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Liangwen Chen,1,2,* Ziqiao Tang,1,* Liangliang Fu,1 Yang Xie,1 Junyi Xu,1 Haibin Xia,1,3 Ting Xia,3 Min Wang1,3 1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China; 2Center for Prosthodontics and Implant Dentistry, Optics Valley Branch, School and Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China; 3Department of Oral Implantology, School & Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ting Xia; Min Wang, Department of Dental Implantology, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan, Hubei Province, 430079, People’s Republic of China, Email tingzi90s@whu.edu.cn; 83wangmin@whu.edu.cnBackground: Peri-implantitis (PI) is a prevalent complication of implant treatment. Pyroptosis, a distinctive inflammatory programmed cell death, is crucial to the pathophysiology of PI. Despite its importance, the pyroptosis-related genes (PRGs) influencing PI’s progression remain largely unexplored.Methods: This study conducted histological staining and transcriptome analyze from three datasets. The intersection of differentially expressed genes (DEGs) and PRGs was identified as pyroptosis-related differentially expressed genes (PRDEGs). Functional enrichment analyses were conducted to shed light on potential underlying mechanisms. Weighted Gene Co-expression Network Analysis (WGCNA) and a pyroptotic macrophage model were utilized to identify and validate hub PRDEGs. Immune cell infiltration in PI and its relationship with hub PRDEGs were also examined. Furthermore, consensus clustering was performed to identify new PI subtypes. Protein-protein interaction (PPI) network, competing endogenous RNA (ceRNA) network, mRNA-mRNA binding protein regulatory (RBP) network, and mRNA-drugs regulatory network of hub PRDEGs were also analyzed.Results: Eight hub PRDEGs were identified: PGF, DPEP1, IL36B, IFIH1, TCEA3, RIPK3, NET7, and TLR3, which are instrumental in the PI’s progression. Two PI subtypes were distinguished, with Cluster 1 exhibiting higher immune cell activation. The exploration of regulatory networks provided novel mechanisms and therapeutic targets in PI.Conclusion: Our research highlights the critical role of pyroptosis and identifies eight hub PRDEGs in PI’s progression, offering insights into novel immunotherapy targets and laying the foundation for advanced diagnostic and treatment strategies. This contributes to our understanding of PI and underscores the potential for personalized clinical management.Keywords: peri-implantitis, pyroptosis, consensus clustering, immune cell infiltration, regulatory network

Jin J, Xia H, Su Y, et al. J Multidiscip Healthc. 2023;16:4139-4147. The authors wish to correct Figure 1 on page 4143 and Figure 2 on page 4144 after it came to their attention an error had been made during the process of composing images. The corrected Figure 1 is shown below: Figure 1 Continued. Figure 1 SWE images of postpartum anterior uterine walls.Notes: (A). The SWV of 4.88kPa in the postpartum anterior uterine wall for normal pregnant woman with the placenta not located on the anterior wall during pregnancy. (B). The SWV of 16.60kPa in the postpartum anterior uterine wall for normal pregnant woman with the placenta located on the anterior wall during pregnancy. (C). The SWV of 26.71kPa in the postpartum anterior uterine wall for pregnant woman complicated by diabetes mellitus with the placenta located on the anterior wall during pregnancy. The corrected Figure 2 is shown below: Figure 2 Continued. Figure 2 SWE images of postpartum posterior uterine walls.Notes: (A) The SWV of 13.88kPa in the postpartum posterior uterine wall for normal pregnant woman with the placenta not located on the posterior wall during pregnancy. (B) The SWV of 23.40kPa in the postpartum posterior uterine wall for normal pregnant woman with the placenta located on the posterior wall during pregnancy. (C) The SWV of 35.02kPa in the postpartum posterior uterine wall for pregnant woman complicated by diabetes mellitus with the placenta located on the posterior wall during pregnancy. The authors apologize for any inconvenience caused by these errors and for any confusion that may have arisen as a result. They would like to assure the readers that these corrections do not affect the results or conclusions of the paper.

Xian Ding,1,* Wenqi Liang,2,* Hongjuan Xia,1,* Yuee Liu,2 Shuxiong Liu,1 Xinyu Xia,1 Xiaoli Zhu,1 Yongyan Pei,3 Dewen Zhang4 1Department of Emergency, Third Affiliated Hospital of Naval Medical University, Shanghai, People’s Republic of China; 2Department of Emergency, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 3School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, People’s Republic of China; 4Longhua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongyan Pei, School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, No. 9-13, Zhongshan Campus, No. 13, Changmingshui Avenue, Wuguishan, Zhongshan City, Guangdong Province, People’s Republic of China, Email peiyongyan@gdpu.edu.cn Dewen Zhang, Longhua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New Area, Shanghai, People’s Republic of China, Email zhangdewen120@hotmail.comBackground: Sepsis was a high mortality and great harm systemic inflammatory response syndrome caused by infection. lncRNAs were potential prognostic marker and therapeutic target. Therefore, we expect to screen and analyze lncRNAs with potential prognostic markers in sepsis.Methods: Transcriptome sequencing and limma was used to screen dysregulated RNAs. Key RNAs were screened by correlation analysis, lncRNA-mRNA co-expression and weighted gene co-expression network analysis. Immune infiltration, gene set enrichment analysis and gene set variation analysis were used to analyze the immune correlation. Kaplan–Meier curve, receiver operator characteristic curve, Cox regression analysis and nomogram were used to analyze the correlation between key RNAs and prognosis. Sepsis model was established by lipopolysaccharide-induced HUVECs injury, and then cell viability and migration ability were detected by cell counting kit-8 and wound healing assay. The levels of apoptosis-related proteins and inflammatory cytokines were detected by RT-qPCR and Western blot. Reactive Oxygen Species and superoxide dismutase were detected by commercial kit.Results: Fourteen key differentially expressed lncRNAs and 663 key differentially expressed genes were obtained. And these lncRNAs were closely related to immune cells, especially T cell activation, immune response and inflammation. Subsequently, Subsequently, lncRNA PRKCQ-AS1 was identified as the regulator for further investigation in sepsis. RT-qPCR results showed that PRKCQ-AS1 expression was up-regulated in clinical samples and sepsis model cells, which was an independent prognostic factor in sepsis patients. Immune correlation analysis showed that PRKCQ-AS1 was involved in the immune response and inflammatory process of sepsis. Cell function tests confirmed that PRKCQ-AS1 could inhibit sepsis model cells viability and promote cell apoptosis, inflammatory damage and oxidative stress.Conclusion: We constructed immune-related lncRNA-mRNA regulatory networks in the progression of sepsis and confirmed that PRKCQ-AS1 is an important prognostic factor affecting the progression of sepsis and is involved in immune response.Keywords: sepsis, immune-related lncRNA, lncRNA-mRNA, PRKCQ-AS1, prognosis and progress

