Electronic symptom monitoring after lung cancer surgery: establishing a core set of patient-reported outcomes for surgical oncology care in a longitudinal cohort study.

BACKGROUND: Electronic symptom monitoring via patient-reported outcome in surgical oncology is limited owing to lengthy instruments and non-specific items in common patient-reported outcome instruments. To establish electronic symptom monitoring through a clinically relevant and fit-for-purpose core set of patient-reported outcome in patients undergoing lung cancer surgery. MATERIALS AND METHODS: One qualitative (Cohort 1) and two prospective studies (Cohorts 2 and 3) were conducted between 2018 and 2023. Patients undergoing lung cancer surgery were recruited. Items of symptoms and daily functioning were generated through extensive interviews in Cohort 1 and incorporated into a smartphone-based platform to establish the electronic Perioperative Symptom Assessment for Lung surgery (ePSA-Lung). This tool was finalized and validated in Cohort 2. Patients in Cohort 3 were longitudinally monitored for the first year post-surgery using the validated ePSA-Lung. RESULTS: In total, 1,037 patients scheduled for lung cancer surgery were recruited. The 11-item draft PSA-Lung was generated based on qualitative interview with 39 patients and input from a Delphi study involving 42 experts. A 9-item ePSA-Lung was finalized by assessing 223 patients in the validation cohort; the results supported the instrument's understandability, reliability, sensitivity, and surgical specificity. In Cohort 3 (n=775), compliance ranged from 63.21% to 84.76% during the one-year follow-up after discharge. Coughing, shortness of breath, and disturbed sleep were the most severe symptoms after discharge. Longitudinally, patients who underwent single-port video-assisted thoracic surgery had a lower symptom burden than those who underwent multi-port video-assisted thoracic surgery or thoracotomy (all symptoms, P<0.001). CONCLUSION: The ePSA-Lung is valid, concise, and clinically applicable as it supports electronic symptom monitoring in surgical oncology care. The need for long-term extensive care was identified for patients after discharge, even in early-stage cancer with potential curative treatment.

Electronic Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results of a Multicenter, Randomized, Controlled Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported superior symptom control of electronic patient-reported outcome (ePRO)-based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where patients were assigned 1:1 to receive postoperative ePRO-based symptom management or usual care daily postsurgery, twice weekly postdischarge until 1 month, and at 3, 6, 9, and 12 months postdischarge. Long-term patient-reported outcomes were assessed with MD Anderson Symptom Inventory-Lung Cancer module. Per-protocol analyses were performed with 55 patients in the ePRO group and 57 in the usual care group. At 12 months postdischarge, the ePRO group reported significantly fewer symptom threshold events (any of the five target symptom scored ≥4; median [IQR], 0 [0-0] v 0 [0-1]; P = .040) than the usual care group. From 1 to 12 months postdischarge, the ePRO group consistently reported significantly lower composite scores for physical interference (estimate, -0.86 [95% CI, -1.32 to -0.39]) and affective interference (estimate, -0.70 [95% CI, -1.14 to -0.26]). Early intensive ePRO-based symptom management after lung cancer surgery reduced symptom burden and improved functional status for up to 1 year postdischarge, supporting its integration into standard care.

Hypomethylation-associated LINC00987 downregulation induced lung adenocarcinoma progression by inhibiting the phosphorylation-mediated degradation of SND1.

