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Xingzhi Li,1,2,&ast; Zhihong Tang,1,&ast; Qingqing Pang,1,&ast; Xiaobo Wang,1 Tao Bai,1 Jie Chen,1 Meng Wei,1 Tao Wei,1 Lequn Li,1 Feixiang Wu1,3 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Hepatobiliary Surgery, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College, Nanchong, People’s Republic of China; 3Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feixiang Wu; Lequn Li, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of China, Email wufeixiang@gxmu.edu.cn; lilequngx@163.comBackground: The prognosis of initially unresectable hepatocellular carcinoma (iuHCC) has been improved by TACE with TKIs and PD-1 inhibitors (TTP). However, the role of timing of tumor progression and and early salvage surgery during TTP therapy remains unclear.Patients and Methods: The data of 151 patients who received TTP for iuHCC consecutively between November 2019 and December 2022 were retrospectively analyzed. The X-Tile software was used to determine the optimal threshold of progression timing to differentiate the post-progression survival (PPS) for patients with tumor progression, ultimately yielding 9 months as the optimal cut-off time. Early tumor progression was defined as patients with tumor recurrence (surgical patients) or progressive disease by mRECIST (nonsurgical patients) within 9 months of initial treatment. Accordingly, early salvage surgery was defined as salvage surgery performed within 9 months of the initial treatment.Results: Out of all the patients, 55 (36.4%) patients showed early tumor progression, 33 (34.4%) showed late tumor progression, and 63 (41.7%) showed non-progression. Patients who experienced early tumor progression had a median PPS of 5.2 months, while those with late tumor progression had a median PPS of 16.8 months (P < 0.001). Multivariable analysis revealed a robust independent correlation between early tumor progression and PPS (HR = 3.279, 95% CI: 1.591– 6.756; P = 0.001). Patients who received early salvage surgery showed a considerably lower early tumor progression rate when compared with patients who did not receive early surgery (12.5% vs 42.9%, P = 0.002). The multivariable analysis revealed that early salvage surgery was an independent factor influencing early tumor progression (OR = 0.246; 95% CI: 0.078– 0.773; P = 0.016).Conclusion: Early tumor progression is associated with worse PPS in patients with iuHCC receiving TTP therapy. Early salvage surgery can further improve patient outcomes by lowering the incidence of early progression.Keywords: Hepatocellular carcinoma, salvage surgery, early tumor progression, post-progression survival, real-world

Liguo Lu,1,2 Chengdong Zhu,3 Jian Xu,4 Yulan Hu,2 Juxiang Dai,2 Sheng Wang,2 Tao Wei1,5 1Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Shuyang Hospital, The Affiliated Shuyang Hospital of Xuzhou Medical University, Suqian, People’s Republic of China; 3Department of Traditional Chinese Medicine, Shuyang Hospital, The Affiliated Shuyang Hospital of Xuzhou Medical University, Suqian, People’s Republic of China; 4Taian Maternal and Child Health Hospital, Tai An, Shandong, People’s Republic of China; 5Public Experimental Research Center, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Tao Wei, 209 Tongshan Road, Xuzhou City, Jiangsu Province, People’s Republic of China, Tel +8613815303574, Email weitaoxy@126.comIntroduction: The Lifei Decoction (LD) is a commonly utilized Chinese medicine for the treatment of sepsis and bronchial inflammation. However, its therapeutic potential in chronic obstructive pulmonary disease (COPD) remains unknown. Therefore, the objective of this study was to investigate the therapeutic efficacy and underlying mechanism of LD in a mouse model of COPD induced by cigarette smoke (CS) combined with lipopolysaccharide (LPS).Methods: Hematoxylin-eosin (H&E) staining was employed to observe the pathological alterations in lung tissue, while ELISA was utilized for the detection of levels of inflammatory factors in both lung tissue and bronchoalveolar lavage fluid (BALF). Additionally, Western blot analysis was conducted to assess the expression of p-NF-κB, GDF11, ZO-1, and Occludin-1 proteins. The changes in intestinal flora were evaluated using the viable bacteria count method.Results: The administration of LD demonstrates significant efficacy in mitigating pulmonary tissue damage in a murine model, while concurrently inhibiting the activation of the inflammatory pathway NF-κB to attenuate the levels of pro-inflammatory factors. Moreover, LD exhibits the capacity to enhance the expression of intestinal functional proteins ZO-1 and Occludin-1, thereby rectifying dysbiosis within the gut microbiota.Conclusion: The LD shows great promise as a potential treatment for COPD.Keywords: COPD, lifei decoction, inflammation, intestinal flora