Jing Jin,1,&ast; Han Xia,1,&ast; Yanan Su,2 Tingyue Qi,1 Xia Hong,3 Yanyan Xie,3 Jun Xu1 1Department of Ultrasound, Medical Imaging Center, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225009, People’s Republic of China; 2Department of Radiology, Baoying County People’s Hospital, Yangzhou, 225800, People’s Republic of China; 3Department of Gynaecology and Obstetrics, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Xu, Department of Ultrasound, Medical Imaging Center, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 45 Taizhou Road, Guangling District, Yangzhou, 225009, People’s Republic of China, Tel +86 13665277765, Email xuu_jun@163.comObjective: To investigate postpartum myometrial elasticity in pregnant women with gestational diabetes mellitus (GDM) using shear wave elastography (SWE) and analyze the correlation between myometrial SWE values and obstetric complications.Methods: Clinical data of women who gave birth at Affiliated Hospital of Yangzhou University from August 2022 to July 2023 were retrospectively analyzed and divided into two groups based on GDM diagnosis: the GDM group and the healthy control group. SWE was used to measure the elasticity values of the anterior and posterior myometrial walls in both groups. Differences in placental attachment position and SWE values at the placental attachment site were compared between the two groups. Spearman correlation analysis was utilized to evaluate the correlation between SWE values and obstetric complications.Results: Glycated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (FPG), 2-hour postprandial glucose (2h PG), triglycerides (TG), and total cholesterol (TC) levels were higher in the GDM group than in the healthy control group (P< 0.05). There was a statistically significant difference in placental attachment position between the two groups (P< 0.05). In both the GDM (17.52± 0.42 vs 25.29± 0.74, P=0.001) and control groups (14.06± 5.01 vs 22.20± 6.34, P=0.001), mean SWE values were significantly lower for anterior versus posterior placental attachment, and mean SWE values were also significantly higher in the GDM versus control group for both anterior (17.52± 0.42 vs 14.06± 5.01, P=0.001) and posterior placental attachment (25.29± 0.74 vs 22.20± 6.34, P=0.001). Spearman correlation analysis showed that postpartum hemorrhage (r=0.632, P=0.017), preeclampsia (r=0.818, P=0.014), premature rupture of membranes (r=0.710, P=0.012), placental abruption (r=0.732, P=0.031), and ketoacidosis (r=0.729, P=0.022) were negatively correlated with average myometrial SWE values in the GDM group (P< 0.05).Conclusion: SWE values at the placental attachment site were higher in GDM patients than in healthy pregnant women, and myometrial elasticity was positively correlated with obstetric complications.Keywords: elastography, gestational diabetes, myometrium, pregnancy complications

Lietao Wang,1,&ast; Xin Fu,1,&ast; Min He,1,&ast; Lvyuan Shi,1 Dingyuan Wan,1 Yucong Wang,1 Qin Wu,1 Jing Yang,1 Bayuan Cai,2 Hongtao Xia,3 Hongxu Chen,4 Ge Zhang,5 Xianying Lei,6 Wei Zhang,7 Zhongxue Feng,7 Bo Wang,1 Zhongwei Zhang1 On behalf of Heat Stroke Research Group in Southwestern China1Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Critical Care Medicine, The People’s Hospital of Jiajiang, Leshan, People’s Republic of China; 3Department of Critical Care Medicine, Suining Central Hospital, Suining, People’s Republic of China; 4Department of Critical Care Medicine, The Hospital of Traditional Chinese Medicine of Leshan, Leshan, People’s Republic of China; 5Department of Critical Care Medicine, The First People’s Hospital of Longquanyi District, Chengdu, People’s Republic of China; 6Department of Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 7Department of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Wang; Zhongwei Zhang, Department of Critical Care Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, People’s Republic of China, Tel/Fax +86-28-85422739, Email wchicu@126.com; 716461751@qq.comObjective: The aim of this nationwide multicenter study was to ascertain the risk factors associated with in-hospital mortality in patients with heat stroke admitted to intensive care units (ICUs) and to develop a nomogram for prognostic prediction.Methods: A retrospective analysis was conducted on clinical data collected from ICU patients diagnosed with heat stroke across multiple centers nationwide. Univariate and multivariate logistic regression analyses were performed to identify significant risk factors for in-hospital mortality. Based on the results of the multivariate analysis, a nomogram was constructed to estimate the individualized probability of mortality. Internal validation of the nomogram was performed, and its performance was assessed using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA).Results: A total of 292 ICU patients with heat stroke were included in this study. Three risk factors, namely Cr (creatinine), AST (aspartate aminotransferase), and SBP (systolic blood pressure), were found to be significantly associated with in-hospital mortality. These risk factors were incorporated into the nomogram, which exhibited good discriminative ability (area under the ROC curve of the training and validation cohorts were 0.763 and 0.739, respectively) and calibration. Internal validation and decision curve analysis confirmed the stability and reliability of the nomogram.Conclusion: This nationwide multicenter study identified key risk factors for in-hospital mortality in ICU patients with heat stroke. The developed nomogram provides an individualized prediction of mortality risk and can serve as a valuable tool for clinicians in the assessment and management of ICU patients with heat stroke.Keywords: heat stroke, intensive care unit, in-hospital mortality, risk factors, nomogram

