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Yuanna Zhou,* Lin Han,* Wuxing Zhang, Yujun Fan, Wenjian Liu, Muzi Liu, Yishan Fan, Xiaoyuan Qu* School of Nursing and Health, Henan University, Kaifeng, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyuan Qu, School of Nursing and Health, Henan University, Jinming Avenue, Kaifeng City, Henan Province, People’s Republic of China, Email quxiaoyuan@henu.edu.cnPurpose: China has made considerable efforts to promote the development of maternal and child health (MCH) care since the new health system reform in 2009. This study aims to evaluate the trend and equity of MCH resources allocation in China from 2008 to 2020 and provide a reference for rational distribution of MCH resources.Methods: Data were collected from the China Health Statistics Yearbook and China Statistics Yearbook. The number of MCH hospitals, licensed (assistant) physicians, registered nurses and beds were selected for the measurement of the equity of MCH resources allocation. The Health Resource Agglomeration Degree and Theil index were used in evaluating MCH resource allocation equity and to compare differences among regions.Results: From 2008 to 2020, the average annual growth rates for MCH hospitals, beds, licensed (assistant) physicians, and registered nurses were 0.72%, 6.95%, 5.04%, and 9.57%, respectively. However, regional disparities in the equity of MCH resource allocation have been identified. Although the western region has shown growth in MCH resource allocation by geography, the agglomeration degree of the four indicators remains less than 1, significantly lower than the average value of greater than 2 in the eastern region. Additionally, the equity of human resource allocation in the western region is lower than the equity in the allocation of institutions. In the densely populated eastern region, the equity of MCH resource allocation by population is decreasing, with the agglomeration degree of all four indicators below 1 in 2020. The disparity in healthcare resource allocation within regions is the main cause of inequitable MCH resource allocation in China.Conclusion: The allocation of MCH resources in China has improved since 2009, however, geographic equity needs further improvement, particularly in densely populated regions. Population and geographic balances should be considered in the development and implementation of MCH resource allocation policies, and improving intraregional equity should be the focus.Keywords: maternal and child health, resources allocation, equity, health resource agglomeration degree, theil index

Lin Qi,1,* Yanglei Li,2,* Chengqi Kong,2,* Siqi Li,2 Qinyue Wang,2 Hanqin Pan,2 Shuyi Zhang,3 Xinkai Qu,2 Ming Li,1 Mingxuan Li,2,4 Kailei Shi2 1Department of Computed Tomography, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Department of Cardiac Care Unit, Tongren Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Cardiology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kailei Shi; Mingxuan Li, Email shikailei@fudan.edu.cn; 19211280015@fudan.edu.cnBackground: Inflammation triggers atherosclerotic plaque rupture, leading to acute myocardial infarction (AMI). Following AMI, peri-coronary adipose tissue (PCAT) undergoes a transition from lipid-rich to hydrophilic characteristics due to vascular inflammation. This study investigates PCAT changes and neutrophil-to-lymphocyte ratio levels during AMI.Patients and Methods: 60 AMI patients undergoing coronary computed tomography angiography and angiography (Jan 2020-Jun 2022) were studied 60 age, gender, BMI-matched stable angina, and 60 non-coronary artery disease patients were included. Siemens VB20.0 measured PCAT-volume and fat attenuation index (FAI). Neutrophil-to-lymphocyte ratio levels were calculated by peripheral blood tests.Results: The PCAT volume and PCAT-FAI gradually increased across the control, stable angina, and AMI groups, with a corresponding gradual rise in NLR. NLR exhibited weak positive correlation with PCAT-FAI (r=0.35) and PCAT-volume (r=0.24). Multivariable logistic regression identified increased PCAT-volume, PCAT-FAI and neutrophil-to-lymphocyte ratio as possible independent AMI risk factors. No significant PCAT-volume difference was observed between infarct-related artery (IRA) and non-IRA for all three coronary arteries. Only PCAT-FAI around IRA-LAD was higher than non-IRA-LAD (− 74.84± 6.93 HU vs − 79.04± 8.68 HU). PCAT-FAI around culprit vessels in AMI was higher than corresponding lesion related vessel in SA. PCAT-volume around narrowed non-IRA in AMI was higher than that of corresponding LRV in SA. PCAT-FAI of narrowed non-IRA-LADs and non-IRA-LCXs in AMI were elevated compared to LADs (− 78.46± 8.56HU vs − 83.13± 8.34 HU) and LCXs (− 73.83± 10.63 HU vs − 81.38± 7.88 HU) of lesion related vessel in stable angina.Conclusion: We found an association between AMI and inflammation in the coronary perivascular adipose tissue and systemic inflammatory response.Keywords: peri-coronary adipose tissue, neutrophil-to-lymphocyte ratio, fat attenuation index, acute myocardial infarction

Xiuying Li,1 Xin Wang,1 Xiuwu Qu,1 Ningning Shi,1 Qinqing Li,1 Zhifang Yan,1 Yandong Li,2 Yingli Wang3 1Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of China; 2Xi’an International Medical Center Hospital, Xi’an, People’s Republic of China; 3Shanxi Modern Traditional Chinese Medicine Engineering Laboratory, Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of ChinaCorrespondence: Yandong Li; Yingli Wang, Email liyandongzhongnan@163.com; wyl@sxtcm.edu.cnPurpose: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease involving synovial inflammation and joint destruction. Although therapeutic drugs for RA have some efficacy, they usually cause severe side effects and are expensive. RA is characterized by synovial hyperplasia, intra-articular hypoxia, upregulated expression of matrix metalloproteinases, and excessive accumulation of reactive oxygen species. The adverse microenvironment further aggravates activated macrophage infiltration. Therefore, controlling the microenvironment of diseased tissues and targeting the activated macrophages have become new therapeutic targets in RA patients.Methods: Here, microenvironment-targeting micelles (PVGLIG-MTX-Que-Ms) were synthesized using the thin film hydration method. In the inflammatory microenvironment, PVGLIG was cleaved by the highly expressed MMP-2, PEG5000 was eliminated, MTX was exposed, macrophage activation was targeted, and Que enrichment was enhanced. The cytotoxicity, targeting, antioxidant, and anti-inflammatory properties of drug-loaded micelles were tested in vitro. The drug-loaded micelles were used to treat CIA rats. In vivo targeting, expression of serum inflammatory factors, immunohistochemistry of the articular cartilage, and changes in immunofluorescence staining were observed.Results: The developed micelles had a particle size of (89.62 ± 1.33) nm and a zeta potential of (− 4.9 ± 0.53) mV. The IC50 value of PVGLIG-MTX-Que-Ms (185.90 ± 6.98) μmol/L was significantly lower than that of free Que (141.10 ± 6.39) μmol/L. The synthesized micelles exhibited slow-release properties, low cytotoxicity, strong targeting abilities, and significant anti-inflammatory effects in vitro. In vivo, the drug-loaded micelles accumulated at the joint site for a long time. PVGLIG-MTX-Que-Ms significantly reduced joint swelling, improved bone destruction, and decreased the expression of serum inflammatory factors in CIA rats.Conclusion: The smart-targeting micelles PVGLIG-MTX-Que-Ms with strong targeting, anti-inflammatory, cartilage-protective, and other multiple positive effects are a promising new tool for RA treatment.Keywords: matrix metalloproteinases, quercetin, macrophages, methotrexate, anti-inflammatory

