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Wenqing Wang,1,2,* Chuchu Ye,2,3,* Bing Zhao,1 Yingjie Zheng,4 Ge Zhang,5 Jinghua Su,1 Hong Huang,1 Lipeng Hao,1,2 Mingliang Chen6 1Department of Microbiology, Pudong New Area Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 2Fudan University Pudong Institute of Preventive Medicine, Shanghai, People’s Republic of China; 3Department of Infectious Disease Control and Prevention, Pudong New Area Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 4Department of Epidemiology/Key Laboratory for Health Technology Assessment, National Commission of Health and Family Planning/Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 5School of Public Health, Dali University, Yunnan, People’s Republic of China; 6Research and Translational Laboratory of Acute Injury and Secondary Infection, and Department of Laboratory Medicine, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingliang Chen; Lipeng Hao, Email cmlbright@126.com; hlpmail@126.comBackground: The occurrence and dissemination of hypermucoviscous and hypervirulent Klebsiella pneumoniae (hm-hvKp) isolates in clinical settings are a critical public health problem in the world. However, the data on these isolates in community populations are limited. This study aims to understand the prevalence and molecular characteristics of hm-hvKp isolates in community patients in Shanghai, China.Methods: In 2018, an active surveillance system focused on hm-hvKp in community diarrhoeal cases was implemented in Pudong New Area, Shanghai, China, involving 12 sentinel hospitals. The antimicrobial susceptibility of hm-hvKp isolates from fecal samples was tested, and whole-genome sequencing (WGS) was performed to predict the serotypes and sequence types and to identify antimicrobial resistance determinants, virulence determinants, and phylogenetic clusters.Results: The overall prevalence of hm K. pneumoniae isolates was 2.48% (31/1252), with the proportions of 1.76% (22/1252) for hm-hvKp and 0.72% (9/1252) for hm not hv K. pneumoniae. The prevalence of hm-hvKp isolates among different age groups and different months was statistically significant. All the 22 hm-hvKp isolates were susceptible to 20 antimicrobial agents and only carried blaSHV gene, and KL1 and KL2 accounted for eight (36.36%) cases and seven (31.82%) cases, respectively. The eight ST23/KL1 isolates belonged to the predominant CG23-I clade, which typically possessed the virulence determinants profile of rmpA/rmpA2-iro-iuc-ybt-irp-clb. The five ST86/KL2 isolates were assigned to the global clusters ST86/KL2-1 (n=2), ST86/KL2-2 (n=2), ST86/KL2-3 (n=1), all lack of the clb gene. Shanghai ST23/KL1 and ST86/KL2 isolates were closely related to the global isolates from liver abscesses, blood, and urine.Conclusion: Hm-hvKp is carried by the community population of Shanghai, with ST23/KL1 and ST86/KL2 isolates predominant. Hm-hvKp isolates of different continents, different sources, and different virulence levels were closely related. Ongoing surveillance of hm-hvKp isolates in the community population is warranted.Keywords: hypermucoviscous, hypervirulent, Klebsiella pneumoniae, drug resistance determinants, virulence determinants, whole-genome sequencing

Chenglin Ye,1,* Sizhe Zhu,2,* Jingping Yuan,1 Xiuxue Yuan3 1Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, People’s Republic of China; 3Medical College of Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingping Yuan; Xiuxue Yuan, Email yuanjingping@whu.edu.cn; exiuwust@gmail.comPurpose: Crohn’s disease (CD) represents a multifaceted inflammatory gastrointestinal condition, with a profound significance placed on unraveling its molecular pathways to enhance both diagnostic capabilities and therapeutic interventions. This study focused on identifying a robust macrophage-related signatures (MacroSig) for diagnosing CD, emphasizing the role of FPR1 in macrophage polarization and its implications in CD.Patients and Methods: Expression profiles from intestinal biopsies and macrophages of 1804 CD patients were retrieved from the Gene Expression Omnibus (GEO). Utilizing CIBERSORTx, differential expression analysis, and weighted correlation network analysis to to identify macrophage-related genes (MRGs). By unsupervised clustering, distinct clusters of CD were identified. Potential biomarkers were identified via using four machine learning algorithms, leading to the establishment of MacroSig which combines insights from 12 machine learning algorithms. Furthermore, the expression of FPR1 was verified in intestinal biopsies of CD patients and two murine experimental colitis models. Finally, we further explored the role of FPR1 in macrophage polarization through single-cell analysis as well as through the study of RAW264.7 cells and peritoneal macrophages.Results: Two distinct clusters with differential levels of macrophage infiltration and inflammation were identified. The MacroSig, which included FPR1 and LILRB2, exhibited high diagnostic accuracy and outperformed existing biomarkers and signatures. Clinical analysis demonstrated a strong correlation of FPR1 with disease activity, endoscopic inflammation status, and response to infliximab treatment. The expression levels of FPR1 were validated in our CD cohort by immunohistochemistry and confirmed in two colitis mouse models. Single-cell analysis indicated that FPR1 is predominantly expressed in macrophages and monocytes. In vitro studies demonstrated that FPR1 was upregulated in M1 macrophages, and its activation promoted M1 polarization.Conclusion: We developed a promising diagnostic signature for CD, and targeting FPR1 to modulate macrophage polarization may represent a novel therapeutic strategy.Keywords: Crohn’s disease, macrophage, diagnostic signature, FPR1, machine learning