Manjiao Zhuang,1,&ast; Lei Rao,2,3,&ast; Yadi Chen,1 Shangying Xiao,1 Haishan Xia,1 Jiangyong Yang,2 Xiaohua Lv,1 Dongyun Qin,1 Chunjie Zhu1 1Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People’s Republic of China; 2Medical College, Shaoguan University, Shaoguan, 512026, People’s Republic of China; 3Department of Biomedicine, Chengdu Medical College, Chengdu, 610500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Manjiao Zhuang, Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People’s Republic of China, Email manjiao@163.com Chunjie Zhu, School of Basic Medicine, Guangdong Medical University, Dongguan, 523808, People’s Republic of China, Email zhuchunjie718@163.comIntroduction: Quercetin has an ideal therapeutic effect on islet function improvement in type 2 diabetes mellitus (T2DM). However, the therapeutic benefit of quercetin is hindered by its poor bioavailability and limited concentration in pancreatic islets. In this study, superparamagnetic iron oxide nanoparticle (SPION)-modified exosomes were prepared to load quercetin, hoping to endow quercetin with enhanced water solubility and active targeting capacity with the help of magnetic force (MF).Methods: Transferrin-modified SPIONs (Tf-SPIONs) were synthesized by exploiting N-hydroxysuccinimidyl (NHS) conjugation chemistry, and quercetin-loaded exosomes (Qu-exosomes) were acquired by electroporation. Tf-SPION-modified quercetin-loaded exosomes (Qu-exosome-SPIONs) were generated by the self-assembly of transferrin (Tf) and the transferrin receptor (TfR). The solubility of quercetin was determined by high-performance liquid chromatography (HPLC) analysis. The pancreatic islet targeting capacity and insulin secretagogue and antiapoptotic activities of Qu-exosome-SPIONs/MF were evaluated both in vitro and in vivo.Results: The Qu-exosome-SPIONs were well constructed and harvested by magnetic separation with a uniform size and shape in a diameter of approximately 86.2 nm. The water solubility of quercetin increased 1.97-fold when loaded into the SPION-modified exosomes. The application of SPIONs/MF endowed the Qu-exosomes with favorable targeting capacity. In vitro studies showed that Qu-exosome-SPIONs/MF more effectively inhibited or attenuated β cell apoptosis and promoted insulin secretion in response to elevated glucose (GLC) compared with quercetin or Qu-exosome-SPIONs. In vivo studies demonstrated that Qu-exosome-SPIONs/MF displayed an ideal pancreatic islet targeting capacity, thereby leading to the restoration of islet function.Conclusion: The Qu-exosome-SPIONs/MF nano-delivery system significantly enhanced the quercetin concentration in pancreatic islets and thereby improved pancreatic islet protection.Keywords: quercetin, exosome, SPION, solubility, targeted delivery, islet function

Jiequn Huang,1 Changzhi Liu,1 Zhujiang Zhou,1 Han Xia,2 Zhensheng Zhu,2 Jianhai Lu,1 Jingcheng Lin,1 Zhen Chen,1 Qimei Ye,1 Liuer Zuo1 1Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan), Foshan, Guangdong, People’s Republic of China; 2Department of Scientific Affairs, Hugobiotech Co, Ltd, Beijing, People’s Republic of ChinaCorrespondence: Liuer Zuo, Department of Intensive Care Unit, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde, Foshan), Foshan, Guangdong, People’s Republic of China, Email 13500276597@163.comBackground: Pneumonia infected by Chlamydia abortus (C. abortus) is rare, especially complicated with severe acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS).Case Presentation: We presented the clinical details of a 44-year-old male who was diagnosed with C. abortus pneumonia, which rapidly progressed and ultimately led to ARDS, sepsis and MODS. Although he was initially diagnosed with pneumonia upon admission, no pathogenic bacteria were detected in sputum by conventional tests. Empirical intravenous infusion of meropenem and moxifloxacin was administered, but unfortunately, his condition deteriorated rapidly, especially respiratory status. On Day 2 after extracorporeal membrane oxygenation (ECMO) initiation, metagenomic next-generation sequencing (mNGS) was performed on the patient’s bronchoalveolar lavage fluid, which indicated an infection with C. abortus. The patient’s antimicrobial therapy was adjusted to oral doxycycline (0.1g every 12h), intravenous azithromycin (0.5g every day), and imipenem and cilastatin sodium (1g every 6h). The patient’s condition improved clinically and biologically. However, the patient was discharged due to financial reasons and unfortunately passed away eight hours later.Conclusion: Infections with C. abortus can result in severe ARDS and serious visceral complications which necessitate prompt diagnosis and active intervention by clinicians. The case highlights the significance of mNGS as an essential diagnostic tool for uncommon pathogens. Tetracyclines, macrolides or their combinations are effective choices for treatment of C. abortus pneumonia. Further study is needed to explore the transmission routes of C. abortus pneumonia and establish precise guidelines for antibiotic treatment.Keywords: Chlamydia abortus, ECMO, pneumonia, acute respiratory distress syndrome, metagenomic next-generation sequencing