Cong Xia,1 Ting Wei,2,3 Qi Tang,2,3 Hongying Zheng,2,3 Mei Sun,2,3 Gang Chen,2,3 Jun Lv2,3 1School of Health Management Anhui Medical University, Hefei, People’s Republic of China; 2School of Public Health, Fudan University, Shanghai, People’s Republic of China; 3China Research Center on Disability, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Gang Chen; Jun Lv, School of Public Health, Fudan University, 130 Dong’an Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86-13661432703 ; +86-13671684324, Email gchen@shmu.edu.cn; lujun@shmu.edu.cnPurpose: To investigate the family support, anxiety, depression, health-related quality of life (HRQoL), and their associations among parents and grandparents of children with disabilities.Methods: This is a cross-sectional study and a total of 327 family caregivers were included. Chi-square test, Mann–Whitney U-test, and two independent t-test were used to identify the intergenerational differences in sociodemographic characteristics, received family support, anxiety, depression, and HRQoL. Eight generalized linear models were developed to examine the associations in both generations.Results: Parents and grandparents were most in need of rehabilitation and financial support, but both populations received the least amount of financial support. 33.6% and 36.1% of family caregivers had the risk of anxiety and depression and found no significant intergenerational differences. As for HRQoL, intergenerational differences were found in the physical component score, but not found in the mental component score. Among parents, childcare support of respite care and household tasks assistance was negatively associated with their depression (p< 0.05), professional support of appropriate surgery for children (p< 0.05) and psychological support from professional psychologists (p< 0.01) were negatively associated with their anxiety and depression, psychological support from relatives and friends was negatively associated with their depression (p< 0.05) whereas was positively associated with their mental HRQoL (p< 0.01). As for grandparents, financial support for daily living expenses was negatively associated with depression (p< 0.05), and psychological support from families was negatively associated with depression (p< 0.05) whereas was positively associated with mental HRQoL (p< 0.05). However, no relationship was found between family support and anxiety among grandparents. Notably, no association was found between family support and physical HRQoL among both populations.Conclusion: Both parents and grandparents had high risks of anxiety, depression and low levels of mental HRQoL. To efficiently improve psychological health, care providers and policymakers may consider intergenerational differences and provide targeted family support.Keywords: mental health, health-related quality of life, family support, children with disabilities, intergenerational differences