DNA methylation, an epigenetic regulatory mechanism dictating gene transcription, plays a critical role in the occurrence and development of cancer. However, the molecular underpinnings of LINC00987 methylation in the regulation of lung adenocarcinoma (LUAD) remain elusive. This study investigated LINC00987 expression in LUAD patients through analysis of The Cancer Genome Atlas data sets. Quantitative real-time polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization assays were used to assess LINC00987 expression in LUAD. The bisulfite genomic sequence PCR (BSP) assay was used to determine the methylation levels of the LINC00987 promoter. The interaction between LINC00987 and SND1 was elucidated via immunoprecipitation and RNA pull-down assays. The functional significance of LINC00987 and SND1 in Calu-3 and NCI-H1688 cells was evaluated in vitro through CCK-8, EdU, Transwell, flow cytometry, and vasculogenic mimicry (VM) tube formation assays. LINC00987 expression decreased in LUAD concomitant with hypermethylation of the promoter region, while hypomethylation of the LINC00987 promoter in LUAD tissues correlated with tumor progression. Treatment with 5-Aza-CdR augmented LINC00987 expression and inhibited tumor growth. Mechanistically, LINC00987 overexpression impeded LUAD progression and VM through direct binding with SND1, thereby facilitating its phosphorylation and subsequent degradation. Additionally, overexpression of SND1 counteracted the adverse effects of LINC00987 downregulation on cell proliferation, apoptosis, cell migration, invasion, and VM in LUAD in vitro. In conclusion, this pioneering study focuses on the expression and function of LINC00987 and reveals that hypermethylation of the LINC00987 gene may contribute to LUAD progression. LINC00987 has emerged as a potential tumor suppressor gene in tumorigenesis through its binding with SND1 to facilitate its phosphorylation and subsequent degradation.

Neoadjuvant savolitinib targeted therapy for stage IIIB-N3 lung adenocarcinoma harboring mesenchymal-epithelial transition exon 14 skipping mutation: a case report and literature review.

Savolitinib is a selective inhibitor that specifically targets the phosphorylation of mesenchymal-epithelial transition (MET) kinase. It has demonstrated significant inhibitory effects on the proliferation of tumor cells with METex14 skipping mutation, making it a promising treatment option. While it is the first approved small-molecule inhibitor specifically targeting MET kinase in China, there is limited information about its efficacy as neoadjuvant therapy for patients with supraclavicular lymph node metastasis (N3). In this case report, we presented the successful outcome of a 48-year-old male patient who was diagnosed with stage IIIB (T2bN3M0) lung adenocarcinoma originating from the left upper lobe. The patient exhibited the METex14 skipping alteration. Following two months of neoadjuvant savolitinib treatment, the patient achieved partial remission, with a significant reduction in the size of the primary tumor and metastatic lymph nodes. Postoperative pathological confirmation revealed a pathological complete response, and subsequent imaging examinations, including computed tomography scan and circulating tumor DNA-based molecular residual disease detection, showed no sign of recurrence at 7 months after surgery. Based on this case, neoadjuvant and adjuvant savolitinib therapy may be considered as a favorable alternative to chemotherapy for marginally resectable nonsmall cell lung cancer patients with METex14 skipping mutation.

Development and validation of a prognostic nomogram for gallbladder papillary adenocarcinoma.

Background: Gallbladder papillary adenocarcinoma (GBPA) is an uncharacteristically gallbladder cancer subtype. Although some studies have shown that the prognosis of GBPA patients is significantly better than that of gallbladder adenocarcinoma (GBA) and gallbladder mucinous adenocarcinoma (GBMA) due to its rarity, there is a lack of large sample studies necessary to confirm the clinical characteristics and survival rate of GBPA. Therefore, this study aimed to describe the clinicopathological characteristics affecting survival in GBPA. This data was then used to establish a prognostic nomogram for GBPA. Methods: The data of patients diagnosed with gallbladder cancer between 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The clinical features and survival of patients with GBPA were compared with those of GBA and GBMA after balancing the baseline characteristics using propensity score matching (PSM). Univariate and multivariate Cox analyses were used to identify the prognostic factors for GBPA. Subsequently, the overall survival (OS) and cancer-specific survival (CSS) nomograms were established to predict GBPA prognosis. The performance and discrimination of the nomogram were measured using concordance index (C-index), calibration curves, receptor operating characteristic curves(ROC), and decision curve analysis (DCA) was applied to examine the net benefit of tients with GBPA, 5798 patients with GBA, and 223 patients with GBMA. The mean 1-, 3- and 5-year OS rates for GBPA were 81.3%, 58.8%, and 49.1%, respectively, while the mean 1-, 3- and 5-year CSS rates were 85.0%, 68.1%, and 61.0%, respectively. The median OS rates was 58 months (95% CI: 43-88), while the median CSS was not reached. The PSM analysis showed a differ statistically significantly in the OS between GBPA and GBA. However, there has no statistically difference in CSS. Conversely, the OS and CSS between GBPA and GBMA have statistically significant differences. Age, marital, T stage, and M stage were strongly linked to the prognosis for OS, while T-stage, M-stage, and surgery were significantly associated with the prognosis for CSS in GBPA patients. The AUC for the 1-, 3-, and 5-year OS were 0.722 (95%CI: 0.630-0.813), 0.728 (95%CI: 0.665-0.790), and 0.706 (95%CI: 0.641-0.771), respectively. The AUC for the 1-, 3-, and 5-year CSS were 0.749 (95%CI: 0.659-0.840), 0.698 (95%CI: 0.627-0.770), and 0.665 (95%CI: 0.594-0.735), respectively. The C-indices for the OS and CSS nomograms were 0.701 (95% CI: 0.634-0.744) and 0.651 (95% CI: 0.598-0.703), respectively. The calibration curves showed that the nomograms were well consistency. The DCA showed that compared with the TNM system, the nomogram models had a significant positive net benefit in survival prediction. Conclusion: GBPA has distinct clinicopathological characteristics and survival compared to other gallbladder carcinomas. The established nomogram provided a better prediction of survival for GBPA patients than the traditional TNM models.

