Adult acute leukemia patients with gram-negative bacteria bloodstream infection: Risk factors and outcomes of antibiotic-resistant bacteria.

This study aims to analyze the risk factors for the development of multidrug-resistant (MDR) and carbapenem-resistant (CR) bacteria bloodstream infection (BSI) in a patient with acute leukemia (AL) and the mortality in gram-negative bacteria (GNB) BSI. This is a retrospective study conducted at West China Hospital of Sichuan University, which included patients diagnosed with AL and concomitant GNB BSI from 2016 to 2021. A total of 206 patients with GNB BSI in AL were included. The 30-day mortality rate for all patients was 26.2%, with rates of 25.8% for those with MDR GNB BSI and 59.1% for those with CR GNB BSI. Univariate and multivariate analyses revealed that exposure to quinolones (Odds ratio (OR) = 3.111, 95% confidence interval (95%CI): 1.623-5.964, p = 0.001) within the preceding 30 days was an independent risk factor for MDR GNB BSI, while placement of urinary catheter (OR = 6.311, 95%CI: 2.478-16.073, p < 0.001) and exposure to cephalosporins (OR = 2.340, 95%CI: 1.090-5.025, p = 0.029) and carbapenems (OR = 2.558, 95%CI: 1.190-5.497, p = 0.016) within the preceding 30 days were independently associated with CR GNB BSI. Additionally, CR GNB BSI (OR = 2.960, 95% CI: 1.016-8.624, p = 0.047), relapsed/refractory AL (OR = 3.035, 95% CI: 1.265-7.354, p = 0.013), septic shock (OR = 5.108, 95% CI: 1.794-14.547, p = 0.002), platelets < 30 × 109/L before BSI (OR = 7.785, 95% CI: 2.055-29.492, p = 0.003), and inappropriate empiric antibiotic therapy (OR = 3.140, 95% CI: 1.171-8.417, p = 0.023) were independent risk factors for 30-day mortality in AL patients with GNB BSI. Prior antibiotic exposure was a significant factor in the occurrence of MDR GNB BSI and CR GNB BSI. CR GNB BSI increased the risk of mortality in AL patients with GNB BSI.

A novel color-aided system for diagnosis of early gastric cancer using magnifying endoscopy with narrow-band imaging.

BACKGROUND: The Pink Zone Pattern (PP) sign is a typical color alteration of early gastric cancer (EGC) under magnifying endoscopic narrow-band imaging (ME-NBI). By integrating the color changes (PP sign) with the "vessel plus surface (VS)" classification system, we developed an innovative diagnostic system for EGC and named it "Pink Microsurface Microvascular (PSV)" system. Here, we aimed to elucidate the diagnostic performance of the PSV system for EGC. METHODS: We conducted a single-center prospective clinical study (before-after design) consisting of 2 cross-sectional studies at 2 separate periods. In the before phase, 184 suspected lesions were evaluated using the VS system under ME-NBI; in the after phase, 183 suspected lesions were evaluated using the PSV system. We compared the diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) between the VS group and the PSV group. RESULTS: The accuracy, sensitivity, specificity, PPV, and NPV of the VS system for EGC were 84.6%, 87.0%, 83.6%, 67.8%, and 94.2%, respectively, and those for the PSV system were 93.0%, 92.0%, 93.4%, 85.2%, and 96.6%, respectively. The accuracy, specificity, and PPV of the PSV system were superior to those of the VS system. However, the sensitivity and NPV did not significantly differ between the VS system and the PSV system. The VS system was inconclusive for 22 lesions (12.0%) and the PSV system was inconclusive for 11 lesions (6.0%). The PSV system could identify more suspicious lesions than the VS system. CONCLUSIONS: We propose a new PSV diagnostic system by combining the VS system and the PP sign. Compared with the VS system, the PSV system could identify more suspected lesions and improve the diagnostic performance of EGC.

Incidence, prognostic factors, and survival outcomes in patients with blastic plasmacytoid dendritic cell neoplasm: A retrospective study in the Surveillance, Epidemiology, and End Results database.

