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Linyuan Gui,1,* Qingyuan Ye,2,* Lu Yu,3 Geng Dou,1 Yang Zhou,1 Yang Liu,4 Yanqi Zhang,5 Xiaoshan Yang,1,6 Fang Jin,5 Shiyu Liu,1 Yan Jin,1 Lili Ren1 1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 2State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Digital Dentistry Center, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 3Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, 250012, People’s Republic of China; 4Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 5State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 6Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lili Ren; Yan Jin, State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China, Email lanyangddgy@qq.com; yanjin@fmmu.edu.cnBackground: Osteoporosis is a highly prevalent disease that causes fractures and loss of motor function. Current drugs targeted for osteoporosis often have inevitable side effects. Bone marrow mesenchymal stem cell (BMSCs)-derived apoptotic extracellular vesicles (ApoEVs) are nanoscale extracellular vesicles, which has been shown to promote bone regeneration with low immunogenicity and high biological compatibility. However, natural ApoEVs cannot inherently target bones, and are often eliminated by macrophages in the liver and spleen. Thus, our study aimed to reconstruct ApoEVs to enhance their bone-targeting capabilities and bone-promoting function and to provide a new method for osteoporosis treatment.Methods: We conjugated a bone-targeting peptide, (Asp-Ser-Ser)6 ((DSS)6), onto the surface of ApoEVs using standard carbodiimide chemistry with DSPE-PEG-COOH serving as the linker. The bone-targeting ability of (DSS)6-ApoEVs was determined using an in vivo imaging system and confocal laser scanning microscopy (CLSM). We then loaded ubiquitin ligase RING finger protein146 (RNF146) into BMSCs via adenovirus transduction to obtain functional ApoEVs. The bone-promoting abilities of (DSS)6-ApoEVs and (DSS)6-ApoEVsRNF146 were measured in vitro and in vivo.Results: Our study successfully synthesized bone-targeting and gained functional (DSS)6-ApoEVsRNF146 and found that engineered ApoEVs could promote osteogenesis in vitro and exert significant bone-targeting and osteogenesis-promoting effects to alleviate osteoporosis in a mouse model.Conclusion: To promote the bone-targeting ability of natural ApoEVs, we successfully synthesized engineered ApoEVs, (DSS)6-ApoEVsRNF146 and found that they could significantly promote osteogenesis and alleviate osteoporosis compared with natural ApoEVs, which holds great promise for the treatment of osteoporosis. Keywords: osteoporosis, mesenchymal stem cells, apoptotic extracellular vesicles, bone-targeting, bone regeneration

Runmin Zhang, Muzhe Li, Huiyun Li, Xun Ran, Fengtian Jin, Qingshan Tan, Zhiwei Chen Department of Orthopaedics, The First Affiliated Hospital of University of South China, Hengyang, People’s Republic of ChinaCorrespondence: Zhiwei Chen, Department of Orthopaedics, The First Affiliated Hospital of University of South China, 69| Chuanshan Road, Hengyang, Hunan, People’s Republic of China, Tel +86-13973409923, Email CZW9915@sina.comAbstract: Inflammation is a common feature of many inflammatory diseases and tumors, and plays a decisive role in their development. Exosomes are extracellular vesicles unleashed by assorted types of cells, and it is widely known that exosomes of different immune cell sources play different functions. Exosome production has recently been reported for immune cells comprising macrophages, T cells, B cells, and dendritic cells (DCs). Immune cell-derived exosomes are involved in a variety of inflammatory responses.Herein, we summarize and review the role of macrophages, T cells, B cells, and dendritic cells (DC) in inflammatory diseases, with a focus on the role of immune cell-derived exosomes in osteoarthritis, rheumatoid arthritis, and the inflammatory tumor microenvironment (TME).These findings are expected to be important for developing new treatments for inflammatory diseases and ameliorating tumor-related inflammation. Keywords: inflammatory diseases, immune cell-derived exosomes, osteoarthritis, rheumatoid arthritis, inflammatory tumor microenvironment