Huan Xia,1,2,&ast; Juan Jin,3,&ast; Huanhuan Ba,3 Yuan Zhang,3 Jiajia Li,3 Rui Guo,3 Ying Li,3 Ping Ma,1,2 Yan Zhang3 1Department of Infectious Diseases, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China; 2Tianjin Association of STD/AIDS Prevention and Control, Tianjin, 300011, People’s Republic of China; 3Department of Infectious Diseases, Xi’an Eighth’s Hospital, Xi’an, Shaanxi, 710061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Zhang, Xi’an Eighth’s Hospital, 2 Zhangba East Road, Yanta District, Xi’an, Shaanxi, 710061, People’s Republic of China, Tel/Fax +86-29-85393973, Email 1522649620@qq.com Ping Ma, Tianjin Second People’s Hospital, 7 Sudi South Road, Nankai District, Tianjin, Tianjin, 300192, People’s Republic of China, Tel/Fax +86-22-27468129, Email mapingtianjin@163.comPurpose: The genetic diversity and genetic predisposition for drug resistance mutations are the primary features of human immunodeficiency virus type 1 (HIV-1), which could cause the incidence of failure of antiretroviral therapy (ART). This study investigates the distribution of various HIV-1 genotypes and the incidence of pretreatment drug resistance (PDR) in the antiretroviral-naive HIV-1 infected participants in Xi’an, China.Patients and Methods: In this study, a cross-sectional analysis was carried out at the Xi’an Eighth Hospital between January 2020 and December 2021 among newly-diagnosed ART-naive HIV-1 infected participants. A nested PCR technique was used for amplifying the target segment of 1.3 kb present in the pol gene that spanned the reverse transcriptase and the protease regions. HIV-1 genotypes and the PDR-associated mutations were identified using the Stanford HIV Drug Resistance Database.Results: A total of 317 pol gene sequences were retrieved, amplified, and sequenced. The circulating recombinant form (CRF), CRF07_BC (51.7%) was seen to be the most prevalent HIV-1 genotype, followed by other genotypes like CRF01_AE (25.9%), B (14.2%), and CRF55_01B (4.7%). PDR was found in 18.3% of the population. The PDR mutation frequency in the non-nucleoside reverse transcriptase inhibitor (NNRTI) (16.1%) was significantly higher compared to that of the nucleoside reverse transcriptase inhibitor (NRTI) (4.4%) and the protease inhibitor (0.9%). V179D/E (both were 4.4%) was seen to be the most predominant type of NNRTI mutation. K65R and M184V (1.3%) were the most frequent NRTI-associated mutations. About half (48.3%) of the sequenced HIV-1 strains that had mutations could show a potential low-level NNRTI resistance owing to V179D/E. Multivariate regression analysis revealed one PDR mutation associated with subtype CRF01_AE (p=0.002) and CRF55_01B (p< 0.001) as a higher risk mutation.Conclusion: Diverse and complex HIV-1 genotypes are distributed in Xi’an, China. Considering new evidence, it is necessary to screen for baseline HIV-1 drug resistance among the newly-diagnosed HIV-1 individuals.Keywords: human immunodeficiency virus, drug resistance, pre-treatment, China

Yang Zheng,1 Hui Xia,1 Xundi Bao,2 Bing Zhao,1 Ping He,1 Yanlin Zhao1 1National Tuberculosis Reference Laboratory, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Laboratory Department, Anhui Chest Hospital, Anhui, People’s Republic of ChinaCorrespondence: Yanlin Zhao, National Center for TB Control and Prevention, Chinese Center for Disease Control and Prevention, No. 155 Chang Bai Road, Changping District, Beijing, 102206, People’s Republic of China, Tel +86-10-58900517, Fax +86-10-58900556, Email zhaoyl@chinacdc.cnPurpose: The drug resistance of Mycobacterium tuberculosis constitutes a major public health threat. Existing approaches make it challenging to detect low levels of drug-resistant TB, also known as heteroresistance (HR), in a population. The recently found droplet digital PCR (ddPCR) is a sensitive method for determining the precise amount of nucleic acid in a sample. We used ddPCR to test the Mycobacterium tuberculosis heteroresistance because it delivers more exact quantitative data without the need for a reference curve.Patients and Methods: A TaqMan-MGB probe mutation detection assay was developed in order to determine the mutant and wild-type sequences of the isoniazid resistance katG (315) gene. We produced heteroresistant MTB combinations, which were subsequently identified by ddPCR, qPCR, and MeltPro/INH. In addition, 21 clinical sputum samples with positive smears were used to validate each method’s capacity to determine HR in sputum.Results: We discovered that ddPCR can detect mutant sequences in as few as 0.01% of a combination. DeepMelt TB/INH, which is less sensitive in comparison, cannot detect HR with high resolution and requires a mutation rate of 50% to identify. qPCR likewise has a high resolution of 0.02%, but unlike ddPCR, it cannot determine the exact number of mutations. Our assay is applicable to sputum as well. ddPCR found a katG 315 substitution in two sputums with extremely low values of HR (0.26% and 0.14%). In 21 samples of clinical sputum, the HR prevalence of INH was 9.5%.Conclusion: This work demonstrates that a well-designed ddPCR HR detection test can detect low levels of HR with high accuracy and consistency and gives new information for the clinical diagnosis of drug resistance.Keywords: Mycobacterium tuberculosis, drug-resistant, isoniazid, heteroresistance

