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Jian Yang,1,* Jing Zhang,1,* Jiayan Luo,2 Jie Ouyang,1 Qicai Qu,1 Qitao Wang,1 Yongyu Si1 1Department of Anesthesiology, Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, People’s Republic of China; 2Department of Anesthesiology, People’s Hospital of Yanting, Sichuan, 621600, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongyu Si, Department of Anesthesiology, Second Affiliated Hospital of Kunming Medical University, No. 374 of Dianmian Road, Wuhua District, Kunming, 650101, People’s Republic of China, Tel +86 10 65333681, Fax +86 10 65334416, Email siyongyyu@126.comObjective: In this study, we evaluated the efficacy of tranexamic acid (TXA) and acute normovolemic hemodilution (ANH) with 6% hydroxyethyl starch (130/0.4) in minimizing blood loss during open partial liver resection. Coagulation function was assessed using thromboelastography (TEG) and hemostasis tests, while renal function changes were tracked through serum creatinine values post-surgery.Methods: Thirty patients undergoing open partial liver resection were allocated to two groups: Group T received TXA + ANH, and Group A received ANH alone. Blood was drawn from the radial artery under general anesthesia. Both groups received peripheral vein injections of 6% hydroxyethyl starch 130/0.4. Group T additionally received intravenous TXA. Primary outcomes included blood loss and allogeneic blood transfusions. TEG assessed coagulation status and renal function was monitored.Results: Group T demonstrated superior outcomes compared to Group A. Group T had significantly lower intraoperative blood loss (700 mL vs 1200 mL) and a lower bleeding rate per kilogram of body weight (13.3 mL/kg vs 20.4 mL/kg). Coagulation parameters favored Group T, with higher TEG maximum amplitude (55.91 mm vs 45.88 mm) and lower activated partial thromboplastin time (38.04 seconds vs 41.49 seconds). Neither group experienced acute renal injury or kidney function deficiency during hospitalization.Conclusion: TXA and ANH in a small dose during liver resection stabilize clotting, reduce blood loss by 6% compared to hydroxyethyl starch 130/0.4, and do not affect renal function.Keywords: acute normovolemic hemodilution, coagulation function, liver resection, thromboelastography, tranexamic acid

Ying Hu,1,* Wei Zhang,1,* Xiufen Shen,1,* Qiaoli Qu,1 Xiao Li,2 Rucai Chen,3 Zhuo Wang,1 Run Ma,1 Zaikun Xiong,3 Yuming Wang,1 Pengfei Wang3 1Department of Clinical Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, and Key Laboratory for Southwest Microbial Diversity of the Ministry of Education, Yunnan University, Kunming, People’s Republic of China; 3Department of Key Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuming Wang, Department of Clinical Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China, Tel +86 13708406058, Fax +86-0871-65334416, Email wangym992011@163.com Pengfei Wang, Department of Key Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China, Tel +86 15288453604, Email 196545723@qq.comIntroduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been widespread in coastal cities of eastern China since 2009. However, how CRKP spreads and evolves in southwest China is unclear.Aim: We investigated the genetic characteristics and dissemination mechanisms of carbapenemase genes in forty-one non-repetitive CRKP isolates collected from a southwest hospital, Kunming, Yunnan, during 2010– 2013.Methodology: Drug susceptibilities were analyzed by using VITEK 2 compact system. Genetic relationships were ascertained based on multilocus sequence typing (MLST) and Pulsed-field gel electrophoresis (PFGE) analysis. Genetic backgrounds of blaKPC-2 and blaNDM-1 were revealed by DNA walking and high-throughput sequencing.Results: All isolates were highly resistant to common antibiotics except for tigecycline. In total, 34 blaKPC-2, 3 blaNDM-1, 1 blaIMP-4 and 3 blaIMP-26 genes were identified and KP67 plasmid 1 co-harbored blaNDM-1 and blaIMP-26. Five sequence types, namely ST11, ST290, ST340, ST395 and ST437, were recognized by