Qian Fan,1,&ast; Zhongmei Bai,2,&ast; Fabrice Yves Ndjana Lessomo,3,&ast; Bingqing Dong,1 Weiqin Zhong,1 Fenglin Jin,1 Zhiquan Wang3 1Department of Cardiology, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong Province, People’s Republic of China; 2Department of Cardiology, The People’s Hospital of Huangmei, Huanggang, Hubei Province, People’s Republic of China; 3Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiquan Wang; Fenglin Jin, Email 2839515516@qq.com; cardio7788@163.comBackground: Low volume change and minimal trauma observed during angiography are the reason why physicians often overlook any changes affecting pre-operative electrolytes levels after coronary intervention. However, few studies have addressed the issue of electrolyte changes after the coronary intervention. Therefore, our study investigates coronary angiography’s effect on electrolytes and provides the quick identification of groups more prone to electrolyte changes.Methods: From the department of cardiology of the second affiliated hospital of Shandong’s first medical university, 374 patients undergoing coronary angiography were selected. Pre-intervention and post-intervention serums, sodium (Na+), potassium (K+), chloride (Cl−), magnesium (Mg2+) and renal function were analyzed. The correlation between influential factors was also assessed. The association of hypokalemia with short-major adverse cardiac events (MACE) and arrhythmia was evaluated.Results: Among the 374 subjects including 264 patients who had a simple angiography and 110 patients who received coronary artery interventional therapy. A decrease in potassium levels was found in 81.8% of the patients, and post-interventional hypokalemia was observed in 15.0%. After the intervention, the hypokalemia among males was 2.18 times than that of females, and the pre-operative serum potassium level was 3.5mmol/L≤K+< 4.0mmol/L and was 2.09 times than that of K+≥ 4.0 mmol/L, but was not associated with age and either simple coronary angiography or PCI (percutaneous coronary intervention). Hypernatremia was also prevalent in males under 60 years and with pre-operative hypernatremia. Significant variations were found between hypokalemia and influential factors like hypertension, diabetes, and gastrointestinal disease. We also found that there was no obvious correlation between hypokalemia and recurrent angina, heart failure and death, but significantly increased the risk of some arrhythmias.Conclusion: Male patients are more likely to suffer from electrolyte disturbance after coronary intervention. There is a need to emphasize monitoring and managing electrolyte changes to prevent severe complications in the peri-operative period.Keywords: coronary angiography, electrolytes, hypokalemia, hypernatremia, risk factors

Yefu Yu,1,&ast; Guier Yang,2,&ast; Yanan Wang,1 Faxiang Jin,1 Huiyu Wang,1 Zhongqiang Yu,3 Lanqing Li,4 Xiangcheng Li,4 Junshun Gao,4 Wenfang Xu1 1Department of Clinical Laboratory, Affiliated Hospital of Shaoxing University, Shaoxing, 312000, People’s Republic of China; 2Emergency Ward of Affiliated Hospital of Shaoxing University, Shaoxing, 312000, People’s Republic of China; 3Department of Imaging, Affiliated Hospital of Shaoxing University, Shaoxing, 312000, People’s Republic of China; 4Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, 310016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenfang Xu, Department of Clinical Laboratory, Affiliated Hospital of Shaoxing University, 999 Zhongxing South Road, Yuecheng District, Shaoxing, People’s Republic of China, Tel +8613857589470, Email 0052019050@usx.edu.cn Junshun Gao, Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, 3 Qingchun East Road, Shangcheng District, Hangzhou, People’s Republic of China, Email gjs_919@zuaa.zju.edu.cnBackground: Actinomadura geliboluensis was first isolated in 2012 in Gelibolu, Canakkale, Turkey, and has not been reported to be isolated from humans until now. We have isolated it from the bronchoalveolar lavage fluid (BLF) of a patient with pneumonia and found its drug resistance. It is the first time that Actinomadura geliboluensis has been isolated from humans since its discovery and naming. This case may provide new ideas and methods for the clinical diagnosis and treatment of pulmonary actinomycosis.Case Description: The patient was a 75-year-old male who was hospitalized in a township hospital and failed to improve after penicillin treatment. After admission to our hospital, the patient was treated with piperacillin/tazobactam according to clinical guidelines for 14 days. Actinomadura geliboluensis was isolated from the patient’s BLF and was identified by 16S rRNA sequencing. This report shows the biological characteristics and in vitro