognostic variables for conditional survival in patients with esophageal squamous cell carcinoma who underwent minimally invasive surgery.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) survival is mainly reported at the time of treatment. Conditional survival is another prognostic tool to evaluate ESCC patients who has survived more than one year since treatment. METHODS: We analyzed data from 705 ESCC patients who underwent minimally invasive surgery between 2013 and 2016. Using the Kaplan-Meier method, we computed a 5-year relative conditional survival. We also investigated the prognostic factors associated with survival using Cox proportional hazards models. RESULTS: Conditional survival improved over time for all cohorts of ESCC patients who survived a period after surgery. The greatest improve in conditional survival were observed in patients 2 years after surgery. In addition, the results of the Cox survival model from the time of surgery, T stage (p < 0.001), N stage (p < 0.001), and anastomotic leak (p = 0.022), were significantly associated with survival. However, the results of the Cox survival model from 2 years after surgery, N stage (p < 0.001), and anastomotic leak (p = 0.032) were significantly associated with survival. CONCLUSION: For ESCC patients who survived a period after surgery, the largest increases in conditional survival were observed in patients 2 years after surgery. We suggest that patients with anastomotic leakage and higher T and N stages should be strictly screened according to various time, and that conditional survival should be used as a powerful prognostic tool for ESCC patients.

Understanding the tunable sodium storage performance in pillared MXenes: a first-principles study.

Pillared MXenes with large interlayer spacing have shown great potential as an anode material for sodium-ion batteries (SIBs). To better understand the underlying mechanism of the pillar effect in enhancing the electrochemical performance, first-principles calculations were used to investigate the adsorption and diffusion of Na in MXenes (Ti2CO2 and Ti3C2O2), as well as the mechanical properties of the system under different MXenes layer spacings. The results showed that when the MXene layer spacing was ∼4 Å, the strongest adsorption of Na on MXenes was achieved due to the interlayer synergy effect. However, when the MXene layer spacing was greater than 5 Å, double Na-atomic layer adsorption would be formed, which increased the Na storage capacity. Interestingly, the diffusion of Na was not only affected by the interlayer spacing of MXenes, but also by the interlayer stacking mode of MXenes. Moreover, it was found that when the MXene layer spacing was more than 8 Å, the sodium storage properties basically did not change significantly. The optimal layer spacing for Ti2CO2 and Ti3C2O2 was predicted to be 7 and 6 Å, respectively. This work provides valuable theoretical guidance for developing high-performance anode materials for SIBs.

Influence of ligand geometry on cholinesterase enzyme - A comparison of 1-isoindolinone based structural analog with Donepezil.

Donepezil (DNPZ) is one of the few FDA-approved widely used medication in the clinical care of Alzheimer's disease (AD) patients. To investigate the effect of geometry and to find the significance of an enol form if any in DNPZ on acetylcholinesterase (AChE) inhibition, we changed the tetrahedral geometry of DNPZ to planar trigonal pyramidal geometry by replacing the α-carbon atom next to ketone functionality with a nitrogen atom. To mimic 1-indanone in DNPZ, we selected 1-isoindolinone framework to synthesize 25 new DNPZ derivatives and characterized using 1H NMR, 13C NMR and ESI-MS spectroscopy methods. Drug likeliness profile for each compound was predicted using Molinspiration online software following Lipinski's rule. Commercially available assay kits were used to measure AChE and butyrylcholinesterase (BuChE) inhibitory effects. NIH/3T3 mouse embryonic fibroblast cell line was used to measure cytotoxic and proliferation effects using LDH and MTT assay, respectively. Compound #20 was selected for comparative computational docking, modelling and physicochemical studies. Our results show that DNPZ with tetrahedral geometry has 3-fold higher AChE inhibition as compared to compound #20 with planar trigonal pyramidal geometry. Our approach may be useful as a novel indirect method to study the significance of the enol form in DNPZ (or similar compounds), since constant interconversion between the keto and enol forms does not permit a direct determination of the effect of the enol form of DNPZ in vivo. Overall, we conclude that the tetrahedral is a better fit and any change in geometry significantly drives down the cholinesterase inhibitory effect of DNPZ.

