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Zhaobai Lao,1,* Xuliang Fang,1,* Shuchao Shen,1,* Yuliang Zhang,2,* Xin Chen,1 Helou Zhang,1 Yishan Bian,1 Chengcong Zhou,1 Ronghua Bao,2 Taotao Xu,3 Hongting Jin,1 Fangda Fu,1 Chengliang Wu,1 Changfeng Hu,4 Hongfeng Ruan1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Hangzhou Fuyang Hospital of TCM Orthopedics and Traumatology, Hangzhou, Zhejiang, 311400, People’s Republic of China; 3Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China; 4College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changfeng Hu, College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China, Email zhudianzhuifeng@163.com Hongfeng Ruan, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email rhf@zcmu.edu.cnPurpose: Systemic lupus erythematosus (SLE) is an autoimmune disorder marked by immune system dysregulation and autoantibodies production, causing widespread inflammation and damage across various body systems. Despite the prevalent back pain in SLE patients, the link between SLE and intervertebral disc (IVD) degeneration, a primary contributor to back pain, remains inadequately understood. This study explored the impact of SLE on IVD degeneration using the MRL/lpr mouse model, which effectively replicates human SLE manifestations.Methods: The study utilized MRL/lpr mice to investigate the effects of SLE on IVD degeneration. The mice were evaluated for typical SLE phenotypes and indicators of IVD degeneration, including IVD height, IVD score, tissue integrity, extracellular matrix degradation, and apoptosis of IVD cells. Additionally, the study examined nucleus pulposus (NP) pyroptosis and inflammatory cytokine secretion. Mechanistic analysis focused on the antioxidant pathway, specifically the expression levels of NRF2, HO-1, KEAP1, and the phosphorylation levels of p65.Results: MRL/lpr mice displayed typical SLE phenotypes and exacerbated profiles of IVD degeneration, including reduced IVD height, lower IVD score, significant IVD tissue impairment, extracellular matrix degradation, and increased apoptosis of IVD cells. Notably, SLE stimulated NP pyroptosis and excessive secretion of inflammatory cytokines. Mechanistic analysis indicated that the progression of SLE impedes the antioxidant pathway by downregulating NRF2 and HO-1 expression, upregulating KEAP1, and enhancing phosphorylation levels of p65.Conclusion: Our findings highlight the mechanistic link between SLE and IVD degeneration, suggesting potential therapeutic targets for mitigating back pain in SLE patients.Keywords: systemic lupus erythematosus, intervertebral disc degeneration, nucleus pulposus, pyroptosis, NRF2/KEAP1/NF-κB pathway

Xiaofen Xu,1,* Wumeng Jin,1,* Jingyi Song,1 Xuanming Hu,1 Lu Lu,2 Jida Zhang,1 Changfeng Hu1 1College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jida Zhang; Changfeng Hu, College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China, Email zhjd82@tom.com; zhudianzhuifeng@163.comBackground: Liver injury, such as nonalcoholic fatty liver disease, is a common symptom observed in patients with gout/hyperuricaemia. However, the exact mechanisms are still unclear. There is ongoing controversy about whether representative agents like colchicine and febuxostat, commonly used to manage gout, could also help prevent the liver injury. Liver plays a crucial role in uric acid (UA) production and lipid metabolism. Thus, the study aimed to investigate the aberrant lipid metabolism in the liver during injury and the effects of these drugs.Methods: An advanced multi-dimensional mass spectrometry-based shotgun lipidomics technology was employed for class-targeted lipid analysis of cellular lipidomes in hepatic tissue of a gouty model induced by a combination of monosodium urate crystals and high-fat diet with or without treatment with colchicine and febuxostat. Serum UA, blood urea nitrogen, creatinine, proinflammatory cytokines, expression of AMP-activated protein kinase protein, footpad histopathology, and footpad swelling and pain threshold of these mice were assessed to evaluate the progression of gout.Results: Lipidomics analysis clearly demonstrated that the ectopic fat accumulation as well as changes in fatty acyls composition in TAG pool, impaired mitochondrial function resulted by decreased tetra 18:2 cardiolipin, and reduced 4-hydroxyalkenal bioavailability in liver tissue could contribute to liver damage to the gouty model. Treatment with colchicine or febuxostat not only ameliorated gouty symptoms but also corrected these abnormal hepatic lipid metabolism patterns.Conclusion: This study shed light on underlying mechanism(s) for liver injury in gout/hyperuricaemia and suggested that administration of drugs like colchicine and febuxostat could prevent liver injury.Keywords: gout, hepatic lipidome, febuxostat, colchicine, inflammation

Zhen Cheng,&ast; Chunyu Hu,&ast; Yalan Zhang, Jie Zhou, Jiayang Shi, Li Sun, Zongtao Chen Health Management Centre, First Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongtao Chen; Li Sun, Health Management Centre, First Affiliated Hospital of Army Medical University, No. 30, Gaotanyan Street, Shapingba District, Chongqing, People’s Republic of China, Tel +86 2368765191 ; +86 2368765228, Email zongtaochen@126.com; 51088031@qq.comPurpose: The aim of this study was to comprehensively compare the predictive effect of 10 body fat indexes on MAFLD in different sex, age and BMI subgroups.Patients and Methods: A total of 5403 physical examination data were included and divided into the MAFLD group (N=2632) and non-MAFLD group (N=2771). The differences and correlation of 10 promising indicators between the two groups were compared, including fatty liver index (FLI), hepatic steatosis index (HSI), lipid accumulation product (LAP), visceral fat index (VAI), cardiometabolic index (CMI), body adiposity index (BAI), and triglyceride-glucose index (TyG), waist circumference index (WC), body mass index (BMI), waist to height ratio (WHtR). Logistic regression was used to analyze the risk of MAFLD under different adjustment conditions. The operating characteristic curve of different genders, BMI levels and age subgroups was plotted.Results: Male gender, smoking, alcohol drinking, and higher age are risk factors for MAFLD. In addition to BAI, the other 9 indicators had a high correlation with MAFLD, the area under the curve (AUC) value was > 0.7, and the prediction effect was better in females, BMI< 24 kg/m2, age < 35 years subgroup, among which FLI (AUC: 0.912, 95% CI: 0.905– 0.920), LAP (AUC: 0.894, 95% CI: 0.8866– 0.903), and HSI (AUC: 0.881, 95% CI: 0.872– 0.890) have better prediction effects.Conclusion: Our study confirmed the accuracy of body fat-related indexes in predicting MAFLD in people of different sexes, ages, and BMI levels. Among them, FLI, LAP and HSI have high predictive value and can be utilized as simple and cost-effective tools for screening MAFLD in clinical settings.Keywords: metabolic dysfunction-associated fatty liver disease, body fat index, metabolic index, cross-sectional study

Rong Hong,1,2,&ast; Xiaoxia Ping,2,3,&ast; Yuanying Liu,2 Feiwen Feng,2 Su Hu,2,3 Chunhong Hu2,3 1Department of Radiology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, 215100, People’s Republic of China; 2Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, People’s Republic of China; 3Institute of Medical Imaging, Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunhong Hu; Su Hu, Department of Radiology, The First Affiliated Hospital of Soochow University; Institute of Medical Imaging, Soochow University, Suzhou, Jiangsu, People’s Republic of China, Email sdhuchunhong@sina.com; husu@suda.edu.cnPurpose: The clinical, pathological, gene expression, and prognosis of invasive mucinous adenocarcinoma (IMA) differ from those of invasive non-mucinous adenocarcinoma (INMA), but it is not easy to distinguish these two. This study aims to explore the value of combining CT-based radiomics features with clinic-radiological characteristics for preoperative diagnosis of solitary-type IMA and to establish an optimal diagnostic model.Methods: In this retrospective study, a total of 220 patients were enrolled and randomly assigned to a training cohort (n = 154; 73 IMA and 81 INMA) and a testing cohort (n = 66; 31 IMA and 35 INMA). Radiomics features and clinic-radiological characteristics were extracted from plain CT images. The radiomics models for predicting solitary-type IMA were developed by three classifiers: linear discriminant analysis (LDA), logistic regression-least absolute shrinkage and selection operator (LR-LASSO), and support vector machine (SVM). The combined model was constructed by integrating radiomics and clinic-radiological features with the best performing classifier. Receiver operating characteristic (ROC) curves were used to evaluate models’ performance, and the area under the curve (AUC) were compared by the DeLong test. Decision curve analysis (DCA) was conducted to assess the clinical utility.Results: Regarding CT characteristics, tumor lung interface, and pleural retraction were the independent risk factors of solitary-type IMA. The radiomics model using the SVM classifier outperformed the other two classifiers in the testing cohort, with an AUC of 0.776 (95% CI: 0.664– 0.888). The combined model incorporating radiomics features and clinic-radiological factors was the optimal model, with AUCs of 0.843 (95% CI: 0.781– 0.906) and 0.836 (95% CI: 0.732– 0.940) in the training and testing cohorts, respectively.Conclusion: The combined model showed good ability in predicting solitary-type IMA and can provide a non-invasive and efficient approach to clinical decision-making.Keywords: computed tomography, invasive mucinous adenocarcinoma, radiomics, machine learning

Ying Yang,1– 3,&ast; Bixia Zhou,1,2,&ast; Min Li,4 Yishuai Sun,1,2 Xulei Jiang,1,2 Xinxin Zhou,1,2 Chengjun Hu,1,2 Dou Zhang,3 Hang Luo,3 Wuyuan Tan,1,2 Xinghua Yang,1,2 Shaorong Lei1,2 1Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, Hunan, People’s Republic of China; 3State Key Laboratory of Powder Metallurgy, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Oncology, Changsha Central Hospital, University of South China, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaorong Lei, Department of Plastic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of China, Tel +86 73189753014, Email leishaorong@csu.edu.cn Xinghua Yang, Department of Plastic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of China, Tel +86 73189753014, Email yxhua8805@sina.comPurpose: The treatment of craniofacial bone defects caused by trauma, tumors, and infectious and degenerative diseases is a significant issue in current clinical practice. Following the rapid development of bone tissue engineering (BTE) in the last decade, bioactive scaffolds coupled with multifunctional properties are in high demand with regard to effective therapy for bone defects. Herein, an innovative bone scaffold consisting of GO/Cu nanoderivatives and GelMA-based organic-inorganic hybrids was reported for repairing full-thickness calvarial bone defect.Methods: In this study, motivated by the versatile biological functions of nanomaterials and synthetic hydrogels, copper nanoparticle (CuNP)-decorated graphene oxide (GO) nanosheets (GO/Cu) were combined with methacrylated gelatin (GelMA)-based organic-inorganic hybrids to construct porous bone scaffolds that mimic the extracellular matrix (ECM) of bone tissues by photocrosslinking. The material characterizations, in vitro cytocompatibility, macrophage polarization and osteogenesis of the biohybrid hydrogel scaffolds were investigated, and two different animal models (BALB/c mice and SD rats) were established to further confirm the in vivo neovascularization, macrophage recruitment, biocompatibility, biosafety and bone regenerative potential.Results: We found that GO/Cu-functionalized GelMA/β-TCP hydrogel scaffolds exhibited evidently promoted osteogenic activities, M2 type macrophage polarization, increased secretion of anti-inflammatory factors and excellent cytocompatibility, with favorable surface characteristics and sustainable release of Cu2+. Additionally, improved neovascularization, macrophage recruitment and tissue integration were found in mice implanted with the bioactive hydrogels. More importantly, the observations of microCT reconstruction and histological analysis in a calvarial bone defect model in rats treated with GO/Cu-incorporated hydrogel scaffolds demonstrated significantly increased bone morphometric values and newly formed bone tissues, indicating accelerated bone healing.Conclusion: Taken together, this BTE-based bone repair strategy provides a promising and feasible method for constructing multifunctional GO/Cu nanocomposite-incorporated biohybrid hydrogel scaffolds with facilitated osteogenesis, angiogenesis and immunoregulation in one system, with the optimization of material properties and biosafety, it thereby demonstrates great application potential for correcting craniofacial bone defects in future clinical scenarios. Keywords: nanomaterials, hybrid hydrogel, bone scaffolds, craniofacial bone defects, bone regeneration