drug susceptibility testing, as well as the genomics analysis based on next-generation sequencing (NGS). The results demonstrated that Actinomadura geliboluensis was easy to be mistakenly identified as Actinomyces dental caries by using the Merieux ANC identification card. Based on the MIC test, Actinomadura geliboluensis was susceptible to tetracyclines, quinolones and sulfonamides, but resistant to carbapenems, penicillins and cephalosporins. The K-B test results showed Actinomadura geliboluensis was highly sensitive to piperacillin/tazobactam. Genomic analysis based on NGS showed that the Actinomadura geliboluensis belongs to Planobispora rosea EF-Tu mutants conferring resistance to inhibitor GE2270A, AAC(3)-VIIa, vanRO, chrB, and mexY.Conclusion: Actinomycetes is generally sensitive to Penicillin but Actinomadura geliboluensis is not. In vitro drug susceptibility test is needed to support individualized drug use to avoid delay in the disease.Keywords: Actinomadura geliboluensis, pulmonary actinomycosis, antibiotic resistance, next generation sequencing, genomics

Xiao Lei,1,&ast; Guodong Tan,2,&ast; Yiming Wang,3,&ast; Li Chen,4,&ast; Yuan Cao,1 Bingxin Si,2 Zhen Zhen,2 Bei Li,5 Yan Jin,5 Wei Wang,6 Fang Jin1 1Shaanxi Clinical Research Center for Oral Disease & Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Air Force Medical Center, Fourth Military Medical University, Beijing, People’s Republic of China; 3Shaanxi Clinical Research Center for Oral Diseases & Department of Oral Surgery, School of Stomatology, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 4Shaanxi Key Laboratory of Energy Chemical Process Intensification & Institute of Polymer Science in Chemical Engineering, School of Chemical Engineering and Technology, Xi’an Jiao Tong University, Xi’an, Shaanxi, People’s Republic of China; 5State Key Laboratory of Military Stomatology & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 6State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Jin, Shaanxi Clinical Research Center for Oral Disease & Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China, Email fangjin191@163.com Wei Wang, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China, Email weiwang_0510@163.comIntroduction: Osteoarthritis (OA) is a chronic degenerative joint disease accompanied by an elevated macrophage proinflammatory phenotype, which is triggered by persistent pathologically elevated calcium ion levels in mitochondria. However, existing pharmacological compounds targeting the inhibition of mitochondrial calcium ion (m[Ca2+]) influx are currently limited in terms of plasma membrane permeability and low specificity for ion channels and transporters. In the present study, we synthesized mesoporous silica nanoparticle-amidated (MSN)-ethylenebis (oxyethylenenitrilo)tetraacetic acid (EGTA)/triphenylphosphine (TPP)-polyethylene glycol (PEG) [METP] nanoparticles (NPs), which specifically target mitochondria and block excess calcium ion influx.Methods: m[Ca2+] overload in OA mouse bone marrow-derived macrophages (BMDMs) was detected by a fluorescence probe. A tissue in situ fluorescence colocalization assay was used to evaluate METP NP uptake by macrophages. BMDMs from healthy mice were pretreated with a concentration gradient of METP NPs followed by lipopolysaccharide (LPS) stimulation and detection of m[Ca2+] levels in vitro. The optimal METP NP concentration was further applied, and the endoplasmic reticulum (ER) and cytoplasm calcium levels were detected. The inflammatory phenotype was measured by surface markers, cytokine secretion and intracellular inflammatory gene/protein expression. A Seahorse cell energy metabolism assay was performed to elucidate the mechanism by which METP NPs reverse the BMDM proinflammatory phenotype.Results: The present study identified calcium overload in BMDM mitochondria of OA mice. We demonstrated that METP NPs reversed the increased m[Ca2+] levels in mitochondria and the proinflammatory phenotype of BMDMs, with both in vivo and in vitro experiments, via the inhibition of the mitochondrial aspartate-arginosuccinate shunt and ROS production.Conclusion: We demonstrated that METP NPs are effective and highly specific regulators of m[Ca2+] overload. In addition, we demonstrated that these METP NPs reverse the macrophage proinflammatory phenotype by restoring m[Ca2+] homeostasis, thereby inhibiting the tissue inflammatory response and achieving a therapeutic effect for OA.Graphical Abstract: Keywords: nanoparticle, macrophage, mitochondria, calcium homeostasis, osteoarthritis