Zhichao Xing,1,&ast; Anping Su,1,&ast; Li Mi,1 Yujie Zhang,1 Ting He,1 Yuxuan Qiu,2 Tao Wei,1 Zhihui Li,1 Jingqiang Zhu,1 Wenshuang Wu1 1Division of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingqiang Zhu; Wenshuang Wu, Division of Thyroid Surgery, Department of General Surgery and Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China, Email zhujingqiang@scu.edu.cn; wenshuang_wu@163.comAbstract: Cancer, as the leading cause of death worldwide, poses a serious threat to human health, making the development of effective tumor treatments a significant challenge. Natural products continue to serve as crucial resources for drug discovery. Among them, Withaferin A (WA), the most active phytocompound extracted from the renowned dietary supplement Withania somnifera (L.) Dunal, exhibits remarkable anti-tumor efficacy. In this manuscript, we aim to comprehensively summarize the pharmacological characteristics of WA as a potential anti-tumor drug candidate, with the objective of contributing to its further development and the discovery of prospective drugs. Through an extensive review of literature from PubMed, Science Direct, and Web of Science, we have gathered substantial evidence showcasing WA’s significant anti-tumor effects against a wide range of cancers in both in vitro and in vivo studies. Mechanistically, WA exerts its anti-tumor influence by inducing cell cycle arrest, apoptosis, autophagy, and ferroptosis. Additionally, it inhibits cell proliferation, cancer stem cells, tumor metastasis, and also suppresses epithelial-mesenchymal transition (EMT) and angiogenesis. Several studies have identified direct target proteins of WA, such as vimentin, Hsp90, annexin II and mFAM72A, while BCR-ABL, Mortalin (mtHsp70), Nrf2, and c-MYB are potential targets of WA. Notwithstanding its remarkable anti-tumor efficacy, there are some limitations associated with WA, including potential toxicity and poor oral bioavailability, which need to be addressed when considering it as an anti-tumor candidate agent. Nevertheless, I given its promising anti-tumor attributes, WA remains an encouraging candidate for future drug development. Unveiling the exact target and comprehensive mechanism of WA’s action represents a crucial research direction to pursue in the future.Graphical Abstract: Keywords: Withaferin A, Withania somnifera, dietary supplement, anti-cancer activity, pharmacological mechanism, direct target

Tianjun Wei,1,2 Wei Wei,2 Qiang Ma,2 Zhongbing Shen,2 Kebing Lu,2 Xiangming Zhu1,2 1School of Continuing Education, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2Department of Ultrasound, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, People’s Republic of ChinaCorrespondence: Xiangming Zhu, School of Continuing Education, Anhui Medical University, NO. 81 Meishan Road, Shushan District, Hefei City, Anhui Province, 230032, People’s Republic of China, Tel +86 553-5739808, Email xiangmingzhudr@yeah.netBackground and Objectives: Papillary thyroid carcinoma (PTC) is a prevalent histological type of thyroid cancer; however, noninvasive assessment of cervical lymph node metastasis (LNM) poses a challenge. This study aims to develop a novel clinical-radiomics nomogram that utilizes ultrasound (US) images to predict the presence of cervical LNM metastasis in patients with PTC.Methods: A total of 423 patients with PTC were recruited to participate in this study between January 2020 and December 2022, of which 282 were classified into the training group and 141 patients were classified into the validation set. Contrast-enhanced ultrasound (CEUS) and B-mode ultrasound (BMUS) images were subjected to radiomic analysis, leading to the extraction of 912 radiomic features. Thereafter, a radiomics score (Radscore) was developed to effectively integrate the information derived from BMUS and CEUS modalities. Univariate and multivariate backward stepwise logistic regression analysis techniques were used to construct the clinical and clinical-radiomics models, respectively.Results: The findings revealed that the clinical-radiomics nomogram incorporated age, sex, CEUS Radscore, and US-reported LNM as risk factors. The nomogram demonstrated good performance using data from the training (AUC = 0.891) and validation (AUC = 0.870) sets. The decision curve analysis implied that this nomogram exhibited good clinical utility, which was further supported by the results of the calibration curves and Hosmer-Lemeshow test.Conclusion: The CEUS Radscore-based clinical radiomics nomogram could serve as a valuable tool for predicting cervical LNM metastasis in patients with PTC, thereby tailoring individualized treatment strategies for them.Keywords: lymph node metastasis, radiomics, papillary thyroid carcinoma, contrast-enhanced ultrasound, B-mode ultrasound