Upregulation of long intergenic non-coding RNA LINC00326 inhibits non-small cell lung carcinoma progression by blocking Wnt/ß-catenin pathway through modulating the miR-657/dickkopf WNT signaling pathway inhibitor 2 axis.

BACKGROUND: Long intergenic non-coding RNA 326 (LINC00326) modulates hepatocarcinogenic lipid metabolism. However, the ability of LINC00326 to modulate the highly aggressive non-small cell lung carcinoma (NSCLC) is unknown. Here, LINC00326 in NSCLC was investigated, together with its effects on tumor malignancy and the underlying mechanisms of action. METHODS: LINC00326 levels in tumor tissues and cell lines were measured by Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and RNA fluorescence in situ hybridization (FISH). Proliferation and apoptosis were assessed in cell lines by Cell Counting Kit-8 (CCK-8), EdU staining assays and flow cytometry, respectively, and tumor growth was measured in mouse models. Possible microRNA targets of LINC00326 were predicted by bioinformatics and verified by RNA pull-down and immunoprecipitation and luciferase reporter assays. Western blotting was used to evaluate the expression of Wnt/ß-catenin-associated proteins. RESULTS: LINC00326 was downregulated in tumor tissues and cell lines. Knockdown of LINC00326 stimulated NSCLC cell proliferation and suppressed apoptosis in vitro, as well as enhancing xenograft tumor growth. LINC00326 sponged miR-657, and dickkopf WNT signaling pathway inhibitor 2 (DKK2) was found to be directly targeted by miR-657, with LINC00326 positively regulating its expression through sponging miR-657. The actions of LINC00326 knockdown on proliferation and apoptosis were reversed by stimulation of the miR-657/DKK2 axis. Furthermore, overexpression of miR-657 mitigated DKK2 inhibition on Wnt/ß-catenin signaling. CONCLUSIONS: LINC00326/miR-657/DKK2 axis signaling blocked tumor-associated functions in NSCLC cells through the targeting Wnt/ß-catenin pathway. This suggests that this pathway could be a target for NSCLC treatment.

Live-Cell Imaging of the Assembly and Ejection Processes of the Bacterial Flagella by Fluorescence Microscopy.

Bacterial flagella are molecular machines used for motility and chemotaxis. The flagellum consists of a thin extracellular helical filament as a propeller, a short hook as a universal joint, and a basal body as a rotary motor. The filament is made up of more than 20,000 flagellin molecules and can grow to several micrometers long but only 20 nanometers thick. The regulation of flagellar assembly and ejection is important for bacterial environmental adaptation. However, due to the technical difficulty to observe these nanostructures in live cells, our understanding of the flagellar growth and loss is limited. In the last three decades, the development of fluorescence microscopy and fluorescence labeling of specific cellular structure has made it possible to perform the real-time observation of bacterial flagellar assembly and ejection processes. Furthermore, flagella are not only critical for bacterial motility but also important antigens stimulating host immune responses. The complete understanding of bacterial flagellar production and ejection is valuable for understanding macromolecular self-assembly, cell adaptation, and pathogen-host interactions.