MLST. Surprisingly, blaKPC-2 was only detected in ST11 strains. We described a clonal dissemination of fosA3-positive IncR-IncF33:A-:B- multireplicon plasmid carrying the gene cassettes IS 26-ΔTn 3-ISKpn27-blaKPC-2-ΔISKpn6-korC-klcA-ΔrepB-Tn 1721 in all ST11 isolates. Three blaNDM-1 positive isolates belonged to three different ST types and their blaNDM-1 genetic backgrounds were also distinct. Interestingly, the flanking regions of blaNDM-1 in KP67 and KP72 were duplicated into one to five copies in a form of tandem repeat by the transposition of IS 91 like element. The blaNDM-1 of KP82 was carried on a common IncX3 plasmid.Conclusion: This study described the early epidemiological characteristics of blaKPC-2/blaNDM-1-carrying CRKP, and reported a new tandem repeat pattern of blaNDM-1 cluster in Yunnan. These findings extend our knowledge on the carbapenemase gene evolutions.Keywords: carbapenem-resistant Klebsiella pneumoniae, clonal dissemination, genetic backgrounds, IS 91 transposons, blaNDM-1 duplication

Mo Chen,1 Yanhua Li,1 Shu Li,2 Wenqiang Cui,2 Yonghui Zhou,3 Qianwei Qu,1 Ruixiang Che,4 Lu Li,5 Shuguang Yuan,2 Xin Liu3 1College of Veterinary Medicine, Northeast Agricultural University, Harbin, People’s Republic of China; 2Research Center for Computer-Aided Drug Discovery, Shenzhen Institutes of Advanced Technology, Shenzhen, People’s Republic of China; 3College of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, People’s Republic of China; 4College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, People’s Republic of China; 5College of Life Sciences, Northeast Agricultural University, Harbin, People’s Republic of ChinaCorrespondence: Shuguang Yuan, Research Center for Computer-Aided Drug Discovery, Shenzhen Institutes of Advanced Technology, Shenzhen, People’s Republic of China, Tel +86-150-0209-0670, Email shuguang.yuan@siat.ac.cn Xin Liu, College of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, People’s Republic of China, Tel +86-188-8605-6643, Email 1046977102@qq.comPurpose: Drug resistance presents an ever-increasing global public health threat that involves all major microbial pathogens and antimicrobial drugs. Strains that are resistant to multiple drugs pose severe clinical problems and cost lives. However, systematic studies on cross-resistance of Staphylococcus xylosus have been missing.Methods: Here, we investigated various mutations in the sequence of ribosomal proteins involved in cross-resistance. To understand this effect on a molecular basis and to further elucidate the role of cross-resistance, we computationally constructed the 3D model of the large ribosomal subunit from S. xylosus as well as its complexes with both tylosin and florfenicol. Meanwhile, all-atom molecular dynamics simulations was used. In addition, the regulation of protein networks also played an essential role in the development of cross-resistance in S. xylosus.Results: We discovered that the minimum inhibitory concentration against both tylosin and florfenicol of the mutant strain containing the insertion L22 97KRTSAIN98 changed dramatically. Further, we found that unique structural changes in the β-hairpin of L22 played a central role in this variant in the development of antibiotic resistance in S. xylosus. The regulation of protein networks also played an essential role in the development of cross-resistance in S. xylosus.Conclusion: Our work provides insightful views into the mechanism of S. xylosus resistance that could be useful for the development of the next generation of antibiotics.Keywords: antimicrobial resistance, Staphylococcus xylosus, cross-resistance evolution, ribosomal protein L22

