Diagnostic Discordance, Uncertainty, and Treatment Ambiguity in Community-Acquired Pneumonia : A National Cohort Study of 115 U.S. Veterans Affairs Hospitals.

BACKGROUND: Evidence-based practice in community-acquired pneumonia often assumes an accurate initial diagnosis. OBJECTIVE: To examine the evolution of pneumonia diagnoses among patients hospitalized from the emergency department (ED). DESIGN: Retrospective nationwide cohort. SETTING: 118 U.S. Veterans Affairs medical centers. PATIENTS: Aged 18 years or older and hospitalized from the ED between 1 January 2015 and 31 January 2022. MEASUREMENTS: Discordances between initial pneumonia diagnosis, discharge diagnosis, and radiographic diagnosis identified by natural language processing of clinician text, diagnostic coding, and antimicrobial treatment. Expressions of uncertainty in clinical notes, patient illness severity, treatments, and outcomes were compared. RESULTS: Among 2 383 899 hospitalizations, 13.3% received an initial or discharge diagnosis and treatment of pneumonia: 9.1% received an initial diagnosis and 10.0% received a discharge diagnosis. Discordances between initial and discharge occurred in 57%. Among patients discharged with a pneumonia diagnosis and positive initial chest image, 33% lacked an initial diagnosis. Among patients diagnosed initially, 36% lacked a discharge diagnosis and 21% lacked positive initial chest imaging. Uncertainty was frequently expressed in clinical notes (58% in ED; 48% at discharge); 27% received diuretics, 36% received corticosteroids, and 10% received antibiotics, corticosteroids, and diuretics within 24 hours. Patients with discordant diagnoses had greater uncertainty and received more additional treatments, but only patients lacking an initial pneumonia diagnosis had higher 30-day mortality than concordant patients (14.4% [95% CI, 14.1% to 14.7%] vs. 10.6% [CI, 10.4% to 10.7%]). Patients with diagnostic discordance were more likely to present to high-complexity facilities with high ED patient load and inpatient census. LIMITATION: Retrospective analysis; did not examine causal relationships. CONCLUSION: More than half of all patients hospitalized and treated for pneumonia had discordant diagnoses from initial presentation to discharge. Treatments for other diagnoses and expressions of uncertainty were common. These findings highlight the need to recognize diagnostic uncertainty and treatment ambiguity in research and practice of pneumonia-related care. PRIMARY FUNDING SOURCE: The Gordon and Betty Moore Foundation.

Epidemiological Insights into Autoimmune Bullous Diseases in China: A Comprehensive Analysis.

OBJECTIVE: This study aims to conduct an extensive analysis of autoimmune bullous diseases, particularly pemphigus vulgaris and bullous pemphigoid, in Shanghai, China, from 2016 to 2023. It seeks to understand the demographic profiles, comorbidities, mortality rates, risk factors, and socioeconomic impacts associated with autoimmune bullous disease. METHODS: A cross-sectional study design was employed, enrolling 1,072 patients. Diagnostic measures included clinical manifestations, histopathology, direct immunofluorescence, and serologic tests. The study also involved a detailed socioeconomic analysis and evaluation of occupational risks. RESULTS: The findings highlight a significant occupational risk in industries requiring enhanced safety measures, with a notable prevalence of autoimmune bullous disease among workers in these sectors. A considerable portion of the patients were from low-income backgrounds with limited literacy, indicating the economic burden of autoimmune bullous disease. A key discovery of the study is the potential pathological link between autoimmune bullous disease and interstitial lung disease. CONCLUSION: This research, one of the first comprehensive studies on autoimmune bullous disease in China, underscores the need for targeted healthcare strategies and further investigation into autoimmune bullous disease, particularly its relationship with interstitial lung disease.

Stratifying risk of failure to achieve textbook outcomes among patients undergoing hepatectomy for hepatocellular carcinoma: A multicenter score validation study.