Longitudinal patient-reported outcomes 1 year after thoracoscopic segmentectomy versus lobectomy for early-stage lung cancer: a multicentre, prospective cohort study protocol.

INTRODUCTION: Segmentectomy and lobectomy are the main surgical procedures for early-stage lung cancer. However, few studies have analysed patient-reported outcomes after segmentectomy versus lobectomy. This study aims to compare patient-reported outcomes-such as symptoms, daily functioning and quality of life-between thoracoscopic segmentectomy and lobectomy for early-stage lung cancer during the 1 year after surgery. METHODS AND ANALYSIS: Overall, 788 newly diagnosed patients with early-stage lung cancer (tumour size ≤2 cm), who are scheduled to undergo thoracoscopic segmentectomy or lobectomy, will be recruited in this multicentre, prospective cohort study. The patients will receive standardised care after surgery. The Perioperative Symptom Assessment for Lung Surgery-a validated lung cancer surgery-specific scale-will be used to assess the symptoms and functions at baseline, at discharge and monthly after discharge for 1 year. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Lung Cancer module 29 will be used to assess the patients' quality of life at the same time points. The primary outcome will be the shortness of breath scores during the first year after thoracoscopic segmentectomy and lobectomy and will be compared using mixed-effects models. The secondary outcomes will include other symptoms, indicators of daily functioning, quality of life scores and traditional clinical outcomes. These will be compared using mixed-effects models and the Student's t-test, non-parametric test or Χ2 test. Propensity score matching will be used to ensure an even distribution of known confounders between the groups. ETHICS AND DISSEMINATION: The Ethics Committee for Medical Research and New Medical Technology of Sichuan Cancer Hospital approved this study (approval number: SCCHEC-02-2022-002). All participants will be instructed to provide informed consent. The manuscript is based on protocol version 3.0. The study results will be presented at medical conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2200060753.

De novo analysis of bulk RNA-seq data at spatially resolved single-cell resolution.

Uncovering the tissue molecular architecture at single-cell resolution could help better understand organisms' biological and pathological processes. However, bulk RNA-seq can only measure gene expression in cell mixtures, without revealing the transcriptional heterogeneity and spatial patterns of single cells. Herein, we introduce Bulk2Space ( https://github.com/ZJUFanLab/bulk2space ), a deep learning framework-based spatial deconvolution algorithm that can simultaneously disclose the spatial and cellular heterogeneity of bulk RNA-seq data using existing single-cell and spatial transcriptomics references. The use of bulk transcriptomics to validate Bulk2Space unveils, in particular, the spatial variance of immune cells in different tumor regions, the molecular and spatial heterogeneity of tissues during inflammation-induced tumorigenesis, and spatial patterns of novel genes in different cell types. Moreover, Bulk2Space is utilized to perform spatial deconvolution analysis on bulk transcriptome data from two different mouse brain regions derived from our in-house developed sequencing approach termed Spatial-seq. We have not only reconstructed the hierarchical structure of the mouse isocortex but also further annotated cell types that were not identified by original methods in the mouse hypothalamus.

miR-657 Targets SRCIN1 via the Slug Pathway to Promote NSCLC Tumor Growth and EMT Induction.