Jin Wang,1,* Ling Gao,1,* Jie Liu,1 Liangjun Dang,1 Shan Wei,1 Ningwei Hu,1 Yao Gao,1 Wei Peng,1 Suhang Shang,1 Kang Huo,1 Jingyi Wang,2 Qiumin Qu1,3 1Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Huyi Hospital of Traditional Chinese Medicine, Xi’an, People’s Republic of China; 3Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiumin Qu, Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, 710061, People’s Republic of China, Tel/Fax +86 29 8532 4083, Email quqiumin@xjtufh.edu.cnPurpose: This study investigates the relationship between baseline plasma Aβ and cognitive decline during follow-up in cognitively unimpaired population.Materials and Methods: Cognitively unimpaired population was selected from people who lived in the suburbs of Xi’an, China. The levels of plasma Aβ1-42 and Aβ1-40 were tested using commercial enzyme-linked immunosorbent assay (ELISA). The mini-mental state examination (MMSE) and neuropsychological battery were used to assess cognition. Two years later, MMSE was tested again, and significant cognitive decline was defined as a decrease in MMSE scores ≥ 5 points. Logistic regression analysis was performed to analyze the relationship between baseline plasma Aβ and cognitive change during the two-year follow-up.Results: A total of 1144 participants completed the study, among whom 59 subjects (5.2%) presented significant cognitive decline. The high plasma Aβ1-42 level group had more significant cognitive decline (P = 0.023). Multivariable logistic regression analysis showed that significant cognitive decline was associated with the high levels of baseline plasma Aβ1-42 (OR = 1.043, 95% CI: 1.005– 1.083, P = 0.026). However, significant cognitive decline was not associated with baseline plasma Aβ1-40 levels and Aβ1-42 /Aβ1-40 ratio.Conclusion: Population with high level of baseline plasma Aβ1-42 manifested significant cognitive decline over 2 years; however, further investigation on the dynamics of plasma Aβ and long-term follow-up are needed.Keywords: Alzheimer’s disease, cognitive decline, plasma amyloid β, cohort study, plasma biomarker

Jian Qu,1,2 Ting-Ting Qi,1,2 Qiang Qu,3,4 Wen-Ming Long,5 Ying Chen,6 Yue Luo,7 Ying Wang1,2 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China; 2Institute of Clinical Pharmacy, Central South University, Changsha, 410011, People’s Republic of China; 3Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410078, People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410078, People’s Republic of China; 5Department of Pharmacy, Jingzhou District, Second People’s Hospital of Huaihua City, Huaihua, 418400, People’s Republic of China; 6Department of Pharmacy, Wuhan University, Renmin Hospital, Wuhan, 430060, People’s Republic of China; 7Department of Pharmacy, The People’s Hospital of Liuyang, Liuyang, 410300, People’s Republic of ChinaCorrespondence: Ying Wang, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Institute of Clinical Pharmacy, Central South University, No. 139 Middle Renmin Road, Changsha, 410011, People’s Republic of China, Tel +86-15173198700, Fax +86-731-85292072, Email wangying5211@csu.edu.cnBackground: The increasing prevalence of carbapenem-resistant Gram-negative bacteria (CR-GNB) represents a global healthcare crisis. This study explored the efficacy and safety of Polymyxin B (PMB)-based regimens and factors influencing their effectiveness.Methods: Patients with CR-GNB infections treated with PMB for more than three days were enrolled in this retrospective study from 1st June 2018 to 30th April 2020. Data were collected on patient characteristics, bacterial culture, and drug-sensitivity test results; anti-infection treatment regimens, particularly details of PMB use; and adverse drug reactions. Clinical and microbiological efficacy, mortality, and safety of PMB-based regimens in CR-GNB infected patients were evaluated. Univariate analysis and multivariate logistic regression analyses were used to assess factors influencing efficacy and mortality.Results: A total of 373 CR-GNB strains were cultured from 268 patients. About 41.04% of patients used PMB loading dose of 1.01 (0.84– 1.69) mg/kg. Maintenance dose was 0.85 (0.82– 1.00) mg/kg q12h. The clinical efficacy rate was 36.57% (98/268), the total bacterial clearance rate of PMB was 39.42%, and the all-cause mortality rate was 33.96%. The adverse drug reaction rate was 19.58%, among which the incidence of renal toxicity was highest (8.21%). Multivariate logistic regression analysis