Shang Gao,1 Chenmoji Wang,1 Lijie Qi,2 Songlin Liang,1 Xintian Qu,1 Wei Liu,3,* Nianhu Li4,* 1The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 2Qilu Hospital of Shandong University, Jinan, Shandong Province, People’s Republic of China; 3Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 4Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nianhu Li; Wei Liu, Email tigerlee073@126.com; weiliu800109@163.comBackground: The method of action of Bushen Formula (BSHXF) in the treatment of intervertebral disc degeneration (IVDD) was uncovered in this work using in vivo and in vitro tests. To clarify the mechanism of action of BSHXF, we validated the rat intervertebral disc degeneration model and the nucleus pulposus cell degeneration model.Methods: In an in vivo model of IVDD the study explores the impact of BSHXF on mitochondrial function, pro-inflammatory cytokines, pro-apoptotic factors, and matrix metalloproteinases. Additionally, it evaluates the induced degeneration of nucleus pulposus (NP) cells in an in vitro model stimulated by interleukin-1 β (IL-1β). The study measures the effects of BSHXF on both the inflammatory response and mitochondrial function.Results: The MRI results showed that BSHXF reduced intervertebral disc volume reduction and degradation of NP tissue. HE, SO-FG and immunofluorescence further confirmed the protective effect of BSHXF on degenerative intervertebral discs. BSHXF reduced the inflammatory levels of IL-6 IL-1β and TNF-α in degenerative intervertebral disc tissue. Meanwhile, JC-1, mPTP and ROS detection revealed that BSHXF can restore mitochondrial function by regulating the expression of antioxidant proteins, playing a protective role in NP cells. Finally, the WB results showed that BSHXF can alleviate IL-1β mediate the degeneration of NP cells. BSHXF can alleviate NP cell apoptosis by inhibiting the expression of bax, cleaved caspase-3, caspase-3, and cyt-c, and increasing the expression of Bcl-2.Conclusion: This study reveals that BSHXF inhibits the development of inflammatory factors, which may play a significant role in intervertebral disc degeneration. This implies that BSHXF is a suitable herbal medication for future research into inflammatory cytokine treatment.Keywords: intervertebral disc degeneration, nucleus pulposus cell, BSHXF, apoptosis, inflammatory

Jiangqin Tan,1,* Wanxiang Zheng,2,* Chen Xu,3 Xiaolong Qu,2 Jingxing Wu,3 Min Jiang,2 Haiyan Xu4 1Team 17, Group 5, School of Basic Medicine, Army Military Medical University, Chongqing, People’s Republic of China; 2Department of Cardiology, Southwest Hospital, Army Military Medical University, Chongqing, People’s Republic of China; 3Department of Military Psychology, School of Psychology, Army Military Medical University, Chongqing, People’s Republic of China; 4Experimental Research Center for Medical and Psychological Science, School of Psychology, Army Military Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haiyan Xu, Army Military Medical University, No. 30, Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Email xhycq007@163.comAbstract: New approaches to medication adherence interventions are needed. This manuscript presents a highly structured protocol of a single-session solution-focused brief therapy (SFBT) for medication adherence intervention (SFBT-MAI) delivered by general providers. It conceptually integrates the procedure of tailored interventions, techniques of SFBT, and the four steps of Qitang Lin’ conceptualization of single-session SFBT. With specific techniques and examples to reduce operational difficulties, the SFBT-MAI includes two parts. The first part focuses on selecting non-adherent patients and clarifying their barriers to medication adherence. The second part focuses on individualized interventions with four steps: closing, hoping, empowering, and changing and acting. It is hoped that this work will improve the effectiveness of medication adherence interventions for patients with coronary heart disease and to promote the use of brief psychological interventions in clinical practice.Keywords: medication adherence, tailored intervention, psychological intervention, solution-focused brief therapy, general provider, coronary heart disease

Mingping He,1,&ast; Wenzheng Han,1,&ast; Chuan Shi,1 Ming Wang,1 Junheng Li,2 Wei He,2 Xinxin Xu,3 Qian Gan,1 Shaofeng Guan,1 Liang Zhang,1 Yang Chen,1 Xifeng Chang,1 Tianqi Li,1 Xinkai Qu1 1Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Department of Nuclear Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Clinical Research Center for Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenzheng Han; Xinkai Qu, Department of Cardiology, Huadong Hospital Affiliated to Fudan University, No. 221, Yan’an Road (W), Shanghai, People’s Republic of China, Email wzhan_cardiology@foxmail.com; qxkchest@126.comBackground: Microvascular dysfunction in patients with non-obstructive epicardial coronary may aggravate patient’s symptoms or lead to various clinical events.Objective: To investigate the correlation between dynamic single photon emission computed tomography (D-SPECT) derived coronary flow reserve (CFR) and TIMI frame count (TFC) in patients with non-obstructive epicardial coronary patients.Methods: Patients with suspected or known stable CAD who were recommended to undergo invasive coronary angiography were prospectively enrolled in this study. Those who had non-obstructive coronary received TIMI frame count (TFC) and D-SPECT. A cut-off value of > 40 was defined as slow flow referred to TFC.Results: A total of 47 patients diagnosed with non-obstructive coronary were enrolled. The mean age of patients was 66.09 ± 8.36 years, and 46.8% were male. Dynamic SPECT derived coronary flow reserve (CFR) was significantly correlated with TIMI frame count in 3 epicardial coronary (LAD: r=− 0.506, P = 0.0003; LCX: r= − 0.532, P = 0.0001; RCA: r= − 0.657, P < 0.0001). The sensitivity and specificity of CFR in identifying abnormal TIMI frame count < 40 was 100.0% and 57.6% in LAD, 62.5% and 87.0% in LCX, 83.9% and 75.0% in RCA, respectively. The optimal CFR cut-off values were 2.02, 2.47, and 1.96 among the three vessels.Conclusion: In patients with non-obstructive coronary, CFR derived from D-SPECT was strongly correlated with TFC. This study demonstrates that that CFR may be an alternative non-invasive method for identifying slow flow in non-obstructive coronary.Keywords: dynamic single photon emission computed tomography, thrombolysis in myocardial infarction frame count, slow flow, non-obstructive coronary, coronary flow reserve