Background: MicroRNA- (miR-) 657 has been shown to regulate immunological and inflammatory activity, and it has also been defined to be dysregulated in both non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma. The mechanistic role whereby miR-657 influences NSCLC progression, however, has yet to be clarified. Methods: miR-657 and SRCIN1 expression levels were assessed via qPCR in the cell lines and tissues of NSCLC. Besides, correlations between the levels of miR-657 and NSCLC patient pathological characteristics were examined, and the Kaplan-Meier approach was employed for the evaluation of the prognostic utility of miR-657 in these patients. Moreover, the Pearson correlation analyses and dual-luciferase reporter assessments were used for detecting interactive relationships between miR-657 and SRCIN1. In addition, CCK-8, EdU, and Transwell assessments were employed for the appraisal of the ability of miR-657/SRCIN1 to regulate NSCLC cell proliferation and invasion. Western blotting was employed for the assessment of the levels of NSCLC cell proteins associated with the epithelial-mesenchymal transition (EMT) that were influenced by miR-657. The nude mice xenograft tumor model is established to observe the effect of miR-657 on NSCLC growth in vivo. Results: NSCLC patient tissues and cell lines exhibited upregulated miR-657 expression that was closely related to tumor differentiation, lymphoid metastasis, and TNM stage. High levels of miR-657 were predictive of a poorer NSCLC patient prognosis, and overexpressing miR-657 resulted in the more rapid growth of NCI-H1650 and A549 cells, with a concomitant increase in their invasion. In addition, miR-657 overexpression raised the levels of Slug, N-cadherin, and Vimentin in these two cell lines while promoting E-cadherin downregulation. Dual-luciferase reporter assays confirmed that miR-657 was capable of binding to the SRCIN1 gene, and SRCIN1 expression levels were negatively associated with those of miR-657, indicating that it acts as a negative regulator of this gene. Knocking down SRCIN1 was capable to reverse the influences of miR-657 inhibitor treatment on NSCLC cell behavior. Finally, in vivo studies showed that miR-657 promoted NSCLC cell growth. Conclusion: The obtained findings illuminate that miR-657 can promote the growth of tumors and the induction of the EMT in NSCLC cells by targeting SRCIN1 expression and modulating Slug pathway activation, highlighting this pathway as a promising therapeutic target in cases suffering from NSCLC.

Identifying patients who suffered from post-discharge cough after lung cancer surgery.

PURPOSE: To establish a discharge cutoff point (CP) on a simple patient-reported cough score to identify patients requiring post-discharge cough intervention. METHODS: Data were extracted from a prospective cohort study of patients undergoing lung cancer surgery. Symptoms were assessed using the MD Anderson Symptom Inventory-Lung Cancer Module. Group-based trajectory modeling was used to identify patient subgroups defined by post-discharge cough trajectories. Generalized linear model and bootstrap resampling with 2000 samples were used to determine the optimal cutoff points of discharge cough scores and their robustness. Analysis of variance, chi-square test, and mixed-effects model were used to validate the optimal cutoff points. RESULTS: The cough trajectories of post-discharge followed three patterns (high, middle, low); higher cough was associated with poor recovery of the enjoyment of life within 4 weeks after discharge (P < 0.001). The CP (3, 6) of discharge cough demonstrated as the optimal CP (F = 21.72). When discharged, 45.66% (179/392) of patients suffered a none/mild cough (0-2 points), 41.82% (164/392) suffered a moderate cough (3-5 points), and 12.5% (49/392) suffered a severe cough (6-10 points). Among these patients, there was a significant difference in the proportion of returning to work at 1 month after discharge (non-mild: 77.70%; moderate: 60.74%; severe: 48.57%; p < 0.001). CONCLUSIONS: Moderate-to-severe cough is relatively common in patients undergoing lung cancer surgery, and the higher the cough trajectory, the worse the recovery to normal life. Therefore, these patients with a cough score ≥ 3 or ≥ 6 at discharge may require additional medical intervention and extensive care.

Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: A Multicenter Randomized Controlled Trial.