There are few large-scale epidemiological and prognostic studies on blastic plasmacytoid dendritic cell neoplasm (BPDCN) due to its rarity. We used the Surveillance, Epidemiology, and End Results database to investigate the incidence, clinical characteristics, prognostic factors, and survival trends of BPDCN. The age-adjusted incidence of BPDCN had a bimodal pattern with peaks in those under 20 and 60 years and older. Of 697 patients, the median age at diagnosis was 31 years. The most common primary sites were lymph nodes (59.4%), followed by bone marrow (17.1%) and skin (11.6%). Extranodal involvement (59.7%) was more common in patients aged 60 years and older, while lymph node involvement was predominant in other age groups. The 1-year, 3-year, and 5-year overall survival (OS) rates were 90.7%, 83.7%, and 82.3% in patients aged under 20, but dropped to 53.1%, 27.7%, and 20.0% in patients aged 60 and older. Multivariate Cox regression analysis revealed that age, sex, and first malignancy were independent prognostic factors for OS. Based on this regression model, a nomogram was built with high discrimination and calibration. The incidence, clinical characteristics, and prognosis of BPDCN patients vary by age group. Moreover, using the nomogram to predict OS can help guide individualized evaluations and clinical decisions.

Prevention of Esophageal Stricture After Endoscopic Submucosal Dissection: A Systematic Review.

BACKGROUND: Endoscopic submucosal dissection (ESD) is rapidly becoming a favored method for removing early esophageal cancer, but the residual defects can be complicated with strictures that require repeated endoscopic balloon dilatation. Measures for preventing the post-ESD strictures have been sought. We conducted a systematic review of recent studies to evaluate these methods. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and Google Scholar until November 30, 2014. Included studies were prospective and retrospective one- and two-arm studies. All studies had to include at least on preventive method for post-ESD stricture. Thirteen studies were included in the review. RESULTS: Among the studies that used corticosteroids to prevent post-ESD stricture, we found that (1) injection of triamcinolone acetonide into the esophageal lesion resulted in a substantial reduction in the rate of stricture, and (2) the use of oral prednisolone was associated with a significantly reduced rate of dilatation sessions and stricture. Studies of other preventative measures included more recently developed scaffold-based and cell-based tissue-engineering approaches which seem very promising but require additional rigorously controlled studies to test their effectiveness. CONCLUSIONS: Until a safer and more effective method is developed, our review supports the use of corticosteroids, either through injection or oral route, together with endoscopic dilatation in prevention of post-ESD strictures.

Development of a cell adhesion-based prognostic model for multiple myeloma: Insights into chemotherapy response and potential reversal of adhesion effects.

Multiple myeloma (MM) is a hematologic malignancy notorious for its high relapse rate and development of drug resistance, in which cell adhesion-mediated drug resistance plays a critical role. This study integrated four RNA sequencing datasets (CoMMpass, GSE136337, GSE9782, and GSE2658) and focused on analyzing 1706 adhesion-related genes. Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes, including KIF14, TROAP, FLNA, MSN, LGALS1, PECAM1, and ALCAM, which demonstrated the strongest associations with poor overall survival (OS) in MM patients. To comprehensively evaluate the impact of cell adhesion on MM prognosis, an adhesion-related risk score (ARRS) model was constructed using Lasso Cox regression analysis. The ARRS model emerged as an independent prognostic factor for predicting OS. Furthermore, our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs, protein kinase inhibitors, and drugs targeting the PI3K/Akt/mTOR signaling pathway. Nevertheless, we identified promising drug candidates, such as tirofiban, pirenzepine, erlotinib, and bosutinib, which exhibit potential in reversing this resistance. In vitro, experiments employing NCIH929, RPMI8226, and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs. By employing siRNA-mediated knockdown of the key ARRS model gene KIF14, we observed suppressed proliferation of NCIH929 cells, along with decreased adhesion to BMSCs and fibronectin. This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM. Additionally, potential molecular mechanisms underlying adhesion-related resistance are proposed, along with viable strategies to overcome such resistance. These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.

Development and validation of an interpretable delta radiomics-based model for predicting invasive ground-glass nodules in lung adenocarcinoma: a retrospective cohort study.