Jin Wang, Chaoying Hu, Lan Zhang Department of Pharmacy, Phase I Clinical Trial Center, Xuanwu Hospital Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Chaoying Hu; Lan Zhang, Email hucarol@126.com; xwzhanglan@126.comPurpose: SHR6390 is an oral, potent and selective small-molecule CDK4/6 inhibitor for the treatment of human breast, ovarian and colon cancer. Previous studies have shown that SHR6390 in combination with rifampicin, a potent inducer of CYP3A4, significantly reduces exposure levels. Therefore, we further investigated the effect of efavirenz, a moderate CYP3A4 inducer, on a single oral dose of SHR6390 in healthy volunteers.Patients and Methods: Twenty healthy subjects were enrolled in this single-center, open, single-dose, self-controlled DDI study. On Day 1, subjects received a single oral dose of 150mg SHR6390; on Day 8-26, subjects received 600 mg efavirenz orally at night, with a single dose of 150 mg SHR6390 on Day 22. Blood samples for pharmacokinetic analyses were collected.Results: The geometric mean ratios of the maximum concentration(Cmax) and the area under the concentration curve from zero to infinity (AUC0-inf) between combination therapy and SHR6390 monotherapy (combination therapy/SHR6390 monotherapy) and their 90% confidence intervals were 0.562 (0.482, 0.654) and 0.328 (0.278, 0.386), respectively. This indicates that the Cmax and AUC0 inf of SHR6390 decreased by approximately 43.8% and 67.2%, respectively. Oral administration of 150 mg SHR6390 alone or together with efavirenz was safe and tolerable in healthy subjects.Conclusion: It is suggested that under the action of the moderate CPY3A4 inducer efavirenz, the exposure AUC of SHR6390 exhibits a moderate level of induction. It is recommended to avoid concomitant administration of moderate inducers of CYP3A4 during treatment with SHR6390.Trial Registration: http://www.chinadrugtrials.org.cn/index.html, CTR20211571/ https://classic.clinicaltrials.gov, NCT04973020.Keywords: SHR6390, efavirenz, drug-drug interaction, pharmacokinetics, tolerability

Biao Hou,1– 3,&ast; Bo Li,4,&ast; Wanjun Deng,3,&ast; Bo Li,1,2 Bibo Ren,5 Chao Hu,3 Guowei Zhang,1,2 Fen Yang,6 Meimei Xiao,3 Songlin Xie,3 Denghui Xie1,2 1Department of Joint Surgery and Sports Medicine, Center for Orthopedic Surgery, Orthopedic Hospital of Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Academy of Orthopedics, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Hand and Foot Microsurgery, The affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, People’s Republic of China; 4Department of Radiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5College of Biomass Science and Engineering, Sichuan University, Chengdu, People’s Republic of China; 6Department of Infectious Diseases, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Denghui Xie; Songlin Xie, Email smuspine@163.com; xiesonglin0929@163.comPurpose: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation.Methods: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme’s size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA).Results: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes’ potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections.Conclusion: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.Keywords: copper nanozyme, aggregate induced emission, photodynamic antibacterial therapy, antimicrobial resistance, diabetic wound healing

Yan Zhang,1,&ast; Qixing Wu,2,&ast; Mingming Han,2 Chengwei Yang,2 Fang Kang,2 Juan Li,2 Chengwen Hu,1 Xia Chen1 1Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Chen; Chengwen Hu, Email chenxiaahslyy@163.com; huchengwen318@126.comObjective: Frailty, representing the physiological reserve and tolerance of the body, serves as a crucial evaluation index of the overall status of the older adults. This study aimed to investigate the prevalence of preoperative frailty and its impact on postoperative outcomes among older adults with lumbar degenerative disease in China.Patients and Methods: In this prospective study, a total of 280 patients aged 60 and above, diagnosed with lumbar degenerative disease and scheduled for surgical intervention were enrolled. The prevalence of frailty pre-surgery was evaluated using the Tilburg Frailty Indicator (TFI) and the modified Frailty Index 11 (mFI-11). The primary outcome was postoperative complication within 30 days post-surgery. The secondary outcomes were the length of hospital stay, hospital costs, reoperation within 30 days post-surgery and unplanned readmission within 30 days post-discharge. Both univariable and multivariable logistic regression were employed to screen and identify the risk factors predisposing patients to postoperative complications.Results: A total of 272 older adults were included in the study ultimately. The frailty detection rates of TFI and mFI-11 were 15.8% (43/272) and 10.7% (29/272) respectively. Thirty-four patients (12.5%) encountered complications. Significantly elevated rates of complications, prolonged hospital stays, increased hospital costs, and heightened readmission rates were observed in the frail group compared to the non-frail group (P< 0.05). Univariable analysis showed that the potential factors related to complications are TFI, mFI-11 and albumin. Multivariable logistic regression revealed that TFI was an independent risk factor for postoperative complications (OR=5.371, 95% CI: 2.338– 12.341, P < 0.001).Conclusion: Frailty was an independent predictor of postoperative complications in older adults undergoing lumbar fusion surgery. Frailty assessment should be performed in such patients to improve preoperative risk stratification and optimize perioperative management strategies.Keywords: lumbar degenerative disease, older adults, frailty, postoperative outcome

Lin Tang,1,&ast; Jian Liu,2,&ast; Hui Yang,2,&ast; Hong-Qing Zhao,3 Chao Hu,4 Si-Jing Ma,5 Yu-Hui Qing,6 Lei Yang,1 Rong-Rong Zhou,5 Shui-Han Zhang6 1Hospital-Made Preparations Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 2Medical Innovation Experiment Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 3Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 4Department of Pharmacy, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 5The Affiliated Hospital, Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 6Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong-Rong Zhou; Shui-Han Zhang, Tel +86-0731-85920129, Email rrzhou0823@163.com; zhangshuihan0220@126.comPurpose: The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This study aimed to reveal mechanisms of anxiolytic effects of BDD with multidimensional omics.Methods: First, 28-day chronic restraint stress (CRS) was used to create a rat model of anxiety, and the open field test and elevated plus maze were used to assess anxiety-like behavior. Enzyme-linked immunosorbent assay (ELISA), hematoxylin–eosin staining, and immunofluorescence staining were used to evaluate inflammatory response. Besides, 16S rRNA gene sequencing assessed fecal microbiota composition and differential microbiota. Non-targeted metabolomics analysis of feces was performed to determine fecal biomarkers, and targeted metabolomics was used to observe the levels of hippocampus neurotransmitters. Finally, Pearson correlation analysis was used to examine relationships among gut microbiota, fecal metabolites, and neurotransmitters.Results: BDD significantly improved anxiety-like behaviors in CRS-induced rats and effectively ameliorated hippocampal neuronal damage and abnormal activation of hippocampal microglia. It also had a profound effect on the diversity of microbiota, as evidenced by significant changes in the abundance of 10 potential microbial biomarkers at the genus level. Additionally, BDD led to significant alterations in 18 fecal metabolites and 12 hippocampal neurotransmitters, with the majority of the metabolites implicated in amino acid metabolism pathways such as D-glutamine and D-glutamate, alanine, arginine and proline, and tryptophan metabolism. Furthermore, Pearson analysis showed a strong link among gut microbiota, metabolites, and neurotransmitters during anxiety and BDD treatment.Conclusion: BDD can effectively improve anxiety-like behaviors by regulating the gut–brain axis, including gut microbiota and metabolite modification, suppression of hippocampal neuronal inflammation, and regulation of neurotransmitters. Keywords: Baihe Dihuang decoction, 16S rRNA, metabolomics, anxiety, neurotransmitter

Chenxiao Hu,&ast; Mingwei Sheng,&ast; Ke Wang,&ast; Zi Yang, Shiping Che Solicitation Office, The First Hospital of Lanzhou University, Lanzhou, Gansu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiping Che, The First Hospital of Lanzhou University, No. 1 Donggang West Road, Lanzhou, Gansu, 730000, People’s Republic of China, Email ldyycheshiping@163.comObjective: Identify the collaborations between authors, countries, and institutions, respectively, and explore the hot issues and prospects for research on hospital medication management.Materials and Methods: Publications on hospital medication management were retrieved from the Web of Science Core Collection. Bibliometric analyses were performed using CiteSpace 6.1.R3, HistCite 2.1, and VOSviewer 1.6.16. The network maps were created between authors, countries institutions, and keywords.Results: A total of 18,723 articles related to hospital medication management studies were identified. Rapid growth in the number of publications since 2017. The high papers were published in AM J HEALTH-SYST PH, while JAMA-J AM MED ASSOC was the most co-cited journal. Manias E and WHO ranked first in the author and cited author. There were active collaborations among the top authors. Bates DW was the key author in this field. The authors have active collaborations in adverse drug events, acute coronary syndrome, in-hospital major bleeding, and so on. The US was the leading contributor in this field. The UK, Australia, and China are also very active. Active cooperation between countries and between institutions was observed. The main hot topics included matters related to outcome indicators, hospital pharmacy service behaviors, and medication use in pain management. More recent keywords focus on chronic disease medication management and clinical medication management.Conclusion: Hospital medication management studies have significantly increased after 2017. There was active cooperation between authors, countries, and institutions. The application of hospital medication management in the emergency department and the relationship between medication management and medication adherence are current research hotspots. In addition, with the continuous progress of society, chronic diseases have become an important factor affecting people’s health, and medication management is becoming more and more subdivided, so the direction of chronic disease medication management as well as precise medication may become the development direction of future research.Keywords: bibliometric analysis, medication management, hospital, development trends, hot topics

Xiaomeng Tang,1– 4,&ast; Qi Wang,2– 4,&ast; Ronghua Jin,2– 4 Caixia Hu1 1Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Infectious Diseases, Beijing, People’s Republic of China; 3National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Caixia Hu, Interventional therapy center for oncology; Beijing You’an Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai Street, Fengtai District, Beijing, People’s Republic of China, Tel/Fax +86-13811395702, Email hucaixia1217@126.com Ronghua Jin, Beijing Ditan Hospital, Capital Medical University, 8 Jingshun East Street, Chaoyang District, Beijing, People’s Republic of China, Tel/Fax +86-13811611118, Email ronghuajin@ccmu.edu.cnPurpose: Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer. Early diagnosis is crucial for improving prognosis. Elderly HCC patients often have underlying liver diseases such as chronic hepatitis and cirrhosis, leading to impaired liver function and suboptimal liver reserve. Radiofrequency ablation (RFA) has rapidly become one of the most important methods for treating early-stage hepatocellular carcinoma (EHCC) due to its advantages, including minimal trauma, short operation time, less intraoperative bleeding, quick postoperative recovery, cost-effectiveness, and few postoperative-complications. However, the prognostic model for early recurrence after local ablation in elderly EHCC patients has not been widely evaluated. We have developed a prognostic model for the recurrence of local RFA in elderly EHCC patients. This is expected to provide a new early warning system for preventing early recurrence in elderly EHCC patients, prolonging patient’s life, and improving overall quality of life.Methods: In this study, we included 661 EHCC patients who underwent local ablation, dividing them into a Primary cohort and a Validation cohort in a 7:3 ratio. We characterized the cohorts and utilized the primary cohort to develop a prognostic nomogram model for recurrence after local ablation in elderly EHCC patients. Additionally, the validation cohort was used to assess the potential of the nomogram as a non-invasive biomarker for post-ablation recurrence in EHCC.Results: The user-friendly nomogram incorporates common clinical variables including gender, BCLC stage, tumor number, tumor size, red blood cell (RBC), gamma-glutamyl transferase (GGT), and prothrombin time activity (PTA). The nomogram constructed using the identified seven variables exhibits robust discriminatory capabilities, favorable predictive performance, and noteworthy clinical utility.Conclusion: We developed a user-friendly nomogram based on the BCLC stage classification, which may provide prognostic assessments for elderly EHCC patients at 1, 3, and 5 years post-RFA.Keywords: hepatocellular carcinoma, elderly, radiofrequency ablation, EHCC, relapse, prognostic model