BACKGROUND AND AIMS: The concept of textbook outcomes (TOs) has gained increased attention as a critical metric to assess the quality and success of outcomes following complex surgery. A simple yet effective scoring system was developed and validated to predict risk of not achieving textbook outcomes (non-TOs) following hepatectomy for hepatocellular carcinoma (HCC). METHODS: Using a multicenter prospectively collected database, risk factors associated with non-TO among patients who underwent hepatectomy for HCC were identified. A predictive scoring system based on factors identified from multivariate regression analysis was used to risk stratify patients relative to non-TO. The score was developed using 70 % of the overall cohort and validated in the remaining 30 %. RESULTS: Among 3681 patients, 1458 (39.6 %) failied to experience a TO. Based on the derivation cohort, obesity, American Society of Anaesthesiologists score(ASA score), Child-Pugh grade, tumor size, and extent of hepatectomy were identified as independent predictors of non-TO. The scoring system ranged from 0 to 10 points. Patients were categorized into low (0-3 points), intermediate (4-6 points), and high risk (7-10 points) of non-TO. In the validation cohort, the predicted risk of developing non-TOs was 39.0 %, which closely matched the observed risk of 39.9 %. There were no differences among the predicted and observed risks within the different risk categories. CONCLUSIONS: A novel scoring system was able to predict risk of non-TO accurately following hepatectomy for HCC. The score may enable early identification of individuals at risk of adverse outcomes and inform surgical decision-making, and quality improvement initiatives.

Long-term outcomes following hepatectomy in patients with lean non-alcoholic fatty liver disease-associated hepatocellular carcinoma versus overweight and obese counterparts: A multicenter analysis.

BACKGROUND & AIMS: With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) as a significant etiology for hepatocellular carcinoma (HCC), lean NAFLD-HCC has emerged as a specific distinct subtype. This study sought to investigate long-term outcomes following curative-intent hepatectomy for early-stage NAFLD-HCC among lean patients compared with overweight and obese individuals. METHODS: A multicenter retrospective analysis was used to assess early-stage NAFLD-HCC patients undergoing curative-intent hepatectomy between 2009 and 2022. Patients were stratified by preoperative body mass index (BMI) into the lean (<23.0 kg/m2), overweight (23.0-27.4 kg/m2) and obese (≥27.5 kg/m2) groups. Study endpoints were overall survival (OS) and recurrence-free survival (RFS), which were compared among groups. RESULTS: Among 309 patients with NAFLD-HCC, 66 (21.3 %), 176 (57.0 %), and 67 (21.7 %) were lean, overweight, and obese, respectively. The three groups were similar relative to most liver, tumor, and surgery-related variables. Compared with overweight patients (71.3 % and 55.6 %), the lean individuals had a worse 5-year OS and RFS (55.4 % and 35.1 %, P = 0.017 and 0.002, respectively), which were comparable to obese patients (48.5 % and 38.2 %, P = 0.939 and 0.442, respectively). After adjustment for confounding factors, multivariable Cox-regression analysis identified that lean bodyweight was independently associated with decreased OS (hazard ratio: 1.69; 95 % confidence interval: 1.06-2.71; P = 0.029) and RFS (hazard ratio: 1.72; 95 % confidence interval: 1.17-2.52; P = 0.006) following curative-intent hepatectomy for early-stage NAFLD-HCC. CONCLUSIONS: Compared with overweight patients, individuals with lean NAFLD-HCC had inferior long-term oncological survival after hepatectomy for early-stage NAFLD-HCC. These data highlight the need for examination of the distinct carcinogenic pathways of lean NAFLD-HCC and its potential consequences in HCC recurrence.

Association of Pringle maneuver with postoperative recurrence and survival following hepatectomy for hepatocellular carcinoma: a multicenter propensity score and competing-risks regression analysis.