Hao Zhang,&ast; Baoting Yu,&ast; Hongsheng Yang, Hongfei Ying, Xiaolong Qu, Lilan Zhu, Cong Wang, Jun Ding Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, 130021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Ding, Department of Radiology, China-Japan Union Hospital of Jilin University, No. 829 of Xinmin Street, Chaoyang District, Changchun, 130021, People’s Republic of China, Tel/Fax +86 04 70 8499 7637, Email dingjun@jlu.edu.cnObjective: To explore the value of 1.5T magnetic resonance (MR) fat saturation-T2-weighted imaging (FS-T2WI) and apparent diffusion coefficient (ADC) imaging texture features in distinguishing the renal changes of patients with stage III type 2 diabetic kidney disease (DKD) from healthy people.Methods: This study collected 55 patients with stage III DKD (39 males and 16 females) and 33 healthy controls (13 males and 20 females) from December 2021 to June 2022 in the China-Japan Union Hospital of Jilin University. All subjects were randomly divided in a ratio of 6:4 to extract and screen the FS-T2WI and ADC texture features of the right kidney of the subjects. The area under the curve (AUC) was used to assess the diagnostic accuracy of each model.Results: There were significant differences between urea, creatinine and sex (p< 0.05) of the two groups in the training and test set, and no significant difference in age and body mass index (BMI). We extracted 1409 imaging features from the original ADC sequence and selected them by wavelet and Laplace-Gaussian filter and LASSO algorithm, and using the same methods of FS-T2WI. Finally, FS-T2WI and ADC models were selected to construct the united model, including 3 first-order features and 8 texture features. The AUC values of the training set of FS-T2WI, ADC, FS-T2WI+ADC combined logistic regression model were 0.96, 0.91, 0.98; the AUC values of the test set were 0.91, 0.89 and 0.93, and the specificity and accuracy values of the united model were 0.90 and 0.89, respectively.Conclusion: FS-T2WI and ADC imaging features based on 1.5 T MR had diagnostic value in the early diagnosis of DKD stage III, and the combined model of FS-T2WI and ADC had high diagnostic efficiency.Keywords: diabetic kidney disease, magnetic resonance imaging, radiomics

Qi Zhao,1,&ast; Siyuan Sun,2,&ast; Fanghui Zhou,3,&ast; Jingkun Yue,2 Xing Luo,4 Xiufen Qu1 1Department of Cardiology, 1st Affiliated Hospital of Harbin Medical University, Harbin, 150086, People’s Republic of China; 2Department of Cardiology, People’s Hospital of Taihe County, Taihe, Anhui, 236600, People’s Republic of China; 3Department of Hematology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China; 4Department of Cardiology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xing Luo; Xiufen Qu, Email luoxing321@163.com; quxiufenhmu@126.comPurpose: The effects of combing evolocumab and statin on the clinical outcome and physiological function of coronary arteries in STEMI patients with non-infarct-related artery (NIRA) disease are still unclear.Methods: A total of 355 STEMI patients with NIRA were enrolled in this study, who underwent combined quantitative flow ratio (QFR) at baseline and after 12 months of treatment with statin monotherapy or statin plus evolocumab.Results: Diameter stenosis and lesion length were significantly lower in the group undergoing statin plus evolocumab. While the group exhibited significantly higher minimum lumen diameter (MLD), and QFR values. Statin plus evolocumab (OR = 0.350; 95% CI: 0.149– 0.824; P = 0.016) and plaque lesion length (OR = 1.223; 95% CI: 1.102– 1.457; P = 0.033) were independently associated with rehospitalization for unstable angina (UA) within 12 months.Conclusion: Evolocumab combined with statin therapy can significantly improve the anatomical and physiological function of the coronary arteries and downregulate the re-hospitalization rate due to UA in STEMI patients with NIRA.Keywords: PCSK9 inhibition, C-reactive protein, inflammation, physiological assessment, quantitative flow ratio, non-infarct-related artery

Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for obtaining precise information about the local bonding of materials, but difficult to interpret without a well-vetted dataset of reference spectra. The ability to predict NMR parameters and connect them to three-dimensional local environments is critical for understanding more complex, long-range interactions. New computational methods have revealed structural information available from 29Si solid-state NMR by generating computed reference spectra for solids. Such predictions are useful for the identification of new silicon-containing compounds, and serve as a starting point for determination of the local environments present in amorphous structures. In this study, we have used 42 silicon sites as a benchmarking set to compare experimentally reported 29Si solid-state NMR spectra with those computed by CASTEP-NMR and Vienna Ab Initio Simulation Program (VASP). Data-driven approaches enable us to identify the source of discrepancies across a range of experimental and computational results. The information from NMR (in the form of an NMR tensor) has been validated, and in some cases corrected, in an effort to catalog these for the local spectroscopy database infrastructure (LSDI), where over 10,000 29Si NMR tensors for crystalline materials have been computed. Knowledge of specific tensor values can serve as the basis for executing NMR experiments with precision, optimizing conditions to capture the elements accurately. The ability to predict and compare experimental observables from a wide range of structures can aid researchers in their chemical assignments and structure determination, since the computed values enables the extension beyond tables of typical chemical shift (or shielding) ranges.