PURPOSE: We aimed to evaluate the efficacy and feasibility of patient-reported outcome (PRO)-based symptom management in the early period after lung cancer surgery. METHODS: Before surgery, patients with clinically diagnosed lung cancer were randomly assigned 1:1 to receive postoperative PRO-based symptom management or usual care. All patients reported symptoms on MD Anderson Symptom Inventory-Lung Cancer presurgery, daily postsurgery, and twice a week after discharge for up to 4 weeks via an electronic PRO system. In the intervention group, treating surgeons responded to overthreshold electronic alerts driven by any of the five target symptom scores (score ≥ 4 on a 0-10 scale for pain, fatigue, disturbed sleep, shortness of breath, and coughing). The control group patients received usual care and no alerts were generated. The primary outcome was the number of symptom threshold events (any target symptom with a score of ≥ 4) at discharge. Per-protocol analyses were conducted. RESULTS: Of the 166 participants, 83 were randomly allocated to each group. At discharge, the intervention group reported fewer symptom threshold events than the control group (median [interquartile range], 0 [0-2] v 2 [0-3]; P = .007). At 4 weeks postdischarge, this difference was maintained between the intervention and control groups (median [interquartile range], 0 [0-0] v 0 [0-1]; P = .018). The intervention group had a lower complication rate than the control group (21.5% v 40.6%; P = .019). Surgeons spent a median of 3 minutes managing an alert. CONCLUSION: PRO-based symptom management after lung cancer surgery showed lower symptom burden and fewer complications than usual care for up to 4 weeks postdischarge.

Unresected small lymph node assessment predicts prognosis for patients with pT3N0M0 thoracic esophageal squamous cell carcinoma.

BACKGROUND: The role of unresected small lymph nodes (LNs) which may contain metastases for thoracic esophageal squamous cell carcinoma (TESCC) has not been addressed. The aim of the study was to investigate the role of unresected small LNs assessment using computed tomography (CT) in prognostic estimates of pT3N0M0 TESCC patients. METHODS: Between January 2009 and December 2017, 294 patients who underwent esophagectomy with R0 resection at Sichuan Cancer Hospital were retrospectively examined, and the last follow-up time was July 2018. Patients were classified into CT-suspect and CT-negative groups according to the shortest diameter and the shape (axial ratio) of the unresected small LNs on preoperative CT. The Kaplan-Meier method was used to compare survival differences in prognostic factors. Univariate and multivariate analyses were performed to identify prognostic factors for survival and recurrence. RESULTS: Eighty-four patients (28.6%) were classified as CT-suspect group according to the diagnostic criteria; survival analysis suggested that CT-suspect group of patients had a relatively poorer prognosis (P<0.05). Cox regression analysis indicated that unresected small LNs status, tumor grade, and postoperative adjuvant therapy were independent prognostic factors for patients with pT3N0M0 TESCC (P<0.05). Further analysis shown the rates of total recurrence (TR) and locoregional recurrence (LR) in the CT-suspect group were significantly higher than that in the CT-negative group (TR, P<0.001; LR, P<0.001). Among the LRs, the rate of supraclavicular lymph node recurrence in the CT-suspect group was significantly higher than that in the CT-negative group (P<0.001). CONCLUSIONS: Unresected small lymph node assessment is critically important and predict prognosis for pT3N0M0 TESCC patients.

scDeepSort: a pre-trained cell-type annotation method for single-cell transcriptomics using deep learning with a weighted graph neural network.

Advances in single-cell RNA sequencing (scRNA-seq) have furthered the simultaneous classification of thousands of cells in a single assay based on transcriptome profiling. In most analysis protocols, single-cell type annotation relies on marker genes or RNA-seq profiles, resulting in poor extrapolation. Still, the accurate cell-type annotation for single-cell transcriptomic data remains a great challenge. Here, we introduce scDeepSort (https://github.com/ZJUFanLab/scDeepSort), a pre-trained cell-type annotation tool for single-cell transcriptomics that uses a deep learning model with a weighted graph neural network (GNN). Using human and mouse scRNA-seq data resources, we demonstrate the high performance and robustness of scDeepSort in labeling 764 741 cells involving 56 human and 32 mouse tissues. Significantly, scDeepSort outperformed other known methods in annotating 76 external test datasets, reaching an 83.79% accuracy across 265 489 cells in humans and mice. Moreover, we demonstrate the universality of scDeepSort using more challenging datasets and using references from different scRNA-seq technology. Above all, scDeepSort is the first attempt to annotate cell types of scRNA-seq data with a pre-trained GNN model, which can realize the accurate cell-type annotation without additional references, i.e. markers or RNA-seq profiles.

