The later-line efficacy and safety of immune checkpoint inhibitors plus anlotinib in EGFR-mutant patients with EGFR-TKI-resistant NSCLC: a single-center retrospective study.

BACKGROUND: Effective treatment after EGFR-TKI resistance is of great clinical concern. We aimed to investigate the efficacy and safety of anlotinib in combination with an anti-PD-1/PD-L1 antibody in later-line therapy for EGFR-mutant NSCLC patients after TKI treatment failure and to explore the independent predictive factors of therapeutic efficacy. METHODS: A total of 71 patients with confirmed advanced EGFR-mutated NSCLC who progressed after previous standard EGFR-TKI therapy but still failed after multiline treatments were included retrospectively in this study. Most of the patients had previously received at least three lines of treatment. All were treated with anlotinib combined with anti-PD-1 or anti-PD-L1 therapy. The safety of this combined treatment was assessed by the incidence of adverse events. The efficacy of the regimens was evaluated by survival analysis (OS, PFS, ORR, DCR). RESULTS: The median follow-up period was 28.6 months (range: 2.3-54.0 months), and the median number of treatment lines was 4. The overall response rate (ORR) and disease control rate (DCR) were 19.7% and 77.5%, respectively. The median PFS was 5.8 months (95% CI 4.2-7.4 months), and the median OS was 17.1 months (95% CI 12.0-22.3 months). Patients who received immune checkpoint inhibitors plus anlotinib had an encouraging intracranial ORR of 38.5% and a DCR of 80.8%. ECOG performance status < 2 at baseline was independent protective factors of PFS. Metastatic organs and ECOG performance status were independent parameters in predicting OS. Treatment-related adverse events occurred in 66 (93.0%) patients; most of the adverse events were Grade 1-2, and no increase in adverse events was observed compared to monotherapy. CONCLUSION: Anlotinib combined with an anti-PD-1/PD-L1-based regimen exhibited promising efficacy and tolerance in NSCLC patients with EGFR mutations after previous TKI failure. The efficacy of this combined regimen in patients with EGFR mutations should be further evaluated.

A Randomized Controlled Study of Enhanced External Counterpulsation with Cardiac Rehabilitation in Patients with Nonobstructive Coronary Artery Disease and Coronary Microvascular Dysfunction.

Treatment with enhanced external counterpulsation (EECP) or cardiac rehabilitation (CR) benefits patients with coronary heart disease; this paper intends to explore the feasibility of EECP combined with CR in patients with nonobstructive coronary heart disease (NOCAD) and coronary microcirculation disorders (CMD).In January 2021-2022 month June our income NOCAD patients as the research object, the line of cardiac magnetic resonance (CMR), myocardial perfusion reserve (MPR) < 2.0 coronary microcirculation disorders (CMD, 80 cases). Random indicator method 80 CMD patients divided into two groups, 40 cases in each. Usual treatment group: conventional drugs and CR therapy. EECP treatment group: on the basis of standard treatment group, employ EECP therapy. Comparing the two groups before and after the treatment curative effect cardiac function index, endothelial unction index, adverse cardiovascular events, etc.After EECP treatment, the treatment group showed a higher effective rate compared to the usual treatment group (P < 0.05). EECP group curative effect, left ventricular ejection fraction,plasma NO and vascular endothelial growth factor levels higher than the usual group, the incidence of adverse cardiovascular events is lower than the usual group. The difference was statistically significant (P < 0.05).EECP combined with cardiac rehabilitation in patients with CMD symptoms has better effect and safety and provides reference for treatment of CMD patients.

Predictive value of serum myoglobin and lactate dehydrogenase in rhabdomyolysis-induced acute kidney injury from severe heatstroke.