Ruirui Zhang,1 Fanfu Jin,1 Lanlan Zheng,1 Tingwei Liao,1 Guangling Guan,1 Jianfei Wang,1 Shoucai Zhao,1 Shizao Fei,2,&ast; Zhaohu Chu,1,&ast; Yang Xu1,3,&ast; 1Department of Neurology, The First Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of China; 2Wuhu Hospital, East China Normal University, Wuhu, People’s Republic of China; 3Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institutes, Wannan Medical College, Wuhu, Anhui Province, China; Department of Neurology, The First Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Xu; Zhaohu Chu, Department of Neurology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241000, People’s Republic of China, Tel/Fax +86 0553-5739542, Email southtv@163.com; chuzhaohu878@163.comBackground: Hemorrhagic transformation (HT) is one of the most common and severe complications in patients with acute ischemic stroke (AIS). It indicates a poor prognosis in AIS patients. However, the association of neutrophil to high-density lipoprotein ratio (NHR) with HT remains unclear.Purpose: This study examined whether the NHR has a predictive effect on HT in AIS patients and explored the predictive cutoff value of the NHR.Methods: This is a retrospective study and consecutively included AIS patients admitted to the Department of Neurology of the First Affiliated Hospital of Wannan Medical College between December 2019 and January 2022. All subjects had blood samples collected within 24 h of admission, and neutrophil counts and high-density lipoprotein counts were detected. HT was diagnosed with hemorrhage on subsequent magnetic resonance imaging (MRI) or computed tomography (CT) of the brain. Univariate logistic regression analysis was performed to identify confounding factors, and multivariate logistic regression analysis determined the correlation between NHR and HT. Receiver operating characteristic (ROC) curves were used to evaluate the clinical predictive value of NHR.Results: A total of 725 patients were finally included in this study, of which 87 (12%) developed HT. The median NHR value in the HT group was 4.31, which was significantly higher than that in the non-HT group, and the difference was statistically significant [4.31 (3.54– 6.24) vs 3.63 (2.68– 4.64), p < 0.001]. The binary logistic regression analysis showed that NHR was independently associated with HT in AIS patients (OR: 1.180, 95% CI: 1.036– 1.344, p = 0.013). The area under ROC curve (AUC) of NHR for predicting HT in AIS patients was 0.633 (95% CI: 0.567– 0.699, p < 0.001), and its optimal cutoff were 3.52.Conclusion: The NHR was a reliable and simple independent predictor of HT in AIS patients.Keywords: neutrophil to high-density lipoprotein ratio, neutrophil, high-density lipoprotein cholesterol, hemorrhagic transformation, acute ischemic stroke, neuroinflammation

Xu Huang,1 Mingxiao Han,2 Fei Jin,3 Zhichen Zhu,2 Haifang Zhang2 1Department of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Department of Laboratory, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Haifang Zhang, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, People’s Republic of China, Tel +86 512 67783550 ; +86 18896808917, Email haifangzhang@suda.edu.cnAbstract: We report our clinical exploration experience treating a 6-year-old girl with a postoperative central nervous system (CNS) infection of prolonged invasion with Klebsiella pneumoniae (K. pneumoniae) co-resistant to carbapenems and polymyxin B. Although rational antibiotic therapy and effective source control measures were applied, the infection was not controlled eventually. To understand the mechanism of infection, whole-genome sequencing (WGS) was used to explore the resistance mechanism, and the susceptibility test was used to observe the efficacy of ceftazidime–avibactam (CAZ-AVI) in vitro. It is currently uncertain whether CAZ-AVI could be used as a salvage therapy for pediatric CNS infection. Therefore, we hope to share this case to seek medical help worldwide to treat pediatric CNS infection.Keywords: central nervous system, co-resistant to carbapenems and polymyxin B, Klebsiella pneumoniae, whole-genome sequencing, ceftazidime–avibactam