Background: The application of Pringle maneuver (PM) during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion, but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma (HCC) remains controversial. We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC. Methods: Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified. Using two propensity score methods [propensity score matching (PSM) and inverse probability of treatment weight (IPTW)], cumulative recurrence rate and cancer-specific mortality (CSM) were compared between the patients in the PM and non-PM groups. Multivariate competing-risks regression models were performed to adjust for the effect of non-cancer-specific mortality and other prognostic risk factors. Results: Of the 2,798 included patients, 2,404 and 394 did and did not adopt PM (the PM and non-PM groups), respectively. The rates of intraoperative blood transfusion, postoperative 30-day mortality and morbidity were comparable between the two groups (all P>0.05). In the PSM cohort by the 1:3 ratio, compared to 382 patients in the non-PM group, 1,146 patients in the PM group also had the higher cumulative 5-year recurrence rate and CSM (63.9% and 39.1% vs. 55.3% and 31.6%, both P<0.05). Similar results were also yielded in the entire cohort and the IPTW cohort. Multivariate competing-risks regression analyses demonstrated that no application of the PM was independently associated with lower recurrence rate and CSM based on various analytical cohorts [hazard ratio (HR), 0.82 and 0.77 in the adjusted entire cohort, HR 0.80 and 0.73 in the PSM cohort, and HR 0.80 and 0.76 in the IPTW cohort, respectively]. Conclusions: The findings suggested that no application of PM during hepatectomy for patients with HCC reduced the risk of postoperative recurrence and cancer-specific death by approximately 20-25%.

The Barthel Index predicts surgical textbook outcomes following hepatectomy for elderly patients with hepatocellular carcinoma: A multicenter cohort study.

BACKGROUND: The burgeoning demand for hepatectomy in elderly patients with hepatocellular carcinoma (HCC) necessitates improved perioperative care. Geriatric populations frequently experience functional decline and frailty, predisposing them to adverse postoperative outcomes. The Barthel Index serves as a reliable measure for assessing functional capacity, and this study evaluates its impact on surgical textbook outcomes (TOs) in elderly HCC patients. METHODS: A multicenter retrospective cohort study analyzed elderly patients (≥70 years) following hepatectomy for HCC between 2013 and 2021. Utilizing a Barthel Index cut-off value of 85, patients were divided into two groups: with and without preoperative functional decline and frailty. The primary outcome was the rate of TO, encompassing seven criteria. TO rates were compared between groups, and multivariate logistic regression analyses identified independent risks for achieving TOs. RESULTS: Of 497 elderly patients, 157 (31.6 â€‹%) exhibited preoperative functional decline and frailty (Barthel Index score <85). The overall TO rate was 58.6 â€‹%. Patients with preoperative Barthel Index score <85 had significantly lower TO rates compared to patients with score ≥85 (29.3 â€‹% vs. 72.1 â€‹%, P â€‹< â€‹0.001). Multivariate analysis revealed preoperative Barthel Index score <85 as an independent risk for achieving TO (odds ratio 3.413, 95 â€‹% confidence interval 1.879-6.198, P â€‹< â€‹0.001). Comparable results were observed in the subgroups of patients undergoing open and laparoscopic hepatectomy. CONCLUSION: Preoperative Barthel Index-based assessment of functional decline and frailty significantly predicts TOs following hepatectomy in elderly HCC patients, enabling identification of high-risk patients and informing preoperative management and postoperative care within geriatric oncology.

The relationship between patient-reported and objective measures of physical function among cancer survivors receiving rehabilitation care: A correlation analysis.