OBJECTIVE: To explore the predictive utility of serum myoglobin (Mb) and lactate dehydrogenase (LDH) for acute kidney injury (AKI) secondary to rhabdomyolysis (RM) in severe heatstroke patients. METHODS: A retrospective analysis of 58 RM patients with severe heatstroke at Shanghai Ninth People's Hospital from June 2019 to May 2022 was conducted. Patients were categorized into AKI and non-AKI groups. Laboratory indices were compared, and receiver operating characteristic (ROC) curves were used to assess the predictive value of serum biomarkers for AKI. RESULTS: Creatine kinase, Mb, LDH, creatinine, and blood urea nitrogen levels were significantly higher in the AKI group (P<0.05). Serum Mb and LDH were positively correlated with serum creatinine (r=0.6772 and r=0.6816, respectively; P<0.05). The area under the ROC curve (AUC) for serum Mb was 0.6692 (95% CI: 0.5253-0.8131) with a cut-off of 1024 ng/ml, while for LDH it was 0.8277 (95% CI: 0.7182-0.9371) with a cut-off of 1342 U/L. Combining serum Mb and LDH improved the AUC to 0.9116 (95% CI: 0.8219-1.001). CONCLUSION: Serum Mb and LDH levels are elevated in RM-induced AKI following severe heatstroke, and their combination offers substantial predictive value for AKI in these patients.

Phase I/II clinical trial of efficacy and safety of EGCG oxygen nebulization inhalation in the treatment of COVID-19 pneumonia patients with cancer.

BACKGROUND: The antiviral drug Nirmatrelvir was found to be a key drug in controlling the progression of pneumonia during the infectious phase of COVID-19. However, there are very few options for effective treatment for cancer patients who have viral pneumonia. Glucocorticoids is one of the effective means to control pneumonia, but there are many adverse events. EGCG is a natural low toxic compound with anti-inflammatory function. Thus, this study was designed to investigate the safety and efficacy of epigallocatechin-3-gallate (EGCG) aerosol to control COVID-19 pneumonia in cancer populations. METHODS: The study was designed as a prospective, single-arm, open-label phase I/II trial at Shandong Cancer Hospital and Institute, between January 5, 2023 to March 31,2023 with viral pneumonia on radiographic signs after confirmed novel coronavirus infection. These patients were treated with EGCG nebulization 10 ml three times daily for at least seven days. EGCG concentrations were increased from 1760-8817umol/L to 4 levels with dose escalation following a standard Phase I design of 3-6 patients per level. Any grade adverse event caused by EGCG was considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the highest dose with less than one-third of patients experiencing dose limiting toxicity (DLT) due to EGCG. The primary end points were the toxicity of EGCG and CT findings, and the former was graded by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. The secondary end point was the laboratory parameters before and after treatment. RESULT: A total of 60 patients with high risk factors for severe COVID-19 pneumonia (factors such as old age, smoking and combined complications)were included in this phase I-II study. The 54 patients in the final analysis were pathologically confirmed to have tumor burden and completed the whole course of treatment. A patient with bucking at a level of 1760 umol/L and no acute toxicity associated with EGCG has been reported at the second or third dose gradients. At dose escalation to 8817umol/L, Grade 1 adverse events of nausea and stomach discomfort occurred in two patients, which resolved spontaneously within 1 hour. After one week of treatment, CT showed that the incidence of non-progression of pneumonia was 82% (32/39), and the improvement rate of pneumonia was 56.4% (22/39). There was no significant difference in inflammation-related laboratory parameters (white blood cell count, lymphocyte count, IL-6, ferritin, C-reactive protein and lactate dehydrogenase) before and after treatment. CONCLUSION: Aerosol inhalation of EGCG is well tolerated, and preliminary investigation in cancer population suggests that EGCG may be effective in COVID-19-induced pneumonia, which can promote the improvement of patients with moderate pneumonia or prevent them from developing into severe pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.

The application of different machine learning models based on PET/CT images and EGFR in predicting brain metastasis of adenocarcinoma of the lung.