Xiang-Rong Bai,1,&ast; Jing-Rong Cao,2,&ast; Zhi-Zhou Wang,1 Wen-Chao Li,1 Dian-Dian Chen,2 Ran Lou,3 Xin Qu,4 Su-Ying Yan1 1Department of Pharmacy, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, Beijing, 100053, People’s Republic of China; 2Department of Clinical Laboratory, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, Beijing, 100053, People’s Republic of China; 3Department of Intensive Medicine, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, Beijing, 100053, People’s Republic of China; 4Intensive Care Unit, Department of Neurosurgery, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, Beijing, 100053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Su-Ying Yan, Department of Pharmacy, Xuan Wu Hospital Capital Medical University, National Gerontic Disease Clinical Research Center, No. 45 Changchun Street, Xi Cheng District, Beijing, 100053, People’s Republic of China, Tel/Fax +86 10-63012837, Email yansuying10@sina.cnPurpose: Tigecycline is an agent for carbapenemase-producing Klebsiella pneumonia (KPC-KP), given its penetration into lung tissues. Our study focused on the molecular and clinical efficacy of tigecycline for hospital-acquired pneumonia (HAP) in the ICU.Patients and Methods: A retrospective cohort study of 52 adult KPC-KP HAP patients by searching hospital medical records from January 2018 to December 2020 was established to investigate the epidemiology of KPC-KP infections for tigecycline treatment and the associated clinical efficacy of tigecycline. The KPC-KP isolates underwent multilocus sequence typing. Molecular typing, antimicrobial resistance, and virulence profiling were also analyzed by whole-genome sequencing of KPC-KP.Results: Among 52 patients with KPC-KP, the ICU mortality rate was 14/52 (27%), and there was no significant statistical difference in mortality between the effective group and failure group (p = 0.754). However, the duration of tigecycline was statistically different between the two groups of patients (14.4 vs 10 days, p=0.046). The total bacterial clearance rate was 6/52 (11.5%). There was no significant statistical difference in both groups (p=0.416). Antibiotic resistance genes (aac3iia) and virulence gene (AREO-iutA, Capsule-wzc) were negatively correlated with clinical efficacy (p = 0.011, OR = 1.237).Conclusions: Blakpc was the main carbapenemase in all K. pneumoniae strains. ST11-KL64 KPC-KP was the most common virulence factors in KPC-KP isolates. This study suggested that antibiotic resistance genes (aac3iia) and virulence gene (AREO-iutA, Capsule-wzc) were independent mortality risk factors for patients with Klebsiella pneumoniae carbapenemase-2 producing K. pneumoniae infections, when during the tigecycline treatment. Molecular analysis of K. pneumoniae may provide an option when choosing the antimicrobial treatment.Keywords: Klebsiella pneumoniae, carbapenemase, virulence factors, resistance genes, hospital-acquired pneumonia

Qingyu Wang,1,2 Xing Qu,3 Shannon H Houser,4 Yan Zhang,5 Meirong Tian,3 Qiong Zhang,6,7 Wei Zhang3 1West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, People’s Republic of China; 2HEOA Group, Institute for Healthy Cities and West China Research Center for Rural Health Development, Sichuan University, Chengdu, People’s Republic of China; 3Institute of Hospital Management, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Department of Health Services Administration, the University of Alabama at Birmingham, Birmingham, AL, USA; 5Department of Maternity and Child Health Management, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, People’s Republic of China; 6Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 7State Key Laboratory of Oral Diseases & National Clinical Research, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xing Qu, Institute of Hospital Management, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041, People’s Republic of China, +86 13880713452, Email qvxing@163.comBackground: Limited information is known about dental implementation by pediatric primary care physicians (PCPs) at the primary care level in China. This study aimed to explore the current status of primary oral care implementation and related influencing factors.Methods: A cross-sectional survey was conducted among PCPs in Sichuan Province, China. Multivariable logistic regression was used to analyse factors associated with CRA and dental referral for high caries-risk children.Results: A total of 504 out of 524 questionnaires remained for analysis. In all, 93.8% of PCPs reported that they usually or sometimes performed dental screening for children, 31.3% performed CRA, and 49.0% referred high caries-risk children to dentists. More CRA activities were associated with PCPs who encountered a greater number of children with caries during systematic care (adjusted OR: 2.37, 95% CI:[1.08,5.18], had dental knowledge training by pediatric dentists (aOR: 2.26, 95% CI:[1.36, 3.75], and learned pediatric dental knowledge on their own (aOR: 2.87, 95% CI: [1.51, 5.45]). In addition to the above associators, a higher rate of dental referrals for high caries-risk children was associated with having a dental department in the same work institute (aOR: 1.72, 95% CI: [1.09, 2.70] and having more confidence in their dental knowledge (aOR: 1.29, 95% CI: [1.04, 1.61]).Conclusion: Paediatric PCPs commonly implement dental screening but perform fewer CRAs and dental referrals for high caries-risk children during systematic health management in western China. To increase CRA activities and dental referral by paediatric PCPs, health policymakers could encourage interdisciplinary cooperation between dental professionals and paediatric PCPs.Keywords: caries risk assessment, dental referral, paediatric physicians, primary care, China

Jinghua Sun,1,&ast; Ge Sun,1,&ast; KeMou Lu,1 Lingling Xu,1 XiaoNa Qu,1 Ye Cheng,1 Evenki Pan,2 Peng Yang,2 Tingting Wu,2 Yang Zhang,1 HongMei He1 1The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Nanjing Geneseeq Technology Inc., Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Zhang; HongMei He, The Second Affiliated Hospital of Dalian Medical University, Dalian, No. 467, Zhongshan Road, Shahekou District, Dalian, People’s Republic of China, Email zydley@163.com; hongmeihe1976@163.comAbstract: For advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, EGFR tyrosine kinase inhibitors (TKIs) have been approved as the standard therapy and shown clinical benefits. However, the emergence of drug resistance is inevitable. Tumor heterogeneity was often observed by imaging method to evaluate the progression of primary and metastatic lesions. Tissue biopsy was also unlikely to accurately capture the complete genomic landscape from a single tissue sample. Recently, genomic characterization of circulating tumor DNA (ctDNA) offer an opportunity to reveal the clonal dynamics throughout the course of a patient’s illness and provide comprehensive genomic landscape of tumors to assess tumor heterogeneity. Here, we reported a lung adenocarcinoma (LADC) with EGFR mutations who was treated with sequential EGFR TKIs. The CT image of the patient’s different lesions suggested that dynamic change of tumor heterogeneity had occurred. Targeted next-generation sequencing (NGS) analysis of ctDNA revealed dynamic changes of mutational profiles between the primary and metastatic tumors to discover tumor evolution to guide treatment decision-making.Keywords: tumor heterogeneity, circulating tumor DNA, ctDNA, resistance mutation, next-generation sequencing, NGS