Qiong Wu,1,&ast; Shiying An,1,&ast; RueyJyh Lee,1 Dongwen Gao,2 Yinyifan Zhou,1 Longping Peng,1 Chunrui Hu,1 Lei Yao,3 Chang Zhou,4 Li Zhou,5 Junjie Gao,6 Min Cao,1 Meijiao Mao,1 Guanghao Li,1 Bing Deng,1 Yingjia Xu,4 Youhua Wang1 1Department of Cardiology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Ultrasound, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Cardiology, Shanghai Fifth People’s Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 5Department of Cardiology, Shanghai Jiading Nanxiang Hospital, Shanghai, People’s Republic of China; 6Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingjia Xu, Shanghai Fifth People’s Hospital, Fudan University, Minhang District, 128 Ruili Road, Shanghai, 200240, People’s Republic of China, Tel +862164308151, Email xuyingjia@5thhospital.com Youhua Wang, Department of cardiology, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Xunhui, 725 South Wan-Ping Road, Shanghai, 200032, People’s Republic of China, Tel +862164385700, Email doctorwyh@163.comBackground: Dilated cardiomyopathy (DCM) is a severe heterogeneous cardiomyopathy characterized by cardiac enlargement and declining heart function, often leading to refractory heart failure and life-threatening outcomes, particularly prevalent in China. The challenge lies in the scarcity of targeted therapies with substantial efficacy for DCM. Additionally, traditional anti-heart failure drugs are constrained due to hypotension propensity or limited symptom improvement. Kuoxin Formula (KXF), internally endorsed at Longhua Hospital, demonstrates clear biological evidence for enhancing cardiac function and myocardial remodeling. Previous clinical studies suggest its potential to enhance patients’ quality of life. This trial aims to further evaluate KXF’s safety and efficacy in managing DCM-related heart failure.Methods: This prospective, randomized, double-blind, placebo-controlled, multicenter trial aims to recruit 230 DCM patients from five centers. Participants will be randomly assigned to either KXF or placebo for 12 weeks, with careful monitoring of key indicators and adverse events. The primary outcome measures the proportion of patients with NT-proBNP reduction exceeding 30%. Secondary outcomes include New York Heart Association functional classification, Traditional Chinese Medicine syndrome scores, 6-minute walk test, Lee’s heart failure score, and Minnesota Heart Failure Quality of Life Scale score. Ventricular remodeling will be assessed using cardiac ultrasound and ELISA. Safety metrics and adverse events will be meticulously recorded.Discussion: This study will be the first multicentered research conducted in China that utilizes a randomized, double-blind, placebo-controlled design to investigate the use of TCM in the treatment of DCM. It seeks to develop new theoretical frameworks and provide solid clinical data to support the integration of TCM and modern medicine in treating heart failure in DCM patients.Trial Registration: China Clinical Trial Registry, ChiCTR2300068937. Registered on March 1, 2023. https://www.chictr.org.cn/bin/project/edit?pid=190926.Keywords: dilated cardiomyopathy, heart failure, Kuoxin Formula, traditional Chinese medicine, clinical trials

Wenying Qiao,1– 5,&ast; Shugui Sheng,1– 3,&ast; Junnan Li,1– 3,&ast; Ronghua Jin,1– 4 Caixia Hu5 1Beijing Key Laboratory of Emerging Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Changping Laboratory, Beijing, People’s Republic of China; 5Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghua Jin, Beijing Key Laboratory of Emerging Infectious Diseases, BeijingDitan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email ronghuajin@ccmu.edu.cn Caixia Hu, Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China, Email hucaixia1217@126.comPurpose: The aim of the study is to identify and evaluate multifaceted factors impacting the survival of elderly cirrhotic HCC patients following ablation therapy, with the goal of constructing a nomogram to predict their 3-, 5-, and 8-year overall survival (OS).Patients and Methods: A retrospective analysis was conducted on 736 elderly cirrhotic HCC patients who underwent ablation therapy between 2014 and 2022. LASSO regression, random survival forest (RSF), and multivariate Cox analyses were employed to identify independent prognostic factors for OS, followed by the development and validation of a predictive nomogram. Harrell’s concordance index (C-index), calibration plot and decision curve analysis (DCA) were used to assess the performance of the nomogram. The nomogram was finally utilized to stratify patients into low-, intermediate-, and high-risk groups, aiming to assess its efficacy in precisely discerning individuals with diverse overall survival outcomes.Results: Alcohol drinking, tumor number, globulin (Glob) and prealbumin (Palb) were identified and integrated to establish a novel prognostic nomogram. The nomogram exhibited strong discriminative ability with C-indices of 0.723 (training cohort) and 0.693 (validation cohort), along with significant Area Under the Curve (AUC) values for 3-year, 5-year, and 8-year OS in both cohorts (0.758, 0.770, and 0.811 for training cohort; 0.744, 0.699 and 0.737 for validation cohort). Calibration plots substantiated its consistency, while DCA curves corroborated its clinical utility. The nomogram further demonstrated exceptional effectiveness in discerning distinct risk populations, highlighting its robust applicability for prognostic stratification.Conclusion: Our study successfully developed and validated a robust nomogram model based on four key clinical parameters for predicting 3-, 5- and 8-year OS among elderly cirrhotic HCC patients following ablation therapy. The nomogram exhibited a remarkable capability in identifying high-risk patients, furnishing clinicians with invaluable insights for postoperative surveillance and tailored therapeutic interventions.Keywords: hepatocellular carcinoma, HCC, nomogram, LASSO regression, random survival forest, RSF, overall survival, OS

Linqi Zhou,1 Changyuan Qiao,1 Jialing Huang,2 Jian Lin,2 Haisheng Zhang,2 Jian Xie,2 Yonggui Yuan,3 Changchun Hu2 1School of the Fourth Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Clinical Psychology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Psychosomatics and Psychiatry, Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of ChinaCorrespondence: Changchun Hu, Department of Clinical Psychology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, No. 261 Huansha Road, Shangcheng District, Hangzhou, 310002, People’s Republic of China, Tel +86-571-56006902, Email chuntianjs@163.comBackground: Previous studies have demonstrated a strong association between recent stressful life events and non-suicidal self-injury (NSSI) among adolescents. Internalizing symptoms and difficulty in emotion regulation (DER) may mediate this relationship. This study aimed to investigate the relationship between recent stressful life events and NSSI severity in adolescents and the potential moderating role of internalizing symptoms and DER.Methods: A total of 224 adolescent inpatients (78.6% female) participated in the study, with an age range of 12– 18 years old. Data on recent stressful life events, internalizing symptoms, DER, and NSSI behaviors were collected using a clinician-rated questionnaire. A structural equation model was used to test the hypothesized model.Results: The rate of NSSI reporting among adolescents in the past 12 months was 65.18%. Recent stressful life events were found to be directly associated with NSSI severity (β = 0.128, P = 0.023). A chain-mediating effect between recent stressful life events and NSSI was also confirmed (β = 0.034, P = 0.023), with DER and internalizing symptoms playing a chain-mediating role and DER having a significantly indirect association with NSSI through internalizing symptoms.Conclusion: Recent stressful life events appear to play a role in the etiology of NSSI, particularly punishment and interpersonal relationship events that warrant special attention. DER and internalizing symptoms play a chain-mediating role in the relationship between life events and NSSI. Reducing recent stressful life events, screening for internalizing symptoms, and improving emotion regulation may decrease NSSI behavior among adolescents.Keywords: non-suicidal self-injury, adolescents, recent stressful life events, internalizing symptoms, difficulty in emotion regulation, structural equation model

Heli Li,1,&ast; Jinru Cui,1,&ast; Cong Hu,1 Hao Li,2 Xiaoping Luo,3 Yan Hao1 1Division of Child Healthcare, Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Hao, Email haoyaner@163.comObjective: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with significant genetic heterogeneity. The ZIC gene family can regulate neurodevelopment, especially in the cerebellum, and has been implicated in ASD-like behaviors in mice. We performed bioinformatic analysis to identify the ZIC gene family in the ASD cerebellum.Methods: We explored the roles of ZIC family genes in ASD by investigating (i) the association of ZIC genes with ASD risk genes from the Simons Foundation Autism Research Initiative (SFARI) database and ZIC genes in the brain regions of the Human Protein Atlas (HPA) database; (ii) co-expressed gene networks of genes positively and negatively correlated with ZIC1, ZIC2, and ZIC3, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and receiver operating characteristic (ROC) curve analysis of genes in these networks; and (iii) the relationship between ZIC1, ZIC2, ZIC3, and their related genes with cerebellar immune cells and stromal cells in ASD patients.Results: (i) ZIC1, ZIC2, and ZIC3 were associated with neurodevelopmental disorders and risk genes related to ASD in the human cerebellum and (ii) ZIC1, ZIC2, and ZIC3 were highly expressed in the cerebellum, which may play a pathogenic role by affecting neuronal development and the cerebellar internal environment in patients with ASD, including immune cells, astrocytes, and endothelial cells. (iii) OLFM3, SLC27A4, GRB2, TMED1, NR2F1, and STRBP are closely related to ZIC1, ZIC2, and ZIC3 in ASD cerebellum and have good diagnostic accuracy. (iv) ASD mice in the maternal immune activation model demonstrated that Zic3 and Nr2f1 levels were decreased in the immune-activated cerebellum.Conclusion: Our study supports the role of ZIC1, ZIC2, and ZIC3 in ASD pathogenesis and provides potential targets for early and accurate prediction of ASD.Keywords: autism, ZIC1, ZIC2, ZIC3, cerebellum, biomarkers

Dianming Li,1,&ast; Weiman Shi,1,&ast; Changfeng Hu,1,2 Chengping Wen,1,2 Lin Huang,1,2 Qiao Wang1,2 1College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou City, People’s Republic of China; 2Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, Hangzhou City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Huang; Qiao Wang, College of Basic Medical Sciences, Key Laboratory of Chinese medicine rheumatology of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of China, Tel +86 571-86613587, Email huanglin@zcmu.edu.cn; wangqiao0309@163.comBackground: Gouty arthritis (GA) is a common inflammatory disease caused by deposition of monosodium urate (MSU) crystals in diarthrodial joints. GA attacks commonly involved in joint with red, swollen, heat and pain, and often happened in unilateral foot-first metatarsophalangeal. Accumulated studies have proved that lipids play critical roles in biological processes and lipids biomarkers can substitute for the diagnosis of various diseases.Methods: Herein, shotgun lipidomics was used to quantitatively analyze serum lipidomes of a gouty model which was induced by injecting MSU crystals and feeding high-fat diet with/without treatment with allopurinol. Meanwhile, ELISA kit was used to detect mouse serum levels of inflammatory cytokines (eg, tumor necrosis factor-α, interleukin 1 beta) and HE staining was used to observe the infiltration of inflammatory cells in the foot pad.Results: A total of 9 types of serum lipids were detected in lipidomics by shotguns, and the result of NMDS’ analysis demonstrated significant differences in lipids profiles between the control and model group. It is worth noting that lipid abnormality in GA (such as Ceramide (Cer), sphingomyelin (SM), 4-hydroxyalkenals (HNE), phosphatidylinositol (PI), ethanolamine glycerophospholipid (PE), etc.) is related with phospholipid and energy metabolism, and allopurinol treatment could correct the aberrant metabolism of lipid to some extent.Conclusion: Our results indicated that various aberrant lipid metabolisms were present in the established gouty model, and allopurinol treatment could relief this aberrant metabolism of lipids to some degree.Keywords: gouty arthritis, lipidomics, autoimmune reaction, glycerophospholipid metabolism, sphingolipid metabolism, inflammation

Chuling Hu,1,&ast; Yan Liu,2,&ast; Wei Cao,3,&ast; Na Li,4 Shen Gao,5 Zhuo Wang,5 Fenfen Gu2 1Department of Pharmacy, Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children’s Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 2Department of Clinical Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Neurovascular Disease, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 4Department of Pathology, Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children’s Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 5Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuo Wang; Fenfen Gu, Email wangzhou088@163.com; fenfen09@163.comIntroduction: Chemotherapy is still the treatment of choice for advanced triple-negative breast cancer. Chemotherapy combined with immunotherapy is being tried in patients with triple-negative breast cancer. As a kind of “cold tumor”, triple-negative breast cancer has a bottleneck in immunotherapy. Indoleamine 2, 3-dioxygenase-1 inhibitors can reverse the immunosuppressive state and enhance the immune response.Methods: In this study, mesoporous silica nanoparticles were coated with the chemotherapeutic drug doxorubicin and indoleamine 2, 3-dioxygenase 1 inhibitor 1-Methyl-DL-tryptophan (1-MT), and then encapsulate the surfaces of a triple-negative breast cancer cell membrane to construct the tumor dual-targeted delivery system CDIMSN for chemotherapy and immunotherapy, and to investigate the immunogenic death effect of CDIMSN.Results and discussion: The CDIMSN could target the tumor microenvironment. Doxorubicin induced tumor immunogenic death, while 1-MT reversed immunosuppression. In vivo findings showed that the tumor size in the CDIMSN group was 2.66-fold and 1.56-fold smaller than that in DOX and DIMSN groups, respectively. CDIMSN group was better than naked DIMSN in stimulating CD8+T cells, CD4+T cells and promoting Dendritic Cells(DC) maturation. In addition, blood analysis, biochemical analysis and Hematoxylin staining analysis of mice showed that the bionic nanoparticles had good biological safety. Keywords: immunogenic cell death, doxorubicin, bionic nanoparticle, IDO1 inhibitor, triple-negative breast cancer