OBJECTIVE: To explore the value of six machine learning models based on PET/CT radiomics combined with EGFR in predicting brain metastases of lung adenocarcinoma. METHODS: Retrospectively collected 204 patients with lung adenocarcinoma who underwent PET/CT examination and EGFR gene detection before treatment from Cancer Hospital Affiliated to Shandong First Medical University in 2020. Using univariate analysis and multivariate logistic regression analysis to find the independent risk factors for brain metastasis. Based on PET/CT imaging combined with EGFR and PET metabolic indexes, established six machine learning models to predict brain metastases of lung adenocarcinoma. Finally, using ten-fold cross-validation to evaluate the predictive effectiveness. RESULTS: In univariate analysis, patients with N2-3, EGFR mutation-positive, LYM%≤20, and elevated tumor markers(P<0.05) were more likely to develop brain metastases. In multivariate Logistic regression analysis, PET metabolic indices revealed that SUVmax, SUVpeak, Volume, and TLG were risk factors for lung adenocarcinoma brain metastasis(P<0.05). The SVM model was the most efficient predictor of brain metastasis with an AUC of 0.82 (PET/CT group),0.70 (CT group),0.76 (PET group). CONCLUSIONS: Radiomics combined with EGFR machine learning model as a new method have higher accuracy than EGFR mutation alone. SVM model is the most effective method for predicting brain metastases of lung adenocarcinoma, and the prediction efficiency of PET/CT group is better than PET group and CT group.

Construction and validation of a predictive model for major adverse cardiovascular events in the long term after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction.

PURPOSE: Construction of a prediction model to predict the risk of major adverse cardiovascular events (MACE) in the long term after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). METHOD: Retrospective analysis of STEMI patients treated with PCI from April 2018 to April 2021 in Fuyang People's Hospital. Lasso regression was used to screen the risk factors for the first occurrence of MACE in patients, and multifactorial logistic regression analysis was used to construct a prediction model. The efficacy was evaluated by area under the ROC curve (AUC), Hosmer-Lemeshow deviance test, calibration curve, clinical decision curve (DCA) and clinical impact curve (CIC). RESULTS: Logistic regression results showed that hypertension, diabetes mellitus, left main plus three branches lesion, estimated glomerular filtration rate and medication adherence were influential factors in the occurrence of distant MACE after PCI in STEMI patients (P < 0.05). The AUC was 0.849 in the modeling group and 0.724 in the validation group; the calibration curve had a good fit to the standard curve, and the result of the Hosmer-Lemeshow test of deviance was x2 = 7.742 (P = 0. 459); the DCA and the CIC indicated that the predictive model could provide a better net clinical benefit for STEMI patients. CONCLUSION: A prediction model constructed from a total of five predictor variables, namely hypertension, diabetes, left main + three branches lesions, eGFR and medication adherence, can be used to assess the long-term prognosis after PCI in STEMI patients and help in early risk stratification of patients.

Voice treatment of school-aged children with vocal nodules with ABCLOVE rehabilitation.

BACKGROUND: This study was to explore the effectiveness of the ABCLOVE exercise on school-aged children with vocal nodules after the treatment of budesonide. METHODS: Eighty-six school-aged children with vocal nodules were divided into control and ABCLOVE therapy groups. Subjective voice assessment and dysphonia severity index (DSI) assessment were performed before and after the 3-month of therapy. RESULTS: A significant improvement was observed in the ABCLOVE therapy group as compared with the control group (p = 0.035). ABCLOVE therapy significantly reduced the hoarseness and roughness scores in school-aged children with vocal nodules. Additionally, a significant reduction in functional score, physical score, emotional score, and total pVHI score was observed in the ABCLOVE therapy group. Moreover, acoustic parameters including jitter (%) and shimmer (%) were significantly reduced, whereas MPT and DSI were increased in school-aged children with vocal nodules who received 3 months of ABCLOVE treatment. CONCLUSION: ABCLOVE therapy displayed effectiveness on school-aged children with vocal nodules after the treatment of budesonide.

Effect of different salt additions on the taste and flavor-related compounds in chicken soup.