Xiaoxiao Qu,1,&ast; Shishi Wang,1,&ast; Ying Qu,2 Huiyan Wang,1 Xuanmei Ye,1 Luming Tang,3 Qipeng Xie1 1Department of Clinical Laboratory, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2Department of Clinical Laboratory, Wenzhou People’s Hospital, The Third Affiliated Hospital of Shanghai University, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China; 3Emergency Department, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qipeng Xie, Department of Clinical Laboratory, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China, Tel +86 151 577 87159, Email pandon2002@163.comPurpose: To clarify the distribution of pathogenic bacteria by analyzing the bacterial susceptibility characteristics and risk factors for adult sepsis in The Wenzhou city, Zhejiang province, China, and to aid early diagnosis, monitoring, and prognosis prediction in cases of bacterial sepsis.Patients and Methods: We retrospectively analyzed 329 patients with sepsis admitted to the Second Affiliated Hospital of Wenzhou Medical University between January 2018 and March 2021. Laboratory data were collected before and after treatment; moreover, the bacterial susceptibility characteristics and risk factors for sepsis were comprehensively analyzed using the Sequential Organ Failure Assessment (SOFA) score.Results: The SOFA score was negatively correlated with the prognosis (P < 0.05). We isolated 47 pathogenic strains from blood culture samples, including 29 gram-positive strains, 18 gram-negative strains. The most common gram-negative pathogens in blood cultures are Klebsiella pneumoniae and Escherichia coli, while the most common gram-positive pathogens are Staphylococcus aureus and Staphylococcus hominis. Gram-negative pathogens had resistance rates of 77% and 62.5% to ciprofloxacin and ceftriaxone, respectively. Gram-positive bacteria had a high resistance to penicillin at 100%. Prognostic factors for sepsis included patients’ consciousness, SOFA score, prothrombin time, international normalized ratio, fibrinogen, D-dimer, and aspartate aminotransferase (P < 0.05). Of these, the D-dimer level could predict the outcome of patients with sepsis (AUC = 0.661, P < 0.05).Conclusion: The pathogens detected in adult sepsis in Wenzhou are mainly Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Staphylococcus hominis. The pathogens exhibited differences in drug susceptibility. The optimal antibiotics should be chosen based on the principles of rational use and drug susceptibility. Combined with D-dimer levels, these parameters can be used to determine the optimal strategy for preventing and treating pathogenic bacteria.Keywords: adult sepsis, drug susceptibility characteristics, risk factors, D-dimer

Xiaojun Wang,1,2,&ast; Xuanqi Liu,3,&ast; Yiding Qi,4,&ast; Shuyi Zhang,4 Kailei Shi,4 Huagang Lin,5 Paul Grossfeld,6 Wenhao Wang,1,2 Tao Wu,1,2 Xinkai Qu,4 Jing Xiao,5 Maoqing Ye2,4 1Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 2Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 4Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 5Department of Nephrology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 6Division of Cardiology UCSD School of Medicine, Rady Children’s Hospital of San Diego, La Jolla, CA, 92093, USA&ast;These authors contributed equally to this workCorrespondence: Maoqing Ye, Department of Cardiology, Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China, Tel +86-18930721396, Email yemaoqing@fudan.edu.cn Jing Xiao, Department of Nephrology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China, Tel +86-13817100256, Email jingxiao13@Fudan.edu.cnBackground: Serum uric acid (SUA) is suspected to be associated with atherosclerosis and calcium deposition in atherosclerosis is known to related poor prognosis, yet there is no cohort study on the aged in China. We aimed to investigate the relationships between SUA levels and coronary calcium deposition in the middle-aged and elderly populations in China.Methods: A total of 326 participants between the ages of 50 and 85 who had undergone a coronary CT scan in 2015 at the Huadong Hospital Affiliated to Fudan University (Shanghai, China) were included in this study. Univariate and multivariate binary logistic regression was performed to analyze the correlation between SUA levels and coronary artery calcium score (CACS). The changes in CACS during a five-year follow-up were analyzed through Kaplan–Meier survival and binary cox regression analysis. An observational study was done on another 104 asymptomatic middle-aged and elderly patients to compare relative mRNA expressions of proinflammatory factors in peripheral blood mononuclear cells (PBMCs) from 104 subjects.Results: Based on the first year of follow-up data analysis, the elevation of SUA levels (P< 0.001) is an independent risk factor for the increase of CACS after coordinating the confounding factors. According to five-year follow-up data, cox regression analysis proved that SUA was a risk factor for CACS (HR =5.86, P< 0.001). The mRNA expression of IL-6 and CXCL8 in the HUA and HUA patients with CAC (HUA-CAC) groups was significantly higher than that in the normal control (NC) and coronary calcium deposition (CAC) groups.Conclusion: Taken together, the findings in this study indicate that high SUA levels (P< 0.001) are an independent risk factor for CACS and elevated SUA levels increase the risk of developing coronary calcium deposition among middle-aged and old people in the Chinese population, which may be related to an increase of pro-inflammatory cytokines in the PBMCs.Keywords: serum uric acid, calcium deposition, coronary artery calcium score, monocyte inflammation

Solar-driven oxygen evolution is a critical technology for renewably synthesizing hydrogen- and carbon-containing fuels in solar fuel generators. New photoanode materials are needed to meet efficiency and stability requirements, motivating materials explorations for semiconductors with (i) band-gap energy in the visible spectrum and (ii) stable operation in aqueous electrolyte at the electrochemical potential needed to evolve oxygen from water. Motivated by the oxygen evolution competency of many Mn-based oxides, the existence of several Bi-containing ternary oxide photoanode materials, and the variety of known oxide materials combining these elements with Sm, we explore the Bi-Mn-Sm oxide system for new photoanodes. Through the use of a ferri/ferrocyanide redox couple in high-throughput screening, BiMn2O5 and its alloy with Sm are identified as photoanode materials with a near-ideal optical band gap of 1.8 eV. Using density functional theory-based calculations of the mullite Bi3+Mn3+Mn4+O5 phase, we identify electronic analogues to the well-known BiVO4 photoanode and demonstrate excellent Pourbaix stability above the oxygen evolution Nernstian potential from pH 4.5 to 15. Our suite of experimental and computational characterization indicates that BiMn2O5 is a complex oxide with the necessary optical and chemical properties to be an efficient, stable solar fuel photoanode.