Background: Radiomics models based on computed tomography (CT) can be used to differentiate invasive ground-glass nodules (GGNs) in lung adenocarcinoma to help determine the optimal timing of GGN resection, improve the accuracy of prognostic prediction, and reduce unnecessary surgeries. However, general radiomics does not fully utilize follow-up data and often lacks model interpretation. Therefore, this study aimed to build an interpretable model based on delta radiomics to predict GGN invasiveness. Methods: A retrospective analysis was conducted on a set of 303 GGNs that were surgically resected and confirmed as lung adenocarcinoma in Shanghai Chest Hospital between September 2017 and August 2022. Delta radiomics and general radiomics features were extracted from preoperative follow-up CT scans and combined with clinical features for modeling. The performance of the delta radiomics-clinical model was compared to that of the radiomics-clinical model. Additionally, Shapley additive explanations (SHAP) was employed to interpret and visualize the model. Results: Two models were constructed using a combination of 34 radiomic features and 10 delta radiomic features, along with 14 clinical features. The radiomics-clinical model and the delta radiomics-clinical model exhibited area under the curve (AUC) of 0.986 [95% confidence interval (CI): 0.977-0.995] and 0.974 (95% CI: 0.959-0.987) in the training set, respectively, and 0.949 (95% CI: 0.908-0.978) and 0.927 (95% CI: 0.879-0.966) in the test set, respectively. The DeLong test of the two models showed no statistical significance (P=0.10) in the test set. SHAP was used to output a summary plot for global interpretation, which showed that preoperative mass, three-dimensional (3D) length, mean diameter, volume, mean CT value, and delta radiomics feature original_firstorder_RootMeanSquared were the relatively more important features in the model. Waterfall plots for local interpretation showed how each feature contributed to the prediction output of a given GGN. Conclusions: The delta radiomics-based model proved to be a helpful tool for predicting the invasiveness of GGNs in lung adenocarcinoma. This approach offers a precise, noninvasive alternative in informing clinical decision-making. Additionally, SHAP provided insightful and user-friendly interpretations and visualizations of the model, enhancing its clinical applicability.

The Pink Zone Pattern (PP) sign: A novel simple marker for early gastric cancer.

BACKGROUND: We previously found a pink-colored change in early gastric cancer (EGC) lesions under magnifying endoscopy with narrow-band imaging (ME-NBI) and named it the "Pink Zoon Pattern" (PP) sign, which appeared independent of microvascular and microstructural changes. The aim of this study was to further investigate the characteristics of the PP sign in EGC. METHODS: The consecutive patients with suspicious gastric lesions detected by ME-NBI and confirmed by pathology at Zhejiang Cancer Hospital between November 2020 and December 2021 were enrolled in the study. The suspicious lesions were observed and assessed by the "VS" system and the PP sign respectively. RESULTS: We found that in the PP-positive group, 238 lesions (96.0%) were diagnosed as malignant. The overall accuracy, sensitivity, and specificity were 84.7%, 85.3%, and 81.8%. Among 164 EGC lesions diagnosed with low confidence (Grades 2, 3, and 4) using the VS system, the overall accuracy of PP to discriminate tumor from normal was 82.3%. The sensitivity and specificity were 82.7% and 81.5% respectively. CONCLUSIONS: The PP sign could be a new simple sign for the diagnosis of EGC and as an effective supplement to VS system when using ME-NBI.

Efficacy and safety of histone deacetylase inhibitors in peripheral T-cell lymphoma: a systematic review and meta-analysis on prospective clinical trials.

Background: The overall survival of peripheral T-cell lymphoma (PTCL) is dismal. Histone deacetylase (HDAC) inhibitors have exhibited promising treatment outcomes for PTCL patients. Therefore, this work aims to systematically evaluate the treatment outcome and safety profile of HDAC inhibitor-based treatment for untreated and relapsed/refractory (R/R) PTCL patients. Methods: The prospective clinical trials of HDAC inhibitors for the treatment of PTCL were searched on the Web of Science, PubMed, Embase, ClinicalTrials.gov, and Cochrane Library database. The pooled overall response rate, complete response (CR) rate, and partial response rate were measured. The risk of adverse events was evaluated. Moreover, the subgroup analysis was utilized to assess the efficacy among different HDAC inhibitors and efficacy in different PTCL subtypes. Results: For untreated PTCL, 502 patients in seven studies were involved, and the pooled CR rate was 44% (95% CI, 39-48%). For R/R PTCL patients, there were 16 studies included, and the CR rate was 14% (95% CI, 11-16%). The HDAC inhibitor-based combination therapy exhibited better efficacy when compared with HDAC inhibitor monotherapy for R/R PTCL patients (P = 0.02). In addition, the pooled CR rate was 17% (95% CI, 13-22%), 10% (95% CI, 5-15%), and 10% (95% CI, 5-15%) in the romidepsin, belinostat, and chidamide monotherapy subgroups, respectively. In the R/R angioimmunoblastic T-cell lymphoma subgroup, the pooled ORR was 44% (95% CI, 35-53%), higher than other subtypes. A total of 18 studies were involved in the safety assessment of treatment-related adverse events. Thrombocytopenia and nausea were the most common hematological and non-hematological adverse events, respectively. Conclusion: This meta-analysis demonstrated that HDAC inhibitors were effective treatment options for untreated and R/R PTCL patients. The combination of HDAC inhibitor and chemotherapy exhibited superior efficacy to HDAC inhibitor monotherapy in the R/R PTCL setting. Additionally, HDAC inhibitor-based therapy had higher efficacy in angioimmunoblastic T-cell lymphoma patients than that in other subtypes.