Hui Xia,1 Yuanyuan Song,1 Yang Zheng,1 Shengfen Wang,1 Bing Zhao,1 Wencong He,1 Dongxin Liu,2 Xichao Ou,1 Yang Zhou,1 Yanlin Zhao1 1National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Yanlin Zhao, National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, No. 155, Changbai Road, Changping District, Beijing, People’s Republic of China, Tel +86 10-58900517, Email zhaoyl@chinacdc.cnObjective: To compare the ability of detection of borderline rifampicin resistance in Mycobacterium tuberculosis between molecular assay and phenotypic drug susceptibility tests.Methods: Fifty-seven isolates with His445Leu, Asp435Tyr, Leu452Pro, Leu430Pro, His445Asn, Ile491Phe, and His445Ser mutations in rpoB gene identified by whole-genome sequencing conferring borderline rifampicin resistance were included. Molecular-based Xpert MTB/RIF, phenotypic Löwenstein–Jensen (L-J) medium-based drug susceptibility test (DST) with a critical concentration of 40.0μg/mL and minimal inhibitory concentration (MIC) assay were performed to detect borderline rifampicin resistance.Results: When using Xpert MTB/RIF, 48/57 (84.2%) isolates exhibited resistance to rifampicin. 25/57 (43.9%) and 33/57 (57.9%) isolates showed rifampicin resistance by L-J medium-based DST with 4 and 6 weeks of incubation, respectively. 30/57 (52.6%) and 40/57 (70.2%) strains were resistant to rifampicin by MIC method at cutoff values of 1.0 and 0.5μg/mL, respectively. The detection rate of rifampicin resistance of Xpert MTB/RIF was significantly higher than that of phenotypic methods (p < 0.001). Of the 57 isolates with borderline rpoB mutations, 5 (8.8%) had MICs of 0.25 or 0.12μg/mL, 22 (38.6%) had MICs of 0.5μg/mL or 1.0μg/mL, and 30 (52.6%) other isolates showed MICs ≥ 2.0μg/mL.Conclusion: Molecular-based Xpert MTB/RIF showed superior ability to detect borderline rifampicin resistance over phenotypic DST methods. Extending the incubation time of L-J DST or lowering the cutoff value of the MIC method can improve borderline rifampicin resistance detection.Keywords: Mycobacterium tuberculosis, rifampicin, borderline resistance, phenotypic drug susceptibility test

Yu H, Dong L, Wang H, et al. Cancer Manag Res. 2021;13:1803–1815. We, the Editor and Publisher of Cancer Management and Research are retracting the published article. Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The authors listed in this publication have been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

The spatial distributions of single‐frequency and dual‐frequency Electromagnetic ion cyclotron (EMIC) waves in the subauroral ionosphere are investigated under varying geomagnetic activities, using high‐resolution magnetic field data from dual Swarm satellites spanning from 2015 to 2017. Single‐frequency EMIC waves predominantly occur in the dawn sector, whereas dual‐frequency waves exhibit peaks around both dawn and dusk. The occurrence rate of dual‐frequency waves shows a more pronounced increase with increasing geomagnetic activity. As magnetic storms evolve, both types of EMIC waves shift from dusk to dawn. The South Atlantic Anomaly (SAA) emerges as a high‐incidence region for ionospheric EMIC waves. Dual‐frequency EMIC waves display lower frequencies compared to other regions. Additionally, the low‐frequency components of dual‐frequency waves observed at higher latitudes demonstrate greater power density and longer durations than their high‐frequency counterparts. This suggests that higher frequency waves experience more significant damping during propagation. Most dual‐frequency EMIC waves observed in the ionosphere belong to the O‐band and He‐band waves, indicating that magnetospheric bands below the cyclotron frequency of H+ are more likely to propagate into the ionosphere. Key Points: Single‐frequency ionospheric electromagnetic ion cyclotron (EMIC) waves mainly occur in the dawn sector while dual‐frequency EMIC waves peak around dawn and duskThe occurrence rate of dual‐frequency waves increases more significantly with enhanced geomagnetic activity than single‐frequency wavesLow‐frequency components of dual‐frequency waves observed at higher latitudes exhibit greater power density and extended duration [ABSTRACT FROM AUTHOR]