Yonggui Zhang,1 Xianzhong Lin,2 Chen Ye,2 Peiling Zhang3 1Department of Anesthesiology, The Second Hospital of Longyan, Fujian, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of ChinaCorrespondence: Xianzhong Lin, Department of Anesthesiology, the First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, People’s Republic of China, Email lxzyjs@fjmu.edu.cnBackground: With the aging of the population and the increasing incidence of neurological diseases, amnestic mild cognitive impairment (aMCI) has attracted attention. Hyperbaric oxygen (HBO) has gradually shown the potential in the treatment of aMCI as an emerging treatment method in recent times. This study is to observe the effect of HBO on the long-term learning memory of aMCI rats, and investigate the associated mechanisms.Methods: Seventy-two male rats (4-month-old) were randomly divided into control (CON) group, aMCI group, HBO group, 24 rats in each group. Each group was randomly divided into CON1, CON7, CON28; aMCI1, aMCI7, aMCI28; HBO1, HBO7, HBO28, 8 rats in each group. The aMCI model rats were established in aMCI and HBO groups. HBO group was treated with HBO for 7 days. The ethological and cytopathology which include Morris water maze (MWM) test, HE staining, TUNEL staining and the expression of Fas/FasL on neuron membrane were conducted to evaluate the effects of HBO on day 1, day 7 and day 28 after HBO treatment.Results: MWM test showed that the spatial learning and memory ability of the rats decreased in aMCI group, and recovered in HBO group; Compared with aMCI group, the pathological damage of hippocampal nerve cells was alleviated, the number of apoptotic cells was significantly reduced (P < 0.05), and the expression of Fas/FasL on the surface of nerve cell membrane was significantly weakened in HBO group (P < 0.05). There were no significant changes in the spatial learning and memory ability, pathological damage of hippocampal neurons, the number of apoptotic cells, and the changes of Fas/FasL on the surface of hippocampal neurons in HBO1, HBO7, and HBO28 groups (P > 0.05). However, in aMCI1, aMCI7, and aMCI28 groups gradually aggravated (P < 0.05).Conclusion: 1. HBO can improve the long-term learning and memory impairment by attenuating neuronal apoptosis in aMCI rats. 2. Fas/FasL mediated cell receptor death pathway is involved in the apoptosis of hippocampal neurons.Keywords: amnesic mild cognitive impairment, hyperbaric oxygen, apoptosis, learning and memory impairment

Zhangrui Zeng,1,&ast; Yueshuai Wei,1,&ast; Caihong Ye,1 Yuan Jiang,1 Chunlin Feng,1 Tongtong Guo,1 Min Song,1 Yinhuan Ding,1 Ping Zhan,2 Jinbo Liu1 1Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 2Department of Gynaecology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo Liu, Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China, Te/Fax +86 0830 3165730, Email liujb7203@swmu.edu.cnPurpose: The isolation rate of carbapenem-resistant Enterobacter cloacae complex (CREC) is continuously increasing. The aims of this study were to investigate the molecular characteristics and risk factors associated with CREC infections.Methods: Bacterial species were identified using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Bruker Daltonik GmbH, Bremen, Germany), and the hsp60 gene was utilized for further typing. Antimicrobial susceptibilities were assessed through the MicroScan WalkAway 96 Plus system (Siemens, Germany) and the microbroth dilution method. Antimicrobial resistance genes were screened through polymerase chain reaction (PCR), while the homologous relationship was assessed using multilocus sequence typing (MLST). Conjugation experiments were performed to verify whether the plasmid could be transferred. Additionally, logistic regression model was employed to analyze risk factors for CREC infections.Results: 32 strains of CREC bacteria were isolated during the study, yet only 20 were retained for preservation. While the isolates demonstrated resistance to the majority of antibiotics, they exhibited high sensitivity to polymyxin B and tigecycline. All isolates carried the blaNDM resistance gene, including 13 blaNDM-1 isolates and 7 blaNDM-5 isolates. MLST homology analysis revealed the presence of seven known ST types and one new ST type. Conjugation experiments confirmed that 13 isolates were capable of transferring the blaNDM resistance gene to Escherichia coli strain EC600. Single-factor analysis identified multiple primary risk factors for CREC infection, but multivariate analysis did not reveal independent risk factors.Conclusion: This study investigates the molecular characteristics and risk factors associated with CREC infections. The detection rate of CREC strains in our hospital is continuously rising and homology analysis suggested that strains might spread in our hospital, emphasizing the importance of implementing effective preventive measures to control the horizontal transmission of plasmid-mediated antimicrobial resistance genes.Keywords: carbapenem-resistant, Enterobacter cloacae complex, antimicrobial resistance, molecular characteristics, risk factors

Jingqian Zhao,1,2,&ast; Chenyu Zhao,1,3,&ast; Tianrong Xun,1 Xiaokang Wang,1 Sui Wei,1,3 Chunxiao Ye,1 Mimi Zhang,1 Dan Guo,4 Xixiao Yang1 1Department of Pharmacy, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 2School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 3School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dan Guo; Xixiao Yang, Email nfyyyxb@smu.edu.cn; yaxx@smu.edu.cnPurpose: This study aims to investigate the effects of Huang Gan formula (HGF), a Chinese herbal prescription used for chronic kidney disease (CKD), on the regulation of the gut microbiota and colonic microenvironment of CKD.Methods: CKD rats were induced by 150 mg/kg adenine gavage for 4 weeks, then orally treated with or without 3.6 g/kg or 7.2 g/kg of HGF for 8 weeks. The renal function and structure were analyzed by biochemical detection, hematoxylin and eosin, Masson’s trichrome, Sirius red and immunochemical staining. Average fecal weight and number in the colon were recorded to assess colonic motility. Further, the changes in the gut microbiota and colonic microenvironment were evaluated by 16S rRNA sequencing, RT-PCR or immunofluorescence. The levels of inflammatory cytokines, uremic toxins, and NF-κB signaling pathway were detected by RT-PCR, ELISA, chloramine-T method or Western blotting. Redundancy analysis biplot and Spearman’s rank correlation coefficient were used for correlation analysis.Results: HGF significantly improved renal function and pathological injuries of CKD. HGF could improve gut microbial dysbiosis, protect colonic barrier and promote motility of colonic lumens. Further, HGF inhibited systemic inflammation through a reduction of TNF-α, IL-6, IL-1β, TGF-β 1, and a suppression of NF-κB signaling pathway. The serum levels of the selected uremic toxins were also reduced by HGF treatment. Spearman correlation analysis suggested that high-dose HGF inhibited the overgrowth of bacteria that were positively correlated with inflammatory factors (eg, TNF-α) and uremic toxins (eg, indoxyl sulfate), whereas it promoted the proliferation of bacteria belonging to beneficial microbial groups and was positively correlated with the level of IL-10.Conclusion: Our results suggest that HGF can improve adenine-induced CKD via suppressing systemic inflammation and uremia, which may associate with the regulations of the gut microbiota and colonic microenvironment.Keywords: chronic kidney disease, systemic inflammation, colonic microenvironment, gut-kidney axis