CDCA7-regulated inflammatory mechanism through TLR4/NF-κB signaling pathway in stomach adenocarcinoma.

To investigate the role of cell division cycle associated 7 (CDCA7) in stomach carcinoma, detect whether CDCA7 knockdown could regulate the development of stomach carcinoma, and further observe the relationship between CDCA7 and inflammation through TLR4/NF-κB signaling pathway in stomach adenocarcinoma (STAD) in vitro and in vivo. TIMER2.0, Kaplan-Meier plotter, Target Gene, and GEPIA systems were used to predict the potential function of CDCA7. Western blot and immunohistochemistry was used to analyze the expression of CDCA7 at different tissue or cell lines. The proliferation, development, inflammation, and apoptosis of STAD in vitro and in vivo were observed by using CDCA7 knockdown lentivirus through TLR4 suppression by its inhibitor. Bioinformatics analysis of CDCA7 with inflammation and western blot of CDCA7 with target protein of immune-associated cells were observed by using CDCA7 knockdown lentivirus in vivo. Finally, the prognosis and associated of CDCA7 in some gene mutations of STAD was observed by Target Gene system. CDCA7 expression in STAD tumor tissue was higher than the normal. The CDCA7 expression in tumor or MGC803 cells was increased. Furthermore, CDCA7 knockdown lentivirus could inhibit STAD development in vitro and in vivo through weakening tumor cells proliferation, reducing tumor volume and biomarker levels, and then increasing apoptotic level. CDCA7 is possibly able to regulate inflammation in STAD through TLR4/NF-κB signaling pathway. Furthermore, CDCA7 may be related with mast cells and the upstream target factor of TLR4/NF-κB signaling pathway in inflammation. These results may provide a new strategy to stomach carcinoma development by regulating inflammation.

Probing bacterial cell wall growth by tracing wall-anchored protein complexes.

The dynamic assembly of the cell wall is key to the maintenance of cell shape during bacterial growth. Here, we present a method for the analysis of Escherichia coli cell wall growth at high spatial and temporal resolution, which is achieved by tracing the movement of fluorescently labeled cell wall-anchored flagellar motors. Using this method, we clearly identify the active and inert zones of cell wall growth during bacterial elongation. Within the active zone, the insertion of newly synthesized peptidoglycan occurs homogeneously in the axial direction without twisting of the cell body. Based on the measured parameters, we formulate a Bernoulli shift map model to predict the partitioning of cell wall-anchored proteins following cell division.

Effect of Preoperative Nutritional Risk Screening and Enteral Nutrition Support in Accelerated Recovery after Resection for Esophageal Cancer.

Patients with esophageal cancer are often accompanied by malnutrition, especially in patients with obvious swallowing tract. Many studies have shown that preoperative nutritional support can reduce postoperative complications, but there are few studies comparing preoperative enteral nutrition with intravenous nutrition. The aim of the study was to compare the effects of the two nutritional support path in esophageal cancer patients undergoing surgery. We used the nutritional risk screening 2002 (NRS2002) for preoperative nutritional risk screening in patients with esophageal cancer treated at our department between April 2016 and March 2019. A total of 56 patients with an NRS2002 score ≥ 3 and with apparent difficulty swallowing received preoperative parenteral nutrition (PN; n = 29) or enteral nutrition (EN; n = 27). Both groups received 7 day of nutritional support before surgery. Nutritional indicators were measured on preoperative day 7, preoperative day 1, and postoperative day 7. The baseline characteristics, perioperative condition, nutritional status, and postoperative complications of the two groups were compared and analysed. There was no significant difference in baseline characteristics and perioperative nutrition indicators between two groups. Postoperative hospital stay and the costs of nutrition support were significantly reduced in the EN group compared with PN group (P = 0.000). The times of first passing gas and bowel movement were shorter in the EN group compared with PN group (P = 0.001). The incidence of gastrointestinal complications was lower in the EN group compared with PN group (P = 0.039). For esophageal cancer patients with an NRS2002 score ≥ 3 and apparent difficulty swallowing, preoperative EN with a gastric tube is safe and easy to perform. Preoperative EN can shorten the recovery time of gastrointestinal function, reduce the incidence of gastrointestinal complications, finally accelerate postoperative recovery.