Wenying Qiao,1– 3,&ast; Zibo Fan,2,&ast; Qi Wang,2,&ast; Ronghua Jin,2,3 Caixia Hu1 1Interventional Therapy Center for Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Changping Laboratory, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Caixia HuInterventional Therapy Center for Oncology; Beijing You’an Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai Street, Fengtai District, Beijing, People’s Republic of China, Tel/Fax +86-13811395702, Email hucaixia1217@126.comRonghua JinBeijing Ditan Hospital, Capital Medical University, 8 Jingshun East Street, Chaoyang District, Beijing, People’s Republic of China, Tel/Fax +86-13811611118, Email ronghuajin@ccmu.edu.cnPurpose: We first aimed to compare the prognostic difference between the application of Contrast-enhanced computed tomography (CECT) and Non-enhanced computed tomography (NECT) in hepatocellular carcinoma(HCC) patients with early-stage immediately after ablation. We secondly propose to explore the risk factors for recurrence in patients undergoing CECT, and then develop a nomogram.Patients and Methods: Clinical data were collected from 711 patients who received TACE combined with ablation from January 1, 2015, to December 31, 2022, at Beijing Youan Hospital. According to the imaging methods applied after ablation, patients were categorized into the CECT group and the NECT group and then were compared by Kaplan-Meier (KM) curves. Lasso regression is used to screen risk factors for recurrence and the nomogram was plotted. Finally, discrimination, calibration plot, and decision curve analysis (DCA) were used to measure the performance of the nomogram.Results: The KM curve indicates that recurrence-free survival (RFS) was longer in the CECT group than in the NECT group (HR =0.759, 95% CI 0.606– 0.951, P=0.016). Six variables were selected to construct the nomogram. 1-, 3-, and 5-year area under the curves (AUCs) (0.867, 0.731, 0.773 and 0.896, 0.784, 0.773) of the training and validation cohorts proved the good predictive performance of the nomogram. Calibration curves and DCA curves suggested accuracy and net clinical benefit rates. The nomogram enabled to classify of patients into three groups according to the risk of recurrence: low risk, intermediate risk, and high risk. There was a statistically significant difference in RFS between the two groups in the training and validation cohorts (P< 0.001).Conclusion: We demonstrated that HCC patients who underwent CECT evaluation after ablation had a better prognosis, making this evaluation method highly recommended for guiding clinical management.Keywords: hepatocellular carcinoma, transcatheter arterial chemoembolization, contrast-enhanced computed tomography, recurrence-free survival, risk factors

Gang Chen,1– 3 Lei Li,2,4 Taipeng Sun,1– 3 Chenguang Jiang,1,2 Wei Xu,1,2 Suzhen Chen,1,2 Changchun Hu,1 Yingying Yue,1,2 Tianyu Wang,1,2 Wenhao Jiang,1,2 Yonggui Yuan1,2 1Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Institute of Psychosomatics, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Medical Psychology, Huai’an NO 3 People’s Hospital, Huaian, People’s Republic of China; 4Department of Sleep Medicine, The Fourth People’s Hospital of Lianyungang, Lianyungang, People’s Republic of ChinaCorrespondence: Wenhao Jiang; Yonggui Yuan, Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao, Gulou District, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel +86-25-83285124, Email wjiang43@outlook.com; yygylh2000@sina.comBackground: Depression is a heritable brain disorder. Laminin genes were recently identified to affect the brain’s overall thickness through neurogenesis, differentiation, and migration in depression. This study aims to explore the effects of the LAMA2’s single nucleotide polymorphisms (SNP), a subunit gene of laminin, on the detected brain regions of patients with major depressive disorder (MDD).Methods: The study included 89 patients with MDD and 60 healthy controls with T1-weighted structural magnetic resonance imaging and blood samples for genotyping. The interactions between LAMA2 gene SNPs and diagnosis as well as duration of illness (DOI) were explored on brain measures controlled for age, gender, and site.Results: The right transverse temporal gyrus and right parahippocampal gyrus showed reduced thickness in MDD. Almost all seven LAMA2 SNPs showed significant interactions with diagnosis on both gyrus (corrected p < 0.05 or trending). In MDD, rs6569604, rs2229848, rs2229849, rs2229850, and rs2784895 interacted with DOI on the right transverse temporal gyrus (corrected p < 0.05), but not the right parahippocampal gyrus.Conclusion: The thickness of the right transverse temporal gyrus in patients with MDD may be affected by LAMA2 gene and DOI.Keywords: major depressive disorder, right transverse temporal gyrus, LAMA2, interaction

Hong-Mei Li,&ast; Wei Huang,&ast; Chao Hu, Zi-Shu Zhang, Yu-Dong Xiao, Tian-Cheng Wang Department of Radiology, the Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tian-Cheng Wang; Yu-Dong Xiao, Tel +8613637403027, Fax +86 0731-85533525, Email wangtiancheng94@csu.edu.cn; xiaoyudong222@csu.edu.cnPurpose: There is a scarcity of predictive models currently accessible for prognosticating proliferative hepatocellular carcinoma (HCC), an integrated class of subtype, characterized by a dismal prognosis. Consequently, this study aimed to develop and validate a novel prognostic model capable of accurately predicting the prognosis of proliferative HCC after curative resection.Patients and Methods: This retrospective multicenter study included patients with solitary HCC who underwent curative liver resection from August 2014 to December 2020 (n = 816). Patients were stratified into either the proliferative HCC cohort (n = 259) or the nonproliferative HCC cohort (n = 557) based on histological criteria. Disease-free survival (DFS) was compared between the two groups before and after one-to-one propensity score matching (PSM). Of all the proliferative HCC patients, 203 patients were assigned to training cohort, and 56 patients were assigned to validation cohort. Univariate and multivariate analyses were performed in training cohort to identify risk factors associated with worse DFS. Thereafter, a predictive model was constructed, subsequently validated in the validation cohort.Results: The DFS of proliferative HCC was significantly worse than nonproliferative HCC before and after PSM. Meanwhile, multivariate regression analysis revealed that liver cirrhosis (P = 0.032) and larger tumor size (P = 0.000) were independent risk factors of worse DFS. Lastly, the discriminative abilities of the predictive model for 1, 3, 5-year DFS rates, as determined by receiver operating characteristic (ROC) curves, were 0.702, 0.720, and 0.809 in the training cohort and 0.752, 0.776, and 0.851 in the validation cohort, respectively.Conclusion: This study developed a predictive model with satisfactory accuracy to predict the worse DFS in proliferative HCCs after liver resection. Moreover, this predictive model may serve as a valuable tool for clinicians to predict postoperative HCC recurrence, thereby enabling them to implement early preventative strategies.Keywords: hepatocellular carcinoma, proliferative, nonproliferative, predictive model, curative resection

Yan Zhang,1,&ast; Wenjun Meng,2,&ast; Chengwen Hu,1 Meirong Dong,1 Youqun Chu,1 Fang Kang,2 Juan Li,2 Xia Chen1 1Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Chen; Juan Li, Department of Nursing; Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of China, Email ChenXiaahslyy@163.com; huamuzi1999@126.comBackground: Sore throat is a common complication after general anesthesia. Oral care solutions have been used to reduce the incidence of oral complications or ventilator-associated pneumonia, but their effect on postoperative sore throat (POST) is unclear. This study aims to investigate whether oral care solution can alleviate POST in patients undergoing i-gel laryngeal mask general anesthesia.Methods: A total of 120 patients who were scheduled for elective surgery under laryngeal mask general anesthesia were enrolled. The patients were randomly assigned to an experimental group (oral care solution) and a control group (0.9% saline) and gargled for 1 min with 10mL of oral care solution or saline 5 min before anesthesia induction. The primary outcomes were the overall incidence of sore throat within 24 h and incidence at 20 min, 1 h, 6 h, 24 h after removal of i-gel. The secondary outcomes were the severity of sore throat at the four time points and incidence of hoarseness, cough within 24 h after removal of i-gel.Results: A total of 111 patients were included in the analysis. The overall incidence of sore throat within 24 h in the experimental group was significantly lower than that in the control group, as was the incidence at four time points (P< 0.05). The VAS scores at the four time points in the experimental group were significantly lower than those in the control group (P< 0.05), and the results of repeated measurement analysis of variance showed that time effect and intergroup effect were statistically significant (P< 0.001). No differences were found between the groups in the incidence of hoarseness and cough.Conclusion: Gargling with oral care solution before anesthesia induction can significantly reduce the incidence and severity of POST in patients undergoing i-gel laryngeal mask general anesthesia.Keywords: oral care solution, laryngeal mask, general anesthesia, postoperative sore throat

Can Hu,1,2,&ast; Yan Qiu,1,2,&ast; Jiajun Guo,1,2 Yuchao Cao,1,2 Dairong Li,3 Yonghong Du1,2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Chongqing Key Laboratory of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dairong Li, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-23-89012745, Fax +86-23-68485021, Email lidairong@hospital.cqmu.edu.cn Yonghong Du, State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, No. 1, Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel/Fax +86-23-68485021, Email duyonghong@cqmu.edu.cnPurpose: Tuberculosis (TB) is a chronic disease caused by Mycobacterium tuberculosis (MTB) that remains a major global health challenge. One of the main obstacles to effective treatment is the heterogeneous microenvironment of TB granulomas. This study aimed to investigate the potential of a hypoxic remission-based strategy to enhance the outcome of tuberculosis treatment when implemented in combination with ultrasound.Methods: A PLGA nanoparticle (LEV@CAT-NPs) loaded with levofloxacin (LEV) and catalase (CAT) was fabricated by a double emulsification method, and its physical characteristics, oxygen production capacity, drug release capacity, and biosafety were thoroughly investigated. The synergistic therapeutic effects of ultrasound (US)-mediated LEV@CAT-NPs were evaluated using an experimental mouse model of subcutaneous tuberculosis granuloma induced by Bacille Calmette-Guérin (BCG) as a substitute for MTB.Results: LEV@CAT-NPs exhibited excellent oxygen production capacity, biosafety, and biocompatibility. Histological analysis revealed that ultrasound-mediated LEV@CAT-NPs could effectively remove bacteria from tuberculous granulomas, significantly alleviate the hypoxia state, reduce the necrotic area and inflammatory cells within the granuloma, and increase the penetration of dyes in granuloma tissues. The combined treatment also reduced the serum levels of inflammatory cytokines (eg, TNF-α, IL-6, and IL-8), and significantly downregulated the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF). These results suggested that the synergistic treatment of ultrasound-mediated LEV@CAT-NPs effectively eradicated the bacterial infection and reversed the hypoxic microenvironment of tuberculous granulomas, further promoting tissue repair.Conclusion: This study provides a non-invasive and new avenue for treating refractory tuberculosis infections. The potential role of regulating hypoxia within infected lesions as a therapeutic target for infection deserves further exploration in future studies.Keywords: tuberculosis granulomatous, hypoxia, catalase, sonodynamic therapy, Bacille Calmette-Guérin