Ning Ma,1– 3,&ast; Lei Zhang,4,&ast; Wufang Zhang,1– 3 Yingying He,1– 3 Chong Ye,4 Xin Li4 1Peking University Sixth Hospital, Beijing, People’s Republic of China; 2Peking University Institute of Mental Health, Beijing, People’s Republic of China; 3NHC Key Laboratory of Mental Health (Peking University), Beijing, People’s Republic of China; 4Xi’an Janssen Pharmaceutical Ltd, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Ma, Peking University Sixth Hospital, NO. 51 Huayuan North Road, Haidian District, Beijing, 100191, People’s Republic of China, Tel +86 010 82801939, Email maning@bjmu.edu.cnAbstract: Evidence of comparative benefits of long-acting injectable (LAI) antipsychotics in Asian patients with schizophrenia has been inconsistent. This scoping review aimed to synthesize the current evidence in the past ten years and provide an overview of efficacy, safety, treatment adherence, patient attitudes, and healthcare resource utilization of LAI in this population. A systematic search was conducted with a pre-defined search strategy in six electronic databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang, PubMed, Embase, CINAHL, and PsycArticles. A total of 46 studies were included, including 15 cohort studies, 13 single-arm trials, 10 randomized controlled trials, four mirror-image studies, three cross-sectional studies, and one controlled clinical trial. Paliperidone palmitate once-monthly injection (27/46) and risperidone LAI (14/46) were the most frequently investigated LAIs. Compared with oral antipsychotic medications (OAMs), LAIs demonstrated a lower rate of relapse/hospitalization and comparable improvement in efficacy. Adverse events (AEs) were similar between LAIs and OAMs, although types and incidence varied. Significant reduction in the length of hospitalization and number of outpatient visits/inpatient admission was observed after initiation of LAIs. These findings suggest that LAI demonstrated comparable efficacy and safety among Asian populations with schizophrenia in comparison to OAMs. Better adherence and lower relapse were observed in patients receiving LAIs from published evidence. Future research is warranted to better understand the comprehensive performance of LAI in specific population or context.Plain Language Summary: LAI antipsychotic drugs for the maintenance treatment of schizophrenia have been considered the therapy of choice in case of poor adherence to treatment and frequent relapses. Few review studies focused on the benefits of LAI antipsychotics for schizophrenia in the Asian population have been conducted to date. Therefore, we conducted this scoping review to comprehensively summarize the current published evidence in terms of LAI efficacy, safety, treatment adherence, patient attitudes, and healthcare resource utilization in Asia.Keywords: long-acting injectable antipsychotics, schizophrenia, Asian, scoping review

Juan Pan,1 Chao Ye,2 Ling-Zhi Zhou,1 Zu-Yi Li,1 Juan Wang,2 Xin He,2 Shen-Jue Chen,2 Guang-Qing Zhou2 1Department of Pharmacy, Liuyang Hospital of Traditional Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Chao Ye, Department of Pharmacy, The Third Hospital of Changsha, No. 176 Laodong West Road, Tianxin District, Changsha, Hunan, 410015, People’s Republic of China, Email yechao1234256@163.com Ling-Zhi Zhou, Department of Pharmacy, Liuyang Hospital of Traditional Chinese Medicine, No. 67, Beizheng Middle Road, Changsha, Hunan, 410300, People’s Republic of China, Email 1024482174@qq.comIntroduction: Tigecycline-induced acute pancreatitis (AP) has been frequently increasingly reported in solid organ transplant patients. This review aimed to summarize the characteristics, possible mechanisms, and management of tigecycline-induced AP.Methods: Case reports of tigecycline-induced AP published in Chinese or English were collected until February 2023 for retrospective analysis.Results: Thirty-four patients from 29 articles were included. Fifteen patients (46.9%) had solid organ transplantation, and 4 patients (12.5%) had malignant tumors. Twenty-five patients (89.3%) received a recommended maintenance dose of tigecycline (50 mg q12 h). The median age was 50 years (range 9– 87). Compared to the nontransplant patients, the median age of the transplant patients was significantly younger, 44 years (range 12.5– 61) versus 57.5 years (range 9– 87) (P=0.03). The median time of symptom onset was 7 days (range 2– 29), and 91.2% (31/34) were less than 14 days. Typical initial symptoms included abdominal pain (90.6%), nausea (46.9%), vomiting (43.8%), and abdominal distention (21.9%). Most cases were accompanied by elevated levels of pancreatic enzymes. The main radiological features included edematous infiltrate and acute pancreatitis on computed tomography (CT) scan and abdominal ultrasound. Except for one patient who continued tigecycline treatment, all patients discontinued treatment and received symptomatic support such as fasting, acid suppression, and enzyme suppression. The median time to recover pancreatic enzymes to the normal range was 5 days (range 1– 43), and the median time to relieve symptoms was 4 days (range 1– 12). Four patients died, of whom two died of severe pancreatitis complications and two of cardiogenic shock and septicemia.Conclusion: Tigecycline-induced AP was a rare and serious complication that occurred mainly within two weeks of the medication. This serious side effect should be kept in mind while treating severe infections especially in transplant recipients.Keywords: tigecycline, pancreatitis, adverse drug reaction, solid organ transplantation

Chunjiang Wang,1 Yulu Zhou,2 Ya Zhou,3 Chao Ye4 1Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 2Department of Pharmacy, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, 410028, People’s Republic of China; 3Department of Pharmacy, People’s Hospital of Ningxiang City Affiliated to Hunan University of Chinese Medicine, Changsha, Hunan, 410600, People’s Republic of China; 4Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan, 410015, People’s Republic of ChinaCorrespondence: Chao Ye, Department of Pharmacy, The Third Hospital of Changsha, No. 176, Laodong West Road, Tianxin District, Changsha, Hunan, 410015, People’s Republic of China, Email yechao1234256@163.comBackground: Neurotoxicity is a rare adverse event for ertapenem. Given the limited evidence, large patient data are needed to aid in the identification and management of this fatal complication. Aim of the review, we summarize the characteristics, risk factors, and treatment of ertapenem-induced neurotoxicity.Methods: Pubmed, Web of Science, Embase, Cochrane library, Wanfang, CNKI, China VIP database were searched up from 31 October 2001 to 31 December 2022. All articles concerning neurotoxicity induced by ertapenem were included. The retrieved articles were screened by two experienced clinicians by reading the titles, abstracts, and full texts.Results: A total of 66 patients were included, with a median age of 71.5 years (range 40– 92), of whom 45 (68.2%) were male. Twelve patients (18.2%) received irrational doses (exceeding the recommended dose), and 30 patients (45.5%) had chronic renal insufficiency. The median time to symptom onset was 5 (range 1– 14). Epileptiform seizures (42.4%), visual hallucinations (36.4%), altered mental status (25.8%), and confusion (22.7%) were the most common symptoms of ertapenem-induced neurotoxicity. Of the 29 patients with reported albumin levels, 25 had serum albumin < 3.5 g/dl. Ertapenem was discontinued in 95.5% of patients, and 90.9% recovered completely. Median time to symptom recovery was 7 days (range 1– 42) after intervention including antiepileptic administration, or hemodialysis.Conclusion: Neurotoxicity is a rare adverse event for ertapenem, especially in patients with advanced age, renal insufficiency, pre-existing neurological disease, and hypoalbuminemia. This adverse reaction usually resolves with medication interruption, or antiepileptic administration and hemodialysis.Keywords: ertapenem, carbapenem, neurotoxicity, encephalopathy, seizures