Construction and Loss of Bacterial Flagellar Filaments.

The bacterial flagellar filament is an extracellular tubular protein structure that acts as a propeller for bacterial swimming motility. It is connected to the membrane-anchored rotary bacterial flagellar motor through a short hook. The bacterial flagellar filament consists of approximately 20,000 flagellins and can be several micrometers long. In this article, we reviewed the experimental works and models of flagellar filament construction and the recent findings of flagellar filament ejection during the cell cycle. The length-dependent decay of flagellar filament growth data supports the injection-diffusion model. The decay of flagellar growth rate is due to reduced transportation of long-distance diffusion and jamming. However, the filament is not a permeant structure. Several bacterial species actively abandon their flagella under starvation. Flagellum is disassembled when the rod is broken, resulting in an ejection of the filament with a partial rod and hook. The inner membrane component is then diffused on the membrane before further breakdown. These new findings open a new field of bacterial macro-molecule assembly, disassembly, and signal transduction.

Atypical juvenile hereditary hemochromatosis onset with positive pancreatic islet autoantibodies diabetes caused by novel mutations in HAMP and overall clinical management.

BACKGROUND: Atypical clinical symptoms of juvenile hereditary hemochromatosis (JHH) often leads to misdiagnosis and underdiagnosis bringing ominous outcomes, even death. METHODS: The whole exome was sequenced and interpreted. A literature review assisted to analyze and verify the phenotype-genotype relationships. We revealed the entire process of diagnosis, treatments, and outcome of two diabetic onset of JHH families to provide new insights for genotype-phenotype relation with novel compound heterozygous mutations in the hepcidin antimicrobial peptide (HAMP, OMIM: 606464). RESULTS: Two probands were diagnosed and treated as type 1 diabetes initially because of specific symptoms and positive islet autoantibodies. Poor control of hyperglycemia and progressive symptoms occurred. Sequencing informed that the compound heterozygous and homozygous mutations c.166C>G and c.223C>T in HAMP caused type 1 diabetic-onset JHH. The two patients accessed irregular phlebotomy treatments, and then, experienced poor prognosis. We summarized the process of overall clinical management of reported 26 cases comparing to our novel atypical diabetic onsets Juvenile Hereditary Hemochromatosis cases. CONCLUSION: It was first reported that positive pancreatic islet autoantibodies diabetes onset of JHH resulted from loss-of-function mutations of HAMP, of which the atypical JHH should be differentially diagnosed with type 1 diabetes at the onset. Early administration of phlebotomy and vital organs protection and surveillance might be important for the treatment of atypical JHH.

An improved method for gastric tube and anastomotic anvil placement during thoracoscopic and laparoscopic Ivor Lewis esophagectomy.

BACKGROUND: During esophagectomy for esophageal cancer, a gastric tube is necessary for the perioperative period. However, the gastric tube and anastomotic anvil placement is often extremely difficult and time consuming during surgery. METHODS: We used the traditional method or improved method to place the gastric tube and anastomotic anvil during thoracoscopic and laparoscopic Ivor Lewis esophagectomy. Thirty-seven patients were in the improved group: the gastric tube and anastomotic anvil were placed using the improved method; 35 patients were in the traditional group: the gastric tube and anastomotic anvil were placed using the traditional method. Retrospectively, we analyze the basic clinical characteristics, perioperative clinical features, and postoperative complications of the two groups of patients. RESULTS: The two groups were matched well for baseline characteristics. There was no significant difference between the two groups in blood loss, postoperative hospital stay, postoperative fasting time, drainage volume, and overall complications. But significant between-group differences were observed in time consuming and chest tube indwelling time (P < 0.05), both of which were significantly shorter in the improved group than in the traditional group. CONCLUSIONS: This improved method can reduce the difficulty of placing anastomotic anvil and gastric tube and prevent damage to the anastomosis during surgery.