Characterization of Size and Aggregation for Cellulose Nanocrystal Dispersions Separated by Asymmetrical-Flow Field-Flow Fractionation.

Cellulose nanocrystals (CNCs) derived from various types of cellulose biomass have significant potential for applications that take advantage of their availability from renewable natural resources and their high mechanical strength, biocompatibility and ease of modification. However, their high polydispersity and irregular rod-like shape present challenges for the quantitative dimensional determinations that are required for quality control of CNC production processes. Here we have fractionated a CNC certified reference material using a previously reported asymmetrical-flow field-flow fractionation (AF4) method and characterized selected fractions by atomic force microscopy (AFM) and transmission electron microscopy. This work was aimed at addressing discrepancies in length between fractionated and unfractionated CNC and obtaining less polydisperse samples with fewer aggregates to facilitate microscopy dimensional measurements. The results demonstrate that early fractions obtained from an analytical scale AF4 separation contain predominantly individual CNCs. The number of laterally aggregated "dimers" and clusters containing 3 or more particles increases with increasing fraction number. Size analysis of individual particles by AFM for the early fractions demonstrates that the measured CNC length increases with increasing fraction number, in good agreement with the rod length calculated from the AF4 multi-angle light scattering data. The ability to minimize aggregation and polydispersity for CNC samples has important implications for correlating data from different sizing methods.

Temperature induced lipid membrane restructuring and changes in nanomechanics.

The naturally occurring milk sphingomyelin is of particular interest owing to its complex composition and involvement in the formation of the milk fat globule membrane (MFGM). Knowledge of membrane organization and nanomechanical stability has proved to be crucial in understanding their properties and functions. In this work, two model membrane systems composed of 1, 2 dioleoyl-sn-glycero-3-phosphocholine (DOPC), egg sphingomyelin (egg-SM) and cholesterol, and DOPC, milk sphingomyelin (milk-SM) and cholesterol were exposed to both RT and 10°C. The morphological and nanomechanical changes were investigated using atomic force microscopy (AFM) imaging and force mapping below RT using a designed liquid cell with temperature-control. In both systems, the size and shape of SM/Chol-enriched liquid ordered domains (Lo) and DOPC-enriched liquid disordered phase (Ld) were monitored at controlled temperatures. AFM based force-mapping showed that rupture forces were consistently higher for Lo domains than Ld phases and were decreased for Ld with decreasing temperature while an increase in breakthrough force was observed in Lo domains. More interestingly, dynamic changes and defect formations in the hydrated lipid bilayers were mostly detected at low temperature, suggesting a rearrangement of lipid molecules to relieve additional tension introduced upon cooling. Noteworthy, in these model membrane systems, tension-driven defects generally heal on reheating the sample. The results of this work bring new insights to low temperature induced membrane structural reorganization and mechanical stability changes which will bring us one step closer to understand more complex systems such as the MFGM.

Gel-gel phase separation within milk sphingomyelin domains revealed at the nanoscale using atomic force microscopy.