Qirong Lu,1,&ast; Wantong Han,1,&ast; Defeng Wen,1,&ast; Pu Guo,1 Yu Liu,1 Zhongyuan Wu,1 Shulin Fu,1 Chun Ye,1 Xu Wang,2 Yinsheng Qiu1 1Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan, 430023, People’s Republic of China; 2National Reference Laboratory of Veterinary Drug Residues (HZAU) and Ministry of Agriculture Key Laboratory for the Detection of Veterinary Drug Residues in Foods, Huazhong Agricultural University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pu Guo; Yinsheng Qiu, Wuhan Polytechnic University, Wuhan, Hubei, 430023, People’s Republic of China, Email guopu@whpu.edu.cn; qiuyinsheng6405@whpu.edu.cnBackground: At present, the treatment and prevention of Pasteurella multocida infections in pigs mainly rely on antibiotics and vaccines, but inflammatory injury cannot be eliminated. The compound 18β-glycyrrhetinic acid (GA), a pentacyclic triterpenoid extracted from Glycyrrhiza glabra L. root (liquorice) and with a chemical structure similar to that of steroidal hormones, has become a research focus because of its anti-inflammatory, antiulcer, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and neuroprotective effects, but its potential for the treatment of vascular endothelial inflammatory injury by P. multocida infections has not been evaluated. This study aimed to investigate the effects and mechanisms of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections.Materials and Methods: Putative targets of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections were identified using network pharmacological screening and molecular docking simulation. The cell viability of PIEC cells was investigated via the CCK-8 assay. The mechanism of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections were investigated using cell transfection and western blot.Results: Through network pharmacological screening and molecular docking simulation, this study found that PARP1 may be a core target for GA to exert anti-inflammatory effects. Mechanistically, GA alleviates P. multocida-induced vascular endothelial inflammation by PARP1-mediated NF-κB and HMGB1 signalling suppression.Conclusion: These findings, for the first time, demonstrate the potential therapeutic relationship among GA, PARP1 and inflammatory injury, providing a candidate drug, therapeutic targets and explanation for treating vascular endothelial inflammatory injury caused by P. multocida infection.Keywords: network pharmacology, GA, PARP1, inflammatory injury, P. multocida infection

Israel Guerrero-Arguero,1 Siddiqur Rahman Khan,1 Brandon M Henry,1 Andreu Garcia-Vilanova,1 Kevin Chiem,1 Chengjin Ye,1 Sweta Shrestha,2 Deborah Knight,3 Mark Cristner,4 Shauna Hill,4 W James Waldman,3 Prabir K Dutta,2,5 Jordi B Torrelles,1 Luis Martinez-Sobrido,1 Amber M Nagy1,4 1Disease Intervention & Prevention and Population Health Programs, Texas Biomedical Research Institute, San Antonio, TX, USA; 2ZeoVation Inc., Columbus, OH, USA; 3Department of Pathology, The Ohio State University, Columbus, OH, USA; 4Chief Scientist’s Office of Science and Technology, 59th Medical Wing, Joint Base San Antonio-Lackland, San Antonio, TX, USA; 5Department of Chemistry, The Ohio State University, Columbus, OH, USACorrespondence: Prabir K Dutta; Amber M Nagy, Email dutta.1@osu.edu; AMallory@txbiomed.orgIntroduction: The coronavirus disease 2019 (COVID-19) pandemic has demonstrated the need for novel, affordable, and efficient reagents to help reduce viral transmission, especially in high-risk environments including medical treatment facilities, close quarters, and austere settings. We examined transition-metal nanozeolite suspensions and quaternary ammonium compounds as an antiviral surface coating for various textile materials.Methods: Zeolites are crystalline porous aluminosilicate materials, with the ability of ion-exchanging different cations. Nanozeolites (30 nm) were synthesized and then ion-exchanged with silver, zinc and copper ions. Benzalkonium nitrate (BZN) was examined as the quaternary ammonium ion (quat). Suspensions of these materials were tested for antiviral activity towards SARS-CoV-2 using plaque assay and immunostaining. Suspensions of the nanozeolite and quat were deposited on polyester and cotton fabrics and the ability of these textiles towards neutralizing SARS-CoV-2 was examined.Results: We hypothesized that transition metal ion containing zeolites, particularly silver and zinc (AM30) and silver and copper (AV30), would be effective in reducing the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Additionally, AM30 and AV30 antiviral potency was tested when combined with a quaternary ammonium carrier, BZN. Our results indicate that exposure of SARS-CoV-2 to AM30 and/or AV30 suspensions reduced viral loads with time and exhibited dose-dependence. Antiviral activities of the combination of zeolite and BZN compositions were significantly enhanced. When used in textiles, AM30 and AV30-coated cotton and polyester fabrics alone or in combination with BZN exhibited significant antiviral properties, which were maintained even after various stress tests, including washes, SARS-CoV-2-repeated exposures, or treatments with soil-like materials.Conclusion: This study shows the efficacy of transition metal nanozeolite formulations as novel antiviral agents and establishes that nanozeolite with silver and zinc ions (AM30) and nanozeolite with silver and copper ions (AV30) when combined with benzalkonium nitrate (BZN) quickly and continuously inactivate SARS-CoV-2 in suspension and on fabric materials.Keywords: SARS-CoV-2, disinfection, quats, zeolites, transition metals, coated fabrics