Xiaohui Zhang,1,2,&ast; Fei Jin,1,2,&ast; Yanfei Lu,1,2 Fang Ni,1,2 Yuqiao Xu,1,2 Wenying Xia1,2 1Department of Laboratory Medicine, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, People’s Republic of China; 2Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuqiao Xu; Wenying Xia, Department of Laboratory Medicine, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Street No. 300, Guangzhou, 210029, People’s Republic of China, Tel +8625-6830-6146 ; +8625-6830-6287, Fax +8625-8372-4440, Email joe8165@163.com; xiawenying21106891@163.comPurpose: This study aimed (i) to investigate the clinical characteristics and risk factors related to in-hospital mortality in patients with infective endocarditis (IE) and (ii) to compare the differences in three age groups.Methods: A total of 240 IE cases diagnosed using the modified Duke criteria between January 2016 and December 2019 were included and retrospectively studied. Patients were stratified into three age groups: < 50 y, 50– 65 y, and > 65 y.Results: The mean age of the patients was 51 ± 14 y, and 154 patients (64.2%) were male. In addition, 136 (56.7%) patients with IE had no previous cardiac disease. Congenital heart disease (CHD, 21.3%) was the most common underlying heart disease, followed by rheumatic heart disease (RHD, 8.8%). Streptococcus was found in 55 (22.9%) patients and was the most common causative pathogen, comprising 52.9% of all positive blood cultures. Echocardiography showed the presence of vegetations in 88.3% of cases and the predominant involvement of the left heart valves. Fever and cardiac murmur were the most frequent presentations, with no significant differences among age groups. Compared with younger patients, elderly patients had a lower operation rate and higher in-hospital mortality. The independent risk factors of in-hospital mortality were age > 65 y, intracranial infection, splenic embolization, cerebral hemorrhage, NYHA class III–IV, and prosthetic valve infection.Conclusion: CHD replaces RHD as the most common underlying heart disease in IE patients. Patients without previous cardiac disease are at increased risk of IE. Streptococcus is still the primary causative pathogen of IE. Elderly patients present with more comorbidities and complications, in addition to a more severe prognosis than younger patients. Age older than 65 y, intracranial infection, splenic embolization, cerebral hemorrhage, NYHA class III–IV, and prosthetic valve infection showed poorer in-hospital outcomes.Keywords: infective endocarditis, clinical characteristics, risk factors, elderly patients

Kang Sun,1,2 Wangping Li,1 Yu Li,3,4 Guangyu Li,5 Lei Pan,1 Faguang Jin1 1Department of Respiratory and Critical Care Medicine, Tang Du Hospital, Air Force Military Medical University, Xi’an, Shaanxi Province, 710038, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The 989th Hospital of Joint Support Force of Chinese People’s Liberation Army, Luoyang, Henan Province, 471003, People’s Republic of China; 3Department of Infectious Diseases, Shaanxi Provincial People’s Hospital and The Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi Province, 710068, People’s Republic of China; 4Shaanxi Center for Models of Clinical Medicine in International Cooperation of Science and Technology, Xi’an, Shaanxi Province, 710068, People’s Republic of China; 5Department of Pathology, University of Texas Medical Branch, Galveston, TX, 77555, USACorrespondence: Lei Pan; Wangping Li, Department of Respiratory and Critical Care Medicine, Tang Du Hospital, Air Force Military Medical University, Xi’an, Shaanxi Province, 710038, People’s Republic of China, Email panlei@fmmu.edu.cn; qxd25@163.comBackground: The prognosis of ABA-HAP patients is very poor. This study aimed to develop a scoring model to predict ABA-HAP in patients with GNB-HAP.Methods: A single center retrospective cohort study was performed among patients with HAP caused by GNB in our hospital during January 2019 to June 2019 (the derivation cohort, DC). The variables were assessed on the day when qualified respiratory specimens were obtained. A prediction score was formulated by using independent risk factors obtained from logistic regression analysis. It was prospectively validated with a subsequent cohort of GNB-HAP patients admitted to our hospital during July 2019 to Dec 2019 (the validation cohort, VC).Results: The final logistic regression model of DC included the following variables: transferred from other hospitals (3 points); blood purification (3 points); risk for aspiration (4 points); immunocompromised (3 points); pulmonary interstitial fibrosis (3 points); pleural effusion (1 points); heart failure (3 points); encephalitis (5 points); increased monocyte count (2 points); and increased neutrophils count (2 points). The AUROC of the scoring model was 0.845 (95% CI, 0.796 ∼ 0.895) in DC and 0.807 (95% CI, 0.759 ∼ 0.856) in VC. The scoring model clearly differentiated the low-risk patients (the score < 8 points), moderate-risk patients (8 ≤ the score < 12 points) and high-risk patients (the score ≥ 12 points), both in DC (P < 0.001) and in VC (P < 0.001).Conclusion: This simple scoring model could predict ABA-HAP with high predictive value and help clinicians to choose appropriate empirical antibiotic therapy.Keywords: Acinetobacter baumannii, hospital acquired pneumonia, Gram-negative bacilli, predictive scoring model, empirical antibiotic therapy