Yu Cheng,1– 4 Gang Wu,5 Simeng Zhang,1– 4 Yunpeng Liu,1– 4 Jinglei Qu,1– 4 Xiujuan Qu1– 4 1Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 3Liaoning Province Clinical Research Center for Cancer, Shenyang, People’s Republic of China; 4Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 5Department of Hepatobiliary Surgery, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Xiujuan Qu; Jinglei Qu People’s Republic of ChinaTel +86-24-83282312Fax +86-24-83282543Email xiujuanqu@yahoo.com; qujinglei@hotmail.comBackground: Doublet or triplet chemotherapy plus or minus targeted drugs can achieve a high objective response rate (ORR) and are currently considered to be the backbone of conventional therapy for liver metastatic colorectal cancer (mCRC). However, current biomarkers (such as UGT1A1 and DPYD) are limited to the prediction of toxicity and there are no effective biomarkers to predict chemotherapy response. Therefore, personalized cancer chemotherapy underpinned by genomic alterations in mCRC has received increasing attention.Case Presentation: We present a case of a 28-year-old female rectal cancer patient with multiple liver metastases (clinical risk score, CRS = 5 points). The patient underwent XELOXIRI plus bevacizumab regimen that consisted of irinotecan (150 mg/m2), oxaliplatin (100 mg/m2) on day 1, capecitabine (1700 mg/m2 per day from day 2 to 15), bevacizumab (7.5 mg/kg) on day 1 (on the second cycle), given every three weeks for eight cycles. After multi-disciplinary team (MDT) discussion, the patient underwent right hemihepatectomy, partial liver resection of segment IV and cholecystectomy. Surprisingly, the patient achieved a complete pathologic response (pCR) of the hepatic metastasis and clinical complete response (cCR) of the primary rectal lesion. A paired tumor molecular profile revealed somatic mutations in ataxia-telangiectasia mutated (ATM) genes that may explain why the patient achieved such a dramatic tumor response. Treatment was discontinued after eight cycles of a single oral dose of capecitabine and the patient started a follow-up program of physical and radiological examinations. To monitor the signs of recurrence, we also obtained blood samples to analyze circulating tumor DNA (ctDNA). To date, the patient has remained disease-free.Conclusion: The XELOXIRI-bevacizumab regimen is a feasible and effective regimen for patients with mCRC. Mutations in the ATM genes may characterize a subset of patients with a better prognosis who are more sensitive to chemotherapy plus biological agents.Keywords: XELOXIRI, bevacizumab, ATM, case report, rectal cancer

Rui Ma,1– 4 Xiujuan Qu,1– 4 Xiaofang Che,1– 4 Bowen Yang,1– 4 Ce Li,1– 4 Kezuo Hou,1– 4 Tianshu Guo,1– 4 Jiawen Xiao,5 Yunpeng Liu1– 4 1Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, China Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001, People’s Republic of China; 3Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001, People’s Republic of China; 4Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, 110001, People’s Republic of China; 5Department of Medical Oncology, Shenyang Fifth People Hospital, Shenyang, People’s Republic of ChinaCorrespondence: Yunpeng Liu; Xiujuan QuDepartment of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, People’s Republic of ChinaTel +86-24-83282312Fax +86-24-83282543Email ypliu@cmu.edu.cn; xiujuanqu@yahoo.comPurpose: Immune checkpoints, as pivotal regulators of immune escape in cancer, can motivate the emergence of immune checkpoint inhibitors (ICIs). The aim of this study is to identify the expression of the immune checkpoint genes (ICGs) in colorectal cancer (CRC) and to relate their individual as well as combined expression to prognosis and therapeutic effectiveness in CRC.Methods: RNA expression of 47 ICGs and clinical information of CRC patients were collected from two public databases to elucidate the expression levels and prognostic values of these ICGs in CRC. Then, the Shapiro–Wilk normality test was used to determine the normality of variables. Overall survival (OS) rates of each subset were found by Kaplan–Meier method, and the statistical significance was determined by the Log rank test (p < 0.05).Results: The expression of 13 and 9 ICGs was significantly associated with CRC prognosis in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. A series of ICGs was found to be significantly associated with TMB, neoantigens and MMR in CRC indicating that the combination of immunotherapy treatment biomarkers and ICGs may achieve accurate prognostic stratification of CRC, and potentially identify CRC cases that might respond to checkpoint inhibitors (CPIs). The subsets of high or low PD1/PD-L1/IDO1 expression stratified by CD48 were accurately associated with prognosis in CRC. In addition, in vitro experiments confirmed that VTCN1(B7-H4)-KD increases anti-PD-L1-mediated NK cell cytotoxicity on CRC tumor cells.Conclusion: Although the expression of a single immune-checkpoint molecule does not predict the efficacy of immunotherapy in CRC, our findings infer that subsets defined by ICGs are associated with prognosis and imply the possibility that VTCN1 and CD48 serve as new immunotherapeutic targets.Keywords: immune checkpoint genes, colorectal cancer, prognosis, immunotherapy

In this work, we use computational design to examine 15 new electrolyte salt anions by performing chemical variations and mutations on the bis(trifluoromethane)sulfonamide (TFSI) anion. On the basis of our calculations, we propose two new anions as potential candidates for magnesium energy-storage systems, which are evolved from TFSI with the substitution of sulfur atoms in TFSI and the modification of functional groups. The applicability of these new anion salts is examined through comprehensive calculations using both first-principles as well as benchmarked classical molecular dynamics. We elucidate the important properties of these anions, including the electrochemical stability window, chemical decomposition, preferred solvation structure, diffusion coefficient, and other dynamical properties for 15 rationally designed molecules. Two of the designed anions are found to successfully avoid the vulnerability of TFSI during ion-pair charge-transfer reactions while retaining comparable or better performance of other properties. As such, our work provides, to our knowledge, the first theoretically designed electrolyte salt for contemporary multivalent batteries and provides guidance for the synthesis and testing of novel liquid electrochemical systems. (Figure Presented).