The ability to tune magnetic orders, such as magnetic anisotropy and topological spin texture, is desired to achieve high-performance spintronic devices. A recent strategy has been to employ interfacial engineering techniques, such as the introduction of spin-correlated interfacial coupling, to tailor magnetic orders and achieve novel magnetic properties. We chose a unique polar-nonpolar LaMnO3/SrIrO3 superlattice because Mn (3d)/Ir (5d) oxides exhibit rich magnetic behaviors and strong spin-orbit coupling through the entanglement of their 3d and 5d electrons. Through magnetization and magnetotransport measurements, we found that the magnetic order is interface-dominated as the superlattice period is decreased. We were able to then effectively modify the magnetization, tilt of the ferromagnetic easy axis, and symmetry transition of the anisotropic magnetoresistance of the LaMnO3/SrIrO3 superlattice by introducing additional Mn (3d) and Ir (5d) interfaces. Further investigations using in-depth first-principles calculations and numerical simulations revealed that these magnetic behaviors could be understood by the 3d/5d electron correlation and Rashba spin-orbit coupling. The results reported here demonstrate a new route to synchronously engineer magnetic properties through the atomic stacking of different electrons, which would contribute to future applications in high-capacity storage devices and advanced computing.

Chenchen Ye,1,2 Xinxue Guo,2 Jiani Wu,2 Minhua Wang,2 Haiyan Ding,2 Xianzhi Ren1,3,4 1The First Clinical College, Nanjing University of Chinese Medicine, Nanjing, 210046, People’s Republic of China; 2Department of Pediatrics, Yixing Hospital of Traditional Chinese Medicine, Yixing, 214200, People’s Republic of China; 3Department of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210046, People’s Republic of China; 4Department of Pediatrics, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, 210046, People’s Republic of ChinaCorrespondence: Xianzhi Ren, Department of Pediatrics, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, 210046, People’s Republic of China, Email doctorrxz@126.comBackground: Adenoid hypertrophy (AH) is a chronic or acute obstruction-related ailment of the upper respiratory tract that arises as an inflammatory response to exposure of bacteria, viruses or allergies. Activation and polarization of macrophages are key processes in inflammation-related disorders like AH and CCL20/CCR6 axis is a critical therapeutic target.Purpose: To determine that CCL20/CCR6 mediated macrophage activation and polarization can promote adenoid epithelial inflammation in AH.Methods: To support this claim, CCL20 and CCR6 expressions were studied in clinical AH samples. In addition, the expressions of cytokines such as TNF-α, IL-1β, IL-6, IL-17, IL-10 and TGF-β were analysed. In vitro, human adenoid epithelial cells were co-cultured with polarized THP-1 and T lymphocyte H9 cells to study the expressions of several inflammatory markers.Results: The expressions of M1 macrophage markers CD86 and IL-17 were significantly increased, whereas the expressions of M2 macrophage markers CD206 and FOXP3 were significantly decreased. The THP-1 cells were successfully polarized to M0, M1 and M2 macrophages. The survival of macrophages improved after 24 hr of induction and enhanced TGF-β expression was observed. The expressions of the inflammatory cytokines IL-6, TNF-α, IL-1β and CCL20 increased significantly.Conclusion: Collectively, these results suggest that the CCL20/CCR6 mediated macrophage activation and polarization into M1-type macrophages can promote adenoid epithelial inflammation in AH. Further studies are warranted to determine the roles of inflammatory markers in the pathophysiology of AH and identifying potential targets.Keywords: adenoid hypertrophy, CCL20/CCR6 axis, inflammation, macrophages, markers

Ke-Ke Lu,1 Miao-Miao Zhang,1 Yue-Li Zhu,2 Chen Ye,1 Min Li3 1Emergency Department, Hangzhou Linping Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Nursing, Hangzhou Linping Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 3Department of Infectious Diseases, Hangzhou Linping Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yue-Li Zhu, Department of Nursing, Hangzhou Linping Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang Province, People’s Republic of China, Email lyuezhu@126.comObjective: To explore the effects of the Toyota Production System (TPS) for improving the quality of emergency intrahospital transport for critically ill patients in management.Methods: Between April and June 2021, 68 critically ill patients were transported to corresponding wards, while 63 critically ill patients were transported to corresponding wards between July and September 2021. The pre-TPS and post-TPS management groups each included 30 cases based on their propensity score. The TPS management tool was combined with the PDCA method for analysing the current situation as well as determining the target for improvement, calculating the value and process efficiencies, and modifying and evaluating relevant processes. At last, the changes in transport time, receiving department, patient satisfaction, and adverse event rate of critically ill patients after TPS management were analysed.Results: The total intrahospital transport time of critically ill patients decreased from 39 minutes (median) before the implementation of TPS management to 27 minutes (median) after TPS management, and the difference was statistically significant (P< 0.05). Process efficiency and value efficiency both increased from 33.33% and 38.46% before TPS management to 42.86% and 40.74% after TPS management, respectively. Likewise, the satisfaction of receiving departments and patients increased from 73.33% and 76.67% before TPS management to 96.67% and 96.67% after TPS management (P< 0.001). Finally, the adverse event rate decreased as a result of TPS management from 13.33% to 3.33% (P> 0.05).Conclusion: TPS management may significantly shorten the intrahospital transport time for critically ill patients, reduce the occurrence of adverse events in emergency care, advance patient satisfaction, and improve the overall quality and safety of emergency care.Keywords: Toyota Production System, TPS, critically ill patients, transportation of patients, patient satisfaction, emergency care