Zhiguang Fan,1 Xiaoli Shi,2 Chunjie Hu,3 Liya Zhu,4 Zhe Wang5 1Department of Psychology, Shaoxing University, Zhejiang, 312000, People’s Republic of China; 2School of Education, Jilin International Studies University, Changchun, 130000, People’s Republic of China; 3The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, 130000, People’s Republic of China; 4School of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130000, People’s Republic of China; 5School of Pharmacology, Changchun University of Chinese Medicine, Changchun, 130000, People’s Republic of ChinaCorrespondence: Zhe Wang, Email megaton0514@gmail.comBackground: Individuals who initiate the concealment of their adverse or distressing thoughts from others can trigger off negative psychological experiences and social isolation, and lead to poorer health. Therefore, this study aimed to analyze the psychometric properties of the Self-Concealment Scale (SCS) in Chinese older adults.Methods: A questionnaire was administered to 1085 elderly people using convenience sampling and snowball sampling. Scales used included the SCS, Distress Disclosure Index (DDI), Revised Cheek and Buss Shyness Scale (RCBS), Social Interaction Anxiety Scale (SIAS), Social Phobia Scale (SPS), UCLA Loneliness Scale (ULS-8), and Kessler Psychological Distress Scale (K10).Results: The SCS consisted of 10 items with a one-dimensional structure, explaining 55.66% of the variance. The factor loading values for each item ranged from 0.68 to 0.75, and the covariance ranged from 0.46 to 0.57. Confirmatory factor analysis showed good model fit (χ 2/df=2.829, RMSEA=0.057, CFI=0.981, IFI=0.981, TLI=0.974, PNFI=0.712, PGFI=0.719). The criterion-related validity test found that the SCS was significantly and positively correlated with the RCBS, SIAS, SPS, ULS-8, K10, depression, and anxiety; and the SCS was significantly and negatively correlated with the DDI. The Cronbach’s α coefficient value for the scale was 0.923; the split-half reliability coefficient value was 0.923. In addition, the SCS had cross-gender consistency.Conclusion: The SCS has good reliability and validity in older adults and can be used as a valid tool to assess self-concealment among older people.Keywords: older adult, self-concealment, reliability, validity

Jing Yang,1,&ast; Shuang Liang,1,&ast; Huahui Liu,1 Cai Hu,1 Sainan Guan,1 Haiyu Kang,1 Erjiao Xu,1 Ronghua Yan1,2 1Department of Medical Ultrasonics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong Province, People’s Republic of China; 2Department of Radiology, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghua Yan; Erjiao Xu, Department of Medical Ultrasonics, The Eighth Affiliated Hospital of Sun Yat-sen University, No. 3025 Shennan Middle Road, Futian Street, Futian District, Shenzhen City, Guangdong Province, People’s Republic of China, Tel +86 755 83982222, Fax +86 755 83980805, Email yanrh@mail3.sysu.edu.cn; xuerjiao@mail.sysu.edu.cnPurpose: To investigate the efficacy and safety of microwave ablation (MWA) assisted by ultrasound fusion imaging (FI) for primary and secondary liver cancers with a diameter of 3– 7 cm.Patients and Methods: A retrospective analysis was conducted on patients with primary and secondary liver cancers (3– 7 cm) who underwent MWA with ultrasound FI assistance in our hospital from April 2020 to May 2022. Technical success, technique efficacy, local tumor progression (LTP), major complication, intrahepatic distant recurrence (IDR), and overall survival (OS) were assessed during the follow-up period. In addition, the ablation results of tumors between the medium-sized group (3.1– 5.0 cm) and large-sized group (5.1– 7.0 cm) were compared.Results: 31 patients with 35 primary and secondary liver cancers were treated with MWA assisted by ultrasound FI. Complete ablation was achieved in 34 lesions with a technical success rate of 97.1%. Major complications occurred in 6.5% of patients (2/31), while no ablation-related deaths were reported. The median follow-up time of this study was 24 months (range:10 to 35 months). The technique efficacy rate was 97.1% (34/35), with LTP occurring in three lesions at a rate of 8.8% (3/34). The incidence of IDR was 38.7% (12/31) and the 2-year cumulative OS rate reached 96.7%. Moreover, there were no statistical differences in technique efficacy rate (p=0.286), LTP rate (p=0.328), major complication rate (p=0.503), IDR (p=0.857), and OS (p=0.118) between medium-sized group and large-sized group.Conclusion: Ultrasound FI-assisted MWA has the potential to be an effective and safe therapeutic strategy for primary and secondary liver cancers ranging from 3– 7 cm in size.Keywords: fusion imaging, microwave ablation, liver cancers, ultrasound

Xinyi Li,1,&ast; Tao Wang,2,&ast; Li Jin,3 Zhiqiang Li,4 Cheng Hu,3 Hongliang Yi,1 Jian Guan,1 Huajun Xu,1 Xiaolin Wu5 1Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, People’s Republic of China; 2Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 4Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Ministry of Education, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 5Central Laboratory of Shanghai Eighth People’s Hospital, Xuhui Branch of Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huajun Xu, Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, 200233, People’s Republic of China, Email sunnydayxu2010@163.com Xiaolin Wu, Central Laboratory of Shanghai Eighth People’s Hospital, Xuhui Branch of Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China, Email wuxiaolin999@hotmail.comObjective: Both obstructive sleep apnea (OSA) and obesity are highly prevalent worldwide, and are intrinsically linked. Previous studies showed that obesity is one of the major risk factors for OSA, but the causality of the relationship is still unclear. The study was to investigate the causal relationships of overall obesity and abdominal obesity with OSA and its quantitative traits.Methods: In this case-control study, a total of 7134 participants, including 4335 moderate-to-severe OSA diagnosed by standard polysomnography and 2799 community-based controls were enrolled. Anthropometric and biochemical data were collected. Mendelian randomization (MR) analyses were performed using the genetic risk score, based on 29 body mass index (BMI)- and 11 waist-hip-ratio (WHR)-associated single nucleotide polymorphisms as instrumental variables. The causal associations of these genetic scores with OSA and its quantitative phenotypes were analyzed.Results: Obesity was strongly correlated with OSA in observational analysis (β= 0.055, P = 3.7 × 10− 5). In MR analysis, each increase by one standard deviation in BMI was associated with increased OSA risk [odds ratio (OR): 2.21, 95% confidence interval (CI): 1.62– 3.02, P = 5.57 × 10− 7] and with 2.72-, 4.68-, and 3.25-fold increases in AHI, ODI, and MAI, respectively (all P

Meng Zhou,1 Ying Peng,2 Kui Liu,2 Lin Zhou,2 Fei Wang,2 Xinyi Chen,2 Bin Chen,2,3,&ast; Chonggao Hu2,&ast; 1Department of Social Medicine of School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Tuberculosis Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, People’s Republic of China; 3School of Public Health, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Chen; Chonggao Hu, Department of Tuberculosis Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, People’s Republic of China, Email bchen@cdc.zj.cn; chghu@cdc.zj.cnBackground: Multidrug-resistant (MDR) and rifampicin-resistant (RR) tuberculosis (TB) is related to high healthcare costs. However, studies on direct healthcare expenditure in different settings remain inconclusive. Hence, we aimed to examine the direct medical expenses (DME) of patients with MDR/RR-TB and assessed which patient characteristics were associated with higher costs.Methods: DME was evaluated using records from the hospital information system in three cities with different economic levels in Zhejiang Province, Eastern China, matching with data (including socio-demographics, disease treatment status, etc.) collected in the Tuberculosis Management Information System. A logistic regression model was used to identify variables associated with higher costs.Results: Of 193 patients with MDR/RR-TB, the average DME was &dollar;10,491 (interquartile range (IQR) &dollar;4679– 16,710), consisting of &dollar;2696 (IQR &dollar;1019– 5100) out-of-pocket costs, medical reimbursement, and subsidies, accounting for 32%, 50.3% and 14%, respectively. A total of 74.2% and 56% of DME were for drugs and anti-TB drugs, respectively. Only 16.9% of the patients were treated with an all-oral regimen. Higher DME was significantly associated with local residents 7.29 (95% confidence interval (CI) [2.62– 20.3]), hospitalization experience 7.63 (95% (CI) [2.54– 22.95]), longer duration of treatment 6.63 (95% CI [2.27– 19.35]), and lower health insurance reimbursement 5.65 (95% CI [1.90– 16.79]).Conclusion: DME of patients with MDR/RR-TB was still significant, and domestic migrants, hospitalization, long treatment duration, and high health insurance rates increased the financial burden on MDR/RR-TB patients. Reasonable intervention programs should be developed to reduce the medical burden of patients with MDR/RR-TB, according to the DME and its component of MDR-TB patients, besides the economic status of their regions.Keywords: multidrug-resistant tuberculosis, rifampicin-resistant tuberculosis, direct medical expenses, anti-TB drugs, burden

Shan Yang,1 Lirui Cao,2 Yongfang Zhou,3 Chenggong Hu1 1Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 3Department of Respiratory Care, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Chenggong Hu; Yongfang Zhou, Email huchenggong@scu.edu.cn; zyfmg@163.comObjective: The aim of this study was to develop and validate a machine learning-based predictive model that predicts 90-day mortality in ICU trauma patients.Methods: Data of patients with severe trauma were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The performances of mortality prediction models generated using nine machine learning extreme gradient boosting (XGBoost), logistic regression, random forest, AdaBoost, multilayer perceptron (MLP) neural networks, support vector machine (SVM), light gradient boosting machine (GBM), k nearest neighbors (KNN) and gaussian naive bayes (GNB). The performance of the model was evaluated in terms of discrimination, calibration and clinical application.Results: We found that the accuracy, sensitivity, specificity, PPV, NPV and F1 score of our proposed XGBoost model were 82.8%, 79.7%, 77.6%, 51.2%, 91.5% and 0.624, respectively. Among the nine models, the XGBoost model performed best. Compared with traditional logistic regression, the calibration curves of the XGBoost model and decision curve analysis (DCA) performed well.Conclusion: Our study shows that the XGBoost model outperforms other machine learning models in predicting 90-day mortality in trauma patients. It can be used to assist clinicians in the early identification of mortality risk factors and early intervention to reduce mortality.Keywords: MIMIC-III, severe trauma patient, intensive care unit, XGBoost, mortality, prediction model

Xinyu Nie,1,2 Xinru Dong,1,2 Yuge Hu,1,2 Fangjun Xu,1 Cong Hu,2 Chang Shu1 1Obstetrics and Gynecology Center, First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Reproductive Medicine Center, Prenatal Diagnosis Center, First Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Chang Shu, Email shu_chang@jlu.edu.cnAbstract: Female infertility and pregnancy maintenance are associate with various factors, including quantity and quality of oocytes, genital inflammation, endometriosis, and other diseases. Women are even diagnosed as unexplained infertility or unexplained recurrent spontaneous abortion when failed to achieve pregnancy with current treatment, which are urgent clinical issues need to be addressed. Coenzyme Q10 (CoQ10) is a lipid-soluble electron carrier in the mitochondrial electron transport chain. It is not only essential for the mitochondria to produce energy, but also function as an antioxidant to maintain redox homeostasis in the body. Recently, the capacity of CoQ10 to reduce oxidative stress (OS), enhance mitochondrial activity, regulate gene expression and inhibit inflammatory responses, has been discovered as a novel adjuvant in male reproductive performance enhancing in both animal and human studies. Furthermore, CoQ10 is also proved to regulate immune balance, antioxidant, promote glucose and lipid metabolism. These properties will bring highlight for ovarian dysfunction reversing, ovulation ameliorating, oocyte maturation/fertilization promoting, and embryonic development optimizing. In this review, we systematically discuss the pleiotropic effects of CoQ10 in female reproductive disorders to investigate the mechanism and therapeutic potential to provide a reference in subsequent studies.Keywords: coenzyme Q10, oxidative stress, reactive oxygen species, reproductive, oocyte, endometriosis

Yiran Fu,1 Weishe Zhang,1,2 Qi Wang,1 Caihong Hu,1 Qi Li,3 Jingrui Huang1 1Department of Obstetrics, Xiangya Hospital Central South University, Changsha, People’s Republic of China; 2Hunan Engineering Research Center of Early Life Development and Disease Prevention, Changsha, People’s Republic of China; 3Reproductive Medicine Center, Xiangya Hospital Central South University, Changsha, People’s Republic of ChinaCorrespondence: Jingrui Huang, Department of Obstetrics, Xiangya Hospital Central South University, 87 Xiangya Road, Changsha, 410008, People’s Republic of China, Email jingruihuang@hotmail.com; huangjingrui@csu.edu.cnIntroduction: To evaluate the methodological quality of diagnosis and treatment guidelines/consensus related to ectopic pregnancy.Materials and methods: Use the “Appraisal of Guidelines and Research and Evaluation” (AGREE II) method to evaluate the differences among the guideline/consensus.Results: We appraised 9 clinical practice guidelines for ectopic pregnancy (9 clinical practice guidelines from 5 countries) including the United States, United Kingdom, Ireland, Canada, and China. The guidelines received the highest scores for clarity of presentation (82.72%) and lowest scores for editorial independence (30.56%). The comprehensive recommendations of the 7 guidelines were Grade B, the other 2 guidelines were Grade C.Conclusion: The overall quality of the ectopic pregnancy guidelines had room for improvement. It is recommended to supplement and improve the four fields of “independence”, “rigor”, “participants” and “application”, especially the “independence” and “application” fields.Keywords: guidelines, ectopic pregnancy, pelvic pain, AGREE II, clinical practice