Yuliang Shi,1,2 Yuxian Yang,1,2 Miaoling Feng,1,2 Weihan Ling,1,2 Tongguo Wei,1,2 Yumin Cao,1,2 Rui Zhong,1,2 Heming Wu2 1Department of Neurology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Center for Precision Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Heming Wu, Center for Precision Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email wuheming1986@126.comBackground: Cytochrome P450 2C19 (CYP2C19) genotypes and metabolic phenotypes (extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM)) are related to the metabolism of therapeutic drugs for cardiovascular and cerebrovascular diseases. This study aimed to investigate the differences of CYP2C19 gene polymorphism distribution between coronary artery disease (CAD) patients and cerebral infarction (CI) patients.Methods: We identified 413 CI patients, 509 CAD patients, and 241 CI+CAD patients from 2016 to 2020 and studied genotypes of CYP2C19 rs4986893 (636G>A) and rs4244285 (681G>A) polymorphisms using PCR-gene chip detection method. Differences in CYP2C19 genotypes and metabolic phenotypes between the groups were compared. To analyze the efficacy of CYP2C19 metabolic phenotypes in discriminating between cerebral infarction and coronary artery disease, multiple logistic regression analysis was conducted after adjusting for gender, age, smoking history, drinking history, hypertension, and diabetes.Results: There were significant differences in the distribution of CYP2C19 genotypes and metabolic phenotypes between CI and CAD patients. The results of multivariate logistic regression (adjusted for sex, age, smoking, drinking, hypertension, and diabetes) indicated that CYP2C19 IM phenotype (IM vs EM: OR 1.443, 95% CI: 1.086– 1.918, P=0.011) and CYP2C19 IM+PM phenotype (IM or PM vs EM: OR 1.440, 95% CI: 1.100– 1.885, P=0.008) may be indicators of CI from CAD.Conclusion: CYP2C19 EM metabolic phenotype was dominant in CAD patients, and CYP2C19 IM metabolic phenotype was dominant in CI patients. After adjusting for other confounding factors, patients with the CYP2C19 IM metabolic phenotype were more likely to develop CI than CAD.Keywords: CYP2C19, genotype, metabolic phenotype, cerebral infarction, coronary artery disease

Shuang Qu,1,&ast; Xiaoli Huang,2,&ast; Xiaoling Guo,3 Zhihai Zheng,1 Tiannan Wei,1 Biyun Chen1 1Department of Hematology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 2Department of Clinical Laboratory Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 3Translational Medicine Centre, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuang Qu, Email shuangerqu@163.comBackground: Acute myeloid leukemia (AML) is a highly heterogenous disease with varying clinical outcomes among patients. Epithelial-mesenchymal transition (EMT) is an important mechanism underlying cancer metastasis and chemotherapy resistance. However, few EMT-based signatures have been established to predict AML prognosis and treatment efficacy.Methods: By conducting comparative RNA-seq analysis, we discovered the differential expression of EMT genes between AML patients with relapse and those without relapse. Based on the prognostic analysis of the differentially expressed EMT genes, a metastasis-related EMT signature (MEMTs) was constructed. An analysis was conducted on both TARGET and TCGA cohorts to explore the possible association between MEMTs and prognosis in AML. Three separate chemotherapy treatment cohorts were utilized to assess the predictive efficacy of MEMTs for chemotherapy response. In addition, the potential correlation between MEMTs and the tumor microenvironment was also investigated. Finally, random forest analysis and functional experiments were conducted to verify the key MEMTs gene associated with AML metastasis.Results: Based on expression and prognostic analysis, we constructed MEMTs that include three EMT genes (CDH2, LOX, and COL3A1). Our findings suggested that the MEMTs could act as a prognostic factor for AML patients, and furthermore, it proved to be a predictor of their response to chemotherapy. Specifically, high MEMTs was associated with worse prognosis and poor response to chemotherapy, while low MEMTs was linked to better prognosis and higher response rates. Random forest and functional experiments demonstrate that CDH2 is a key gene promoting leukemia cell metastasis among the three MEMTs genes.Conclusion: The identification of MEMTs could potentially act as a predictor for the prognosis and the response to chemotherapy in AML patients. Individual tumor evaluation based on MEMTs could provide personalized treatment options for AML patients in the future.Keywords: acute myeloid leukemia, prognosis, metastasis, epithelial-mesenchymal transition, chemotherapy