Pei Chen, Mengyun Yao, Tao Fang, Chaoshuang Ye, Yongjiang Du, Yang Jin, Ruijin Wu Department of Obstetrics and Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Ruijin Wu, Department of Obstetrics and Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China, Tel +86 571-8706223, Email wurj@zju.edu.cnBackground: Endometriosis (EMS) is a common and highly recurrent gynecological disease characterized by chronic pain and infertility. There are no definitive therapies for endometriosis since the pathogenesis remains undetermined. This study aimed to identify EMS-related functional modules and hub genes by integrated bioinformatics analysis.Methods: Three endometriosis expression profiling series (GSE25628, GSE23339, and GSE7305) were obtained from Gene Expression Omnibus (GEO). The EMS-related module was constructed by weighted gene co-expression network analysis (WGCNA), followed by Gene Ontology (GO) enrichment analyses. Cytohubba and the MCODE plug-ins of Cytoscape were used to screen out the hub genes, which were verified via receiver operating characteristic (ROC) curves. Immunohistochemistry was performed to verify the protein expression of the hub genes in ectopic endometrial tissues. Moreover, CIBERSORT was used to analyze the relationship between the abundance of immune cells infiltration and the expression of hub genes.Results: Among the 18 modules obtained, the darkmagenta module was identified as the EMS-related module, genes of which were significantly enriched to terms referring to cell migration and neurogenesis. NFASC and CHL1 were screened out and prioritized as hub genes through Cytoscape and confirmed to be differentially upregulated in ectopic endometrial samples. Finally, the expression of hub genes was related to the abundance of immune cells infiltration. The higher expression of NFASC or CHL1 correlated with increased M2 macrophages and decreased natural killer (NK) cells in ectopic lesions.Conclusion: This study provided new insights into the molecular factors underlying the pathogenesis of endometriosis and provided a theoretical basis for the potential that the two hub genes, NFASC and CHL1, might be novel biomarkers and therapeutic targets in the future.Keywords: endometriosis, bioinformatics analysis, WGCNA, immune cell infiltration

Chenglin Ye,1 Sizhe Zhu,2 Jingping Yuan1 1Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Jingping Yuan; Sizhe Zhu Email yuanjingping@whu.edu.cn; zhusizhe@hust.edu.cnPurpose: We aimed to construct a competing endogenous RNA (ceRNA) network and explore the potential biomarkers in Crohn’s disease (CD) via bioinformatics analysis. Validation of candidate biomarkers in a 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced experimental colitis model and ceRNA network in an HCT116 cell line was also an aim, along with purposing to reveal the pathogenesis of CD.Methods: GSE102134 and GSE67106 datasets were obtained and used to screen the differentially expressed genes. WCGNA was applied to identify the relative model to construct the ceRNA network. Furthermore, the relationship between candidate gene and immune infiltration was investigated. Then, the expression of potential biomarkers was validated via qRT-PCR in a TNBS induced experimental colitis model. Finally, the ceRNA network was confirmed by RNAi experiments in an HCT116 cell line.Results: The ceRNA network, consisting of four lncRNAs, four miRNAs, and eight mRNAs, was constructed and the ROC analysis showed four mRNAs (PTGS2, LPL, STAT1, and TRIB2) had high diagnostic accuracy (AUC> 0.9). In addition, upregulated PTGS2 was positively correlated with immune cell infiltration, including Natural killer cells, exhausted T-cells, monocytes, and Dendritic cells. The outcome of this TNBS induced experimental colitis model verified that the expression of PTGS2 and mir-429 was consistent with results of previous bioinformatics analysis. Furthermore, the predicted ceRNA network MIR3142HG/mir-429/PTGS2 were validated via RNA interference. Knockout of MIR3142HG decreased the mRNA level of PTGS2, whereas inhibition of mir-429 increased the mRNA level of PTGS2 in the HCT116 cell line.Conclusion: The exploration of the ceRNA network in this work might contribute to understanding the pathogenesis of CD. The constructed MIR3142HG/mir-429/PTGS2 ceRNA network may play a role in CD, and PTGS2 can be a potential immune-related biomarker in CD.Keywords: Crohn’s disease, ceRNA network, bioinformatics analysis, WCGNA, validation, experimental colitis mice model

Jun Tao,1,&ast; Chenglin Ye,2,&ast; Wen Dai,1 Di Li,1 Man Zhou,1 Yan Li1 1Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Department of Urology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Li; Wen Dai Tel +8613886079252; +8613476029919Email yanlitf1120@163.com; 527638620@qq.comBackground: As an inflammatory factor, complement C1q is related to the prevalence and progression of atherosclerosis; however, in patients undergoing emergency percutaneous coronary intervention (PCI), it is unclear whether C1q is related to the prevalence of contrast-associated acute kidney injury (CA-AKI).Methods: From November 2018 to March 2021, 1182 patients who underwent emergency PCI were continuously recruited. Patients were divided into CA-AKI group (n = 234) and non-CA-AKI group (n = 948). CA-AKI was defined as an increase in serum creatinine from the baseline level (≥ 25% or ≥ 0.5 mg/dL) 48– 72 hours after contrast exposure. All subjects were tested for serum C1q levels when they were admitted to the hospital.Results: Among the 1182 patients undergoing emergency PCI, 234 patients (19.80%) developed CA-AKI. The level of preoperative serum complement C1q in the CA-AKI group was significantly higher than that in the non-CA-AKI group. Logistic regression and restricted cubic spline analyses showed that the incidence of CA-AKI was positively associated with the serum C1q level pre-PCI. Univariate and multivariate logistic regression analyses showed that C1q was an independent predictor of whether CA-AKI occurred after emergency PCI. The area under the curve (AUC) of the C1q was 0.703 [95% confidence interval (CI) 0.667– 0.739] in patients receiving emergency PCI. CA-AKI model included the following three predictors: C1q, eGFR, and IABP use. The AUC of forecast probability was 0.718 [95% CI 0.682– 0.754].Conclusion: In patients receiving emergency PCI procedure, a high C1q level before PCI is associated with the increased risk of CA-AKI.Keywords: complement C1q, contrast-associated acute kidney injury, percutaneous coronary intervention, coronary heart disease, inflammation

Objective: This study aimed to investigate the efficacy and safety of laparoscopic-assisted radical surgery for right hemicolonic cancer with a combined approach. Methods: We conducted a retrospective review of clinical data from 102 patients who underwent laparoscopic-assisted radical right hemicolectomy for right hemicolonic cancer at the Department of General Surgery, Zhujiang Hospital, Southern Medical University, between January 2021 and September 2023. All patients received preoperative diagnoses of right hemicolonic cancer via CT and e-colonoscopy. Patients were categorized into two groups based on the surgical approach: the combined approach group (n = 51) and the traditional approach group (n = 51). Perioperative outcomes and follow-up data were compared between the two groups. Results: A total of 102 patients were included in the statistical criteria. Comparison of baseline data between the two groups showed no statistically significant differences (all p > 0.05). Compared with the traditional access group, the surgical stem-oriented combined access group had a shorter operative time [(180.69 ± 47.484) min vs. (226.18 ± 45.884) min, t = – 4.920, p < 0.001] and less intraoperative blood loss [(89.71 ± 79.350) ml vs. (149.31 ± 104.633) ml. Z = – 3.370, p = 0.001. Conclusions: Surgical stem-oriented modified combined approach laparoscopic radical right hemicolectomy for right hemicolonic cancer is safe and feasible and has the advantages of low surgical difficulty, shortened operative time, reduced intraoperative bleeding, and accelerated postoperative recovery. In addition, the combined approach may be more agreeable for beginners to master, and the procedure may be easier to promote and popularize. Trial registration: ClinicalTrials.gov (2024-KY-026–01). [ABSTRACT FROM AUTHOR]