BACKGROUND: Physical function is associated with cancer-related quality of life and survival. The correlation of patient-reported and objective measures of physical function has not been quantified previously in the cancer rehabilitation medicine setting. OBJECTIVE: To correlate patient-reported physical function with objective measures of physical function. The secondary aim is to correlate fatigue and social participation levels with objective measures of physical function. DESIGN: Retrospective. SETTING: Tertiary university cancer center. PARTICIPANTS: A total of 226 cancer survivors referred to an outpatient cancer rehabilitation medicine clinic. INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: Correlation of Patient-Reported Outcomes Measurement Information System (PROMIS) Cancer Function Brief 3D Profile domains with objective physical function measured by the 30-second sit-to-stand and hand grip strength. RESULTS: Pearson correlation analysis revealed a moderate correlation between patient-reported physical function and the 30-second sit-to-stand test (r = 0.57; p <.001), and a weak correlation of patient-reported physical function and handgrip strength (r = 0.27; p <.001). Multivariable regression modeling controlling for age, gender, and receipt of systemic therapy demonstrated a significant association between patient-reported physical function and the 30-second sit-to-stand test (estimated confidence interval 0.76 [0.60, 0.92], p < .01), in addition to patient-reported function and handgrip strength (estimated 0.22 [0.10, 0.34], p < .01). Multiple myeloma but no other cancer type was inversely associated with lower physical function. CONCLUSIONS: Patient-reported physical function correlated moderately with the 30-second sit-to-stand test, whereas hand grip strength demonstrated a weak correlation. The 30-second sit-to-stand test is a suitable substitute for patient-reported physical function. Further work evaluating how measures relate to each other across cancer populations is needed before recommending a standardized set of outcome measures.

A Pipeline for Evaluation of Machine Learning/Artificial Intelligence Models to Quantify Programmed Death Ligand 1 Immunohistochemistry.

Immunohistochemistry (IHC) is used to guide treatment decisions in multiple cancer types. For treatment with checkpoint inhibitors, programmed death ligand 1 (PD-L1) IHC is used as a companion diagnostic. However, the scoring of PD-L1 is complicated by its expression in cancer and immune cells. Separation of cancer and noncancer regions is needed to calculate tumor proportion scores (TPS) of PD-L1, which is based on the percentage of PD-L1-positive cancer cells. Evaluation of PD-L1 expression requires highly experienced pathologists and is often challenging and time-consuming. Here, we used a multi-institutional cohort of 77 lung cancer cases stained centrally with the PD-L1 22C3 clone. We developed a 4-step pipeline for measuring TPS that includes the coregistration of hematoxylin and eosin, PD-L1, and negative control (NC) digital slides for exclusion of necrosis, segmentation of cancer regions, and quantification of PD-L1+ cells. As cancer segmentation is a challenging step for TPS generation, we trained DeepLab V3 in the Visiopharm software package to outline cancer regions in PD-L1 and NC images and evaluated the model performance by mean intersection over union (mIoU) against manual outlines. Only 14 cases were required to accomplish a mIoU of 0.82 for cancer segmentation in hematoxylin-stained NC cases. For PD-L1-stained slides, a model trained on PD-L1 tiles augmented by registered NC tiles achieved a mIoU of 0.79. In segmented cancer regions from whole slide images, the digital TPS achieved an accuracy of 75% against the manual TPS scores from the pathology report. Major reasons for algorithmic inaccuracies include the inclusion of immune cells in cancer outlines and poor nuclear segmentation of cancer cells. Our transparent and stepwise approach and performance metrics can be applied to any IHC assay to provide pathologists with important insights on when to apply and how to evaluate commercial automated IHC scoring systems.

Right gastroepiploic artery length determined anastomotic leakage after minimally invasive esophagectomy for esophageal cancer: a prospective cohort study.

BACKGROUND: This prospective cohort study, conducted at a high-volume esophageal cancer center from July 2019 to July 2022, aimed to investigate the link between the right gastroepiploic artery (RGEA) length and anastomotic leakage (AL) rates following minimally invasive esophagectomy (MIE). Real-world data on stomach blood supply in the Chinese population were examined. MATERIALS AND METHODS: A total of 516 cases were enrolled, categorized into two groups based on the Youden index-determined optimal cut-off value for the relative length of RGEA (length of RGEA/length of gastric conduit, 64.69%) through ROC analysis: Group SR (short RGEA) and Group LR (long RGEA). The primary observation parameter was the relationship between AL incidence and the ratio of direct blood supply from RGEA. Secondary parameters included the mean length of the right gastroepiploic artery, greater curvature, and the connection type between right and left gastroepiploic vessels. Patient data were prospectively recorded in electronic case report forms. RESULTS: The study revealed median lengths of 43.60 cm for greater curvature, 43.16 cm for the gastric conduit, and 26.75 cm for RGEA. AL, the most common postoperative complication, showed a significant difference between groups (16.88 vs. 8.84%, P =0.01). Multivariable binary logistic regression identified Group SR and LR (odds ratio: 2.651, 95% CI: 1.124-6.250, P =0.03) and Neoadjuvant therapy (odds ratio: 2.479, 95% CI: 1.374-4.473, P =0.00) as independent predictors of AL. CONCLUSIONS: The study emphasizes the crucial role of RGEA length in determining AL incidence in MIE for esophageal cancer. Preserving RGEA and fostering capillary arches between RGEA and LGEA are recommended strategies to mitigate AL risk.