Chicken soup is popular among consumers because of its delicious taste, strong flavor, and abundant nutritional value. Twenty-four Yunnan local hens were stewed by adding different amounts of NaCl [1.5, 2, 2.5, 3%, m/m, calculated based on chicken carcass weight; chicken: water = 1:2 (m/m)] to study the effect of salt addition on taste- and flavor-related compounds in chicken soup. Sensory evaluation results showed that the 2 and 2.5% NaCl treatment groups had higher scores. Water-soluble small molecule compounds were detected by LC-Q/TOF-MS based metabolomics approach, among which amino acids and their derivatives, nucleic acids, and small peptides were the main components. The concentration of Water-soluble small molecule substances in chicken soup samples with different salt additions showed a clear trend of separation and reached the highest in the 2.5% NaCl treatment group. Volatile flavor compounds in the chicken soup were analyzed by HS-SPME-GC-MS, including aldehydes, and alcohols, and the relative concentration of flavor compounds in the 2.5% salt treatment group was the highest. In summary, the addition of salt could improve the overall flavor of chicken broth, and the optimal salt addition of NaCl in chicken soup is 2.5%.

MFGAN: Multimodal Fusion for Industrial Anomaly Detection Using Attention-Based Autoencoder and Generative Adversarial Network.

Anomaly detection plays a critical role in ensuring safe, smooth, and efficient operation of machinery and equipment in industrial environments. With the wide deployment of multimodal sensors and the rapid development of Internet of Things (IoT), the data generated in modern industrial production has become increasingly diverse and complex. However, traditional methods for anomaly detection based on a single data source cannot fully utilize multimodal data to capture anomalies in industrial systems. To address this challenge, we propose a new model for anomaly detection in industrial environments using multimodal temporal data. This model integrates an attention-based autoencoder (AAE) and a generative adversarial network (GAN) to capture and fuse rich information from different data sources. Specifically, the AAE captures time-series dependencies and relevant features in each modality, and the GAN introduces adversarial regularization to enhance the model's ability to reconstruct normal time-series data. We conduct extensive experiments on real industrial data containing both measurements from a distributed control system (DCS) and acoustic signals, and the results demonstrate the performance superiority of the proposed model over the state-of-the-art TimesNet for anomaly detection, with an improvement of 5.6% in F1 score.

Coronary Artery Calcium and Cognitive Decline in the Diabetes Prevention Program Outcomes Study.

Background Our aim was to investigate the association of coronary artery calcium (CAC) with cognitive function in adults with impaired glucose tolerance or type 2 diabetes. Methods and Results The Diabetes Prevention Program was a randomized controlled trial comparing an intensive lifestyle intervention, metformin, or placebo for prevention of type 2 diabetes among patients with prediabetes. After 3 years, intensive lifestyle intervention and placebo were stopped, the metformin arm was unmasked, and participants continued in the DPPOS (Diabetes Prevention Program Outcomes Study). Approximately 14 years after randomization (Y14), CAC (Agatston score) was assessed with computed tomography, and cognitive performance was assessed with the Spanish English Verbal Learning Test (SEVLT) and Digit Symbol Substitution Test. SEVLT and Digit Symbol Substitution Test were reassessed 5 years later (Y19) along with the Modified Mini-Mental State Exam. We examined cross-sectional and longitudinal associations between CAC and cognition among 1931 participants using linear and logistic regression. In unadjusted analyses, compared with no calcification, CAC score >300 was associated with decreased performance on all cognitive tests at Y14 in both sexes. Additionally, CAC >300 was associated with a greater 5-year decline in SEVLT Immediate Recall in both sexes and SEVLT Delayed Recall in women. After adjustment for demographic, genetic, metabolic, vascular, and behavioral covariates, CAC score >300 remained associated with greater decline in only SEVLT Delayed Recall in women. Conclusions In women with prediabetes or diabetes, CAC >300, compared with no calcification, was independently associated with greater decline in verbal memory. Registration information clinicaltrials.gov. Identifier: NCT00038727.

H2SO4 assisted hydrothermal conversion of biomass with solid acid catalysis to produce aviation fuel precursors.