showed that clinical efficacy, bacterial clearance rate, and all-cause mortality were associated with patient-related facts, including mechanical ventilation use, underlying diseases (such as respiratory disease), the type and site of CR-GNB infection, and PMB administration timing and loading dose.Conclusion: PMB is a relatively safe and effective antibiotic drug for treatment of critically ill patients with CR-GNB infection; however, PMB use should be subject to guidelines recommendations for early administration, loading administration, and adequate administration, which could help to improve the clinical efficacy, microbiological efficacy, and mortality.Keywords: polymyxin B, carbapenem-resistant Gram-negative bacteria, clinical efficacy, bacterial elimination, mortality, adverse effect

Lu Zhang,1 Zitong Yu,2 Qingxi Qu,1 Xiao Li,1 Xue Lu,1 Hui Zhang1 1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 2Department of Obstetrics, Shouguang People’s Hospital, Shouguang, 262700, People’s Republic of ChinaCorrespondence: Hui Zhang, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, No. 107 Wenhua West Road, Jinan, 250012, People’s Republic of China, Email williamzh@126.comBackground: Long non-coding RNA (lncRNA) and exosomes are implicated in endometriosis development. We measured the expression of an exosomal lncRNA, homeobox transcript antisense RNA (HOTAIR), and explored its molecular mechanism in endometriosis progression.Methods: Expression of HOTAIR and microRNA (miR)-761 in different endometrial tissues was measured. Exosomes were isolated from a culture medium of endometrial stromal cells (ESCs). RT-qPCR was used to measure HOTAIR expression in different exosome types. CCK-8, Edu, wound healing, transwell assays, flow cytometry and tube formation were used to detect the role of exosomal HOTAIR on ESCs and human umbilical vein endothelial cells (HUVECs). The relationship among miR-761, HOTAIR, and histone deacetylase 1 (HDAC1) was verified by dual-luciferase reporter assay. ESCs were transfected with miR-761 mimics or HDAC1 small interfering RNA (si-RNA) to ascertain if alterations in expression of miR-761 or HDAC1 could reverse the effect of exosomal HOTAIR. Then, we detected the effect of the HOTAIR/miR-761/HDAC1 axis on signal transducer and activator of transcription 3 (STAT3)-mediated inflammation. In vivo experiments were conducted to verify in vitro results.Results: HOTAIR expression was upregulated and miR-761 expression was downregulated in ectopic endometrium tissues. HOTAIR was packaged into exosomes and transported from ESCs to surrounding cells. Exosomal HOTAIR promoted the proliferation, migration, and invasion, and inhibited the apoptosis of ESCs. Angiogenesis of HUVECs was enhanced after cultured with exosomal HOTAIR. HOTAIR acted as a competing endogenous RNA to downregulate miR-761 and increase HDAC1 expression. miR-761 overexpression or HDAC1 knockdown reversed the role of exosomal HOTAIR on ESCs and HUVECs. The HOTAIR/miR-761/HDAC1 axis could activate STAT3-related proinflammatory cytokines and stattic (inhibitor of phosphorylated-STAT3) could reverse the effect of HOTAIR on ESCs and HUVECs. In vivo experiments suggested that exosomal HOTAIR promoted the growth of endometrial lesions in vivo.Conclusion: Exosomal HOTAIR promoted the progression and angiogenesis of endometriosis by regulating the miR-761/HDAC1 axis and activating STAT3-mediated inflammation in vitro and in vivo, which may provide promising treatment for endometriosis.Keywords: endometriosis, HOTAIR, exosomes, miR-761, HDAC1, STAT3, inflammation