The milk sphingomyelin (MSM) is involved in the formation of ordered lipid domains in the biological milk fat globule membrane (MFGM), where it accounts for about 30%wt of the polar lipids. Moreover, MSM exhibits a large variety in saturated acyl chain lengths (from C16:0 to C24:0-SM) compared to other natural sphingomyelins, which may impact the packing of MSM molecular species in the gel phase domains and the topography of the MFGM. To investigate this, supported lipid bilayers of synthetic sphingomyelins or of MSM-containing mixtures, including a MFGM polar lipid extract, were imaged at temperatures below the Tm of MSM (i.e. <34°C for which MSM is in the gel phase) in hydrated conditions using atomic force microscopy. In all compositions containing MSM, the MSM-rich gel phase domains exhibited lower and upper height levels H, interpreted as two distinct gel phases with ∆H~0.5-1.1nm. Two (lower and upper) gel phases were also found for pure C24:0-SM bilayers or for bilayers of a C16:0-SM/C24:0-SM equimolar mixture, while C16:0-SM bilayers were uniformly flat and less thick than C24:0-SM bilayers. The upper gel phase of MSM-containing bilayers was interpreted as mixed interdigitated C24:0-SM molecules, while the lower gel phase was attributed both to fully interdigitated C24:0-SM molecules and non-interdigitated C16:0-SM molecules. These results show that the composition of natural sphingomyelins, inducing a mismatch between the d18:1 sphingosine and the acyl chains, is important in both the internal organization and the topography of biological membranes, especially that of the MFGM. This organization could be involved in specific biological functions, e.g. the insertion of proteins.

Interaction of saponin 1688 with phase separated lipid bilayers.

Saponins are a diverse family of naturally occurring plant triterpene or steroid glycosides that have a wide range of biological activities. They have been shown to permeabilize membranes and in some cases membrane disruption has been hypothesized to involve saponin/cholesterol complexes. We have examined the interaction of steroidal saponin 1688-1 with lipid membranes that contain cholesterol and have a mixture of liquid-ordered (Lo) and liquid-disordered (Ld) phases as a model for lipid rafts in cellular membranes. A combination of atomic force microscopy (AFM) and fluorescence was used to probe the effect of saponin on the bilayer. The results demonstrate that saponin forms defects in the membrane and also leads to formation of small aggregates on the membrane surface. Although most of the membrane damage occurs in the liquid-disordered phase, fluorescence results demonstrate that saponin localizes in both ordered and disordered membrane phases, with a modest preference for the disordered regions. Similar effects are observed for both direct incorporation of saponin in the lipid mixture used to make vesicles/bilayers and for incubation of saponin with preformed bilayers. The results suggest that the initial sites of interaction are at the interface between the domains and surrounding disordered phase. The preference for saponin localization in the disordered phase may reflect the ease of penetration of saponin into a less ordered membrane, rather than the actual cholesterol concentration in the membrane. Dye leakage assays indicate that a high concentration of saponin is required for membrane permeabilization consistent with the supported lipid bilayer experiments.

Correlating Cellulose Nanocrystal Particle Size and Surface Area.

Cellulose nanocrystals (CNCs) are negatively charged nanorods that present challenges for characterization of particle size distribution and surface area-two of the common parameters for characterizing nanomaterials. CNC size distributions have been measured by two microscopy methods: atomic force microscopy (AFM) and transmission electron microscopy (TEM). The agreement between the two methods is good for length measurements, after taking into consideration tip-convolution effects for AFM. However, TEM widths are almost twice as large as AFM heights-an effect that we hypothesize is due to counting of a larger fraction of laterally associated CNCs in the TEM images. Overall, the difficulty of selecting individual particles for analysis and possible bias due to selection of a specific particle size during sample deposition are the main limitations associated with the microscopy measurements. The microscopy results were compared to Z-average data from dynamic light scattering, which is a useful method for routine analysis and for examining trends in size as a function of sample treatment. Measurements as a function of sonication energy were used to provide information on the presence of aggregates in the sample. Magic-angle-spinning solid-state NMR was employed to estimate the surface area of CNCs based on the ratio of integrated spectral intensities of resonances stemming from C4 sites at the crystallite surfaces and from all C4 sites. Our approach was adapted from the application of solid-state NMR to characterize larger cellulose microfibers and appears to provide a useful estimate that overcomes the limitations of using the BET method for measuring surface areas of highly aggregated nanomaterials. The solid-state NMR results show that the lateral dimension of the CNCs is consistent with that of elementary cellulose crystallites.

Milk sphingomyelin domains in biomimetic membranes and the role of cholesterol: morphology and nanomechanical properties investigated using AFM and force spectroscopy.