With hydrothermal reaction, lignocellulosic biomass can be efficiently converted into furfural (FF) and levulinic acid (LA), both of which are key platform compounds that can be used for the subsequent preparation of aviation fuels. In order to reduce the acid concentration in traditional hydrolysis and provide a reaction system with good catalytic activity, we propose a biomass conversion route as dilute acid hydrolysis coupled with solid acid catalysis. Firstly, at different temperatures, the hemicellulose and cellulose in corn stover were step-hydrolyzed by sulfuric acid solution with a concentration of 0.9 wt. % to produce xylose and glucose, with conversion reaching 100% and 97.3%, respectively. Subsequently, a new resin-derived carbon-based solid acid catalyst was used to catalyze the aforementioned saccharide solutions to obtain FF with yield of 68.7 mol % and LA of 70.3 mol %, respectively. This work provides a promising approach for the efficient production of bio-aviation fuel precursors.

Endoscopic characteristics and high-risk background mucosa factors of early gastric cancer after helicobacter pylori eradication: a single-center retrospective study.

Purpose: Gastric cancer still develops after successful Helicobacter pylori(Hp)eradication. In this study, we aimed to explore the characteristics and risks of mucosal factors. Methods: A total of 139 early gastric cancers (EGC) diagnosed in 133 patients after successful eradication from January 2016 to December 2021 were retrospectively included in the Hp-eradication EGC group and 170 EGCs diagnosed in 158 patients were included in the Hp-positive EGC group. We analyzed the clinical, pathological, and endoscopic characteristics between the two groups to identify the features of EGC after Hp eradication. Another 107 patients with no EGC after Hp eradication were enrolled in a Hp-eradication non-EGC group. The background mucosal factors between the Hp-eradication EGC group and the Hp-eradication non-EGC group were compared to analyze the high-risk background mucosal factors of EGC after eradication. In addition, we divided the EGC group after Hp eradication into IIc type and non-IIc type according to endoscopic gross classification to assess the high-risk background factors of IIc-type EGC after Hp eradication. Results: The endoscopic features of EGC after Hp eradication included location in the lower part of the stomach (p=0.001), yellowish color (p= 0.031), and smaller size (p=0.001). The moderate/severe gastric atrophy (GA), intestinal metaplasia (IM) in the corpus, severe diffuse redness, and map-like redness were risk factors for EGC after eradication (p=0.001, p=0.001, p=0.001, and p= 0.005, respectively). The Kyoto classification total score in the EGC group was higher than the non-EGC group (4 vs.3 p<0.001). A multivariate analysis revealed that depressed erosion (OR=3.42, 95% CI 1.35-8.65, p= 0.009) was an independent risk factor for IIc-type EGC after Hp eradication. Conclusion: EGC after eradication are smaller and yellowish lesions located in the lower part of the stomach. The risk background mucosal factors include moderate/severe GA, IM in the corpus, severe diffuse redness, and map-like redness. The Kyoto classification total score of 4 or more after successful eradication treatment might indicate EGC risk. In addition, the IIc-type EGC should be cautioned in the presence of depressed erosion after Hp eradication.

AP2XII-1 is a negative regulator of merogony and presexual commitment in Toxoplasma gondii.

IMPORTANCE: Sexual development is vital for the transmission, genetic hybridization, and population evolution of apicomplexan pathogens, which include several clinically relevant parasites, such as Plasmodium, Eimeria, and Toxoplasma gondii. Previous studies have demonstrated different morphological characteristics and division patterns between asexual and sexual stages of the parasites. However, the primary regulation is poorly understood. A transition from the asexual to the sexual stage is supposedly triggered/accompanied by rewiring of gene expression and controlled by transcription factors and chromatin modulators. Herein, we discovered a tachyzoite-specific transcriptional factor AP2XII-1, which represses the presexual development in the asexual tachyzoite stage of T. gondii. Conditional knockdown of AP2XII-1 perturbs tachyzoite proliferation by endodyogeny and drives a transition to a morphologically and transcriptionally distinct merozoite stage. The results also suggest a hierarchical transcriptional regulation of sexual development by AP2 factors and provide a path to culturing merozoites and controlling inter-host transmission of T. gondii.