Jieluan Lu,1 Hanbing Xia,2 Wenzhou Li,2 Xianhuan Shen,1 Huijuan Guo,2 Jianping Zhang,1 Xiaomei Fan2 1Department of Clinical Pharmacology, College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China; 2Department of Pharmacy, Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen, 518102, People’s Republic of ChinaCorrespondence: Jianping ZhangDepartment of Clinical Pharmacology, College of Pharmacy, Jinan University, 601 W. Huangpu Avenue, Guangzhou, 510632, People’s Republic of ChinaTel +86 20 85220261Email tzhangjp@jnu.edu.cnXiaomei FanDepartment of Pharmacy, Baoan Women’s and Children’s Hospital, Jinan University, 56# Yulv Road, Baoan District, Shenzhen, 518102, People’s Republic of ChinaTel +86 755 27863999Email xmfane@163.comBackground: Valproic acid (VPA) is recommended as a first-line treatment for children with epilepsy. GABRG2 polymorphism is found to be associated with epilepsy susceptibility and therapeutic response of anti-seizure medications (ASM); however, the role of GABRG2 in VPA treatment still remains unknown.Objective: The purpose of this study was to explore the association of GABRG2 gene polymorphism with the drug response and adverse drug reactions (ADRs) related to VPA.Methods: A retrospective study including 96 Chinese children with epilepsy treated by VPA was carried out. The ADRs were collected during VPA therapy and GABRG2 rs211037 in enrolled patients was genotyped using Sequenom MassArray system. A network pharmacological analysis involved protein–protein interaction and enrichment analysis was constructed to investigate the potential targets and pathways of GABRG2 on VPA-related ADRs.Results: Among 96 patients, 41 individuals were defined as seizure together with 49 patients with seizure-free and 6 patients unclassified. Carriers of homozygote GABRG2 rs211037 CC genotype exhibited seizure-free to VPA (P = 0.042), whereas those with CT genotype showed seizure. Furthermore, CC genotype had predisposition to digestive ADRs (P = 0.037) but was a protective factor for VPA-associated weight gain (P = 0.013). Ten key genes related to digestive ADRs and weight gain induced by VPA were identified by network pharmacological analysis and mainly involved in “GABAergic synaptic signaling”, “GABA receptor signaling”, and “taste transduction” pathways/processes through enrichment analysis.Conclusion: This study revealed that GABRG2 variation exerted a predictable role in the efficacy and safety of VPA treatment for Chinese children with epilepsy.Keywords: children with epilepsy, GABRG2, gene polymorphism, valproic acid, therapeutic response, adverse drug reactions

Shujing Zhang,1,2,&ast; Ping Luo,3,&ast; Juanjuan Xu,1,&ast; Lian Yang,4,&ast; Pei Ma,1,&ast; Xueyun Tan,1,&ast; Qing Chen,5,&ast; Mei Zhou,1 Siwei Song,1 Hui Xia,1 Sufei Wang,1 Yanling Ma,1 Fan Yang,4 Yu Liu,5 Yumei Li,1 Guanzhou Ma,1 Zhihui Wang,6 Yanran Duan,7 Yang Jin1 1Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 2Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 3Department of Translational Medicine Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 4Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 5Health Checkup Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 6Department of Scientific Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 7School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang JinDepartment of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, People’s Republic of ChinaEmail whuhjy@126.comBackground: It remains unclear whether discharged COVID-19 patients have fully recovered from severe complications, including the differences in the post-infection metabolomic profiles of patients with different disease severities.Methods: COVID-19-recovered patients, who had no previous underlying diseases and were discharged from Wuhan Union Hospital for 3 months, and matched healthy controls (HCs) were recruited in this prospective cohort study. We examined the blood biochemical indicators, cytokines, lung computed tomography scans, including 39 HCs, 18 recovered asymptomatic (RAs), 34 recovered moderate (RMs), and 44 recovered severe/ critical patients (RCs). A liquid chromatography-mass spectrometry-based metabolomics approach was employed to profile the global metabolites of fasting plasma of these participants.Results: Clinical data and metabolomic profiles suggested that RAs recovered well, but some clinical indicators and plasma metabolites in RMs and RCs were still abnormal as compared with HCs, such as decreased taurine, succinic acid, hippuric acid, some indoles, and lipid species. The disturbed metabolic pathway mainly involved the tricarboxylic cycle, purine, and glycerophospholipid metabolism. Moreover, metabolite alterations differ between RMs and RCs when compared with HCs. Correlation analysis revealed that many differential metabolites were closely associated with inflammation and the renal, pulmonary, heart, hepatic, and coagulation system functions.Conclusion: We uncovered metabolite clusters pathologically relevant to the recovery state in discharged COVID-19 patients which may provide new insights into the pathogenesis of potential organ damage in recovered patients.Keywords: COVID-19, recovery, metabolomics

Hua Yang,1,* Jian Gao,2,* Shuyu Li,1 Huiling Xia,1 Zhangyan Chen,1 Shanzhu Zhu,1 Zhigang Pan1 1Department of General Practice, Zhongshan Hospital of Fudan University, Shanghai, 200030, People’s Republic of China; 2Department of Nutrition, Zhongshan Hospital of Fudan University, Center of Clinical Epidemiology and Evidence-Based Medicine, Fudan University, Shanghai, 200030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shanzhu Zhu; Zhigang PanDepartment of General Practice, Zhongshan Hospital of Fudan University, No. 180, Road Fenglin, Shanghai, 200030, People’s Republic of ChinaTel +86 13501770447; +86 13681971967Email shanzhu_zhu@163.com; zhigang_pan@163.comBackground and Objectives: Serum uric acid (sUA) level has been reported to be associated with arteriosclerotic cardiovascular risk, yet remains poorly defined in Chinese type 2 diabetes patients. The purpose of the current study was to evaluate gender differences in the association between sUA level and arteriosclerotic cardiovascular risk in Chinese type 2 diabetes patients.Methods: The cross-sectional study was conducted in six community health service centers in Shanghai, China from December 2014 to December 2016. A stratified random sampling method was used to recruit participants. From a total of 3977 type 2 diabetic patients, 2537 were included for the analysis of the association between sUA level and arteriosclerotic cardiovascular risk. Clinical and biochemical data were obtained from participants. Arteriosclerotic cardiovascular risk was evaluated by the ten-year risk profile for arteriosclerotic cardiovascular disease. The associations between sUA level and arteriosclerotic cardiovascular risk were assessed via multiple logistic regression.Results: Of the 2537 participants, the average sUA level was 317± 77umol/L in men and 294± 73 umol/L in women, and 54.8% (1391/2537) of participants had high ten-year risk of arteriosclerotic cardiovascular disease (ASCVD), which was ≥ 20%. High ten-year risk of ASCVD odds ratio was increased by 1.596 (95% CI, 1.113– 2.289, p for trend 0.004) comparing fourth to first quartiles of sUA in women. However, no significant association was found between sUA and high ten-year risk of ASCVD in men.Conclusion: This community-based study indicated that sUA levels were independently associated with high ten-year risk of ASCVD in women with type 2 diabetes mellitus, but not in men.Keywords: serum uric acid, ten-year risk, arteriosclerotic cardiovascular disease, type 2 diabetes mellitus

