Search

Wenjin Zhang,1 Qiang Song,1 Xiaofei Bi,1 Wei Cui,1 Chengmei Fang,1 Jianya Gao,1 Jinan Li,1 Xiang Wang,1 Kai Qu,1 Xian Qin,1 Xuan An,2,3 Cheng Zhang,1,3 Xianxiang Zhang,1,3 Fang Yan,4 Guicheng Wu1– 3 1Chongqing Municipality Clinical Research Center for Endocrinology and Metabolic Diseases, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 2Department of Hepatology, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 3School of Medicine, Chongqing University, Chongqing, People’s Republic of China; 4Geriatric Diseases Institute of Chengdu, Department of Geriatrics, Chengdu Fifth People’s Hospital, Chengdu, People’s Republic of ChinaCorrespondence: Guicheng Wu, Chongqing University Three Gorges Hospital, Xincheng Road 165#, Wanzhou District, Chongqing, 404000, People’s Republic of China, Tel +(86) 58103079, Fax +86 23 581045783, Email wuguicheng@cqu.edu.cn Fang Yan, Geriatric Diseases Institute of Chengdu, Department of Geriatrics, Chengdu Fifth People’s Hospital, Mashi Street 33#, Wenjiang District, Chengdu, 611130, People’s Republic of China, Tel/Fax +86 28 82661127, Email fangyan@cdutcm.edu.cnPurpose: Pueraria lobata (P. lobata), a dual-purpose food and medicine, displays limited efficacy in alcohol detoxification and liver protection, with previous research primarily focused on puerarin in its dried roots. In this study, we investigated the potential effects and mechanisms of fresh P. lobata root-derived exosome-like nanovesicles (P-ELNs) for mitigating alcoholic intoxication, promoting alcohol metabolism effects and protecting the liver in C57BL/6J mice.Methods: We isolated P-ELNs from fresh P. lobata root using differential centrifugation and characterized them via transmission electron microscopy, nanoscale particle sizing, ζ potential analysis, and biochemical assays. In Acute Alcoholism (AAI) mice pre-treated with P-ELNs, we evaluated their effects on the timing and duration of the loss of the righting reflex (LORR), liver alcohol metabolism enzymes activity, liver and serum alcohol content, and ferroptosis-related markers.Results: P-ELNs, enriched in proteins, lipids, and small RNAs, exhibited an ideal size (150.7 ± 82.8 nm) and negative surface charge (− 31 mV). Pre-treatment with 10 mg/(kg.bw) P-ELNs in both male and female mice significantly prolonged ebriety time, shortened sobriety time, enhanced acetaldehyde dehydrogenase (ALDH) activity while concurrently inhibited alcohol dehydrogenase (ADH) activity, and reduced alcohol content in the liver and serum. Notably, P-ELNs demonstrated more efficacy compared to P-ELNs supernatant fluid (abundant puerarin content), suggesting alternative active components beyond puerarin. Additionally, P-ELNs prevented ferroptosis by inhibiting the reduction of glutathione peroxidase 4 (GPX4) and reduced glutathione (GSH), and suppressing acyl-CoA synthetase long-chain family member 4 (ACSL4) elevation, thereby mitigating pathological liver lipid accumulation.Conclusion: P-ELNs exhibit distinct exosomal characteristics and effectively alleviate alcoholic intoxication, improve alcohol metabolism, suppress ferroptosis, and protect the liver from alcoholic injury. Consequently, P-ELNs hold promise as a therapeutic agent for detoxification, sobriety promotion, and prevention of alcoholic liver injury.Keywords: Pueraria lobata root-derived exosome-like nanovesicles, acute alcoholism, loss of the righting reflex, ethanol metabolism, ferroptosis

Yingmu Tong,1,* Qinglin Li,1,* Sinan Liu,1,2 Tong Liu,1 Kai Qu,1 Chang Liu,1,2 Jingyao Zhang1,2 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Department of SICU, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chang Liu; Jingyao Zhang, Department of SICU, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi`an, 710061, People’s Republic of China, Tel +86-29-85323900, Fax +86-29-85324642, Email liuchangdoctor@163.com; you12ouy@163.comPurpose: We describe the clinical characteristics, isolated microorganisms and antibiotics used in patients with cIAIs during ICU stay.Methods: A retrospective analysis of data from Beth Israel Deaconess Medical Center was performed.Results: A total of 316 patients