A Linguistic Analysis Examining the Impact of COVID-19 on Pneumonia Diagnosis and Disease Models.

Written clinical language embodies and reflects the clinician's mental models of disease. Prior to the COVID-19 pandemic, pneumonia was shifting away from concern for healthcare-associated pneumonia and toward recognition of heterogeneity of pathogens and host response. How these models are reflected in clinical language or whether they were impacted by the pandemic has not been studied. We aimed to assess changes in the language used to describe pneumonia following the COVID-19 pandemic.

An exploration of the effect of Chinese herbal compound on the occurrence and development of large intestine cancer and intestinal flora.

This study was conducted to observe the effect of Chinese herbal compound on the treatment of colon cancer using AOM/DSS-induced C57BL/6J colon cancer mice and to validate potential influence on intestinal flora of mice. A colorectal cancer (CRC) mouse model was built with a total of 50 C57BL/6J mice that were induced by administrating AOM/DSS. These experimental animals were split up into 5 groups, a control group, a model group, and low-, medium- and high-dose Chinese herbal compound groups. All mice were given Chinese herbal compound treatment, and the colon tissues of each group were harvested with the length measured and the number of colon polyps accounted. The Ki-67 expression in the colon tissues was detected via immuno-histochemistry. Relative quantification of the expression of genes and proteins was determined through qPCR and WB assays. Contents of IL-6, TNF-α, IFN-γ, and IL-10 in serum and colon tissues of mice were determined by ELISA. An additional 16S rRNA sequencing analysis was implemented for the identification of mouse intestinal flora. The results suggested that all low-, medium- or high-dose Chinese herbal compound could markedly inhibit the shortening of colon length and significant number reduction of colon polyps in the model group. The relative expression of genes and proteins (PCNA, Muc16, and MMP-9) associated with proliferation in mouse colon tissues were inhibited. In addition, compared with the model group, the contents of IL-6, TNF-α, and IFN-γ in serum and colon tissues were substantially decreased in the high-dose Chinese herbal compound group, thereby reducing the structure damage in colon tissues and the infiltration degree of inflammatory cells. Besides, the expression of TLR4/MyD88/NF-κB protein was markedly decreased. The 16S rRNA sequencing analysis demonstrated that mice in the model group had decreased intestinal flora diversity, and there were significant changes in flora abundance and amino acid metabolism between the control group and the model group. Taken together, the treatment of Chinese herbal compound against CRC in this study might be regulated by the TLR4/MyD88/NF-κB signaling pathway, and the imbalance in intestinal flora was also closely related to CRC occurrence.

Development and validation of prealbumin-bilirubin score (preALBI score) for predicting long-term survival after hepatectomy for hepatocellular carcinoma: A multicenter analysis versus ALBI score.