ObjectiveThe A6702 multisite trial confirmed that apparent diffusion coefficient (ADC) measures can improve breast MRI accuracy and reduce unnecessary biopsies, but also found that technical issues rendered many lesions non-evaluable on diffusion-weighted imaging (DWI). This secondary analysis investigated factors affecting lesion evaluability and impact on diagnostic performance.MethodsThe A6702 protocol was IRB-approved at 10 institutions; participants provided informed consent. In total, 103 women with 142 MRI-detected breast lesions (BI-RADS assessment category 3, 4, or 5) completed the study. DWI was acquired at 1.5T and 3T using a four b-value, echo-planar imaging sequence. Scans were reviewed for multiple quality factors (artifacts, signal-to-noise, misregistration, and fat suppression); lesions were considered non-evaluable if there was low confidence in ADC measurement. Associations of lesion evaluability with imaging and lesion characteristics were determined. Areas under the receiver operating characteristic curves (AUCs) were compared using bootstrapping.ResultsThirty percent (42/142) of lesions were non-evaluable on DWI; 23% (32/142) with image quality issues, 7% (10/142) with conspicuity and/or localization issues. Misregistration was the only factor associated with non-evaluability (P = 0.001). Smaller (≤10 mm) lesions were more commonly non-evaluable than larger lesions (p

Background The Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Cancer Research Group A6702 multicenter trial helped confirm the potential of diffusion-weighted MRI for improving differential diagnosis of suspicious breast abnormalities and reducing unnecessary biopsies. A prespecified secondary objective was to explore the relative value of different approaches for quantitative assessment of lesions at diffusion-weighted MRI. Purpose To determine whether alternate calculations of apparent diffusion coefficient (ADC) can help further improve diagnostic performance versus mean ADC values alone for analysis of suspicious breast lesions at MRI. Materials and Methods This prospective trial (ClinicalTrials.gov identifier: NCT02022579) enrolled consecutive women (from March 2014 to April 2015) with a Breast Imaging Reporting and Data System category of 3, 4, or 5 at breast MRI. All study participants underwent standardized diffusion-weighted MRI (b = 0, 100, 600, and 800 sec/mm2). Centralized ADC measures were performed, including manually drawn whole-lesion and hotspot regions of interest, histogram metrics, normalized ADC, and variable b-value combinations. Diagnostic performance was estimated by using the area under the receiver operating characteristic curve (AUC). Reduction in biopsy rate (maintaining 100% sensitivity) was estimated according to thresholds for each ADC metric. Results Among 107 enrolled women, 81 lesions with outcomes (28 malignant and 53 benign) in 67 women (median age, 49 years; interquartile range, 41-60 years) were analyzed. Among ADC metrics tested, none improved diagnostic performance versus standard mean ADC (AUC, 0.59-0.79 vs AUC, 0.75; P = .02-.84), and maximum ADC had worse performance (AUC, 0.52; P < .001). The 25th-percentile ADC metric provided the best performance (AUC, 0.79; 95% CI: 0.70, 0.88), and a threshold using median ADC provided the greatest reduction in biopsy rate of 23.9% (95% CI: 14.8, 32.9; 16 of 67 BI-RADS category 4 and 5 lesions). Nonzero minimum b value (100, 600, and 800 sec/mm2) did not improve the AUC (0.74; P = .28), and several combinations of two b values (0 and 600, 100 and 600, 0 and 800, and 100 and 800 sec/mm2; AUC, 0.73-0.76) provided results similar to those seen with calculations of four b values (AUC, 0.75; P = .17-.87). Conclusion Mean apparent diffusion coefficient calculated with a two-b-value acquisition is a simple and sufficient diffusion-weighted MRI metric to augment diagnostic performance of breast MRI compared with more complex approaches to apparent diffusion coefficient measurement. © RSNA, 2020 Online supplemental material is available for this article.