with cIAIs were included, 57.0% of them were male and the median age was 63 years. A total of 239 patients did have cultures taken, and 74 patients had a positive microbial result. The main pathogens were Escherichia coli, Staphylococci (coagulase negative), Enterococcus sp. and Bacteroides fragilis. The main antibiotics given were vancomycin, metronidazole, piperacillin tazobactam and ciprofloxacin. Univariable and multivariable Cox regression analyses showed that receiving more antibiotics reduced ICU mortality, but the same results were not obtained in the analysis of hospital mortality.Conclusion: The main Gram-positive microorganisms for empirical antimicrobial therapy were Staphylococci (coagulase negative), Enterococcus sp. and Staphylococcus aureus, and Gram-negative microorganisms were Escherichia coli, Bacteroides fragilis and Klebsiella pneumoniae. The use of more antibiotics reduced ICU mortality, but the same results were not obtained in the analysis of hospital mortality.Keywords: intra-abdominal infection, culture, microorganism, antibiotics, intensive care unit, mortality

Lili Dai,1,&ast; Wei Wang,2,&ast; Wenli Li,3 Ya Wu,3 Kaixin Qu2 1Department of Geriatrics, Funan County People’s Hospital, Fuyang, People’s Republic of China; 2Department of Respiratory Medicine, Funan County People’s Hospital, Fuyang, People’s Republic of China; 3Department of Respiratory Medicine, Fuyang Hospital, Anhui Medical University, Fuyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaixin QuDepartment of Respiratory Medicine, Funan County People’s Hospital, No. 18, Santa Road, Funan County, Fuyang City, 236300, People’s Republic of ChinaTel +86 17755806231Email qukaixin19770418@163.comBackground: There are currently no methods for the treatment of reversible drug-resistant EGFR-TKI lung cancer in the clinical setting, and thus, the patients finally return to the currently used drugs. This study aimed to compare the efficacy of chemotherapy alone and gefitinib combined with chemotherapy in the treatment of non-small cell lung cancer (NSCLC) patients in advanced stage with the mutation of epidermal growth factor receptor (EGFR).Methods: A retrospective analysis was carried out on 120 patients with advanced EGFRm+ NSCLC who were divided into the control group (CG, received chemotherapy alone) or the observation group (OG, received chemotherapy and gefitinib) according to the treatment methods.Results: Comparison of the objective response rates (ORRs) showed no statistical significant difference between OG (36.92%) and CG (29.09%, P > 0.05), whereas in OG, disease control rate (DCR) was significantly increased in comparison with CG (P < 0.05). The medians of progression-free survival (PFS) and overall survival (OS) in OG were 8.0 months and 24.0 months, respectively, which were longer than 5.0 months and 18.0 months in CG (P = 0.031). The univariate analysis revealed that clinical stage of tumor (HR = 1.590, 95% CI: 1.097– 2.343) was the prognostic factor for advanced lung cancer. Multi-factor Cox regression analysis revealed that clinical analysis was an independent prognostic factor (HR = 1.701, 95% CI: 1.099– 2.632).Conclusion: In PFS patients, the OS rate was significantly improved, which was worth for clinical use.Keywords: advanced non-small cell lung cancer, NSCLC, anti-vascular therapy, prognosis

Hao Liu,1 Ruirui Zhang,1 Dan Zhang,1 Chun Zhang,1 Zhuo Zhang,1 Xiujuan Fu,1 Yu Luo,1 Siwei Chen,1 Ailing Wu,2 Weiling Zeng,3 Kunyan Qu,1 Hao Zhang,1 Sijiao Wang,1 Houyin Shi4 1School of Pharmacy, Southwest Medical University, Luzhou City, Sichuan, People’s Republic of China; 2Department of Anesthesiology, The First People’s Hospital of Neijiang, Neijiang, Sichuan, People’s Republic of China; 3Department of Scientific Research, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou City, Sichuan, People’s Republic of China; 4Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou City, Sichuan, People’s Republic of ChinaCorrespondence: Hao LiuSchool of Pharmacy, Southwest Medical University, No. 1 Section 1, Xiang Lin Road, Longmatan District, Luzhou City, Sichuan Province, 646000, People’s Republic of