Genomic and Transcriptomic Remodeling by Neoadjuvant Chemoradiotherapy (nCRT) and the Indicative Role of Acquired INDEL Percentage for nCRT Efficacy in Esophageal Squamous Cell Carcinoma.

PURPOSE: The effect of genomic factors on the response of patients with esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemoradiotherapy (nCRT), as well as how nCRT influences the genome and transcriptome of ESCC, remain largely unknown. METHODS AND MATERIALS: In total, 137 samples from 57 patients with ESCC undergoing nCRT were collected and subjected to whole-exome sequencing and RNA sequencing analysis. Genetic and clinicopathologic factors were compared between the patients achieving pathologic complete response and patients not achieving pathologic complete response. Genomic and transcriptomic profiles before and after nCRT were analyzed. RESULTS: Codeficiency of the DNA damage repair and HIPPO pathways synergistically sensitized ESCC to nCRT. nCRT induced small INDELs and focal chromosomal loss concurrently. Acquired INDEL% exhibited a decreasing trend with the increase of tumor regression grade (P = .06, Jonckheere's test). Multivariable Cox analysis indicated that higher acquired INDEL% was associated with better survival (adjusted hazard ratio [aHR], 0.93; 95% CI, 0.86-1.01; P = .067 for recurrence-free survival [RFS]; aHR, 0.86; 95% CI, 0.76-0.98; P = .028 for overall survival [OS], with 1% of acquired INDEL% as unit). The prognostic value of acquired INDEL% was confirmed by the Glioma Longitudinal AnalySiS data set (aHR, 0.95; 95% CI, 0.902-0.997; P = .037 for RFS; aHR, 0.96; 95% CI, 0.917-1.004; P = .076 for OS). Additionally, clonal expansion degree was negatively associated with patient survival (aHR, 5.87; 95% CI, 1.10-31.39; P = .038 for RFS; aHR, 9.09; 95% CI, 1.10-75.36; P = .041 for OS, with low clonal expression group as reference) and also negatively correlated with acquired INDEL% (Spearman ρ = -0.45; P = .02). The expression profile was changed after nCRT. The DNA replication gene set was downregulated, while the cell adhesion gene set was upregulated after nCRT. Acquired INDEL% was negatively correlated with the enrichment of the DNA replication gene set (Spearman ρ = -0.56; P = .003) but was positively correlated with the enrichment of the cell adhesion gene set (Spearman ρ = 0.40; P = .05) in posttreatment samples. CONCLUSIONS: nCRT remodels the genome and transcriptome of ESCC. Acquired INDEL% is a potential biomarker to indicate the effectiveness of nCRT and radiation sensitivity.

Risk factors of lymph node metastasis or lymphovascular invasion for superficial esophageal squamous cell carcinoma: A practical and effective predictive nomogram based on a cancer hospital data.

Background: Lymphovascular invasion (LVI) is mostly used as a preoperative predictor to establish lymph node metastasis (LNM) prediction models for superficial esophageal squamous cell carcinoma (SESCC). However, LVI still needs to be confirmed by postoperative pathology. In this study, we combined LNM and LVI as a unified outcome and named it LNM/LVI, and aimed to develop an LNM/LVI prediction model in SESCC using preoperative factors. Methods: A total of 512 patients who underwent radical resection of SESCC were retrospectively collected. Logistic regression and least absolute shrinkage and selection operator (LASSO) regression were adopted to identify the predictive factors of LNM/LVI. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to select the potential predictive factors from the results of LASSO and logistic regression. A nomogram for predicting LNM/LVI was established by incorporating these factors. The efficacy, accuracy, and clinical utility of the nomogram were, respectively, assessed with the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Finally, the random forest (RF) algorithm was used to further evaluate the impact of these factors included in the nomogram on LNM/LVI. Results: Tumor size, tumor location, tumor invasion depth, tumor differentiation, and macroscopic type were confirmed as independent risk factors for LNM/LVI according to the results of logistic regression, LASSO regression, IDI, and NRI analyses. A nomogram including these five variables showed a good performance in LNM/LVI prediction (AUC = 0.776). The calibration curve revealed that the predictive results of this nomogram were nearly consistent with actual observations. Significant clinical utility of our nomogram was demonstrated by DCA. The RF model with the same five variables also had similar predictive efficacy with the nomogram (AUC = 0.775). Conclusion: The nomogram was adopted as a final tool for predicting LNM/LVI because its risk score system made it more user-friendly and clinically useful than the random forest model, which can help clinicians make optimal treatment decisions for patients with SESCC.