Jinhua Ma, Hongbing Wei, Xianlin Li, Xi Qu Department of Urinary Surgery, The Third People’s Hospital of Hubei Province, Wuhan, Hubei, 430030, People’s Republic of ChinaCorrespondence: Xi QuDepartment of Urinary Surgery, The Third People’s Hospital of Hubei Province, No. 26 Zhongshan Road, Wuhan, Hubei, 430030, People’s Republic of ChinaTel +86 13476046068Email sunl1347@163.comBackground: MicroRNAs (miRNAs) are key players in the progression of human cancers. While several miRNAs have been reported to regulate the development of tumors, the molecular mechanisms and roles of miR-149-5p in prostate carcinoma (PCa) remain unclear. Our aim was to investigate the interaction and functions of miR-149-5p and RGS17 in PCa.Methods: Microarray analysis was performed to identify the key miRNA and gene involved in PCa progression. The expression levels of miRNA and mRNA in PCa tissues and cells were verified by qRT-PCR. MTT assay, BrdU proliferation assay and wound-healing assay were applied to assess the effect of miR-149-5p and RGS17 on PCa cells’ viability, proliferation, and migration ability. The association between RGS17 and miR-149-5p was identify using dual-luciferase reporter assay and Western blot assay.Results: Data analysis indicated the reduction of miR-149-5p expression in PCa tissues and cells. Experimental investigations also showed that this miRNA suppressed the viability, proliferation and migration ability of PCa cells. RGS17 was found to be the target of miR-149-5p, and the low expression of miR-149-5p upregulated RGS17 in PCa tissues and cells. The results of the cell-function assays showed that RGS17 acted as an oncogene in PCa even though its promotive effect could be reversed by miR-149-5p.Conclusion: This research confirmed that by targeting and inhibiting RGS17, miR-149-5p could suppress PCa development.Keywords: miR-149-5p, prostate carcinoma, PCa, RGS17, malignancy

Xiaoyan Qu,1,* Bing Yu,2,* Mengmei Zhu,2,* Xiaomei Li,2,3 Lishan Ma,1 Chuyin Liu,1 Yixing Zhang,1 Zhongping Cheng4 1Department of Gynecology and Obstetrics, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200090, People’s Republic of China; 2Department of Cell Biology, Navy Medical University (Second Military Medical University), Shanghai, 200433, People’s Republic of China; 3Cancer Research Laboratory, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, 563003, People’s Republic of China; 4Department of Gynecology and Obstetrics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhongping ChengDepartment of Gynecology and Obstetrics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Middle Road, Shanghai, 200072, People’s Republic of ChinaTel +86-021-66300588Email mdcheng18@tongji.edu.cnIntroduction: Ovarian cancer is one of the most common gynecological cancers worldwide. While, therapies against ovarian cancer have not been completely effective, sinomenine has been proved to have anti-tumor activity in various cancer cells. However, study of its anti-ovarian cancer effect is still rare, and the underlying mechanism has not been elucidated. Therefore, we aim to explore the mechanism of sinomenine anti-ovarian cancer.Materials and Methods: The effect of anti-ovarian cancer HeyA8 cells was analyzed by CCK8 and colony formation assay. The mechanism of sinomenine anti-ovarian cancer was explored via high throughput RNA-seq, and then the target mRNA and protein expression were verified by real-time PCR and Western blot, respectively.Results: We found that the proliferation and clone formation ability of ovarian cancer HeyA8 cells were markedly reduced by 1.56 mM sinomenine. The transcriptome analysis showed that 2679 genes were differentially expressed after sinomenine treatment in HeyA8 cells, including 1323 down-regulated genes and 1356 up-regulated genes. Gene ontology and KEGG pathway enrichment indicated that differential expression genes (DEGs) between the groups of sinomenine and DMSO-treated HeyA8 cells were mainly involved in the process of the cell cycle, such as kinetochore organization, chromosome segregation, and DNA replication. Strikingly, the top 18 ranked degree genes in the protein–protein interaction (PPI) network were mainly involved in the process of mitosis, such as sister chromatid segregation, condensed chromosome, and microtubule cytoskeleton organization. Moreover, real-time PCR results showed consistent expression trends of DEGs with transcriptome analysis. The results of Western blot showed the expression level of CDK1, which was the highest degree gene in PPI and the main regulator controlling the process of mitosis, and the levels of phosphorylated P-CDK (Thr161) and P-Histone H3 (Ser10) were decreased after being treated with sinomenine.Conclusion: Our results demonstrated that sinomenine inhibited the proliferation of HeyA8 cells through suppressing mitosis by down-regulating the expression and the activity of CDK1. The study may provide a preliminary research basis for the application of sinomenine in anti-ovarian cancer.Keywords: ovarian cancer, sinomenine, high throughput RNA-seq, CDK1, cell proliferation

The rapid growth of portable consumer electronics and electric vehicles demands new battery technologies with greater energy stored at a reduced cost. Energy storage solutions based on multivalent metals, such as Mg, could significantly increase the energy density as compared to lithium-ion based technology. In this paper, we employ density functional theory calculations to systematically evaluate the performance, such as thermodynamic stability, ion diffusivity and voltage, of a group of 3d transition-metal sulfur-spinel compounds (21 in total) for multivalent cathode applications. Based on our calculations, Cr2S4, Ti2S4 and Mn2S4 spinel compounds exhibit improved Mg2+ mobility (diffusion activation energy

This paper introduces FireWorks, a workflow software for running high-throughput calculation workflows at supercomputing centers. FireWorks has been used to complete over 50 million CPU-hours worth of computational chemistry and materials science calculations at the National Energy Research Supercomputing Center. It has been designed to serve the demanding high-throughput computing needs of these applications, with extensive support for (i) concurrent execution through job packing, (ii) failure detection and correction, (iii) provenance and reporting for long-running projects, (iv) automated duplicate detection, and (v) dynamic workflows (i.e., modifying the workflow graph during runtime). We have found that these features are highly relevant to enabling modern data-driven and high-throughput science applications, and we discuss our implementation strategy that rests on Python and NoSQL databases (MongoDB). Finally, we present performance data and limitations of our approach along with planned future work.