Hao Yu,1 Liqian Dong,2 Hongyu Wang,3 Yang Zhang,3 Zhuo Wang,3 Can Wang,3 Hong Xia,1 Huizheng Bao1 1Department of Hematology, Jilin Cancer Hospital, Changchun, Jilin, 130012, People’s Republic of China; 2Department of Nephrology, Jilin Province FAW General Hospital, Changchun, Jilin, 130013, People’s Republic of China; 3Department of Medical Oncology, Jilin Cancer Hospital, Changchun, Jilin, 130012, People’s Republic of ChinaCorrespondence: Huizheng BaoDepartment of Hematology, Jilin Cancer Hospital, 1018 Huguang Road, Changchun, Jilin, 130012, People’s Republic of ChinaEmail hemat_baohuizheng@163.comPurpose: Long intergenic non-protein coding RNA 504 (LINC00504) is a long non-coding RNA that has an important regulatory role in a variety of human cancers. In this study, LINC00504 expression in breast cancer tissues and cell lines was detected. Studies were also conducted to determine the impact of LINC00504 on the tumor behavior of breast cancer cells. The potential mechanisms underlying the oncogenic role of LINC00504 in breast cancer cells were elucidated in detail.Methods: Expression of LINC00504 in breast cancer was analyzed by quantitative real-time polymerase chain reaction. The effects of LINC00504 on proliferation, apoptosis, in vitro migration and invasion, and in vivo tumor growth were elucidated using Cell Counting Kit-8 assay, flow cytometry, Transwell assays, and tumor xenograft models, respectively. Bioinformatics analyses in conjunction with RNA immunoprecipitation, luciferase reporter assays, and rescue experiments were conducted to investigate the underlying molecular mechanisms.Results: LINC00504 was upregulated in breast cancer tissues and cell lines. Knocking down LINC00504 suppressed breast cancer cell proliferation, migration, and invasion and facilitated apoptosis in vitro. In addition, tumor growth in vivo was significantly inhibited by LINC00504 depletion. Regarding the underlying mechanism, LIN00504 could function as a competing endogenous RNA in breast cancer by sponging microRNA-876-3p (miR-876-3p), resulting in the upregulation of high mobility group box 3 (HMGB3). Rescue experiments further revealed that miR-876-3p downregulation or HMGB3 upregulation effectively reversed the inhibitory effects of LIN00504 deficiency on breast cancer cells.Conclusion: The LIN00504-miR-876-3p-HMGB3 axis shows carcinogenic effects in modulating the biological behavior of breast cancer cells. This pathway may represent an effective target for CRC diagnosis and anticancer therapy.Keywords: high mobility group box 3, long intergenic non-protein coding RNA 504, therapeutic target, ceRNA

In addressing challenges associated with behavioural decision-making in intelligent driving, a hybrid algorithm, merging fuzzy classification with neural networks (termed the FC-NN Decision-Making methodology), has been introduced. Features from the driving environment, such as vehicle speed and relative distance, were systematically extracted. Using established traffic rules and vehicular performance metrics, a database linking the driving environment to decision outcomes was formulated. Through defined classification rules, fuzzy categorisation was applied, upon which training was subsequently conducted via NNs. This led to the design of an efficient Fuzzy-NN Decision-maker. Analyses demonstrated that the introduced method yielded an accuracy rate of 94%, markedly surpassing the accuracies of both the RBF NN decision-making at 56% and the direct NN approach at 76%. [ABSTRACT FROM AUTHOR]

Shengming Deng,1– 4,* Zhiyao Fan,1– 4,* Huanyu Xia,1– 4,* Yitao Gong,1– 4 Yunzhen Qian,1– 4 Qiuyi Huang,1– 4 He Cheng,1– 4 Kaizhou Jin,1– 4 Zhiwen Xiao,1– 4 Guopei Luo,1– 4 Xianjun Yu,1– 4 Chen Liu1– 4 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Pancreatic Cancer Institute, Shanghai, People’s Republic of China; 4Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chen Liu; Xianjun YuShanghai Pancreatic Cancer Institute, 270 Dong an Road, Shanghai 200032, People’s Republic of ChinaTel/Fax +86-21-6403-1446Email liuchen@fudanpci.org; yuxianjun@fudanpci.orgBackground: The fibrinogen/albumin ratio (FAR) has been widely reported to be a possible biomarker for predicting prognosis in several types of tumors, but the prognostic value of the FAR in pancreatic neuroendocrine neoplasms (Pan-NENs) has not been systematically studied.Patients and Methods: In total, 324 patients with Pan-NENs were recruited. The patients were divided into 2 subgroups according to the FAR cutoff value, and clinicopathological characteristics of the 2 subgroups were compared. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The prognostic value of the FAR was analyzed in univariate and multivariate analyses.Results: The optimal cutoff value for the FAR was calculated to be 0.08 for OS. The patients with a FAR ≥ 0.08 had higher proportions of nonfunctioning tumors, Pan-NECs, grade 3 tumors, and stage IV tumors than those with a FAR < 0.08. In the univariate analysis, a FAR ≥ 0.08 was associated with poor OS (hazard ratio (HR) = 2.37, P < 0.001) and PFS (HR = 2.37, P < 0.001). In the multivariate analysis, a FAR ≥ 0.08 was an independent risk factor for poor OS (HR = 4.70, P < 0.001) and PFS (HR = 1.80, P = 0.006).Conclusion: The pretreatment FAR, which includes fibrinogen and albumin, was a feasible and predictive biomarker for prognosis in patients with Pan-NENs. An elevated FAR, based on a cutoff value of 0.08, was an independent risk factor for poor OS and PFS.Keywords: pancreatic neuroendocrine neoplasms, survival, fibrinogen/albumin ratio