BACKGROUND: The Albumin-Bilirubin (ALBI) score, widely used in predicting long-term prognosis for patients with hepatocellular carcinoma (HCC), has limitations due to serum albumin variability. This study aimed to develop and validate the Prealbumin-Bilirubin (preALBI) score as a reliable alternative. METHODS: A multicenter cohort of HCC patients who underwent hepatectomy was randomly divided into the training and validation cohorts. The preALBI score was developed using Cox regression models within the training cohort, incorporating serum prealbumin and bilirubin levels as crucial determinants. The survival predictive accuracy was evaluated and compared between the preALBI score with two other staging systems, including the ALBI score and the Child-Pugh grade. RESULTS: A total of 2409 patients were enrolled. In the training cohort, the preALBI score demonstrated superior performance in predicting long-term survival after hepatectomy. The preALBI score was associated with the best monotonicity of gradients (linear trend χ2: 72.84) and homogeneity (likelihood ratio χ2: 74.69), and the highest discriminatory ability (the areas under curves for 1-, 3-, and 5-year mortality: 0.663, 0.654, and 0.644, respectively). In addition, the preALBI was the most informative staging system in predicting survival (Akaike information criterion: 11325.65).The results remained consistent in both training and validation cohorts, indicating its reliable performance across different populations. CONCLUSION: The preALBI score, leveraging the stability of prealbumin, represents a promising tool for better patient stratification, providing more accurate prognostic predictions than the ALBI score and the Child-Pugh grade.

Combined analysis of transcriptomics and metabolomics provide insights into the antibacterial mechanism of bacteriocin XJS01 against multidrug-resistant Staphylococcus aureus.

Multidrug-resistant (MDR) bacteria are widespread in the environment and pose a serious threat to public health. It has been shown that bacteriocins have a great potential in controlling MDR pathogens, including Staphylococcus aureus. A previously reported Lactobacillus salivarius bacteriocin XJS01 exhibited good antibacterial activity against MDR S. aureus 2612:1606BL1486 (henceforth referred to as S. aureus_26), but its molecular mechanism remains unknown. Herein, we investigated the antibacterial mechanism of XJS01 on S. aureus_26 using an approach combining transcriptomics and metabolomics. The results showed that XJS01 induced significant changes at both transcriptional and metabolic levels in S. aureus_26. In total, 231 differentially expressed genes (DEGs) and 206 differentially abundance metabolites (DAMs) were identified in S. aureus_26 treated with 1 × MIC (minimum inhibition concentration) XJS01 compared with untreated (XJS01-free) cells (control). Functional analysis revealed that these DEGs and DAMs, alone with the related pathways and biological processes, were typically involved in stress response, being primarily related to metal uptake, cell virulence, self-help mechanism, amino acid and energy metabolism, bacterial stress response (e.g., two-component system), and membrane transport (e.g., phosphotransferase system). Overall, this study uncovered the multi-target effects of bacteriocins against MDR S. aureus at the genome-wide transcriptional and metabolic levels. These findings might be useful in the development of bacteriocins for the control of MDR S. aureus and other drug-resistant bacteria.

Platelet-related gene risk score: a predictor for pancreatic cancer microenvironmental signature, chemosensitivity and prognosis.

Recent studies have indicated that platelets may play a role in the advancement of pancreatic cancer by supporting tumor growth and increasing resistance to chemotherapy. This study aims to develop a prognostic model for pancreatic cancer using a platelet-related gene risk score. Prognostic platelet-related genes (PRGs) were identified from public databases and analyzed using cluster analysis. We investigated the microenvironment signatures and gene mutation patterns across different PRG-based molecular subtypes of pancreatic cancer. A prognostic model based on PRGs was developed using LASSO-Cox Regression Analysis. Additionally, we examined the correlation between the risk score and tumor clinical characteristics, as well as drug sensitivity. Two molecular subtypes, cluster C1 and C2, were identified. Cluster C2 was associated with a poorer prognosis compared to Cluster C1. The C1 group exhibited higher scores for activated CD8+ T cells, central memory CD4+ T cells, and natural killer T cells. The C2 group demonstrated a higher frequency of gene mutations. We established and validated a novel prognostic prediction model and platelet-related gene risk score for pancreatic cancer. The risk score was positively correlated with T stage, N stage, and tumor grade, and it presented a significant prognostic value compared to other clinical factors. In conclusion, a novel prognostic prediction model focusing on platelet involvement in pancreatic cancer has been developed, offering potential benefits for future drug therapies and clinical prognostic assessments.