Abstract Patient-derived xenograft (PDX) models of breast cancer are an effective discovery platform and tool for preclinical pharmacologic testing and biomarker identification. We established orthotopic PDX models of triple negative breast cancer (TNBC) from the primary breast tumors of patients prior to and following neoadjuvant chemotherapy (NACT) while they were enrolled in the ARTEMIS trial (NCT02276443). Serial biopsies were obtained from patients prior to treatment (pre-NACT), from poorly responsive disease after four cycles of Adriamycin and cyclophosphamide (AC, mid-NACT), and in cases of AC-resistance, after a 3-month course of different experimental therapies and/or additional chemotherapy (post-NACT). Our study cohort includes a total of 269 fine needle aspirates (FNAs) from 217 women, generating a total of 62 PDX models (overall success-rate = 23%). Success of PDX engraftment was generally higher from those cancers that proved to be treatment-resistant, whether poorly responsive to AC as determined by ultrasound measurements mid-NACT (p = 0.063), RCB II/III status after NACT (p = 0.046), or metastatic relapse within 2 years of surgery (p = 0.008). TNBC molecular subtype determined from gene expression microarrays of pre-NACT tumors revealed no significant association with PDX engraftment rate (p = 0.877). Finally, we developed a statistical model predictive of PDX engraftment using percent Ki67 positive cells in the patient’s diagnostic biopsy, positive lymph node status at diagnosis, and low volumetric reduction of the patient’s tumor following AC treatment. This novel bank of 62 PDX models of TNBC provides a valuable resource for biomarker discovery and preclinical therapeutic trials aimed at improving neoadjuvant response rates for patients with TNBC.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype.

Patients with advanced cancers are treated with combined radiotherapy and chemotherapy, however curability is poor and treatment side effects severe. Drugs sensitizing tumors to radiotherapy have been developed to improve cell kill, but tumor specificity remains challenging. To achieve tumor selectivity of small molecule radiosensitizers, we tested as a strategy active tumor targeting using peptide-based drug conjugates. We attached an inhibitor of the DNA damage response to antibody or cell penetrating peptides. Antibody drug conjugates honed in on tumor overexpressed cell surface receptors with high specificity but lacked efficacy when conjugated to the DNA damage checkpoint kinase inhibitor AZD7762. As an alternative approach, we synthesized activatable cell penetrating peptide scaffolds that accumulated within tumors based on matrix metalloproteinase cleavage. While matrix metalloproteinases are integral to tumor progression, they have proven therapeutically elusive. We harnessed these pro-tumorigenic extracellular proteases to spatially guide radiosensitizer drug delivery using cleavable activatable cell penetrating peptides. Here, we tested the potential of these two drug delivery platforms targeting distinct tumor compartments in combination with radiotherapy and demonstrate the advantages of protease triggered cell penetrating peptide scaffolds over antibody drug conjugates to deliver small molecule amine radiosensitizers.

Weiwei Wang, Ting Wei, Suihuai Yu, Jian Chen, Xiaoyan Yang College of Art and Design, Shaanxi University of Science and Technology, Xi’an City, People’s Republic of ChinaCorrespondence: Ting Wei, College of Art and Design, Shaanxi University of Science and Technology, Xi’an City, People’s Republic of China, Email wt@joya.cnIntroduction: The telecommuting experience and job performance have been significantly impacted by the COVID-19 pandemic, and job performance stability of telecommuting employees has become a critical concern.Objective: A decision model for telecommuting experience service design was constructed based on a backpropagation (BP) neural network to provide a theoretical basis for enterprises to evaluate telework performance and the psychological health of employees.Methods: The analytic hierarchy process (AHP) was used to determine the core stakeholders. The grey relational analysis (GRA) method and the NASA Task Load Index (NASA-TLX) scale were used to measure the factors affecting employees’ telecommuting experience and job performance. A BP neural network relationship model of employees’ telecommuting experience was established to predict its impact on employees’ job performance.Results: Based on the model prediction results, a service system map was created, and the potential to enhance the telework performance of employees was evaluated.Discussion: It was concluded that the factors affecting the telecommuting experience were diverse, but emotions had the dominant influence. Significant positive correlations were found between emotional impact and temporal perception, execution difficulty, and communication barriers.Conclusion: The proposed decision model for telecommuting experience service design accurately predicted the impact of telecommuting efficiency, providing an effective approach for innovative remote management.Keywords: design decision, job performance, telecommuting experience, BP neural networks, NASA-TLX scale