Milk sphingomyelin (MSM) and cholesterol segregate into domains in the outer bilayer membrane surrounding milk fat globules. To elucidate the morphology and mechanical properties of theses domains, supported lipid bilayers with controlled molar proportions of MSM, dioleoylphosphatidylcholine (DOPC) and cholesterol were produced in buffer mimicking conditions of the milk aqueous phase. Atomic force microscopy imaging showed that (i) for T < 35 °C MSM segregated in gel phase domains protruding above the fluid phase, (ii) the addition of 20 mol % cholesterol resulted in smaller and more elongated l(o) phase domains than in equimolar MSM/DOPC membranes, (iii) the MSM/cholesterol-enriched l(o) phase domains were less salient than the MSM gel phase domains. Force spectroscopy measurements furthermore showed that cholesterol reduced the resistance of MSM/DOPC membrane to perforation. The results are discussed with respect to the effect of cholesterol on the biophysical properties of lipid membranes. The combination of AFM imaging and force mapping provides unprecedented insight into the structural and mechanical properties of milk lipid membranes, and opens perspectives for investigation of the functional properties of MSM domains during milk fat processing or digestion.

Camrelizumab in combination with chemotherapy versus concurrent chemoradiotherapy for the conversion of locally advanced unresectable oesophageal squamous carcinoma: protocol for a two-arm, open-label phase II trial.

INTRODUCTION: Oesophageal cancer (OC) has higher morbidity and mortality rate than most other malignancies. The standard treatment for unresectable locally advanced oesophageal squamous cell carcinoma (OSCC) is concurrent chemoradiotherapy, with tumour regression observed in a proportion of patients after treatment, but prognostic improvement remains limited. Immunotherapy in combination with chemotherapy (CT) has been shown to be efficacious as the first-line treatment of advanced OC and neoadjuvant therapy. Therefore, we conducted a prospective, two-arm, randomised, unblinded phase II study to explore the efficacy of camrelizumab in combination with CT versus chemoradiotherapy for the conversion of unresectable advanced OSCC. METHODS AND ANALYSIS: All participants meeting the inclusion criteria will be enrolled after signing an informed consent form. Patients with clinically cT4b or spread to at least one group of lymph nodes with possible invasion of surrounding organs and unresectable locally advanced squamous carcinoma of the thoracic segment of the oesophagus will be included in the study. Patients with suspected distant metastases on the preoperative examination will be excluded from this study. Patients eligible for enrolment will be grouped by centre randomisation according to the study plan. Patients will undergo radical surgery after completion of two cycles of chemotherapy (CT) combined with camrelizumab induction therapy or concurrent chemoradiotherapy if assessed to be operable. Patients evaluated as inoperable will be scheduled for a multidisciplinary consultation to determine the next treatment option. The primary endpoint is the R0 resection rate in patients undergoing surgery after treatment. Secondary endpoints are the rate of major pathological remission, pathological complete response rate, overall survival, progression-free survival and adverse events for all patients. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethics committees of Fujian Medical University Union Hospital (No. 2022YF039-02). The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05821452.

Comparison of indocyanine green-near-infrared fluorescence guided and traditional mediastinal lymphadenectomy during radical esophagectomy: A randomized controlled trial.