Yu-Xin Wen,1,2,* Qiang Qu,3,4,* Wen-Ming Long,5 Yue Luo,6 Hai-Hui Zhuang,1 Xin-Qi Teng,1 Jian Qu1 1Department of Pharmacy, The Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University, Changsha, 410011, People’s Republic of China; 2Department of Pharmacy, Lixian People’s Hospital in Hunan, Lixian, 415500, People’s Republic of China; 3Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410078, People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410078, People’s Republic of China; 5Department of Pharmacy, Jingzhou District, Second People’s Hospital of Huaihua City, Huaihua, 418400, People’s Republic of China; 6Department of Pharmacy, The People’s Hospital of Liuyang, Liuyang, 410300, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian QuDepartment of Pharmacy, The Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University, No. 139 Middle Renmin Road, Changsha, 410011, People’s Republic of China, Tel +86-15973190614, Fax +86-731-85292072Email qujianstanley@csu.edu.cnPurpose: This study investigates the nephrotoxicity and efficacy assessment of polymyxin B (PMB) use in renal transplant patients.Patients and Methods: This retrospective study included adult (> 18 years of age) renal transplant patients who received PMB intravenous drip for more than 72 hours. Efficacy assessment of PMB included clinical treatment efficacy, microbiological efficacy at the end of PMB treatment, and in-hospital all-cause mortality. Nephrotoxicity of PMB was evaluated for further group comparison.Results: We enrolled 235 renal transplant patients in our study. After PMB treatment, 45 patients occurred PMB-nephrotoxicity, and the nephrotoxicity rate was 19.15%. Among them, 44 patients were RIFLE R stage, and one patient was RIFLE I stage. The dose of PMB used in patients was 40.0 (40.0– 50.0) mg q12h with a loading dose of 41.8± 9.8 mg. Multivariate logistic regression analysis showed that ICU admission, vasoactive agents, aminoglycosides, creatinine clearance rate before PMB use, and mean total hospital stay were independent risk factors of PMB-nephrotoxicity in kidney transplant patients. The clinical effective rate was 97.9%, and the microbiological clean rate was 66.7%.Conclusion: Our study demonstrated that PMB low dose regimens might achieve good efficacy and less nephrotoxicity in renal transplant patients. We should evaluate the severity of the infection and renal function of patients, avoid the combined use of other nephrotoxic drugs, and minimize the course of use to reduce the occurrence of PMB-nephrotoxicity.Keywords: polymyxin B, nephrotoxicity, renal transplant patients, adverse reactions

Jian Qu,1,&ast; Hai-Hong Zhu,1,&ast; Xue-Jian Huang,1 Ge-Fei He,2 Ji-Yang Liu,2 Juan-Juan Huang,2 Ying Chen,3 Qiang Qu,4 Ya-Li Wu,5 Xiang-Yu Chen,6 Qiong Lu1 1Department of Pharmacy, the Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University, Changsha, 410011, People’s Republic of China; 2Department of Pharmacy, The First Hospital of Changsha, Changsha, 410005, People’s Republic of China; 3Department of Pharmacy, Wuhan University, Renmin Hospital, Wuhan, 430060, People’s Republic of China; 4Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410007, People’s Republic of China; 5Department of Pharmacy, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, 410000, People’s Republic of China; 6Department of Radiology, the Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiong LuDepartment of Pharmacy, the Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University, 139 Middle Renmin Road, Changsha, Hunan, 410011, People’s Republic of ChinaTel +86-731-85292072Fax +86-731-85533525Email christy_luq@csu.edu.cnBackground: SARS-CoV-2 can damage not only the lungs but also the liver and kidney. Most critically ill patients with coronavirus disease 2019 (COVID-19) have liver and kidney dysfunction. We aim to investigate the levels of liver and kidney function indexes in mild and severe COVID-19 patients and their capability to predict the severity of the disease.Methods: The characteristics and laboratory indexes were compared between patients with different conditions. We applied binary logistic regression to find the independent risk factors of severe patients. Receiver operating characteristic (ROC) analysis was used to predict the severity of COVID-19 using the liver and kidney function indexes.Results: This study enrolled 266 COVID-19 patients, including 235 mild patients and 31 severe patients. Compared with mild patients, severe patients had lower albumin (ALB) and higher alanine aminotransferase (ALT), aspartate aminotransferase (AST), and urea nitrogen (BUN) (all p< 0.001). Binary logistic regression analysis also identified ALB [OR=0.273 (0.079– 0.947), p=0.041] and ALT [OR=2.680 (1.036– 6.934), p=0.042] as independent factors of severe COVID-19 patients. Combining ALB, ALT, BUN, and LDH exhibited the area under ROC at 0.914, with a sensitivity of 86.7% and specificity of 83.0%.Conclusion: COVID-19 patients, especially severe patients, have damage to liver and kidney function. ALT, AST, LDH, and BUN could be independent factors for predicting the severity of COVID-19. Combining the ALB, ALT, BUN, and LDH could predict the transition from mild to severe in COVID-19 patients.Keywords: COVID-19, liver damage, kidney damage, predictor of disease severity

Qiong Lu,1,* Guo-Hua Li,1,* Qiang Qu,2 Hai-Hong Zhu,1 Yue Luo,3 Han Yan,1 Hai-Yan Yuan,1 Jian Qu1 1Department of Pharmacy, the Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University, Changsha, People’s Republic of China; 2Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Pharmacy, the People’s Hospital of LIUYANG, Liuyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian QuDepartment of Pharmacy, the Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University, No. 139 Middle Renmin Road, Changsha, People’s Republic of ChinaTel +86-15973190614Fax +86-0731-85292072Email qujianstanley@csu.edu.cnPurpose: Carbapenem-resistant organisms (CROs) pose great challenges for clinical treatment. Polymyxin B (PMB) is one of the “last resort” choices of CRO infections. We explored the possible factors affecting PMB efficacy.Patients and Methods: This retrospective study involved CRO-infected patients treated with PMB for ≥ 72 h. The endpoint indicator was clinical efficacy. We compared the characteristics (demographics, pathogenic bacteria, PMB treatment) between patients who had “clinical success” (CS) and “clinical failure” (CF).Results: A total of 191 patients were enrolled: 110 in the CS group and 81 in the CF group. The total cumulative dose for the CS group was higher than the CF group [1100 (700– 1443.75) vs 800 (500– 1112.5) mg; P = 0.001]. Treatment duration in the CS group was longer than the CF group [11 (8– 14) vs 8 (6– 11) days; P < 0.000]. Multivariate logistic regression analysis showed mechanical ventilation, vasoactive agents, multiple-site infection, and total cumulative dose to be independently associated with clinical efficacy. Cox survival analysis for 30-day mortality also showed that the use of vasoactive agents and the total cumulative dose of PMB could influence survival time and mortality rate independently.Conclusion: PMB had good efficacy and a low prevalence of adverse reactions. The total cumulative dose, duration of PMB treatment, mechanical ventilation, vasoactive agents, and multiple-site infection were factors associated with the clinical efficacy of PMB.Keywords: polymyxin B, carbapenem-resistant organisms, clinical efficacy, adverse effect, cumulative dose

Xin-Qi Teng,1,* Wen-Cheng Gong,2,* Ting-Ting Qi,1 Guo-Hua Li,1 Qiang Qu,3 Qiong Lu,1 Jian Qu1 1Department of Pharmacy, The Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University, Changsha, People’s Republic of China; 2Department of Pharmacy, Jiangxi Cancer Hospital of Nanchang University, Jiangxi Cancer Center, Nanchang, Jiangxi, People’s Republic of China; 3Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian QuDepartment of Pharmacy, The Second Xiangya Hospital, Central South University, No. 139 Middle Renmin Road, Changsha, 410011, People’s Republic of ChinaTel +86-15973190614Fax +86-731-85292128Email qujianstanley@csu.edu.cnIntroduction: Chlamydia psittaci infection is a zoonotic infectious disease, which mainly inhaled through the lungs when exposed to the secretions of poultry that carry pathogenic bacteria. The traditional respiratory specimens or serological antibody testing is slow, and the false-negative rate is high. Metagenomic next-generation sequencing (mNGS) gives a promising rapid diagnosis tool.Methods: We retrospectively summarized the clinical