Yansha Song,1,&ast; Xiaocen Wang,1,&ast; Ke Lang,1,&ast; Tingting Wei,1 Jinlong Luo,1 Yuanlin Song,1,2 Dong Yang1,2 1Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Yang; Yuanlin Song, Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, People’s Republic of China, Tel +86 21 64041990, Email yang.dong@zs-hospital.sh.cn; song.yuanlin@zs-hospital.sh.cnIntroduction: There were few studies on the mortality of severe community-acquired pneumonia (SCAP) in elderly people. Early prediction of 28-day mortality of hospitalized patients will help in the clinical management of elderly patients (age ≥ 65 years) with SCAP, but a prediction model that is reliable and valid is still lacking.Methods: The 292 elderly patients with SCAP met the criteria defined by the American Thoracic Society from 33 hospitals in China. Clinical parameters were analyzed by the use of univariable and multivariable logistic regression analysis. A nomogram to predict the 28-day mortality in elderly patients with SCAP was constructed and evaluated using the area under the receiver operating characteristic curve (AUC) and internally verified using the Bootstrap method.Results: A total of 292 elderly patients (227 surviving and 65 died within 28 days) were included in the analysis. Age, Glasgow score, blood platelet, and blood urea nitrogen values were found to be significantly associated with 28-day mortality in elderly patients with SCAP. The AUC of the nomogram was 0.713 and the calibration curve for 28-day mortality also showed high coherence between the predicted and actual probability of mortality.Conclusion: This study provides a nomogram containing age, Glasgow score, blood platelet, and blood urea nitrogen values that can be conveniently used to predict 28-day mortality in elderly patients with SCAP. This model has the potential to assist clinicians in evaluating prognosis of patients with SCAP.Keywords: severe community-acquired pneumonia, 28-day mortality prediction model, nomogram

Jie Qin,1,2 Chengyun Zou,2 Jianmin Tao,1 Tian Wei,1 Li Yan,1 Yufei Zhang,2 Haiying Wang1 1Department of Clinical Laboratory, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Medical Technology, Yueyang Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Haiying Wang, Email liang19961111@shutcm.edu.cnObjective: The prevalence and clinical impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection are unclear in elderly patients. Here, we aimed to clarify the prevalence, the clinical manifestations, antimicrobial resistance, risk factors and outcomes of elderly inpatients with CRPA infection.Methods: A retrospective study of 600 elderly inpatients infected with P. aeruginosa was conducted at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine from January 1st 2018 to December 31st 2020. All 155 patients with CRPA infection were designated as a case group. Patients with carbapenem-susceptible Pseudomonas aeruginosa (CSPA) were randomly selected from remaining 445 cases in a 1:1 ratio to case group as a control group.Results: Of 600 P. aeruginosa isolates, the overall rates of CRPA, MDR PA (multidrug-resistance Pseudomonas aeruginosa) were 25.8% (155), 22.3% (134), respectively. The rankings of the top five resistant rates of CRPA to tested antimicrobial drugs were imipenem (87.7%), meropenem (70.3%), ciprofloxacin (51.0%), levofloxacin (48.4%), cefoperazone (43.2%). Independent risk factors for patients with CRPA infection were cerebrovascular disease (OR = 3.517, P < 0.001), foley catheter (OR = 2.073, P = 0.018), length of hospital stay ≥ 14 days (OR = 1.980, P = 0.013), albumin < 35 g/L (OR = 2.049, P = 0.020), previous antibiotic exposure to carbapenems (OR = 7.022, P = 0.004), previous antibiotic exposure to third- or fourth-generation cephalosporins (OR = 12.649, P = 0.002). Of 155 patients with CRPA infection, the mortality rate was 16.8% (26/155). Independent risk factors for mortality were receiving mechanical ventilation (OR = 3.671, P = 0.007) and neutrophil percentage ≥ 80% (OR = 2.908, P = 0.024).Conclusion: The study revealed high rates of CRPA, MDR PA among the hospitalized elderly patient with P. aeruginosa infection. The analysis of antimicrobial susceptibility emphasizes the necessity for antimicrobial stewardship and infection control in hospitals. These findings of risk factors are practical significant to identify patients at high risk for CRPA infection and mortality that may benefit from alternate empiric treatment.Keywords: Pseudomonas aeruginosa, carbapenem-resistant, infection, mortality, risk factors