The polymer‐based acetabular cup prosthesis, a vital component of hip replacement surgery, significantly contributes to the recovery of patients afflicted with osteoarthritic conditions. Nevertheless, the current clinical usage of polymer acetabular cup prostheses commonly encounters the challenge of balancing wear resistance and oxidation resistance, significantly impacting both their lifespan and patients′ quality of life. Consequently, researchers have persistently enhanced the attributes of polymer acetabular cup prosthetic materials. These enhancements, including irradiation and filler modifications, are intended to concurrently bolster both the wear and oxidation resistance of the prosthesis materials. This comprehensive approach aims to address wear‐associated clinical complications like osteolysis and oxidative brittleness, ultimately extending their in vivo service life. For this reason, this paper retrospectively discusses the progress of research on the modification of polymer acetabular cup prosthesis materials for high wear and oxidation resistance and explores potential design methods for optimising artificial acetabular cup materials, with a view to providing new ideas for extending the service life of artificial joint implants. [ABSTRACT FROM AUTHOR]

Miaomiao Liu,1,&ast; Hua Jiang,1,&ast; Yujuan Li,1 Chunmei Li,1 Zhijun Tan,2 Faguang Jin,1 Tao Zhang,1 Yandong Nan1 1Department of Respiratory and Critical Care Medicine, Tangdu Hospital, Air Force Military Medical University, Xi’an, 710038, People’s Republic of China; 2Department of Health Statistics, Air Force Military Medical University, Xi’an, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yandong Nan; Tao Zhang Email 13709205538@163.com; zhangft@fmmu.edu.cnObjective: To identify the risk factors for predicting the dynamic progression of COVID-19.Methods: A total of 2321 eligible patients were included in this study from February 4 to April 15, 2020. Two illness conditions, including mild/moderate (M/M) subtype to severe/critical (S/C) and S/C to fatality, were classified. Clinical message was collected and compared, respectively. Kaplan–Meier method, Cox regression model and risk score system were used to predict disease progression in S/C COVID-19.Results: A total of 112 of 1761 patients with M/M subtype were progressors (P) and 1649 non-progressors (NP). Increasing disease progression associated with higher levels of neutrophils count (HR=1.958, 95% CI=1.253– 3.059, P=0.003), CK (HR=2.203, 95% CI=1.048– 4.632, P=0.037), LDH (HR=3.309, 95% CI=2.083– 5.256, P< 0.001) and CRP (HR=2.575, 95% CI=1.638– 4.049, P< 0.001), and lower level of lymphocytes count (HR=1.549, 95% CI=1.018– 2.355, P=0.041), as well as total lesion volume ratio greater than ≥ 10% (HR=2.286, 95% CI=1.451– 3.601, P< 0.001) on admission. In progression to fatality, 56 of the 672 S/C cases died and 616 survived. Increasing fatality associated with lower level of lymphocytes count (HR:2.060, 95% CI:1.000– 4.242, P=0.050), higher levels of BUN (HR:2.715, 95% CI:1.539– 4.790, P< 0.001), CK-MB (HR:3.412, 95% CI:1.760– 6.616, P< 0.001), LDH (HR:5.578, 95% CI:2.317– 13.427, P< 0.001), and PT (HR:3.619, 95% CI:2.102– 6.231, P< 0.001). Furthermore, high risk of neutrophils count, lymphocytes count, CK, LDH, CRP, and total lesion volume ratio was powerfully correlated with the incidence of progression to S/C in patients with NS COVID-19 and high odds of lymphocytes count, BUN, CK-MB, LDH, and PT were significantly associated with death in patients with S/C COVID-19. In addition, the progression and mortality rates increased with increasing risk scores.Conclusion: Elevated LDH level and lymphopenia were independent predictors for COVID-19 sustainable management in classifying non-severe patients who progressed to severe condition and identifying S/C patients who deteriorated to fatal outcomes as well. Total lesion volume ratio ≥ 10% may provide early predictive evidence with COVID-19 patients at high risk of developing into S/C to improve prognosis.Keywords: COVID-19, mild/moderate, severe/critical, progression, fatality, risk factors