Qiulin Xiao,1,2 Bo Chen,1 Zhenya Zhu,1 Ting Yang,1 Enfu Tao,1 Chenmin Hu,1 Wei Zheng,3 Weihong Tang,2 Xiaoli Shu,1 Mizu Jiang1,3 1Gastrointestinal Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, Zhejiang, 310052, People’s Republic of China; 2Department of Gastroenterology, Hangzhou Children’s Hospital, Hangzhou, Zhejiang, 310014, People’s Republic of China; 3Department of Gastroenterology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, Zhejiang, 310052, People’s Republic of ChinaCorrespondence: Mizu Jiang, Department of Gastroenterology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, 3333 Bin Sheng Road, Hangzhou, Zhejiang, 310052, People’s Republic of China, Tel +86-571-87061007, Fax +86-571-86658672, Email mizu@zju.edu.cnObjective: To examine the association between the fecal microbiota of acute diarrhea in children and provide gut microbiota information related the acute diarrhea with rotavirus.Patients and Methods: Children with acute diarrhea aged 3– 60 months were selected for the study. Routine stool examination was performed, and stool samples were collected and stored at − 80 °C until further analysis. Fecal microbial DNA was extracted, and DNA concentration and quality were detected. PCR amplification and 16S rDNA high-throughput sequencing analysis using the Illumina MiSeq platform were performed, and intestinal flora was statistically analyzed.Results: Children with acute diarrhea exhibited gut microbial dysbiosis. Lower microbial diversity and richness were observed in the viral enteritis and bacterial enteritis groups than in the control group. Composition of the microbiota in acute diarrhea differed from that in the control group. The Bacteroidetes/Firmicutes dramatically decreased in the viral enteritis and bacterial enteritis groups. However, the relative abundance of Proteobacteria and Fusobacteria increased, especially in the bacterial enteritis group. In addition, the relative abundance of Actinobacteria had dramatically increased in the viral enteritis group. According to the Kyoto Encyclopedia of Genes and Genomes map analysis, the membrane transport dysfunction was caused by rotavirus infection, while the membrane transport dysfunction was more evident in bacterial infection.Conclusion: Acute diarrhea infections cause fecal microbiota dysbiosis in children. Changes in fecal microflora in children suggest that the regulation of intestinal flora in children with acute diarrhea should be strengthened.Keywords: acute diarrhea, microbiome, Fusobacteria, Firmicutes, Bacteroidetes, 16S rDNA sequencing, rotavirus

Yumei Zhang,1,&ast; Xin Li,1,&ast; Suning Zhang,2 Wei Chen,3 Jianxin Lu,1 Yingxin Xie,1 Shengbin Wu,1 Feng Zhuang,1 Xiao Bi,1 Mingzi Chu,1 Feng Wang,1 Yemin Huang,1 Feng Ding,1 Chun Hu,1 Yu Pan1 1Division of Nephrology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Division of Emergency, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Division of Neurology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Pan; Chun Hu, Division of Nephrology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201900, People’s Republic of China, Tel +86-021-56691101, Email panyu1980@163.com; spring_115@hotmail.comBackground: Since little is known about the acute kidney injury (AKI) in aging population infected with SARS-CoV-2 Omicron variant, we investigated the incidence, clinical features, risk factors and mid-term outcomes of AKI in hospitalized geriatric patients with and without COVID-19 and established a prediction model for mortality.Methods: A real-time data from the Shanghai Ninth People’s Hospital information system of inpatients with COVID-19 from 1 April 2022 to 30 June 2022 were extracted. Clinical spectrum, laboratory results, and clinical prognosis were included for the risk analyses. Moreover, Cox and Lasso regression analyses were applied to predict the 90-day death and a nomogram was established.Results: A total of 1607 SARS-CoV-2 infected patients were enrolled; hypertension was the most common comorbidity, followed by chronic cardiovascular disease, diabetes mellitus, and lung disease. Most of the participants were non-vaccinated and the mean age of patients was 82.6 years old (range, 60– 103 years). The AKI incidence was higher in relatively older patients (16.29% vs 3.63% in patients older than 80 years and 60 to 80 years, respectively). Linear regression models identified some variables associated with the incidence of AKI, such as older age, clinical spectrum, D-dimer level, number of comorbidities, baseline eGFR, and antibiotic or corticosteroid treatment. In this cohort, 11 patients died in-hospital and 21 patients died at 90-day follow-up. The predictive nomogram of 90-day death achieved a good C-index of 0.823 by using 5 predictor variables: ICU admission, D-dimer, peak of serum creatinine, rate of serum creatinine decline and white blood cell count (WBC).Conclusion: Older age, clinical spectrum, D-dimer level, number of comorbidities, baseline eGFR, and antibiotic or corticosteroid treatment are clinical risk factors for the incidence of AKI in geriatric COVID-19 patients. The prediction nomogram achieved an excellent performance at the prediction of 90-day mortality.Keywords: COVID-19, Omicron, acute kidney injury, aging, predictive nomogram

Wa Cai,1,&ast; Xi-Fang Wei,1,&ast; Chen Hu,1 Jun Ji,2 Hua Shun Cui,1 Wei-Dong Shen1 1Department of Acupuncture, Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Acupuncture Literature, Shanghai Research Institute of Acupuncture and Meridian, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei-Dong Shen; Hua Shun Cui, Email shenweidong1018@163.com; cuihuashun@shutcm.edu.cnBackground: Poststroke depression (PSD) is the most frequent neuropsychiatric consequence of stroke. Electroacupuncture (EA) has been found to be an effective therapy for treating PSD. However, the underlying mechanisms of EA’s efficacy remain unclear. This research aimed to investigate the effects of EA on alterations in gut microbiota and fecal metabolome in PSD rats.Methods: Analyses of gut microbiome and fecal metabolome were performed to identify gut microbes and their functional metabolites in a sham group, PSD group, and EA group. We conducted enrichment analysis to identify the differential metabolic pathways in three groups. Correlations between altered gut microbes and differential metabolites after EA treatment were studied.Results: PSD showed decreased species-richness/diversity indices of microbial composition, characterized by an increase in Muribaculaceae, Peptostreptococcaceae, Oscillospiraceae, Ruminococcaceae, and Clostridiaceae and a decrease in Lactobacillaceae, Lachnospiraceae, and Bacteroidaceae. Of these, the abundance of Muribaculaceae, Lactobacillaceae, Lachnospiraceae, Peptostreptococcaceae, and Clostridiaceae were reversed by EA. Furthermore, PSD was associated with 34 differential fecal metabolites, mainly belonging to steroid hormone biosynthesis, that could be regulated by EA.Conclusion: Regulation of gut microbiome and lipid metabolism could be one of the potential mechanisms for EA treatment for alleviating the depressive behaviors of PSD.Keywords: electroacupuncture, gut microbiome, fecal metabolome, metabolic pathways, poststroke depression

Han Li,1,&ast; Yinan Ding,2,&ast; Jiayan Huang,1 Yanyan Zhao,1 Wei Chen,3 Qiusha Tang,2 Yanli An,4 Rong Chen,5 Chunmei Hu1 1Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Medical School of Southeast University, Nanjing, People’s Republic of China; 3Department of Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 4Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, People’s Republic of China; 5Department of Oncology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunmei Hu, Department of tuberculosis, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210009, People’s Republic of China, Email njyy003@njucm.edu.cnBackground: Central nervous system tuberculosis (CNS-TB) is the most devastating form of extrapulmonary tuberculosis. Rifampin (RIF) is a first-line antimicrobial agent with potent bactericidal action. Nonetheless, the blood-brain barrier (BBB) limits the therapeutic effects on CNS-TB. Exosomes, however, can facilitate drug movements across the BBB. In addition, exosomes show high biocompatibility and drug-loading capacity. They can also be modified to increase drug delivery efficacy. In this study, we loaded RIF into exosomes and modified the exosomes with a brain-targeting peptide to improve BBB permeability of RIF; we named these exosomes ANG-Exo-RIF.Methods: Exosomes were isolated from the culture medium of BMSCs by differential ultracentrifugation and loaded RIF by electroporation and modified ANG by chemical reaction. To characterize ANG-Exo-RIF, Western blot (WB), nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were performed. Bend.3 cells were incubated with DiI labeled ANG-Exo-RIF and then fluorescent microscopy and flow cytometry were used to evaluate the targeting ability of ANG-Exo-RIF in vitro. Fluorescence imaging and frozen section were used to evaluate the targeting ability of ANG-Exo-RIF in vivo. MIC and MBC were determined through microplate alamar blue assay (MABA).Results: A novel exosome-based nanoparticle was developed. Compared with untargeted exosomes, the targeted exosomes exhibited high targeting capacity and permeability in vitro and in vivo. The MIC and MBC of ANG-Exo-RIF were 0.25 μg/mL, which were sufficient to meet the clinical needs.Conclusion: In summary, excellent targeting ability, high antitubercular activity and biocompatibility endow ANG-Exo-RIF with potential for use in future translation-aimed research and provide hope for an effective CNS-TB treatment.Graphical Abstract: Keywords: exosome, central nervous system tuberculosis, blood-brain barrier, rifampin

Dong Liu,1,&ast; Huanhuan Wei,2,&ast; Jinyu Huang,1 Hailin Shen,3 Ximing Wang,1 Chunhong Hu1 1Radiological Department, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Academy of Medical Sciences, the People’s Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Radiology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunhong Hu, Email 239847878@qq.comBackground: Endometriosis developing in a cesarean section (CS) scar is an unusual event. Malignant transformation arising on the background of scar endometriosis in the abdominal wall is extremely rare. Herein we report a case of clear cell carcinoma (CCC) arising in the abdominal wall from endometriosis tissues following CS and review previous literature.Case Presentation: A 48-year-old gravida 2 para 1 female presented with an abdominal wall mass at her CS scar, which increased in size and became painful in the last 2 years. Physical examination showed a multilocular solid mass of about 13 cm, at the previous CS scar. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a 12.8cm × 7.7cm multi-septate cystic lesion on the anterior abdominal wall, and histological examination showed that CCC was caused by the transformation of abdominal wall endometriosis (AWE).Conclusion: An endometriosis-associated malignancy should be considered in the differential with any enlarging mass in the abdominal wall scar.Keywords: cesarean section, abdominal wall endometriosis, case report

Biao Hou,1,* Fen Yang,2,* Chaotao Hu,1 Changxiong Liu,1 Xiangjun Xiao,1 Yanming Chen,1 Xiongjie Huang,1 Songlin Xie1 1Department of Hand and Foot Microsurgery, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, People’s Republic of China; 2Department of Infectious Diseases, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Songlin Xie, Department of Hand and Foot Microsurgery, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, No. 336 Dongfeng Nan Road, Zhuhui District, Hengyang, 421002, People’s Republic of China, Tel + 86- 139- 7540- 4959, Email xiesonglin0929@163.comBackground: Photodynamic antimicrobial therapy (PDAT) has been extensively studied because of its potential applications such as precise controllability, high spatiotemporal accuracy, and non-invasiveness. More importantly, it is difficult for bacteria to develop resistance to the aforementioned PDATs. However, the selectivity of traditional PDAT methods to bacteria is generally poor, so it has been proposed to introduce positively charged components such as quaternary ammonium salts to enhance the targeting of bacteria; however, they always possess high toxicity to normal cells. As a result, measures should be taken to enhance the targeting of bacteria and avoid side effects on normal cells.Methods and Results: In our work, we creatively design a nanoplatform with high anti-bacterial efficiency, low side effects and its size is approximately 121 nm. BSA, as a nanocarrier, encapsulates the photosensitizer (E)-4-(4-(diphenylamino)styryl)-1-methylpyridin-1-ium with AIE properties named as BSA-Tpy, which increases its circulation time in vivo and improves the biocompatibility. Under acidic conditions (pH = 5.0), the surface positive charge of the BSA-Tpy is increased to +18.8 mV due to protonation of amine residues to achieve the targeting effect on bacteria. Besides, under the irradiation of white light, the BSA-Tpy will produce ROS to kill bacteria efficiently about 99.99% for both Gram-positive and Gram-negative bacteria, which shows the potential application value for the treatment of infected wounds.Conclusion: We have developed a feasible method for photodynamic antibacterial therapy, possessing excellent biocompatibility and high antibacterial efficiency with good fluorescence imaging property.Keywords: bovine serum albumin nanocarriers, aggregate induced emission, photodynamic antibacterial therapy, antimicrobial resistance