The Endoscopic Submucosal Dissection Surgery in the Whole-Course Antegrade Endoscopic Approach: A More Effective Treatment Strategy for the Siewert II/III Type Mucosal Lesions of Esophagogastric Junction.

Objective: The purpose of this study was to investigate the safety and efficacy of endoscopic submucosal dissection (ESD) for treating cardiac mucosal lesions. Methods: A total of 86 patients with cardiac mucosal lesions were treated with ESD in retrograde endoscopic approach or antegrade endoscopic approach. The relationship between the two methods was analyzed according to the size, location, depth of pathological infiltration, classification, and examination results. The main evaluation indexes of intraoperative complications were operation time, bleeding, perforation, and complete resection (R0 resection). Results: Total R0 excision was performed in 85 patients and curative excision in 77 patients. When the diameter of lesion was 2-4 cm or >4 cm, the median treatment time in the antegrade endoscopic approach group was shorter than that in the retrograde group (P < .001, respectively). When the lesion was confined to the mucosa, the median treatment time in the antegrade endoscopic approach group was shorter than that in the retrograde group (P < .001). When the lesion was located in the posterior wall of the cardia, the average treatment time in the antegrade endoscopic approach group was shorter than that in the retrograde group (P < .05). When the lesion was located in the lesser curvature of the cardia, the average treatment time in the antegrade endoscopic approach group was shorter than that in the retrograde group (P < .001). Conclusion: The ESD surgery in the antegrade endoscopic approach is effective and safe for the treatment of cardiac mucosal lesions.

Role of Phosphorus-Containing Molecules on the Formation of Nano-Sized Calcium Phosphate for Bone Therapy.

Calcium phosphate (CaP) is the principal inorganic constituent of bone and teeth in vertebrates and has various applications in biomedical areas. Among various types of CaPs, amorphous calcium phosphate (ACP) is considered to have superior bioactivity and biodegradability. With regard to the instability of ACP, the phosphorus-containing molecules are usually adopted to solve this issue, but the specific roles of the molecules in the formation of nano-sized CaP have not been clearly clarified yet. Herein, alendronate, cyclophosphamide, zoledronate, and foscarnet are selected as the model molecules, and theoretical calculations were performed to elucidate the interaction between calcium ions and different model molecules. Subsequently, CaPs were prepared with the addition of the phosphorus-containing molecules. It is found that cyclophosphamide has limited influence on the generation of CaPs due to their weak interaction. During the co-precipitation process of Ca2+ and PO4 3-, the competitive relation among alendronate, zoledronate, and foscarnet plays critical roles in the produced inorganic-organic complex. Moreover, the biocompatibility of CaPs was also systematically evaluated. The DFT calculation provides a convincing strategy for predicting the structure of CaPs with various additives. This work is promising for designing CaP-based multifunctional drug delivery systems and tissue engineering materials.

Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials.