Chang Guo, Li Zhao, Yi Ding, Zhicong Zhao, Chenxi Wang, Lian Li, Zhensheng Cai, Yanyan Li, Hong Xia, ZhuanZhuan Zhu, Fan Yu, Meiqing Dai, Xia Deng, Guoyue Yuan Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of ChinaCorrespondence: Guoyue YuanDepartment of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, People’s Republic of ChinaTel +86-135-0528-9352Email yuanguoyue@ujs.edu.cnXia DengDepartment of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of ChinaEmail dengxia11@outlook.comAim: ANGPTL8 is a cytokine expressed and secreted by liver and adipose tissue, and is involved in glucose, lipid, and energy metabolism. Although studies have shown that ANGPTL8 is elevated in type 2 diabetes mellitus (T2DM) and cardiovascular disease, few have examined the association between ANGPTL8 single-nucleotide polymorphisms and the risk of macrovascular complications in T2DM patients. This study aimed to explore the relationship between rs2278426 and carotid intima–media thickening (cIMT) in T2DM.Methods: A total of 217 T2DM patients and 201 healthy control subjects with normal glucose tolerance were recruited in the study. T2DM patients were divided into two groups: T2DM patients without cIM thickening (cIMT < 1 mm, 109 cases) and T2DM patients with cIM thickening (cIMT ≥ 1 mm, 108 cases). rs2278426 genotypes in all 418 subjects were determined and the risk of T2DM and T2DM with cIM thickening analyzed.Results: CT+TT-genotype frequency in T2DM was higher than in controls with normal glucose tolerance, and the proportion of the CT+TT genotype in the group with cIMT was higher than in the group (P< 0.05). In addition, T alleles were associated with waist:hip ratio, triglycerides, high density–lipoprotein cholesterol, plasma glucose at 2 hours’ oral glucose tolerance, and homeostatic model assessment of insulin resistance (P< 0.05).Conclusion: Generally, carriers of the T allele at rs2278426 are more likely to develop T2DM, and the risk of cIM thickening is significantly increased for T-allele carriers with T2DM, which indicates an increased risk of macroangiopathy.Keywords: type 2 diabetes mellitus, angiopoietin‑like protein 8, carotid intima–media thickness, polymorphism, rs2278426

Xia Deng, Li Zhao, Chang Guo, Ling Yang, Dong Wang, Yanyan Li, Hong Xia, Chenxi Wang, Zhensheng Cai, Lian Li, Zhicong Zhao, Guoyue Yuan Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, People’s Republic of ChinaCorrespondence: Guoyue Yuan; Zhicong ZhaoDepartment of Endocrinology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu 212001, People’s Republic of ChinaTel +86-13505289352; +86-18752965615Email yuanguoyue@ujs.edu.cn; 2211517025@stmail.ujs.edu.cnAim: We detected whether serum asprosin levels play a role in the occurrence and development of albuminuria in patients with type 2 diabetes mellitus (T2DM), which has not been previously discussed.Methods: Based on urinary albumin/creatinine ratio (UACR), 207 T2DM patients were divided into T2DM patients with normoalbuminuria (UACR< 30 mg/g), microalbuminuria (30≤UACR< 300 mg/g), and macroalbuminuria (UACR≥ 300 mg/g). Serum asprosin levels were determined by enzyme-linked immunosorbent assay.Results: Comparatively, the serum asprosin levels in T2DM patient groups with macroalbuminuria [2.37 (1.63– 3.57)] and microalbuminuria [2.10 (1.60– 2.90)] were significantly increased than the normoalbuminuria group [1.59 (1.18– 2.09)] (P< 0.001). Importantly, the serum level of asprosin was positively correlated with UACR (r=0.304, P< 0.001), creatinine (r=0.157, P=0.024), blood urea nitrogen (BUN) (r=0.244, P< 0.001), and negatively with glomerular filtration rate (eGFR) (r=− 0.159, P=0.022). Furthermore, multiple stepwise regression analyses showed that asprosin was significantly and independently related to UACR, BUN, DBP, and LDL-C (P< 0.05). Besides, after adjustment for the confounders, the serum asprosin level was constantly and independently associated with the development of albuminuria in T2DM patients [OR (95% CI): 2.003 (1.37∼ 2.928), P < 0.001].Conclusion: Obviously, the serum asprosin level was independently correlated with UACR in T2DM patients, which implies circulating asprosin may play an essential role in the pathogenesis of diabetic nephropathy.Keywords: asprosin, type 2 diabetes mellitus, diabetic nephropathy