ChinaTel +86 830 3162291Email h_lewis@126.comHouyin ShiDepartment of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182 Chunhui Road, Longmatan District, Luzhou City, Sichuan Province, 646000, People’s Republic of ChinaTel +86 830 3162209Email 623340767@qq.comIntroduction: (-)-Gossypol (AT-101), the (-)-enantiomer of the natural compound gossypol, has shown significant inhibitory effects on various types of cancers such as osteosarcoma, myeloma, glioma, lung cancer, and prostate cancer. However, the clinical application of (-)-gossypol was often hindered by its evident side effects and the low bioavailability via oral administration, which necessitated the development of suitable (-)-gossypol preparations to settle the problems. In this study, injectable cyclic RGD (cRGD)-decorated liposome (cRGD-LP) was prepared for tumor-targeted delivery of (-)-gossypol.Methods: The cRGD-LP was prepared based on cRGD-modified lipids. For comparison, a non-cRGD-containing liposome (LP) with a similar chemical composition to cRGD-LP was specially designed. The physicochemical properties of (-)-gossypol-loaded cRGD-LP (Gos/cRGD-LP) were investigated in terms of the drug loading efficiency, particle size, morphology, drug release, and so on. The inhibitory effect of Gos/cRGD-LP on the proliferation of tumor cells in vitro was evaluated using different cell lines. The biodistribution of cRGD-LP in vivo was investigated via the near-infrared (NIR) fluorescence imaging technique. The antitumor effect of Gos/cRGD-LP in vivo was evaluated in PC-3 tumor-bearing nude mice.Results: Gos/cRGD-LP had an average particle size of about 62 nm with a narrow size distribution, drug loading efficiency of over 90%, and sustained drug release for over 96 h. The results of NIR fluorescence imaging demonstrated the enhanced tumor targeting of cRGD-LP in vivo. Moreover, Gos/cRGD-LP showed a significantly enhanced inhibitory effect on PC-3 tumors in mice, with a tumor inhibition rate of over 74% and good biocompatibility.Conclusion: The incorporation of cRGD could significantly enhance the tumor-targeting effect of the liposomes and improve the antitumor effect of the liposomal (-)-gossypol in vivo, which indicated the potential of Gos/cRGD-LP that warrants further investigation for clinical applications of this single-isomer drug.Keywords: RGD peptide, αvβ3 integrin, targeted therapy, AT-101, liposome, fluorescence imaging

Qinglin Li,1 Yingmu Tong,1 Hai Wang,1 Jie Ren,1 Sinan Liu,1,2 Tong Liu,1 Kai Qu,1 Chang Liu,1,2 Jingyao Zhang1,2 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Department of SICU, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of ChinaCorrespondence: Chang Liu; Jingyao ZhangThe First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi`an, 710061, People’s Republic of ChinaTel +86-29-85323900Fax +86-29-85324642Email liuchangdoctor@163.com; you12ouy@163.comObjective: The aim of this study was to compare the clinical characteristics and short-term mortality of patients with abdominal and pulmonary sepsis.Design: Retrospective cohort study.Setting: Adult intensive care units (ICUs) at tertiary hospitals.Participants: Adult ICU patients from 2014 to 2015 in the eICU Collaborative Research Database.Interventions: In univariate analysis, we compared the differences in the characteristics of patients in each group. Logistic regression models were used to evaluate the relationships between primary site of sepsis and short-term prognosis.Primary and Secondary Outcome Measures: Hospital and ICU survival.Results: The final dataset included 7023 pulmonary and 2360 abdominal sepsis patients, who accounted for 74.84% and 25.16%, respectively. We compared the results of the baseline characteristics, vital signs and laboratory indicators between the two groups. In the logistic regression models, we found that the hospital and ICU mortality of patients with abdominal sepsis was higher than that with pulmonary sepsis (p < 0.05, OR = 1.15, p < 0.05, OR = 1.19, respectively), although these results were no longer significantly after adjustment for confounders, but in the subgroups with SOFA score ≧ 8, the adjusted hospital mortality rate of patients with abdominal sepsis was 1.30 times higher than that of patients with pulmonary sepsis (p < 0.005, OR = 1.30, 95% CI 1.09– 1.55), while there was no significant difference in the subgroups that SOFA score < 8.Conclusion: In the patients with SOFA score ≧ 8, the adjusted hospital mortality of patients with abdominal sepsis was higher than patients with pulmonary sepsis.Keywords: sepsis, pulmonary, abdominal, eICU-CRD, ICU