Fangbin Song,1,2 Hui Du,1,2 Aimin Xiao,1,2 Chun Wang,1,2 Xia Huang,1,2 Peisha Yan,1,2 Zhihong Liu,1,2 Xinfeng Qu,3 Jerome L Belinson,4,5 Ruifang Wu1,2 1Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Shenzhen Key Laboratory on Technology for Early Diagnosis of Major Gynecological Diseases, Shenzhen, People’s Republic of China; 3Sanming Project of Medicine in Shenzhen, Peking University Shenzhen Hospital, Shenzen, People’s Republic of China; 4Preventive Oncology International, Inc., Cleveland Heights, OH, USA; 5Gynecologic Oncology Division, Women’s Health Institute, Cleveland Clinic, Cleveland, OH,USACorrespondence: Ruifang Wu; Hui DuDepartment of Obstetrics and Gynecology, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Shenzhen, Guangdong 518036, People’s Republic of ChinaEmail wurfpush@126.com; duhui_107108@163.comPurpose: When used for cervical cancer primary screening, liquid-based cytology (LBC) has a high specificity but a low sensitivity. For histological diagnosis of high-grade lesions, p16INK4a immunostaining has proven to be useful. Therefore, our objective was to evaluate the use of p16INK4a immuno-cytology as a primary screen and a secondary screen after primary high-risk human papillomavirus (hrHPV) screening or LBC screening.Methods: A total of 1197 cytology slides were immuno-stained using automatic p16INK4a staining system (PathCIN®p16INK4a) in two studies from cervical screening programs. In the primary screening study, 875 slides were randomly selected and analyzed for p16INK4a. In the secondary screening study, 322 of the remaining slides were chosen by virtue of being HPV 16/18+, other hrHPV+/LBC≥ASC-US, or HPV-negative/LBC ≥LSIL. The sensitivity and specificity for detection of cervical intraepithelial neoplasia 2/3 or worse (CIN2+/CIN3+) were compared based on p16INK4a, LBC and HPV test results.Results: In combining two studies, there were 431 cases with biopsy pathology. They included 83 cases with CIN2+ and 41 cases with CIN3+. The p16 positivity rate increased with pathologic and cytologic severity (P< 0.0001). For primary screening: p16 immuno-cytology was more specific than HPV testing and was similar in sensitivity. Also, p16 immuno-cytology compared favorably with routine LBC (≥ASC-US or ≥LSIL) in sensitivity and specificity. For secondary screening: after LBC screening, “Triaging ASC-US with p16” gave a higher specificity and a similar sensitivity as compared to the “Triaging ASC-US with hrHPV” algorithm. After HPV primary screening, p16 immuno-cytology was more specific than LBC (≥ASC-US); the calculated colposcopy referral rate was also decreased by using p16 immuno-cytology as triage. Triage of “HPV16/18 and p16” had higher specificity and similar sensitivity as compared to triage of “HPV16/18 and LBC ≥ASC-US”.Conclusion: For primary screening, p16INK4a immuno-cytology compares favorably to routine LBC and HPV testing. p16INK4a immunostaining could be an efficient triage to reduce the colposcopy referral rate after primary hrHPV screening or LBC screening. Therefore, p16INK4a immuno-cytology may be applicable as a favorable technology for cervical cancer screening.Keywords: cervical intraepithelial neoplasia, human papillomavirus, p16, immunochemical staining, cervical cancer screening

Haibin Guo,* Yanqing Xia,* Ke Feng, Xiaowei Qu, Cuilian Zhang, Feng Wan Henan Provincial People’s Hospital, Henan Provincial Reproductive Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan 450003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Wan; Cuilian ZhangHenan Provincial People’s Hospital, Henan Provincial Reproductive Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan 450003, People’s Republic of ChinaTel +86 371 87160762Email fengwanscholar@163.com; zhangcuilian@henu.edu.cnBackground: Metal–organic frameworks (MOFs) have attracted intensive research interest in the biomedical field because of their unique properties. However, in order to realize the high loading capacity and therapeutic efficacy, it is still urgent to develop a multifunctional MOFs-based nanoplatform.Materials and Methods: Herein, a pH/near-infrared (NIR) dual-responsive drug delivery system based on zeolitic imidazolate framework-8 (ZIF-8) is constructed for synergistic chemo-photothermal therapy and dual-modal magnetic resonance (MR)/photoacoustic (PA) imaging. The doxorubicin hydrochloride (DOX) is embedded into ZIF-8 through one-pot method, and the resultant ZIF-8/DOX is then successively modified with polydopamine, Mn ions and poly(ethylene glycol). The obtained ZIF-8/DMPP is systematically characterized, and both its in vitro and in vivo biological effects are evaluated in detail.Results: The ZIF-8/DMPP possesses a high drug-loading content of 18.9% and displays appropriate size and morphology. The pH-dependent degradation and drug release behavior of prepared ZIF-8/DMPP are confirmed. Importantly, the results demonstrate that the photothermal effect of ZIF-8/DMPP under NIR laser irradiation can significantly accelerate its drug releasing rate, further improving the intracellular drug concentrations. Thereafter, the augmented chemotherapeutic efficiency by photothermal effect against cancer cells is verified both in vitro and in vivo. Besides, the favorable MR and PA imaging capacity of ZIF-8/DMPP is also evidenced on the tumor model.Conclusion: Taken together, the surface engineering of ZIF-8-based nanocarrier in this work offers a promising strategy for the multifunctional MOFs-based drug delivery system.Keywords: zeolitic imidazolate framework-8, pH/NIR responsive, chemo-photothermal therapy, dual-modal imaging