Qingsong Li,1– 3,&ast; Cheng Hu,1– 3,&ast; Shengfa Su,1– 3 Zhu Ma,1,2 Yichao Geng,1– 3 Yinxiang Hu,1– 3 Huiqin Li,1,2 Bing Lu1– 3 1Department of Thoracic Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 2Department of Thoracic Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 3Teaching and Research Department of Oncology, Clinical Medical College of Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bing Lu, Department of Thoracic Oncology, Affiliated Hospital of Guizhou Medical University and Affiliated Cancer Hospital of Guizhou Medical University, 1 Beijing Road West, Guiyang, 550004, People’s Republic of China, Tel +86-851-86513076, Email lbgymaaaa@163.comPurpose: The impact of primary tumour radiotherapy on the prognosis for non-small-cell lung cancer (NSCLC) with controlled malignant pleural effusion (MPE-C) (MPE-C-NSCLC) is unclear. This study aimed to analyze the efficacy and safety of primary tumor radiotherapy in patients with MPE-C-NSCLC.Patients and Methods: A total of 186 patients with MPE-C-NSCLC were enrolled and divided into two groups. The patients in the D group were treated with only drugs. Those in the RD group were treated with drugs plus primary tumour radiotherapy. The Kaplan-Meier method was used for survival analysis, and the Log rank test was used for between-group analysis and univariate prognostic analysis. The Cox proportional hazards model was used to perform multivariate analyses to assess the impacts of factors on survival. Propensity score matching (PSM) was matched based on clinical characteristics, systematic drug treatment and drug response to further adjust for confounding factors.Results: The overall survival (OS) rates at 1, 2, and 3 years for the RD group and D group were 54.4%, 26.8%, and 13.3% and 31.1%, 11.5%, and 4.4%, respectively; the corresponding MSTs were 14 months and 8 months, respectively (χ2=15.915, p< 0.001). There was a significant difference in survival by PSM (p=0.027).Before PSM, multivariate analysis showed that metastasis status (organ≤ 3 and metastasis≤ 5), primary tumour radiotherapy, chemotherapy cycles≥ 4, and drug best response (CR+PR) were independent predictors of prolonged OS. After PSM, primary tumour radiotherapy and drug best response (CR+PR) were independent predictors of prolonged OS were still independent predictors of prolonged OS. There were no grade 4– 5 radiation toxicities.Conclusion: For MPE-C-NSCLC, the response of systemic drug treatment plays a crucial role in survival outcomes, and we also should pay attention to primary tumour radiotherapy in addition to systematic drug treatment.Keywords: non-small cell lung cancer, controlled malignant pleural effusion, radiotherapy, overall survival, prognosis

Jie Bai,1– 3,&ast; Bibo Wu,1– 3,&ast; Shasha Zhao,1– 3,&ast; Gang Wang,1– 3,&ast; Shengfa Su,1– 3 Bing Lu,1– 3 Yinxiang Hu,1– 3 Yichao Geng,1,3 Zhengneng Guo,1– 3 Jun Wan,2,3 Weiwei OuYang,1– 3 Cheng Hu,1– 3 Jie Liu1– 3 1Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 2Department of Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 3Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengfa Su, Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China, Tel +8613608550432, Fax +86513076, Email sushengfa2005@163.comPurpose: To explore the effect of PD-1 inhibitors combined with irradiation on myocardial injury and the changes of HMGB1-associated inflammatory markers.Methods: Four groups of five mice were used, each groupformed by randomly dividing 20 mice (group A control; group B PD-1 inhibitors; group C Irradiation; group D PD-1 inhibitors+irradiation; n = 5 for each). The mice were treated with either PD-1 inhibitors or a 15 Gy dose of single heart irradiation, or both. Hematoxylin-eosin staining assessed the morphology and pathology of heart tissue; Masson staining assessed heart fibrosis; Tunel staining evaluated heart apoptosis; flow cytometry detected CD3+, CD4+, and CD8+ T lymphocytes in heart tissues; enzyme linked immunosorbent assay evaluated IL-1β, IL-6, and TNF-ɑ of heart tissue; Western blot and quantitative real-time PCR (qPCR) detected the expression of protein and mRNA of HMGB1, TLR-4, and NF-κB p65 respectively.Results: The degree of heart injury, collagen volume fraction (CVF) and apoptotic index (AI) in groups B, C, and D were higher than group A, but the differences between the CVF and AI of group A and group B were not statistical significance (P> 0.05). Similarly, the absolute counts and relative percentage of CD3+ and CD8+ T lymphocytes and the concentrations of IL-1β, IL-6, and TNF-α in heart tissue with group D were significantly higher than the other groups (P< 0.05). In addition, compared with group A, the expression of protein and mRNA of HMGB1 and NF-κB p65 in other groups were higher, and the differences between each group were statistically significant while TLR4 was not. In addition, interaction by PD-1 inhibitors and irradiation was found in inflammatory indicators, especially in the expression of the HMGB1 and CD8+ T lymphocytes.Conclusion: PD-1 inhibitors can increase the expression of HMGB1-associated inflammatory cytokines and aggravate radiation-induced myocardial injury.Keywords: HMGB1, PD-1 inhibitors, radiotherapy, heart injury

Ling Yang &ast;, Qi Shen &ast;, Chao Hu, Ying Wang, Xiaohong Zhu, Shiqing Shu, Zhu Luo Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhu Luo, Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital Sichuan University, No. 37 Guoxue Lane, Chengdu, Sichuan, 610044, People’s Republic of China, Tel +86 28 85422707, Email luozhu720@163.comBackground: Imrecoxib is a novel and moderately selective cyclooxygenase-2 inhibitor with properties of anti-inflammation and alleviating pain, which is widely applied in osteoarthritis patients. The pharmacokinetic data supporting imrecoxib’s rational use in elderly population are not available.Purpose: The study aims to investigate the pharmacokinetics of imrecoxib and its main metabolites and explore the safety of imrecoxib in elderly healthy subjects.Methods: A total of 19 healthy subjects including 10 non-elderly and 9 elderly subjects received single dose of 100 mg imrecoxib under fasting condition. Pharmacokinetics, safety and tolerability profiles were assessed.Results: After oral administration of single dose of 100 mg imrecoxib, it was absorbed into plasma with median time to reach peak concentration (Tmax) around 2 hours. The concentration–time curves of imrecoxib (M0) showed higher interindividual variability in elderly subjects compared with non-elderly subjects. Peak concentration (Cmax) of M0, its hydroxyl metabolite M1 and carboxylated metabolite M2 in plasma increased by 39%, 21% and 17%, and area under concentration–time curve from time 0 to time t (AUC0-t) of M0, M1 and M2 in plasma increased by 34%, 13% and 27%, respectively, in elderly subjects compared with non-elderly subjects. The 90% CIs of geometric mean ratios of Cmax, AUC0-t and AUC0-∞ of M0, M1 and M2 between the two groups were not located within 80– 125%, indicating Cmax, AUC0-t and AUC0-∞ were not completely equivalent between non-elderly and elderly healthy subjects. However, comparison of pharmacokinetic data of M0, M1 and M2 between the two groups showed no significant difference (P> 0.05). Imrecoxib was well tolerated in both non-elderly and elderly healthy subjects, especially with favorable gastrointestinal and cardiovascular safety profiles.Conclusion: Pharmacokinetic and safety profiles of imrecoxib in elderly healthy subjects indicated that no dose adjustment should be required for elderly population.Keywords: cyclooxygenase-2 inhibitor, imrecoxib, pharmacokinetics, safety, elderly

Qinlin Liu,1 Yixin Zhang,1 Chuan Hu,2 Dongli Yuan,3 Kuiyun Wang,4 Wen Fan,5 Feibao Pan,6 Qin Li,7 Yunfeng Wang,1 Ge Tan1 1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Neurology, People’s Hospital of Bishan District, Bishan, People’s Republic of China; 3Department of Intelligent Medical Systems, Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Neurology, Jintang First People’s Hospital, Sichuan, People’s Republic of China; 5Department of Neurology, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of China; 6Department of Neurology, Suining Central Hospital, Suining, People’s Republic of China; 7Department of Neurology, Chongqing General Hospital, Chongqing, People’s Republic of ChinaCorrespondence: Ge Tan, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, People’s Republic of China, Email 273346692@qq.comPurpose: To explore changes of depression, anxiety and sleep disturbance in patients with episodic cluster headache inside and outside the attack period and assess the therapy to improve the treatment.Patients and Methods: We prospectively recruited 396 patients from 11 specialized headache outpatients and analyzed their headache characteristics, Hospital Anxiety Depression Scale scores, Pittsburgh sleep quality index scores, and the usage of psychiatric medications during as well as 1 month after the attack period.Results: A total of 220 patients completed the follow-up, 52.73% of whom had anxiety, 47.27% had depression and 49.09% had sleep disturbance inside the attack period. At follow-up, the percentage of these patients significantly decreased to 16.36%, 21.82% and 14.55% in the remission period, respectively (p < 0.05). Antidepressants and mood stabilizers were prescribed to 58.18% of the patients. However, both of the changes of Hospital Anxiety Depression Scale scores after the end of the attack period for anxiety (3.52± 2.91 vs 3.32± 3.09, p =0.61) and depression (3.41± 3.33 vs 2.90± 3.58, P =0.28) were comparable in patients with and without taking these medications. Nocturnal onset of headache was positively correlated with Pittsburgh score (OR=8.71), anxiety (OR=2.33) and depression scores (OR=3.56) (p < 0.05).Conclusion: Depression, anxiety and sleep disturbance were significantly alleviated after the attack period. However, psychiatric medications showed limited effect on depression and anxiety. Additionally, the nocturnal attack may cause anxiety and depression in episodic cluster headache.Keywords: cluster headache, depression, anxiety, sleep disturbance, psychiatric comorbidities

Xiaorui Shi,1 Xinan Wang,1 Rong Huang,1 Chu Tang,1 Chong Hu,1 Pengbo Ning,1 Fu Wang1– 3 1Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi’an, 710071, People’s Republic of China; 2Xianyang Key Laboratory of Molecular Imaging and Drug Synthesis, School of Pharmacy, Shaanxi Institute of International Trade & Commerce, Xianyang, Shaanxi, 712046, People’s Republic of China; 3School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of ChinaCorrespondence: Fu Wang; Pengbo Ning, Email fwang@xidian.edu.cn; pbning@xidian.edu.cnBackground: Micro- and nano-sized plastics (MPs and NPs) have become an environmental issue of global concern due to their small size, strong bio-permeability and high specific surface area. However, few studies have assessed the effect of polystyrene MPs and NPs on human lung cells. In this research, we evaluated the cytotoxicity and genotoxicity of polystyrene (PS) MPs and NPs with different sizes (2 μm and 80 nm) and surface modification (carboxy and amino functionalized polystyrene, pristine polystyrene) in A549 cells.Methods: The zeta potential and hydrodynamic particle size of five types of PS plastic solutions were measured by dynamic light scattering, and their morphology and degree of aggregation were observed by scanning electron microscopy. After incubation of the PS plastics with A549 cells, the uptake and toxicity of the cells were assessed by fluorescence microscopy, laser scanning confocal microscopy, flow cytometry, MTT, micronucleus formation assay, and reactive oxygen species.Results: The cytotoxicity and genotoxicity of A549 cells caused by nano-level PS is more serious than that of micro-level. Compared with unmodified PS-NPs, more surface-functionalized PS-NPs were found inside the cells, especially the accumulation of PS-NH2. Cell viability and the induction of micronuclei (MN) are appreciably impacted in a dose-dependent way. Compared with pristine PS-NPs, functionalized PS-NPs showed stronger cell viability inhibitory ability, and induced more MN scores.Conclusion: This study shows that the intrinsic size properties and surface modification of PS plastics, the interaction between PS plastics and the receiving medium, intracellular accumulation are critical factors for evaluating the toxicological influences of PS plastics on humans.Graphical Abstract: Keywords: microplastics, nanoplastics, surface functionalization, cytotoxicity, genotoxicity, oxidative damage