characteristics of five C. psittaci pneumonia patients diagnosed by mNGS, conducted a literature review summarizing the clinical characteristics of patients with C. psittaci pneumonia reported since 2010.Results: Five C. psittaci pneumonia patients confirmed by mNGS aged from 36 to 66 years with three males. About 60% of patients had a history of contact with avian or poultry. All patients had a high fever over 38.5 °C, cough, hypodynamia, hypoxemia, and dyspnea on admission. Two patients had invasive ventilator support and extracorporeal membrane oxygenation support. Inflammatory index levels on admission and follow-up were all higher than normal values. Doxycycline or moxifloxacin and their combination therapy were used in patients. Four patients improved and were discharged, and one patient died due to multiple organ failures and disseminated intravascular coagulation. We summarized 19 articles including 69 C. psittaci pneumonia patients and patients in 11 publications were identified by mNGS, and most patients are treated with tetracycline and quinolone with good outcomes.Conclusion: mNGS is a promising rapid diagnosis tool, which may increase the detection rate and shorten the diagnosis time of C. psittaci pneumonia. Further case-control studies are needed to confirm.Keywords: Chlamydia psittaci, pneumonia, psittacosis, chlamydia, mNGS

Power distribution networks with distributed generation (DG) face challenges in fault diagnosis due to the high uncertainty, randomness, and complexity introduced by DG integration. This study proposes a two-stage approach for fault location and identification in distribution networks with DG. First, an improved bald eagle search algorithm combined with the Dijkstra algorithm (D-IBES) is developed for fault location. Second, a fusion deep residual shrinkage network (FDRSN) is integrated with IBES and support vector machine (SVM) to form the FDRSN-IBS-SVM model for fault identification. Experimental results showed that the D-IBES algorithm achieved a CPU loss rate of 0.54% and an average time consumption of 1.70 seconds in complex scenarios, outperforming the original IBES algorithm. The FDRSN-IBS-SVM model attained high fault identification accuracy (99.05% and 98.54%) under different DG output power levels and maintained robustness (97.89% accuracy and 97.54% recall) under 5% Gaussian white noise. The proposed approach demonstrates superior performance compared to existing methods and provides a promising solution for intelligent fault diagnosis in modern distribution networks. [ABSTRACT FROM AUTHOR]

Xiaoyuan Liu,1,2 Wenhui Li,1 Youfeng Wen,1 Guochang Xu,3,* Guojian Zhou,1,* Quanying Qu,1,* Ying Hu,1,* Yueriguli Saitierding,1,* Maierdanjang Mohetaer,1,* Yeerkenbieke Buerlan,1,* Xuejun Zhong,1,* Huanjiu Xi1,* 1Biological Anthropology Institute, Jinzhou Medical University, Jinzhou, People’s Republic of China; 2Department of Prosthodontics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 3Institute of Anthropology, Nanyang Institute of Technology, Nanyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Youfeng WenBiological Anthropology Institute, Jinzhou Medical University, Jinzhou, 121001, People’s Republic of ChinaTel +86 18641602627Email swyf@163.comIntroduction: This study aimed to investigate the somatotype and obesity of adults in the Xinjiang Uygur Autonomous Region of China and to explore multivariate path analysis for the feasibility and scientificity of using somatotypes to evaluate obesity.Subjects and Methods: According to anthropometric methods, a cross-sectional study was performed on 10 indexes of 3438 adults (1690 men and 1748 women, aged > 20 years) living in the Xinjiang Uygur Autonomous Region of China (including Kazakh, Kyrgyz, Xibe, Uzbek, Tatar and Tajik). The Heath-Carter anthropometric method and body mass index (BMI) were used to evaluate somatotype and obesity, respectively. The feasibility and scientificity of using somatotypes to evaluate obesity were analysed by correspondence analysis.Results: Among the six populations, the somatotypes were mainly