Mingbiao Ma,1– 3,&ast; Minjun Chu,1,2,&ast; Lvyan Tao,3– 5,&ast; Jue Li,1,2 Xiaojuan Li,1,2 Hailin Huang,1,2 Kexuan Qu,6 Haiping Wang,1,2 Li Li,3– 5 Tingyi Du1– 3 1Department of Clinical Laboratory, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of China; 2Department of Clinical Laboratory, Children’s Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 3Yunnan Key Laboratory of Children’s Major Disease Research, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of China; 4Yunnan Institute of Pediatrics, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of China; 5Kunming Key Laboratory of Children Infection and Immunity, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of China; 6Department of Blood Transfusion, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li LiYunnan Institute of Pediatrics, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of ChinaEmail lili@etyy.cnTingyi DuDepartment of Clinical Laboratory, Kunming Children’s Hospital, Kunming, Yunnan, People’s Republic of ChinaEmail dutingyi@etyy.cnPurpose: The present study investigated the prevalence characteristics of oxacillin susceptible mecA-positive Staphylococcus aureus (OS-MRSA) in a children’s hospital in Kunming from January 2019 to December 2020.Methods: A total of 499 S. aureus strains were included in the study and tested for oxacillin susceptibility using the VITEK 2 Compact automated antimicrobial susceptibility test system. All oxacillin-susceptible strains were detected mecA and mecC by polymerase chain reaction (PCR). E-test was used to compare the minimum inhibitory concentration (MIC) values of methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and OS-MRSA for oxacillin, cefoxitin, penicillin, vancomycin, erythromycin, and clindamycin. Molecular typing of OS-MRSA was performed by MLST and SCCmec typing. Toxin genes were detected by PCR.Results: Forty-five OS-MRSA strains were detected, for an overall rate of 9.02% (45/499). The MICs of MSSA, OS-MRSA, and MRSA against oxacillin were concentrated at 0.38, 0.38, and 12 μg/mL, respectively; the cefoxitin MICs of MSSA and MRSA were concentrated at 2 and 32 μg/mL respectively; and MICs of OS-MRSA were concentrated at 2 and 8 μg/mL; penicillin, vancomycin and erythromycin MICs against MSSA, OS-MRSA, and MRSA showed same centralized points and were 32, 1, and 256 μg/mL, respectively; the MICs of clindamycin against MSSA were 0.5 μg/mL, while that against OS-MRSA and MRSA were concentrated at 256 μg/mL. Molecular typing of OS-MRSA was dominated by ST59-SCCmec IV. The carrier rates of hemolysin genes (hl-a, hl-d) and fibrinogen-binding clumping factor genes (clfA, clfB) were 100% in OS-MRSA, followed by 40% (18/45) for enterotoxin genes (sea, seb).Conclusion: OS-MRSA has a high detection rate in children, and main molecular typing is ST59-SCCmecIV in Kunming. The identification ability of automated antibacterial drug sensitivity test detection systems for OS-MRSA is very limited. A combination of phenotypic analysis and molecular detection should be used to improve OS-MRSA identification.Keywords: Staphylococcus aureus, MRSA, OS-MRSA, children, oxacillin