Background: Selinexor (SEL) is an orally bioavailable, highly-selective, and slowly-reversible small molecule that inhibits Exportin 1. Preclinical studies showed that SEL had synergistic antimyeloma activity with glucocorticoids, proteasome inhibitors (PIs) and immunomodulators. The combination of selinexor and dexamethasone (DEX) has been approved in the United States for patients with penta-refractory multiple myeloma in July 2019. This meta-analysis aimed to investigate the safety and efficacy of selinexor based treatment in Multiple myeloma. Methods: We systematically searched the Medline (PubMed), Embase, Web of Science, Cochrane Central Register of Controlled Trials Library databases and ClinicalTrials.gov. Outcome measures of efficacy included overall response rate (ORR), clinical benefit rate (CBR), stringent complete response rate (sCR), complete response rate (CR), very good partial response (VGPR), partial response rate (PR), minimal response (MR), rate of stable disease (SDR), rate of progressive disease (PDR) and median progression-free survival (mPFS). Safety was evaluated by the incidences of all grade adverse events and Grade≥3 adverse events. The subgroup analysis was conducted to analyze the difference in different combination treatment regimens (SEL + DEX + PIs vs SEL + DEX). Results: We included six studies with 477 patients. The pooled ORR, CBR, sCR, CR, VGPR, PR, MR, SDR, and PDR were 43% (18-67%), 55% (32-78%), 5% (-2-13%), 7% (4-11%), 14% (5-24%), 23% (15-31%), 11% (8-14%), 26% (14-38%) and 14% (4-23%), respectively. SEL + DEX + PIs treatment had higher ORR (54 vs 24%, p = 0.01), CBR (66 vs 37%, p = 0.01), sCR (10 vs 2%, p = 0.0008), and VGPR (23 vs 5%, p < 0.00001) compared to SEL + DEX treatment, and lower PDR (4 vs 23%, p < 0.00001) and SDR (17 vs 37%, p = 0.0006). The pooled incidences of any grade and grade≥3 were 45 and 30% in hematological AEs, and in non-hematological AEs were 40 and 30%, respectively. The most common all grade (68%) and grade≥3 (54%) hematological AE were both thrombocytopenia. Fatigue was the most common all grade (62%) and grade≥3 (16%) non-hematological AE. Compared to SEL + DEX treatment, SEL + DEX + PIs treatment had lower incidences of hyponatremia (39 vs 12%, p < 0.00001), nausea (72 vs 52%, p < 0.00001), vomiting (41 vs 23%, p < 0.0001), and weight loss (42 vs 17%, p = 0.03) in all grade AEs. Meanwhile, SEL + DEX + PIs treatment had lower incidences of anemia (36 vs 16%, p = 0.02), fatigue (20 vs 13%, p = 0.04), hyponatremia (22 vs 5%, p < 0.0001) than SEL + DEX treatment in grade≥3 AEs. Conclusion: Our meta-analysis revealed that selinexor-based regimens could offer reasonable efficacy and tolerable adverse events in patients with multiple myeloma. SEL + DEX + PIs treatments had higher efficacy and lower toxicities than SEL + DEX.

Safety Evaluation of Natural Drugs in Chronic Skeletal Disorders: A Literature Review of Clinical Trials in the Past 20 years.

Chronic skeletal disorders (CSDs), including degenerative diseases such as osteoporosis (OP) and autoimmune disorders, have become a leading cause of disability in an ageing society, with natural drugs being indispensable therapeutic options. The clinical safety evaluation (CSE) of natural drugs in CSDs has been given priority and has been intensively studied. To provide fundamental evidence for the clinical application of natural drugs in the elderly population, clinical studies of natural drugs in CSDs included in this review were selected from CNKI, Web of Science, PubMed, Science Direct and Google Scholar since 2001. Seventeen randomized controlled trials (RCTs) met our inclusion criteria: four articles were on OP, seven on osteoarthritis (OA), four on rheumatoid arthritis (RA) and two on gout. Common natural drugs used for the treatment of OP include Epimedium brevicornu Maxim [Berberidaceae], Dipsacus asper Wall ex DC [Caprifoliaceae] root, and Phalaenopsis cornu-cervi (Breda) Blume & Rchb. f[ Orchidaceae], which have been linked to several mild adverse reactions, such as skin rash, gastric dysfunction, abnormal urine, constipation and irritability. The safety of Hedera helix L [Araliaceae] extract, Boswellia serrata Roxb [Burseraceae] extract and extract from perna canaliculus was evaluated in OA and upper abdominal pain, and unstable movements were obsrerved as major side effects. Adverse events, including pneumonia, vomiting, diarrhoea and upper respiratory tract infection, were reported when RA was treated with Tripterygium wilfordii, Hook. F [Celastraceae][TwHF] polyglycosides and quercetin (Capsella bursa-pastoris (L.) Medik [Brassicaceae]). The present review aimed to summarize the CSE results of natural drugs in CSDs and could provide evidence-based information for clinicians.

Retrospective analysis of predictive factors for lymph node metastasis in superficial esophageal squamous cell carcinoma.

This study aimed to identify the risk factors of lymph node metastasis (LNM) in superficial esophageal squamous cell carcinoma and use these factors to establish a prediction model. We retrospectively analyzed the data from training set (n = 280) and validation set (n = 240) underwent radical esophagectomy between March 2005 and April 2018. Our results of univariate and multivariate analyses showed that tumor size, tumor invasion depth, tumor differentiation and lymphovascular invasion were significantly correlated with LNM. Incorporating these 4 variables above, model A achieved AUC of 0.765 and 0.770 in predicting LNM in the training and validation sets, respectively. Adding macroscopic type to the model A did not appreciably change the AUC but led to statistically significant improvements in both the integrated discrimination improvement and net reclassification improvement. Finally, a nomogram was constructed by using these five variables and showed good concordance indexes of 0.765 and 0.770 in the training and validation sets, and the calibration curves had good fitting degree. Decision curve analysis demonstrated that the nomogram was clinically useful in both sets. It is possible to predict the status of LNM using this nomogram score system, which can aid the selection of an appropriate treatment plan.