BACKGROUND: The extent of lymph node dissection during radical esophagectomy remains a controversial topic. Thus, this study mainly aimed to explore the location of sentinel lymph nodes in esophageal squamous cell carcinoma and the application value of the indocyanine green-near-infrared fluorescence system in lymphadenectomy. METHODS: This randomized controlled clinical trial (ClinicalTrials.gov, NCT04615806) included 42 participants without neoadjuvant therapy who were lymph node negative based on positron emission tomography/computed tomography findings. Traditional esophagectomy with indocyanine green-near-infrared fluorescence imaging was performed after injecting 0.5 mL indocyanine green (1.25 mg/mL) into the esophageal submucosa in the 4 peritumoral quadrants. The primary endpoint was to determine the location of the sentinel lymph node in esophageal squamous cell carcinoma based on postoperative pathologic reports. RESULTS: A total of 40 patients, with 20 in each group, were included in the final analysis. In the indocyanine green group, indocyanine green-near-infrared fluorescence imaging was successful in all subjects. Seven cases (cases 2, 3, 9, 11, 17, 18, and 20) in the indocyanine green group exhibited lymph node metastases, all of which were near-infrared positive. The detection rate, positive predictive value, negative predictive value, sensitivity, and specificity were 100% (20 of 20 cases), 8.7% (13/150), 100% (265/265), 100% (13/13), and 65.9% (265/402), respectively. All near-infrared-negative lymph nodes were nonmetastatic lymph nodes. In addition, the number of mediastinal lymph nodes resected in the indocyanine green group was significantly higher than in the non-indocyanine green group. CONCLUSION: Indocyanine green-near-infrared might be an important and promising technique in predicting sentinel lymph nodes of esophageal squamous cell carcinoma and could significantly improve the detection rate of lymph nodes of esophageal squamous cell carcinoma.

Lipid reassembly in asymmetric Langmuir-Blodgett/Langmuir-Schaeffer bilayers.

Molecular-reorganization-induced morphology alteration in asymmetric substrate-supported lipid bilayers (SLBs) was directly visualized by means of atomic force microscopy (AFM) and total internal reflection fluorescence (TIRF) microscopy. SLB samples were fabricated on mica-on-glass and glass substrates by Langmuir-Blodgett (LB)/Langmuir-Schaeffer (LS) using binary lipid mixtures, namely, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and ternary mixtures DOPC/DPPC/1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS), labeled with 0.2 mol % Texas Red 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium salt (TR-DHPE) dye. Phase segregations were characterized by TIRF imaging, and DPPC-enriched domain structures were also observed. Interestingly for ∼40% (n = 6) of the samples with binary mixtures in the LB leaflet and a single component in the LS leaflet, that is, (DOPC/DPPC)(LB)+DOPC(LS), the contrast of the DPPC domains changed from the original dark (without dye) to bright (more TR dye partitioning) on TIRF images, returning to dark again. This contrast reverse was also correlated to AFM height images, where a DPPC-DPPC gel phase was spotted after the TIRF image contrast returned to dark. The rupture force mapping results measured on these binary mixture samples also confirmed unambiguously the formation of DPPC-DPPC gel domain components during the contrast change. The samples were tracked over 48 h to investigate the lipid molecule movements in both the DPPC domains and the DOPC fluid phase. The fluorescence contrast changes from bright to dark in SLBs indicate that the movement of dye molecules was independent of the movement of lipid molecules. In addition, correlated multimodal imaging using AFM, force mapping, and fluorescence provides a novel route to uncover the reorganization of lipid molecules at the solid-liquid interface, suggesting that the dynamics of dye molecules is highly structure dependent.

Measuring the Diameter of Single-Wall Carbon Nanotubes Using AFM.

In this work, we identify two issues that can significantly affect the accuracy of AFM measurements of the diameter of single-wall carbon nanotubes (SWCNTs) and propose a protocol that reduces errors associated with these issues. Measurements of the nanotube height under different applied forces demonstrate that even moderate forces significantly compress several different types of SWCNTs, leading to errors in measured diameters that must be minimized and/or corrected. Substrate and nanotube roughness also make major contributions to the uncertainty associated with the extraction of diameters from measured images. An analysis method has been developed that reduces the uncertainties associated with this extraction to <0.1 nm. This method is then applied to measure the diameter distribution of individual highly semiconducting enriched nanotubes in networks prepared from polyfluorene/SWCNT dispersions. Good agreement is obtained between diameter distributions for the same sample measured with two different commercial AFM instruments, indicating the reproducibility of the method. The reduced uncertainty in diameter measurements based on this method facilitates: (1) determination of the thickness of the polymer layer wrapping the nanotubes and (2) measurement of nanotube compression at tube-tube junctions within the network.