Cong Ma, Bo Wen, Qin Zhang, Pei-Pei Shao, Wen Gu, Kun Qu, Yang Shi, Bei Wang Department of Rheumatology and Immunology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, People’s Republic of China Background: Ankylosing spondylitis (AS) is a type of rheumatoid disease, which has been reported to be associated with the excessive proliferation of fibroblasts recently. Emodin, a single component from a traditional Chinese medicine Rheum palmatum, exerts anti-inflammation and antirheumatic arthritis activities. However, could emodin be used to treat AS remains unclear? Thus, this study aimed to investigate the effect of emodin on AS.Methods: Fibroblasts obtained from patients with AS were used in the current study. In addition, multiple cellular and molecular biology techniques such as Cell Counting Kit-8, Western blotting, flow cytometry, monodansylcadaverine staining, and immunofluorescence assay were applied as well.Results: Emodin-induced apoptosis of fibroblasts obtained from patient with AS via increasing active caspase-9, active caspase-3, and Bax levels and downregulating Bcl-2. Meanwhile, emodin enhanced autophagy in fibroblasts via upregulation of the expression of Atg12, Atg5, and Beclin 1, which was further confirmed by monodansylcadaverine staining. As expected, autophagy inhibitor 3-methyladenine (3MA) completely reversed emodin-induced autophagy in fibroblasts. Moreover, 3MA significantly increased emodin-induced apoptosis of fibroblasts obtained from patient with AS by increasing the levels of γH2AX, active caspase-9, active caspase-3, and cleaved poly ADP-ribose polymerase.Conclusion: Our results indicated that emodin effectively induced apoptosis and autophagy of fibroblasts obtained from patient with AS. In addition, suppression of autophagy enhanced emodin-induced apoptosis in fibroblasts. Therefore, we proposed that combination of emodin with autophagy inhibitor might be a potent strategy for improving the symptoms of AS in the future. Keywords: emodin, apoptosis, autophagy, 3MA, ankylosing spondylitis

Coral reefs, widely distributed in tropical and subtropical waters, generally have uneven flat topography. Sudden changes in reef flat topography significantly impact the propagation and evolution characteristics of tsunami-like waves; however, related studies are rare. This study systematically investigates the propagation and evolution of tsunami-like waves over uneven islands and reefs through wave flume physical experiments, analyzing the influences of incident wave height and reef flat water depth on these characteristics. The experimental results show that an uneven reef flat blocks the propagation of solitary waves and generates reflected waves. The slope, reef margin, and first reef flat in front of the reef are deep underwater, causing solitary waves to undergo shallow deformation without breaking. The wave height increases to a maximum at the step of the reef flat at shallower water depths and then breaks on the second reef flat. After breaking, the solitary wave propagates over the second reef flat as a swell, with wave height slowly attenuated due to energy dissipation from breaking in the limited water depth. As the incident wave height increases, the local wave height at each measuring point rises, with the increase in wave surface further amplified by the shallowing effect at the reef flat step. An increase in incident wave height causes the uneven reef flat to dissipate more wave energy and enhances wave attenuation. Consequently, the spatial distribution of local wave height Hi/H0 decreases with an increase in incident wave height. Increasing the water depth of the reef flat gradually weakens the shallowing effect, resulting in a decrease in the range and peak value of the maximum wave height near the reef flat step. When the water depth of the reef flat exceeds a certain limit, such as hr = 0.05 m in this study, the influence of the uneven reef flat on local wave height diminishes. An increase in the water depth leads to a reduction in wave energy consumed by the uneven reef flat, while the maximum wave height on the second reef flat increases monotonically with deeper water. During the propagation of solitary waves over uneven islands and reefs, two reflections from reef margins and flat steps occur. The reflection coefficient CR1 decreased with increasing incident wave height and reef flat water depth, while the reflection coefficient CR2 decreases significantly with increasing water depth. When the reef flat water depth is low, sudden changes in reef flat terrain greatly enhance the reflection intensity of incident waves. In particular, when hr = 0 m, the reflection coefficient CR2 reaches approximately 0.3.