A Nomogram for Predicting Lymphovascular Invasion in Superficial Esophageal Squamous Cell Carcinoma.

The lymphovascular invasion (LVI) status facilitates the determination of the optimal therapeutic strategy for superficial esophageal squamous cell carcinoma (SESCC), but in clinical practice, LVI must be confirmed by postoperative pathology. However, studies of the risk factors for LVI in SESCC are limited. Consequently, this study aimed to identify the risk factors for LVI and use these factors to establish a prediction model. The data of 516 patients who underwent radical esophagectomy between January 2007 and September 2019 were retrospectively collected (training set, n=361, January 2007 to May 2015; validation set, n=155, June 2015 to September 2019). In the training set, least absolute shrinkage and selection operator (LASSO) regression and multivariate analyses were utilized to identify predictive factors for LVI in patients with SESCC. A nomogram was then developed using these predictors. The area under the curve (AUC), calibration curve, and decision curve were used to evaluate the efficiency, accuracy, and clinical utility of the model. LASSO regression indicated that the tumor size, depth of invasion, tumor differentiation, lymph node metastasis (LNM), sex, circumferential extension, the presence of multiple lesions, and the resection margin were correlated with LVI. However, multivariate analysis revealed that only the tumor size, depth of invasion, tumor differentiation, and LNM were independent risk factors for LVI. Incorporating these four variables, model 1 achieved an AUC of 0.817 in predicting LVI. Adding circumferential extension to model 1 did not appreciably change the AUC and integrated discrimination improvement, but led to a significant increase in the net reclassification improvement (p=0.011). A final nomogram was constructed by incorporating tumor size, depth of invasion, tumor differentiation, LNM, and circumferential extension and showed good discrimination (training set, AUC=0.833; validation set, AUC=0.819) and good calibration in the training and validation sets. Decision curve analysis demonstrated that the nomogram was clinically useful in both sets. Thus, it is possible to predict the status of LVI using this nomogram scoring system, which can aid the selection of an appropriate treatment plan.

"Pink Pattern" Visualized in Magnifying Endoscopy With Narrow-Band Imaging Is a Novel Feature of Early Differentiated Gastric Cancer: A Bridge Between Endoscopic Images and Histopathological Changes.

Background: A pink color change occasionally found by us under magnifying endoscopy with narrow-band imaging (ME-NBI) may be a special feature of early gastric cancer (EGC), and was designated the "pink pattern". The purposes of this study were to determine the relationship between the pink pattern and the cytopathological changes in gastric cancer cells and whether the pink pattern is useful for the diagnosis of EGC. Methods: The color features of ME-NBI images and pathological images of cancerous gastric mucosal surfaces were extracted and quantified. The cosine similarity was calculated to evaluate the correlation between the pink pattern and the nucleus-to-cytoplasm ratio of cancerous epithelial cells. Two diagnostic tests were performed by 12 endoscopists using stored ME-NBI images of 185 gastric lesions to investigate the diagnostic efficacy of the pink pattern for EGC. The diagnostic values, such as the area under the curve (AUC), the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of test 1 and test 2 were compared. Results: The cosine similarity between the color values of ME-NBI images and pathological images of 20 lesions was at least 0.744. The median AUC, accuracy, sensitivity, specificity, PPV, and NPV of test 2 were significantly better than those of test 1 for all endoscopists and for the junior and experienced groups. Conclusions: The pink pattern observed in ME-NBI images correlated strongly with the change in the nucleus-to-cytoplasm ratio of gastric epithelial cells, and could be considered a useful marker for the diagnosis of differentiated EGC.

The ATM rs189037 G>A polymorphism is associated with the risk and prognosis of gastric cancer in Chinese individuals: A case-control study.