distributed as endomorphic mesomorph, mesomorph-endomorph and mesomorphic endomorph populations, accounting for 66.5% of males and 78.8% of females. The obesity rate (27.4% in males, 27.8% in females) of the six populations in the Xinjiang Uygur Autonomous Region of China was much higher than the average Chinese adult obesity rate (12.1%) and the global adult obesity rate (male: 11%, female: 15%). The distribution of BMI was significantly different (male: P= 0.000, female: P= 0.033) in different populations, and the incidence of overweight and obesity in the Xinjiang Uygur Autonomous Region of China increased gradually. This study found that there were significant differences in somatotype distribution among different obesity groups in the Xinjiang Uygur Autonomous Region of China (P=0.000). There was a strong correlation between overweight or obesity and endomorph-mesomorph, endomorphic mesomorph and mesomorphic endomorph. Furthermore, this study indicated that using somatotypes to evaluate obesity was reliable and scientific.Conclusion: This study concluded that the somatotype of overweight or obese people was mainly related to endomorphic mesomorph, mesomorph-endomorph, and mesomorphic endomorph.Keywords: China, obesity, somatotype, Heath-Carter anthropometric method, body mass index, path analysis, Xinjiang

Hongying Ma,1,2 Jian Qu,3 Jian Luo,1,2 Tingting Qi,3 Huanmiao Tan,4 Zhaohui Jiang,1 Haiwen Zhang,1 Qiang Qu1,2 1Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People’s Republic of China; 2Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People’s Republic of China; 3Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha 410078, Hunan, People’s Republic of China; 4College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, Hunan, People’s Republic of ChinaCorrespondence: Qiang QuDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People’s Republic of ChinaTel/Fax +86 731 84327460Email quqiang@csu.edu.cnPurpose: Super-enhancer (SE)-associated oncogenes extensively potentiate the uncontrolled proliferation capacity of cancer cells. In this study, we aimed to identify the SE-associated hub genes associated with the clinical characteristics of chronic myeloid leukemia (CML).Methods: Eigengenes from CML clinical modules were determined using weighted gene co-expression network analysis (WGCNA). Overlapping genes between eigengenes and SE-associated genes were used to construct protein–protein interaction (PPI) networks and annotate for pathway enrichment analysis. Expression patterns of the top-ranked SE-associated hub genes were further determined in CML patients and healthy controls via real-time PCR. After treatment of K562 cells with the BRD4 inhibitor, JQ1, for 24 hrs, mRNA and protein levels of SE-associated hub genes were evaluated using real-time PCR and Western blotting, respectively. H3K27ac, H3K4me1 and BRD4 ChIP-seq signal peaks were used to predict and identify SEs visualized by the Integrative Genomics Viewer.Results: The yellow module was significantly related to the status and pathological phase of CML. SE-associated hub candidate genes were mainly enriched in the cell cycle pathway. Based on the PPI networks of hub genes and the top rank of degree, five SE-associated genes were identified: specifically, BUB1, CENPO, KIF2C, ORC1, and RRM2. Elevated expression of these five genes was not only related to CML status and phase but also positively regulated by SE and suppressed by the BRD4 inhibitor, JQ1, in K562 cells. Strong signal peaks of H3K27ac, H3K4me1 and BRD4 ChIP-seq of the five genes were additionally observed close to the predicted SE regions.Conclusion: This is the first study to characterize SE-associated genes linked to clinical characteristics of CML via weighted gene co-expression network analysis. Our results support a novel mechanism involving aberrant expression of hub SE-associated genes in CML patients and K562 cells, and these genes will be potential new therapeutic targets for human leukemia.Keywords: chronic myeloid leukemia, WGCNA, super-enhancer, hub gene, eigengene