Ultrasonic-pretreated hydrothermal synthesis of less dense zeolite CHA from the transformation of zeolite T.

Because of containing the same double 6-ring (D6R) building unit, the pure zeolite CHA with lower framework density (FDSi = 15.1 T/1000 Å3) has been transformed from zeolite T with higher framework density (FDSi = 16.1 T/1000 Å3) through ultrasonic-pretreated hydrothermal synthesis in MOH (KOH and NaOH) solution without adding organic template or seed crystals. Ultrasonic pretreatment facilitates the transformation rate and generates high-quality zeolite CHA. The ultrasound condition should be precisely controlled because that CHA phase is metastable, which is inclined to transform to other more stable phase. The ultrasonic conditions at 313 K and 333 K have been investigated in detail. In KOH solution, the ultrasonic treatment at 313 K can effectively restrain the generation of MER phase, however, it is hard to avoid the existence of MER phase when ultrasound temperature is 333 K. In NaOH solution, the samples with ultrasonic treatment of 313 K show the small particles size of about 1 µm, and the GIS framework topology starts to grow with the ultrasonic treatment of 333 K. The products prepared with the appropriate ultrasonic pretreatment represents smaller particles size, larger mesopore volume and higher CO2 adsorption capacity than the sample without the ultrasonic pretreatment. The structural evolution of interzeolite transformation has been explored by XRD, FT-IR and SEM observations. With the assistance of ultrasound, the parent zeolite T can quickly decompose into intermediate phase and then regenerate into CHA phase.

Bacillus sp. YC7 from intestines of Lasioderma serricorne degrades nicotine due to nicotine dehydrogenase.

A large number of nicotine-containing wastes produced during the tobacco manufacturing process are seriously harmful to the environment and human health. The degradation and transformation of nicotine-containing environmental contaminants to harmless substances has become an urgent requirement. Lasioderma serricorne can grow and reproduce in nicotine-rich sources, and their intestinal microbiota show promising potential to degrade and utilize nicotine. The purpose of this study is to screen and identify nicotine-degrading bacteria from the intestines of L. serricorne and explore their degradation characteristics. A dominant strain, YC7, with significant nicotine degradation capabilities was isolated from the intestines of L. serricorne. The strain was identified as Bacillus using a polyphasic approach. The test results showed it can produce multiple enzymes that include ß-glucosidase, cellulase, proteases, and amylases. The nicotine-degrading bacteria were functionally annotated using databases. Nicotine dehydrogenase (NDH) was found by combining an activity tracking test and protein mass spectrometry analysis. The YC-7 NDH in the pathway was molecularly docked and functionally verified via the gene knockdown method. The binding ability of nicotine to nicotine-degrading enzymes was investigated using molecular docking. A high-efficiency nicotine-degrading bacteria, YC-7, was isolated and screened from tobacco, and the gene functions related to degradation were verified. This investigation provides a new hypothesis for screening nicotine-degrading bacteria and increases our knowledge of potential nicotine-degrading microbial sources.

CaFANet: Causal-Factors-Aware Attention Networks for Equipment Fault Prediction in the Internet of Things.

Existing fault prediction algorithms based on deep learning have achieved good prediction performance. These algorithms treat all features fairly and assume that the progression of the equipment faults is stationary throughout the entire lifecycle. In fact, each feature has a different contribution to the accuracy of fault prediction, and the progress of equipment faults is non-stationary. More specifically, capturing the time point at which a fault first appears is more important for improving the accuracy of fault prediction. Moreover, the progress of the different faults of equipment varies significantly. Therefore, taking feature differences and time information into consideration, we propose a Causal-Factors-Aware Attention Network, CaFANet, for equipment fault prediction in the Internet of Things. Experimental results and performance analysis confirm the superiority of the proposed algorithm over traditional machine learning methods with prediction accuracy improved by up to 15.3%.