Dong Xie,1,2,* Chenhui Xu,1,* Cheng Ye,1,* Shiqi Mei,3 Longqing Wang,1 Qi Zhu,1 Qing Chen,1 Qi Zhao,1 Zhiyan Xu,3 Jie Wei,3 Lili Yang1 1Spine Center, Department of Orthopaedics, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China; 2Department of Orthopaedics, PLA Navy No.905 Hospital, Shanghai, 200052, People’s Republic of China; 3Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lili Yang Tel +86-021-81885793Email yangll@smmu.edu.cnPurpose: Polyetheretherketone (PEEK) exhibits high mechanical strengths and outstanding biocompatibility but biological inertness that does not excite the cell responses and stimulate bone formation. The objective of this study was to construct submicro-nano structures on PEEK by femtosecond laser (FSL) for exciting the responses of MC3T3-E1 cells and gingival epithelial (GE) cells, which induce regeneration of bone/gingival tissues for long-term stability of dental implants.Materials and Methods: In this study, submicro-nano structures were created on PEEK surface by FSL with power of 80 mW (80FPK) and 160 mW (160FPK).Results: Compared with PEEK, both 80FPK and 160FPK with submicro-nano structures exhibited elevated surface performances (hydrophilicity, surface energy, roughness and protein absorption). Furthermore, in comparison with 80FPK, 160FPK further enhanced the surface performances. In addition, compared with PEEK, both 80FPK and 160FPK significantly excited not only the responses (adhesion, proliferation, alkaline phosphatase [ALP] activity and osteogenic gene expression) of MC3T3-E1 cells but also responses (adhesion as well as proliferation) of GE cells of human in vitro. Moreover, in comparison with 80FPK, 160FPK further enhanced the responses of MC3T3-E1 cells/GE cells.Conclusion: FSL created submicro-nano structures on PEEK with elevated surface performances, which played crucial roles in exciting the responses of MC3T3-E1 cells/GE cells. Consequently, 160FPK with elevated surface performances and outstanding cytocompatibility would have enormous potential as an implant for dental replacement.Keywords: polyetheretherketone; PEEK, surface modification, submicro-nano structures, functional group, cell responses

Ruijie Geng,1 Haibin Li,1 Hao Wang,2 Chenyu Ye,1 Yemeng Mao,3 Xiao Huang1,4 1Department of Psychological Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Teaching Center of Experimental Medicine, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Pharmacy, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Psychological Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, Fujian, People’s Republic of ChinaCorrespondence: Xiao HuangDepartment of Psychological Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, 361015, Fujian, People’s Republic of ChinaTel +86-0592-3501990Email huang.xiao@zs-hospital.sh.cnYemeng MaoDepartment of Pharmacy, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, 600 South Wanping Road, Shanghai, 200030, People’s Republic of ChinaTel +86-21-64387250Email mao_yemeng@163.comObjective: This study aimed to explore the mechanism of venlafaxine in regulating the apoptosis of SHSY-5Y cells induced by hypoxia.Methods: The CoCl2-induced neuronal hypoxia model was established based on SHSY-5Y cells. The morphology and related protein expression of SHSY-5Y cells were detected by qPCR, ELISA and Western blot.Results: Under the condition of hypoxia-induced by CoCl2, the expression of HIF-1α in SHSY-5Y cells was up-regulated and the expression of β-catenin was down-regulated. After adding siRNA targeting HIF-1 α to the culture cell system, down-regulation of β -catenin expression in SHSY-5Y cells was restored. This confirmed the existence of the “hypoxia-HIF-1α-Wnt/β-catenin-depression” axis. Further studies have shown that venlafaxine can alleviate neuronal apoptosis induced by hypoxia by upregulating the Wnt/β-catenin signaling pathway.Conclusion: Venlafaxine regulates apoptosis induced by hypoxia through the Wnt/β-catenin signaling pathway, which provides a new theoretical basis for the treatment of depression.Keywords: venlafaxine, Wnt/β-catenin, SHSY-5Y cells, apoptosis

Approximately 1–2 per 100,000 young athletes die from sudden cardiac death (SCD) and extreme exercise may be associated with myocardial scar and arrhythmias. Racehorses have a high prevalence of atrial fibrillation (AF) and SCD but the presence of myocardial scar and inflammation has not been evaluated. Cardiac tissues from the left (LAA) and right (RAA) atrial appendages, left ventricular anterior (LVAPM) and posterior (LVPPM) papillary muscles, and right side of the interventricular septum (IVS-R) were harvested from racehorses with sudden cardiac death (SCD, n = 16) or other fatal injuries (OFI, n = 17), constituting the athletic group (ATH, n = 33), and compared to sedentary horses (SED, n = 10). Horses in the ATH group had myocyte hypertrophy at all sites; increased fibrosis at all sites other than the LAA; increased fibroblast infiltration but a reduction in the overall extracellular matrix (ECM) volume in the RAA, LVAPM, and IVS-R compared to SED horses. In this horse model, athletic conditioning was associated with myocyte hypertrophy and a reduction in ECM. There was an excess of fibrocyte infiltration and focal fibrosis that was not present in non-athletic horses, raising the possibility of an exercise-induced pro-fibrotic substrate. [ABSTRACT FROM AUTHOR]