Effect of Gupi Xiaoji Decoction on mitochondrial structure and function of human hepatoma cell line HepG2 / 中国药理学通报

Aim To observe the effect of Gupi Xiaoji Decoction (GPXJY) on the structure and function of mitochondria of human hepatoma cell HepG2 cells and explore its possible mechanism. Methods CCK8 was used to detect cell proliferation, Mito-Tracker Green fluorescence staining was used to observe the mitochondrial structure, flow cytometry was used to detect the membrane potential, Elisa was used to detect the ATP content, fluoroscopic electron microscopy was used to observe the microstructure changes, and high-content screening(HCS) was used to detect the related proteins. Results Fluorescence staining showed that GPXJY damaged the mitochondria of HepG2 cells and decreased the content of ATP. The results of flow cytometry showed that GPXJY could reduce the mitochondrial membrane potential of HepG2 cells. The results of electron microscope showed that GPXJY made the mitochondria of cancer cells swell and so on. HCS found that GPXJY significantly reduced the average fluorescence intensity of Bcl-2 in HepG2 cells, and significantly increased the average fluorescence intensity of apoptosis promoting proteins Bax, cytochrome-c, caspase-3 and cleaved-caspase-3, which was statistically significant. Conclusion GPXJY can regulate the structure and function of mitochondria in HepG2 cells.

Surgical approach for esophageal cancer / 中华胃肠外科杂志

Due to the anatomical specificity of esophagus, esophagectomy can be carried out using different approaches, such as left transthoracic, right transthoracic and transhiatal approaches. Each surgical approach is associated with a different prognosis due to the complex anatomy. The left transthoracic approach is no longer the primary choice due to its limitations in providing adequate exposure, lymph node dissection, and resection. The right transthoracic approach is capable of achieving a larger number of dissected lymph nodes and is currently considered the preferred procedure for radical resection. Although the transhiatal approach is less invasive, it could be challenging to perform in a limited operating space and has not been widely adopted in clinical practice. Minimally invasive esophagectomy offers a wider range of surgical options for treating esophageal cancer. This paper reviews different approaches to esophagectomy.

Molecular Mechanism of Qinghuangsan Against Acute Myeloid Leukemia Based on Network Pharmacology and In Vitro Experiments / 中国实验方剂学杂志

ObjectiveTo predict the therapeutic target genes and related signaling pathways of Qinghuangsan （QHP） in the treatment of acute myeloid leukemia （AML） by network pharmacology，molecular docking，and further clarify its mechanisms through in vitro cell experiment. MethodThe active components and targets of QHP were retrieved from traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP），traditional Chinese medicine integrated database （TCMID），TargetNet and SwissTargetPrediction databases，and AML-related target genes were obtained by GeneCards and online mendelian inheritance in man （OMIM） databases. After screening the common targets of QHP and AML，the protein-protein interaction （PPI） network of the common targets was constructed with STRING，followed by gene ontology （GO） term and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analysis based on RStudio software and clusterProfiler，Bioconductor packages. At the same time，Cytoscape software is used to construct the network of "disease-component-target" and "compound-target-pathway". Select the active ingredients of QHP for molecular docking with the top 8 targets in the "compound-target-pathway" network. In vitro cell experiment and Western blot were used to further verify the anti-AML effect of QHP. ResultThe prediction results show that there are 11 main active components of QHP，and 22 common targets of QHP and AML are collected. KEGG pathway analysis results show that phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） and mitogen-activated protein kinase （MAPK） signaling pathways may play a key role in the treatment of AML disease by QHP. "Compound-target-pathway" network analysis showed that the top 8 targets include Akt1，phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha （PIK3CA），mitogen-activated protein kinase kinase 1 （MAP2K1），TP53，serine/threonine kinase （RAF1），B cell lymphoma（Bcl）-2，cysteine aspartic acid specific protease（Caspase）-9 and JUN. Molecular docking results showed that 3-indolyl-β-D-glucopyranoside was optimally docked with MAP2K1，isovitexin docked with PIK3CA，and indirubin docked with Bcl-2. Cell experiments show that 3-indolyl-β-D-glucopyranoside，isovitexin and indirubin can effectively inhibit the proliferation of AML cells，regulate the MAPK/PI3K signaling pathway，and inhibit the expression of Bcl-2 protein. ConclusionQHP can treat AML through "multi-component，multi-target，multi-pathway" synergistic treatment，and its mechanism of pharmacology may be related to the regulation of MAPK signaling pathway and PI3K/Akt signaling pathway.