Learning curve analysis of single-port thoracoscopic combined subsegmental resections.

Background: Combined subsegmental surgery (CSS) is considered to be a safe and effective resection modality for early-stage lung cancer. However, there is a lack of a clear definition of the technical difficulty classification of this surgical case, as well as a lack of reported analyzes of the learning curve of this technically demanding surgical approach. Methods: We performed a retrospective study of single-port thoracoscopic CSS performed by the same surgeon between April 2016 and September 2019. The combined subsegmental resections were divided into simple and complex groups according to the difference in the number of arteries or bronchi which need to be dissected. The operative time, bleeding and complications were analyzed in both groups. Learning curves were obtained using the cumulative sum (CUSUM) method and divided into different phases to assess changes in the surgical characteristics of the entire case cohort at each phase. Results: The study included 149 cases, including 79 in the simple group and 70 in the complex group. The median operative time in the two groups was 179 min (IQR, 159-209) and 235 min (IQR, 219-247) p < 0.001, respectively. And the median postoperative drainage was 435 mL (IQR, 279-573) and 476 mL (IQR, 330-750), respectively, with significant differences in postoperative extubation time and postoperative length of stay. According to the CUSUM analysis, the learning curve for the simple group was divided by the inflection point into 3 phases: Phase I, learning phase (1st to 13th operation); Phase II, consolidation phase (14th to 27th operation), and Phase III, experience phase (28th to 79th operation), with differences in operative time, intraoperative bleeding, and length of hospital stay in each phase. The curve inflection points of the learning curve for the complex group were located in the 17th and 44th cases, with significant differences in operative time and postoperative drainage between the stages. Conclusion: The technical difficulties of the simple group of single-port thoracoscopic CSS could be overcome after 27 cases, while the technical ability of the complex group of CSS to ensure feasible perioperative outcomes was achieved after 44 operations.

Safety and efficacy of camrelizumab combined with radiotherapy as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a prospective single-arm phase II clinical trial protocol.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by esophagectomy is the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 30% of patients still develop distant metastases and have a high incidence of treatment-related adverse events. Immunotherapy, as a new modality for anti-cancer treatment, has shown promising clinical benefits for patients with ESCC. The synergistic effects of immunotherapy and radiotherapy make their combination promising as neoadjuvant treatment for locally advanced ESCC. METHODS: All participants who meet the inclusion criteria will be enrolled after signing the informed consent form. Patients with thoracic segment esophageal cancer with clinical stage T2-3 N0 M0 or T2-3 N + M0 will be included. A total of 25 patients are to be recruited for the study. Twelve patients will be recruited in phase I, with at least two achieving major pathological response (MPR) before entering phase II. They will be treated with radical surgery within 4-8 weeks after the completion of two cycles of neoadjuvant radiotherapy in combination with camrelizumab according to the study schedule. The primary endpoint is the major pathological remission rate of all per-protocol patients. The secondary endpoints are the R0 resection rate, pathological complete remission rate, and adverse events. The interim analysis will be conducted after 12 patients have been enrolled. The trials will be terminated when more than two treatment-related deaths occur or fewer than five patients have major pathological remission. DISCUSSION: We designed this prospective single-arm phase II clinical study to evaluate the combination of camrelizumab and standard radiotherapy as preoperative neoadjuvant therapy for patients with resectable ESCC as part of the quest for better treatment options for patients with locally advanced ESCC. TRIAL REGISTRATION: This trial protocol has been registered on the NIH Clinical Trials database ( www. CLINICALTRIALS: gov/ , NCT05176002. Registered on 2022/01/04). The posted information will be updated as needed to reflect protocol amendments and study progress.

"Separated" precise subsegmentectomy: Single-port thoracoscopic noncombined subsegmentectomy in one lung lobe.