The ataxia telangiectasia mutated (ATM) gene is involved in repairing DNA lesions and maintaining genome stability, which is related to cancer invasion and metastasis. This gene influences the risk of cancers. Many studies have demonstrated that the ATM rs189037 G>A polymorphism is linked with the risks of different types of cancer. However, no study has probed the relationship between the ATM rs189037 G>A polymorphism and gastric cancer (GC) risk. Therefore, the aims of this study were to investigate the association of the ATM rs189037 G>A polymorphism with the risk and prognosis of GC in a case-control investigation of 345 GC patients and 467 controls in China. The rs189037 G>A polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism. This polymorphism was related to a significantly higher risk of GC [AA vs. GG: OR (95% CI): 1.80 (1.20-2.70), P = 0.04; GG vs. AA + GA: 1.46 (1.08-1.98); A vs. G: 1.34 (1.10-1.64), P = 0.004]. Subgroup analyses showed significant associations with female gender, smoking, alcohol consumption, age ≥60 years, and positive Helicobacter pylori status. This polymorphism was also correlated with TNM stage III + IV and tumor size >4 cm. GC patients carrying the AA genotype of the rs189037 polymorphism also had lower overall survival. In conclusion, the ATM rs189037 G>A polymorphism was related to increased susceptibility to and poorer prognosis in GC in this Chinese population.

Pregnenolone Inhibits Osteoclast Differentiation and Protects Against Lipopolysaccharide-Induced Inflammatory Bone Destruction and Ovariectomy-Induced Bone Loss.

Osteolytic bone disease is characterized by excessive osteoclast bone resorption leading to increased skeletal fragility and fracture risk. Multinucleated osteoclasts formed through the fusion of mononuclear precursors are the principle cell capable of bone resorption. Pregnenolone (Preg) is the grand precursor of most if not all steroid hormones and have been suggested to be a novel anti-osteoporotic agent. However, the effects of Preg on osteoclast biology and function has yet to be shown. Here we examined the effect of Preg on receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast formation and bone resorption in vitro, and potential therapeutic application in inflammatory bone destruction and bone loss in vivo. Our in vitro cellular assays demonstrated that Preg can inhibit the formation of TRAP+ve osteoclast formation as well as mature osteoclast bone resorption in a dose-dependent manner. The expression of osteoclast marker genes CTSK, TRAP, DC-STAMP, ATP6V0d2, and NFATc1 were markedly attenuated. Biochemical analyses of RANKL-induced signaling pathways showed that Preg inhibited the early activation of extracellular regulated protein kinases (ERK) mitogen-activated protein kinase (MAPK) and nuclear factor-κB, which consequently impaired the downstream induction of c-Fos and NFATc1. Using reactive oxygen species (ROS) detection assays, we found that Preg exhibits anti-oxidant properties inhibiting the generation of intracellular ROS following RANKL stimulation. Consistent with these in vitro results, we confirmed that Preg protected mice against local Lipopolysaccharide (LPS)-induced inflammatory bone destruction in vivo by suppressing osteoclast formation. Furthermore, we did not find any observable effect of Preg on osteoblastogenesis and mineralization in vitro. Finally Preg was administered to ovariectomy (OVX)-induced bone loss and demonstrated that Preg prevented systemic OVX-induced osteoporosis. Collectively, our observations provide strong evidence for the use of Preg as anti-osteoclastogenic and anti-resorptive agent for the potential treatment of osteolytic bone conditions.

The value of endoscopic ultrasonography in defining longitudinal gross target volumes for esophageal squamous carcinoma.

BACKGROUND AND PURPOSE: To investigate the differences between endoscopic ultrasonography (EUS)-based longitudinal gross target volumes (GTV) (GTV(EUS)) and computed tomography (CT)-based longitudinal GTV (GTV(CT)) in diagnosing esophageal squamous carcinoma. METHODS: Thirty-six patients underwent EUS to define the superior and inferior extents of the tumor by using hemoclips. CT-planning scan was performed with the patient in the supine position during the treatment. GTV(CT) and GTV(EUS) were contoured respectively. The respective lengths (L(CT) and L(EUS)) and spatial locations of longitudinal GTV(CT) and longitudinal GTV(EUS) were compared. RESULTS: The mean LCT was 7.8 ± 3.2 cm and the mean L(EUS) was 7.4 ± 2.7 cm. No statistical difference was found between L(CT) and L(EUS) (P > 0.05) with a correlation coefficient of 0.61 (P<0.05). The mean conformal index was 0.79 ± 0.18 with spatial variations found in 71% (24/34) of the patients. CONCLUSIONS: EUS can provide additional information to CT in defining longitudinal GTV in thoracic esophageal squamous cell carcinoma, especially superficial and submucosal carcinomas, which may contribute to the development of better individual treatment regimens.