Effect of Gupi Xiaoji Decoction on Pyroptosis of HepG2.2.15 Cells Based on Network Pharmacology and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo screen the active antitumor components of Gupi Xiaoji decoction by network pharmacology and molecular docking based on the pyroptosis mediated by cysteinyl aspartate-specific protease 1 （Caspase-1） and explore its molecular mechanism in intervening in the pyroptosis of HepG2.2.15 cells through in vitro experiments. MethodThe compounds and targets of Gupi Xiaoji decoction were screened out by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） to obtain the corresponding gene symbols. The targets of Caspase-1 were collected from GeneCards，online mendelian inheritance in man（OMIM），PharmGKB，and TTD，and the compound-gene target regulatory network was constructed by Cytoscape. The protein-protein interaction（PPI） network was established and analyzed by STRING. The mechanism of the effective components of Gupi Xiaoji decoction on Caspase-1 was predicted by gene ontology（GO） functional enrichment and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses. The molecular docking was verified with AutoDock Vina. The plasma medicated with Gupi Xiaoji Decoction was prepared and HepG2.2.15 cells were cultured in vitro. HepG2.2.15 cells were divided into a blank plasma group，a VX-765 group，a VX-765+medicated plasma group， and a medicated plasma group. After 48 hours of intervention with 15% medicated plasma， the expression and distribution of gasdermin D-N （GSDMD-N） on the surface of the cell membrane were detected by immunofluorescence staining. The release of lactic dehydrogenase （LDH）， interleukin（IL）-1β，and IL-18 in the cell supernatant was measured by enzyme-linked immunosorbent assay（ELISA） kits. The expression of Caspase-1 and GSDMD-N was measured by Western blot. ResultThe mitogen-activated protein kinase 14 （MAPK14），MAPK1，protein kinase B1 （Akt1）， MAPK8， V-Jun sarcoma virus oncogene homolog （JUN）， and TP53 screened by network pharmacology were the main targets. The compounds 7-hydroxy-5，8-dimethoxy-2-phenyl-chromone，wogonin，rhamnazin，moslosooflavone，isorhamnetin，7-O-methylisomucronulatol，formononetin，calycosin，luteolin，quercetin，kaempferol，β-sitosterol，and baicalein screened by network pharmacology were the main active components of Gupi Xiaoji decoction. Go enrichment analysis showed that multiple biological processes were involved， including responses to oxidative stress and metal ions，ubiquitin-like protein ligase binding，and phosphatase binding. KEGG pathway enrichment analysis showed MAPK pathway，nuclear factor（NF）-κB pathway，p53 pathway， and hypoxia-inducible factor-1（HIF-1） pathway were involved. Molecular docking showed that the targets had good binding with the components. In vitro experiments displayed that compared with the blank plasma group，the VX-765 group showed weakened GSDMD-N fluorescence signal，reduced release of LDH，IL-1β，and IL-18，and declining expression of Caspase-1 and GSDMD-N（P<0.01）， and the medicated plasma group showed increased GSDMD-N fluorescence signal， increased release of LDH，IL-1β，and IL-18，and up-regulated expression of Caspase-1 and GSDMD-N（P<0.01）. ConclusionGupi Xiaoji Decoction can induce the pyroptosis of HepG2.2.15 cells by regulating Caspase-1 through multiple targets and multiple pathways.