Efficacy and safety of epigallocatechin-3-gallate in treatment acute severe dermatitis in patients with cancer receiving radiotherapy: a phase I clinical trial.

To evaluate the safety and effectiveness of epigallocatechin-3-gallate (EGCG) solution treating the acute severe dermatitis in patients receiving radiotherapy. This phase I research enrolled patients with thoracic cancer receiving radiotherapy at Shandong Cancer Hospital and Institute in Shandong, China. EGCG solution was sprayed to the radiation field when grade III radiation-induced dermatitis (RID) first appearance. EGCG concentration escalated from 660 to 2574 µmol/L using modified-Fibonacci dose-escalation. RID and related symptoms were followed up every day. Between March 2021 and November 2021, 19 patients were enrolled in this phase I research. The median dose of grade III RID first observation was 44 Gy (30.6-52 Gy). As the EGCG treatment was performed continuously, all these grade III RID reactions were significantly decreased to grade I or grade II RID at three days after use of EGCG (p < 0.001). Significant relief can be observed in burning sensation (p < 0.001), tractive sensation (p < 0.001), tenderness (p < 0.001), erythema (p < 0.001), itching (p < 0.001) and pain (p < 0.001) after 15 days of EGCG treatment. No radiation therapy delay or interruption for all 19 patients. No adverse events were observed and reported associated with EGCG. The highest dose of this Phase I trial (2574 µmol/L) was recommended for continuous Phase II trial for further evaluation. In this phase I clinical research, use of EGCG solution is safe and can significantly relief grade III RID in patients receiving radiotherapy. Thus, EGCG might be a new choice for acute sever RID.Trial Registration: ClinicalTrials.gov Identifier: NCT02580279 (Full date of first registration: 12/2014).

Characteristic analysis of early gastric cancer after Helicobacter pylori eradication: a multicenter retrospective propensity score-matched study.

BACKGROUND: Helicobacter pylori (H. pylori) is recognized as a type I carcinogen in gastric cancer (GC). However, GC still occurs after H. pylori eradication, and its diagnosis is more complicated. This study aimed to summarize the characteristics of early GC (EGC) after H. pylori eradication to help accurately identify EGC and avoid missed diagnosis and misdiagnosis. METHODS: A total of 81 patients of EGC after H. pylori eradication (Hp-eradicated group), resected by endoscopic submucosal dissection (ESD), and 105 cases of H. pylori infection-related EGC (control group) were assessed. After propensity-score matching, the clinical characteristics, endoscopic manifestations, and histopathological features of the 62 matched patients in each group were analyzed. We also conducted specific analyses in combination with endoscopic and histopathological images. RESULTS: There were more patients in the Hp-eradicated group who received proton pump inhibitor (PPI) for >1 year compared to the control group (p < 0.001). More patients at OLGA stages I-II before the diagnosis of EGC were in the control group (p = 0.045), especially at stage II. The mucosa in the Hp-eradicated group showed more moderate-to-severe atrophy (p = 0.047), map-like redness (p < 0.001) and mild activity (p < 0.001). The predominant histopathological types differed between the two groups (p < 0.001), and the majority of cases in the Hp-eradicated group were high-grade intraepithelial neoplasia (HGIN). Ki-67 expression was lower in the Hp-eradicated group (p = 0.025). But different eradication intervals of H. pylori have little effect on the characteristics of EGC. Furthermore, PPI uses for >1 year (p = 0.005), mucosal map-like redness (p < 0.001), moderate mucosal atrophy (p = 0.017), and mild activity of gastric mucosa (p = 0.005) were independent characteristics of EGC after H. pylori eradication. CONCLUSION: Our multicenter study revealed that EGC after H. pylori eradication was characterized by long-term PPI use, moderate mucosal atrophy, mucosal map-like redness, the mild activity of gastric mucosa, a higher proportion of HGIN cases, and lower levels of Ki-67.