The potential application of monolayer MS2 (M = Mo, W) as thermoelectric material has been widely studied since the first report of successful fabrication. However, their performances are hindered by the considerable band gap and the large lattice thermal conductivity in the pristine 2H phase. Recent discoveries of polymorphism in MS2s provide new opportunities for materials engineering. In this work, phonon and electron transport properties of both 2H and 1T′ phases were investigated by first-principle calculations. It is found that upon the phase transition from 2H to 1T′ in MS2, the electron transport is greatly enhanced, while the lattice thermal conductivity is reduced by several times. These features lead to a significant enhancement of power factor by one order of magnitude in MoS2 and by three times in WS2. Meanwhile, the figure of merit can reach up to 0.33 for 1T′–MoS2 and 0.68 for 1T′–WS2 at low temperature. These findings indicate that monolayer MS2 in the 1T′ phase can be promising materials for thermoelectric devices application. Meanwhile, this work demonstrates that phase engineering techniques can bring in one important control parameter in materials design.

Tingting Wei,&ast; Xiaocen Wang,&ast; Ke Lang,&ast; Cuicui Chen, Yansha Song, Jinlong Luo, Zhaolin Gu, Xianglin Hu, Dong Yang Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Yang; Xianglin Hu, Email yang.dong@zs-hospital.sh.cn; xianglinhero@163.comRationale: Eosinophilic inflammation is related to the progression and outcomes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Till now, few studies have focused on low EOS in AECOPD.Objective: To reveal the clinical characteristics, therapeutic responses and prognosis of patients hospitalized of AECOPD with low EOS.Methods: The electronic database of Zhongshan Hospital, Fudan University was used. Cohort 1 included 608 patients with hospitalized AECOPD. Study population 2 consisted of 166 patients with AECOPD admission at least twice. Impact of low EOS on NIMV treatment, length of hospital stays and 12-month AECOPD-related readmission were analyzed with multivariable logistic regression model. Thirty-five hospitalized AECOPD patients were prospectively recruited as cohort 3 to explore the association between EOS and other immune cells using Spearman correlation coefficient for ranked data.Results: EOS level was suppressed on admission in AECOPD patients, and significantly improved after hospitalized treatment (P < 0.05). For inflammatory markers, leucocytes, neutrophils and lactate dehydrogenase levels were higher, while lymphocytes, monocytes and interleukin-6 levels were lower in the low-EOS group than those in the non-low EOS group (P < 0.05). Low EOS (EOS < 50 cells/μL) was an independent risk factor of NIMV use (OR = 1.86, 95% CI = 1.26 ∼ 2.73). The EOS percentage was positively correlated with the T cell percentage (r = 0.46, P < 0.05) and negatively correlated with the natural killer cell percentage (r = − 0.39, P < 0.05). The patients with low EOS had lower level of CD4+ T cell (P < 0.05) than that of patients with non-low EOS.Conclusion: Low EOS might be a stable phenotype in patients with hospitalized AECOPD and could be used to inform NIMV management, hyperinflammatory state and impaired immunity situation.Keywords: chronic obstructive pulmonary disease, acute exacerbation, eosinophilic inflammation, prognostic phenotype, noninvasive mechanical ventilation