Xian Wu,1,* Chaoran Ye,1,* Xingmeng Wang,2 Ruyu Cai,1 Junzhe Yang,1 Xiafei Yu,1 Yi Zhou,1 Li Shen,1 Yanhui Zhu,1 Xiaoan Liu1 1Department of Breast Surgery, The First Affiliated HospitalofNanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of General Surgery, The First People’s Hospital of Yancheng City, Yancheng, 224006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanhui Zhu; Xiaoan Liu Tel +86-25-68308152Email yanhui1002@hotmail.com; liuxiaoan@126.comPurpose: To retrospectively analyze the efficacy and toxicity of epirubicin plus cyclophosphamide followed by docetaxel (EC-D) and epirubicin plus cyclophosphamide followed by paclitaxel (EC-P) efficacy as neoadjuvant chemotherapy regiments by pathological complete response (pCR) in this study.Methods: In total, 455 patients diagnosed with breast cancer who received NAC from January 2014 to January 2019 were enrolled. Of which, 109 patients received EC-D (E: 90, C: 600, D: 80, all in mg/m2) and 346 were treated with EC-P (E: 90, C: 600, D: 175, all in mg/m2). Efficacy of NAC regimens was evaluated by pCR, and the toxicity was studied. Chi-squared test was used at p=0.05.Results: In EC-D, 11 patients received ypT0/isN0, and 6 of them got ypT0N0. Analogously, 67 patients receiving received EC-P obtained ypT0/isN0, and 43 people of them acquired ypT0N0. The rate of pCR in EC-P was higher than EC-D. Patients with ER (-), PR (-), Her-2 (+) and high Ki-67 index were easier to were more likely to acquire pCR. Two pCRs were described, the pCR of NAC differed according to the definition. In terms of side effects, there was no significant difference in platelet and urea, but the decrease of hemoglobin and creatinine levels after EC-P treatment was more significant than that after EC-D treatment.Conclusion: The efficacy of EC-P is better than EC-D if pCR is to be determined as a surrogate end-point for prognosis. The patients with anemia or renal insufficiency who need to receive NAC should choose EC-D.Keywords: neoadjuvant chemotherapy, pathological complete response, EC-D, EC-P, toxicity of anticancer drugs

Jingyun Guo,* Can Luo,* Yuqin Yang,* Jianyu Dong, Zhaoze Guo, Jinlamao Yang, Huining Lian, Changsheng Ye, Minfeng Liu Breast Center, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changsheng Ye; Minfeng LiuBreast Center, Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, People’s Republic of ChinaEmail yechsh2006@126.com; 125556557@qq.comBackground: Large amounts of microRNAs (miRNAs) have been reported to be aberrantly expressed in malignant cancers. MiR-491-5p makes a significant contribution to the inhibition of multiple cancer processes. However, the specific mechanism and function of miR-491-5p and in breast cancer (BC) is still not fully elucidated.Methods: MiR-491-5p and ZNF-703 expressions or gene transfection effects were identified by RT-qPCR or Western blot in BC tissues or cells. And ZNF-703 expression was monitored through immunohistochemistry method. Cellular function was also confirmed using Transwell assay. Besides, AKT/mTOR pathway-related proteins were analyzed using Western blotting analysis. Moreover, the interplay between miR-491-5p and ZNF-703 was verified through dual-luciferase reporter assay.Results: miR-491-5p was lowly expressed, ZNF-703 was highly expressed in BC, and miR-491-5p with low expression and ZNF-703 with high expression were associated with poor prognosis of BC patients. Results of cellular function revealed that overexpression of miR-491-5p markedly suppressed BC cell migration and invasion, and knockdown of miR-491-5p had the opposite effect. Besides, mechanism research disclosed that miR-491-5p directly could bind to ZNF-703 and downregulate ZNF-703. Moreover, we proved that ZNF-703 could prominently reverse the influences of miR-491-5p on the migration and invasion of BC cells. More importantly, the data revealed that miR-491-5p repressed AKT/mTOR pathway by ZNF-703 in BC cells.Conclusion: MiR-491-5p prominently suppresses the metastasis of BC cells through ZNF-703 to regulate AKT/mTOR pathway, indicating that miR-491-5p and ZNF-703 might be served as the potential therapeutic targets for BC.Keywords: breast cancer, miR-491-5p, ZNF-703, AKT/mTOR pathway, migration and invasion

Qi Lu,1,* Xian Wu,2,* Yanhui Zhu,2,* Junzhe Yang,2 Xingmeng Wang,2 Chaoran Ye,2 Ruyu Cai,2 Kai Zhang,2 Tingyu Xu,3 Bing Wang,3 Jordee S Veeramootoo,2 Tiansong Xia,2 Xiaoan Liu2 1Department of Thyroid and Breast Surgery, The Second People’s Hospital of Kunshan, Kunshan Jiangsu 215300, People’s Republic of China; 2Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, People’s Republic of China; 3Department of Information, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tiansong Xia; Xiaoan LiuThe First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, People’s Republic of ChinaTel/fax +86-25-68308152Email liuxiaoan@126.comPurpose: Chemotherapy is a comprehensive therapy for breast cancer; nevertheless, its associated adverse effects are drawing increasing attention with the continuous improvement of the efficacy. The changes in serum lipids of breast cancer patients caused by chemotherapy have been reported by previous studies, whereby the former increase the incidence rate of cardiovascular disorders. However, the variations in the changes of serum lipids with different chemotherapy regimens have seldom been reported.Methods: From January 2011 to December 2017, 1740 breast cancer patients treated with chemotherapy were recruited at the First Affiliated Hospital of Nanjing Medical University. The chemotherapy regimens included anthracycline-based, taxane-based, and anthracycline-plus-taxane-based regimens, dose-dense and standard-interval regimens. Lipid profiles that contained TG (triglyceride), TC (total cholesterol), HDL-C (high-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol) and Lpa (lipoprotein a) levels were collected prior to the first, second and last cycles of chemotherapy. The changes of serum lipids with the same or different chemotherapy regimens were analyzed and compared.Results: It was observed that the levels of TG, TC, LDL-C and Lpa increased significantly while that of HDL-C decreased after adjuvant chemotherapy in breast cancer patients (P< 0.05). Besides, dose-dense regimens had more influence in TG and HDL-C and less influence in TC and LDL-C than standard-interval regimens. HDL-C was more sensitive to anthracycline-based regimens than taxane-based regimens. The level of TG with anthracycline-plus-taxane-based regimens was higher than that with only anthracycline-based or taxane-based regimens, and the level of HDL-C with anthracycline-plus-taxane-based regimen showed lower than that with taxane-based regimen.Conclusion: In summary, this study proposed that dyslipidemia was strongly associated with chemotherapy in Chinese breast cancer patients after operative treatment. Furthermore, the changes in levels of serum lipids varied among patients with different chemotherapy regimens and taxane had less effect on dyslipidemia than anthracycline.Keywords: breast cancer, serum lipids, dyslipidemia, chemotherapy, treatment