EGC after H. pylori eradication was characterized by long-term PPI use, moderate mucosal atrophy, mucosal map-like redness, mild activity of gastric mucosa, a higher proportion of HGIN cases, and lower levels of Ki-67.H. pylori-positive patients at OLGA stages I-II are also more likely to progress to EGC.According to the current data, different eradication intervals of H. pylori have little effect on the characteristics of EGC.

Analysis of spatial perception and the influencing factors of attractions in Southwest China's ethnic minority areas: The case of Dali Bai Autonomous Prefecture.

As standards of material living continue to improve and urbanization advances, an increasing number of remote ethnic minority areas are becoming tourist destinations. Understanding tourists' perceptions on a large scale is thus crucial for the development of the regional tourism industry. However, traditional research methods suffer from high costs, small sample sizes, and low efficiency, making it difficult to measure the spatial perception of remote areas on a large scale. This study constructs a research framework for spatial perception measurement of remote ethnic minority areas by collecting reviews data from Ctrip using spatiotemporal data calculation and the Geodetector model. We considered Dali Prefecture as an empirical case and analyzed tourists' perceptions of the area's attractions, the spatial distribution of the attractions, and the process of change in the explanatory power of their influencing factors over an eight-year period (2014-2021). The results indicated that the most visited attractions were concentrated in Dali City. The perception of humanistic resources (attractions) with historical value was the highest, followed by natural resources. The high perception of attractions was influenced by the level of tourism development, traffic accessibility and attractiveness, and had an increasing influence on tourists' perceptions over time. Additionally, changes in the mode of transportation from road to high-speed rail played an important role in the selection of tourist attractions. Conversely, the tourists paid relatively less attention to humanistic resources (e.g., national cultural heritage protection units and traditional villages). Our study provides a basis for the measurement of spatial perception in remote minority areas and can be used as a reference for tourism development planning in Dali Prefecture, thus promoting the sustainable development of tourism in the area.

Evaluation of a multiphasic parasite clearance profile after treatment of experimental human infection with the investigational anti-malarial M5717 using segmented mixed effect models.

BACKGROUND: Evaluation of parasite clearance patterns in experimental human infection trials helps increase understanding of drug action. In a previously reported phase Ib trial of a new investigational anti-malarial drug M5717, parasite clearance showed a biphasic linear pattern: slow removal phase with a near flat clearance rate followed by a fast clearance phase with a steep slope. In this study three statistical approaches were implemented and compared to estimate the parasite clearance rate for each phase and the time point corresponding to the change of clearance rates (changepoint between the two phases). METHODS: Data using three M5717 doses 150 mg (n = 6), 400 mg (n = 8), 800 mg (n = 8) were used to estimate biphasic clearance rates. Three models were investigated: firstly, segmented mixed models with estimated changepoint-models with/without random effects in various parameters were compared. Secondly, a segmented mixed model using grid search-this method is similar to the first except that changepoints were not estimated, instead they were selected based on model fit from given candidate values. Thirdly, a two-stage approach whereby a segmented regression model fit to each participant followed by a meta-analysis method. Hourly rate of parasite clearance (HRPC) interpreted as the percentage of parasites removed each hour was calculated. RESULTS: The three models generated similar results. Using segmented mixed models, the estimated changepoints after treatment in hours (95% CI) were: 150 mg: 33.9 (28.7, 39.1); 400 mg: 57.4 (52.5, 62.4); and 800 mg: 52.8 (47.4, 58.1). For all three treatment groups, there was nearly no clearance before the changepoints, but rapid clearance in the second phase (HRPC [95% CI]): 150 mg: 16.8% (14.3, 19.1%); 400 mg: 18.6% (16.0, 21.1%); and 800 mg: 11.7% (9.3, 14.1%). CONCLUSIONS: All three statistical approaches are effective tools to characterize the bi-phasic clearance of M5717 in the phase 1b experimental Plasmodium falciparum malaria human infection study. The statistical approaches produced similar results to estimate the two-phase clearance rates and the changepoint for each treatment dose of M5717. However, the segmented mixed model with random changepoints has several advantages: it is computationally efficient, provides precision for changepoint estimates and is robust concerning outlying datapoints or individuals.