BACKGROUND: In clinical practice, combined segmental resection (CSS) can avoid resection of multiple segments to preserve lung function. When two or more distant lung segments or subsegments of the same lobe present with a ground glass opacity (GGO) that meets the indications for sublobar resection, conventional CSS or wedge resection could not remove all the nodules, and lobectomy is performed in most of these patients. For these particular types of nodules, we perform a single lobe noncombined subsegmental resection, or "separated" precise subsegmentectomy, to preserve more lung tissue. This study was designed to initially assess the feasibility and safety of "separated" precise subsegmentectomy. METHODS: Selected cases of specific GGO were subjected to "separated" precise subsegmentectomy and the results of general clinical data, perioperative operative time, bleeding, length of stay, computed tomography (CT) review, lung function and its dynamic changes were collected and analyzed in these patients. RESULTS: "Separated" precise subsegmentectomy was performed in 12 patients and successfully completed. The median operation time, bleeding amount, and length of hospital stay were 96 min, 50 ml and 4 days, respectively. There was one case of pulmonary infection and one case of persistent air leakage, no death or pulmonary torsion, bronchopleural fistula and other pulmonary complications occurred. After 3 months, the median percentage of lung function retention was 91.7%, and the CT scan showed that the reserved lung tissue of 12 patients was well inflated and there was no obvious imaging manifestation of atelectasis. CONCLUSION: "Separated" precise subsegmentectomy is a novel and safe surgical method that provides a more optimized way for patients with specific multiple nodules to preserve lung function. Further prospective large studies are needed to verify this finding.

Comparative analysis of electromagnetic navigation bronchoscopy versus computed tomography-guided lung puncture for the sampling of indeterminate pulmonary nodules in the middle of an anatomic lung segment: A cohort study.

BACKGROUND: To compare the diagnostic positive rate and complication rate between the electromagnetic navigation bronchoscopy (ENB) technique and computed tomography (CT)-guided lung puncture for the biopsy of lung nodules located in the middle of an anatomic lung segment. METHODS: Electronic medical records of 114 patients who underwent lung nodule biopsy between June 2021 and June 2022 were retrospectively evaluated. In all patients, the nodules were located in the middle third lung segment. To compare the diagnostic positive and complication rates between the two biopsy modalities performed in this lung region, clinical data, complication rates, nodule pathology, and imaging results were reviewed based on nodule characteristics retrieved from the electronic medical records. RESULTS: Ninety-three patients underwent CT-guided lung puncture, while the remaining 21 patients underwent the ENB technique. No significant difference was observed in the diagnostic positive rate between the two groups (73.6 and 76.1%, respectively). In the CT-guided lung puncture group, pneumothorax incidence, tube placement, postoperative hemorrhage, and symptomatic hemorrhage rates were 16.1, 6.5, 6.5, and 1.1%, respectively. In contrast, no complications occurred in the ENB group. CONCLUSIONS: The ENB technique is a safe and effective method for performing biopsies of pulmonary nodules with a diagnostic positive rate comparable to that of CT-guided lung puncture and with a lower postoperative complication rate.

A combined vibrational sum frequency generation spectroscopy and atomic force microscopy study of sphingomyelin-cholesterol monolayers.

A combination of vibrational sum frequency generation spectroscopy and atomic force microscopy is used to study the changes in morphology and conformational order in monolayers prepared from three natural sphingomyelin (SM) mixtures as a function of surface pressure and cholesterol concentration. The most homogeneous SM gave monolayers with well-ordered acyl chains and few gauche defects with relatively small effects of either increasing surface pressure or cholesterol addition. Heterogeneous SM mixtures with a mixture of acyl chain lengths or with significant fractions of unsaturated acyl chains had much larger contributions from gauche defects at low surface pressure and gave increasingly well-ordered monolayers as the surface pressure increased. They also showed substantial increases in lipid chain order after cholesterol addition. Overall, these results are consistent with the strong hydrogen bonding capacity of SM leading to well-ordered monolayers over a range of surface pressures. The changes in acyl chain order for natural SMs as a function of cholesterol are relevant to formation of sphingolipid-cholesterol enriched domains in cell membranes.