Feiyang Jin,1 Di Liu,1 Xiaoling Xu,1 Jiansong Ji,2 Yongzhong Du1 1Institute of Pharmaceutics, College of Pharmaceutics Sciences, Zhejiang University, Hangzhou, 310058, People’s Republic of China; 2Department of Radiology, Lishui Hospital of Zhejiang University, Lishui, 323000, People’s Republic of ChinaCorrespondence: Jiansong JiDepartment of Radiology, Lishui Hospital of Zhejiang University, Lishui, 323000, People’s Republic of ChinaTel +86-578-2285011Email lschrjjs@163.comYongzhong DuInstitute of Pharmaceutics, College of Pharmaceutics Sciences, Zhejiang University, 866 Yu-Hang-Tang Road, Hangzhou, 310058, People’s Republic of ChinaTel +86-571-88981651Email duyongzhong@zju.edu.cnAbstract: Benefiting from the rapid development of nanotechnology, photodynamic therapy (PDT) is arising as a novel non-invasive clinical treatment for specific cancers, which exerts direct efficacy in destroying primary tumors by generating excessive cytotoxic reactive oxygen species (ROS). Notably, PDT-induced cell death is related to T cell-mediated antitumor immune responses through induction of immunogenic cell death (ICD). However, ICD elicited via PDT is not strong enough and is limited by immunosuppressive tumor microenvironment (ITM). Therefore, it is necessary to improve PDT efficacy through enhancing ICD with the combination of synergistic tumor therapies. Herein, the recent progress of nanomaterials-based PDT combined with chemotherapy, photothermal therapy, radiotherapy, and immunotherapy, employing ICD-boosted treatments is reviewed. An outlook about the future application in clinics of nanomaterials-based PDT strategies is also mentioned.Keywords: photodynamic therapy, immunogenic cell death, antitumor immunity, immunosuppressive tumor environment, nanomedicines

Fa Jin, Weiyang Ou, Boyang Wei, Haiyan Fan, Chengcong Wei, Dazhao Fang, Guangxu Li, Wenchao Liu, Jiahui Liu, Lei Jin, Xuying He, Chuanzhi Duan Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, People’s Republic of ChinaCorrespondence: Chuanzhi Duan; Xuying He Tel +86 135 399 622 33; +86 136 888 771 33Fax +86 206 164 3010Email doctor_duanzj@163.com; 2517079319@qq.comBackground: Ischemic stroke is one of the leading causes of mortality and disability worldwide. Following stroke, there is secondary neuroinflammation that promotes further injury. Identifying the long non-coding RNA (lncRNA) involved in neuroinflammation after cerebral ischemic stroke will promote the discovery of potential therapeutic targets.Methods: We identified differentially expressed genes from genome-wide RNA-seq profiles of mice with focal ischemia using Gene Ontology Term Enrichment, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment analyses. Immune cell infiltration deconvolution, protein-protein interaction network construction, and co-expression network analyses were also used to screen lncRNAs. In further experiments, lncRNA Neat1 knockdown animal models were developed by intraventricular injection of the antisense oligonucleotide before performing middle cerebral artery occlusion (MCAO). An enzyme-linked immunosorbent assay was performed to measure the level of cytokines. Hematoxylin-eosin staining and immunohistochemical staining were used to observe the changes in morphology.Results: Enrichment analysis revealed that differential mRNAs induced neuroinflammation after MCAO. Immune deconvolution showed that the proportion of microglia gradually increased while monocytes decreased within 24 h. We identified six hub lncRNAs (Neat1, Gm10827, Trp53cor1, Mir670hg, C730002L08Rik, and Mir181a-hg) that were highly correlated with activated-microglia mRNAs (cor > 0.8). We found that Neat1 had the highest correlation coefficient with pro-inflammatory factor mRNA levels. In vivo experiments demonstrated that Neat1 had abnormally high expression after MCAO. Knockdown of Neat1 could significantly alleviate brain damage by reducing the number of activated microglia and reducing their release of proinflammatory cytokines.Conclusion: We identified inflammation-associated lncRNA Neat1 as crucial, which means it is a potential target for ischemic stroke treatment.Keywords: bioinformatics, lncRNA Neat1, ischemic stroke, MCAO, microglia, neuroinflammation