Fenfen Gu,1,&ast; Chuling Hu,2,&ast; Wei Cao,3,&ast; Chao Li,1 Qingming Xia,4 Yuan Gao,4 Yan Liu,1 Shen Gao1,4 1Department of Clinical Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Jiaxing Maternity and Child Health Care Hospital, Jiaxing, People’s Republic of China; 3Department of Neurovascular Disease, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 4Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shen Gao; Yan Liu, Tel/Fax +86 21 81873715 ; +86 21 25077156, Email liullk@126.com; liuyan03@xinhuamed.com.cnIntroduction: Currently, the main treatment for advanced breast cancer is still chemotherapy. Immunological and chemical combination therapy has a coordinated therapeutic effect and achieves some efficacy. However, the immunosuppressive tumor microenvironment is a major cause for the failure of immunotherapy in breast cancer. CpG oligodeoxynucleotides can activate the tumor immune microenvironment to reverse the failure of immunotherapy.Methods: In this study, we designed an amphiphilic peptide micelle system (Co-LMs), which can targeted delivery of the immune adjuvant CpG and the chemotherapeutic drug doxorubicin to breast cancer tumors simultaneously. The peptide micelle system achieved tumor microenvironment pH and redox-sensitive drug release.Results and Discussion: Co-LMs showed 2.3 times the antitumor efficacy of chemotherapy alone and 5.1 times the antitumor efficacy of immunotherapy alone in triple-negative breast cancer mice. Co-LMs activated cytotoxic CD8+ T lymphocytes and CD4+ T cells in mice to a greater extent than single treatments. We also found that Co-LMs inhibited the metastasis of circulating tumor cells in the bloodstream to some extent. These results indicate that the Co-LMs offer a promising therapeutic strategy against triple-negative breast cancer.Keywords: chemo-immunotherapy, tumor microenvironment, CpG, nanoparticles, triple-negative breast cancer

Yongjun Liu,1,2,&ast; Peng Lu,2,3,&ast; Lei Peng,2,3 Jie Chen,4 Chunlin Hu2,3 1Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Department of Emergency Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 4Department of Critical Care Medicine, Dongguan People’s Hospital, Dongguan, 523059, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunlin Hu, Department of Emergency Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China, Email huchunl@mail.sysu.edu.cn Jie Chen, Department of Critical Care Medicine, Dongguan People’s Hospital, Dongguan, 523059, People’s Republic of China, Email cj1982520@163.comObjective: Critical covid-19 patients have complications with acute myocardial injury is still unclear. We observed a series of critically ill patients, paying particular attention to the impact of myocardial injury at admission on short-term outcome.Methods: We prospectively collected and analyzed data from a series of severe covid-19 patients confirmed by real-time RT-PCR. Data were obtained from electronic medical records including clinical charts, nursing records, laboratory findings, and chest x-rays were from Feb 8, 2020, to April 7, 2020. The Acute Physiology and Chronic Health Evaluation (APACHE II) score, CURB-65 Pneumonia Severity Score, Sequential Organ Failure Assessment (SOFA) Score and pneumonia severity index (PSI) score were made within 24 hours of admission. Cardiac injury was diagnosed as hs-cTnI were above > 28 pg/mL. The short-term outcome was defined as mortality in hospital.Results: A total of 100 patients met the diagnostic criteria of severe patients with COVID-19 during 2020.02.08– 2020.04.07. The CURB 65, APACH2, SOFA, and PSI score were significantly higher in Critical group than in Severe group. Univariate regression analysis showed that oxygen flow, PO2/FiO2, SOFA and hs-cTnI were closely related to short-term outcome. The corresponding ROC of hs-cTnI, oxygen flow and SOFA for patient death prediction were 0.949, 0.906 and 0.652. hs-cTnI at 47.8 ng/liter predicted death, sensitivity 92.8%, specificity 92.9%; Oxygen flow at 5.5 liter/minute predicted death sensitivity 100%, specificity 77.9%; SOFA score at 5 predicted death sensitivity 100%, specificity 73.8%.Conclusion: Our cohort study demonstrated that inhaled oxygen flow, SOFA score, and myocardial injury at admission in critically ill COVID-19 patients were important indicators for predicting short-term death of patients, the hs-cTnI can be as a risk stratification, which may provide a simple method for the physicians to identify high-risk patients and give reasonable treatment in time.Keywords: COVID-19, high-sensitivity cardiac troponin I, short-term outcome

Yanqiu He,1,&ast; Cheng Hu,1,&ast; Shiyu Liu,1 Mingjie Xu,1 Ge Liang,2 Dan Du,3 Tingting Liu,1 Fei Cai,1 Zhiyao Chen,1 Qingyuan Tan,1 Lihui Deng,1 Qing Xia1 1Pancreatitis Centre, Department and Laboratory of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Clinical Proteomics and Metabolomics, Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihui Deng, Pancreatitis Centre, Department and Laboratory of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China, Email denglihui@scu.edu.cnBackground: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas without specific treatment. Shenmai injection (SMI) was reported to eliminate the severity of experimental AP. This study aimed to explore the mechanisms underlying the synergistic protective effects of SMI on AP based on network pharmacology and experimental validation.Methods: Network pharmacology analysis and molecular docking based on identified components were performed to construct the potential therapeutic targets and pathways. The principal components of SMI were detected via ultra-high-performance liquid chromatography-coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Effect of SMI and the identified components on cellular injury and IL6/STAT3 signaling was assessed on mouse pancreatic acinar cell line 266– 6 cells. Finally, 4% sodium taurocholate (NaT) was used to induce AP model to assess the effects of SMI in treating AP and validate the potential molecular mechanisms.Results: By searching the TCMSP and ETCM databases, 119 candidate components of SMI were obtained. UHPLC-QTOF/MS analysis successfully determined the representative components of SMI: ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D. Fifteen hub targets and eight related pathways were obtained to establish the main pharmacology network. Subnetwork analysis and molecular docking indicated that the effects of these four main SMI components were mostly related to the interleukin (IL) 6/STAT3 pathway. In vitro, SMI, ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D increased the cell viability of NaT-stimulated mouse pancreatic acinar 266– 6 cells and decreased IL6 and STAT3 expression. In vivo, 10 mL/kg SMI significantly alleviated the pancreatic histopathological changes and the expression of IL6 and STAT3 in the AP mice.Conclusion: This study demonstrated SMI may exert anti-inflammatory effects against AP by suppressing IL6/STAT3 activation, thus providing a basis for its potential use in clinical practice and further study in treating AP.Keywords: acute pancreatitis, Shenmai injection, network pharmacology, molecular docking, IL6/STAT3 signaling pathway

Ming Yang,1– 3 Qi Zhang,1– 3 Yizhong Ge,1– 4 Meng Tang,1– 3 Chunlei Hu,1– 3 Ziwen Wang,1– 3 Xi Zhang,1– 3 Mengmeng Song,1– 3 Guotian Ruan,1– 3 Xiaowei Zhang,1– 3 Tong Liu,1– 3 Hailun Xie,1– 3 Heyang Zhang,1– 3 Kangping Zhang,1– 3 Qinqin Li,1– 3 Xiangrui Li,1– 3 Xiaoyue Liu,1– 3 Shiqi Lin,1– 4 Hanping Shi1– 3 1Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, People’s Republic of China; 3Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, People’s Republic of China; 4The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Hanping Shi, Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China, Tel/Fax +86 10 6392 6983, Email shihp@ccmu.edu.cnPurpose: The incidence, progression, and prognosis of cancer could be affected by inflammation and nutrition. Female patients have different inflammatory and nutritional states depending on their age and tumor types. It is important to screen for suitable prognostic indicators in female patients with cancer of different ages and tumor types.Patients and Methods: Baseline clinicopathologic and laboratory characteristics of 1502 female patients with cancer were obtained from a multicenter cohort study. Concordance indices (C-indices) were used to evaluate the prediction accuracy of following inflammation- and nutrition-based indicators: advanced lung cancer inflammation index (ALI), systemic immune inflammation index (SII), modified geriatric nutritional risk index (mGNRI), albumin-to-globulin ratio (AGR), prognostic nutritional index (PNI), lymphocyte-to-C-reactive protein ratio (LCR), controlling nutritional status score (CONUT), modified Glasgow prognostic score (mGPS), and lymphocyte-to-C-reactive protein score (LCS).Results: The most suitable indicators in different female populations with cancer had C-indices as follows: LCR (0.668; 95% CI, 0.644– 0.693) for all females; AGR (0.681; 95% CI, 0.619– 0.743) for young females; LCR (0.667; 95% CI, 0.628– 0.706) for middle-aged females; ALI (0.597; 95% CI, 0.574– 0.620) for elderly females; LCR (0.684; 95% CI, 0.621– 0.747) for females with reproductive system cancer; and ALI (0.652; 95% CI, 0.624– 0.680) for females with non-reproductive system cancer.Conclusion: The most suitable indicators for the different female populations with cancer are summarized as follows: LCR for all females, AGR for young females, LCR for middle-aged females, ALI for elderly females, LCR for females with reproductive system cancer, and ALI for females with non-reproductive system cancer.Keywords: female, cancer, prognosis, inflammation, nutrition

Sha Li, Cheng Hu, Juan Zhu, Yudi Zhou, Yaomei Cui, Qian Xu, Weiqian Tian Department of Anesthesiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Weiqian Tian, Department of Anesthesiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Hanzhong Road 155, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +86 139 14764426, Email tianweiqiantwq6@126.comObjective: Electroacupuncture (EA) delivered one day before surgery could reduce postoperative pain. Remifentanil-induced post-infusion hyperalgesia (RPH) was occurred after exposure to high-dose remifentanil. This study aimed to investigate the effects of preoperative EA on RPH in patients undergoing thyroidectomy.Methods: A total of 80 patients who were scheduled to undergo elective thyroidectomy were randomly assigned to two groups: an EA group and a sham EA (SEA) group. EA was delivered at the Zusanli (ST36) and Neiguan (PC6) acupoints 24 h before the surgery. To ensure uniformity across all patients, remifentanil was administered at the same set rate (0.3 μg/kg/min) to all patients. Mechanical pain thresholds were recorded by an electronic von Frey device around the skin incision and on the arm before surgery as well as at 30 min and 6, 24, and 48 h after surgery.Results: At 30 min and 6 h after surgery, the EA group showed considerably greater mechanical pain thresholds surrounding the surgical site compared with the SEA group. At 30 min and 6 h after surgery, the patients in the SEA group showed a greater incidence of postoperative hyperalgesia surrounding the surgical site than those in the EA group. At 24 and 48 h after surgery, no significant differences were found between the two groups, although the pain intensity of the EA group was less than that of the SEA group. There were also no substantial differences between the two groups in the frequency of postoperative adverse reactions and rescue analgesia needed.Conclusion: EA administered 24 h before surgery could alleviate RPH in patients undergoing thyroidectomy.Keywords: electroacupuncture, remifentanil-induced, post-infusion hyperalgesia, thyroidectomy, Zusanli acupoint, Neiguan acupoint

Mengfei Sun,1,&ast; Qianqian Yang,2,&ast; Chunling Hu,1 Hengchao Zhang,2 Lihua Xing1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Department of Erythrocyte Biology Laboratory, School of Life Sciences, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihua Xing, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshedong Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel/Fax +8613838095088, Email xinglihua95088@163.comPurpose: Autophagy-related genes (ARGs) play an important role in the pathophysiology processes of sepsis-induced acute respiratory distress syndrome (ARDS). However, expression profiles of ARGs have rarely been used to explore the relationship between autophagy and sepsis-induced ARDS. Therefore, we aim to identify and validate the potential ARGs of sepsis-induced ARDS through bioinformatics analysis and experiment validation.Methods: We downloaded GSE32707 data from the Gene Expression Omnibus (GEO) database. The potential differentially expressed genes (DEGs) and differentially expressed ARGs (DEARGs) of sepsis-induced ARDS were screened by R software. Then, we performed functional enrichment analyses to explore the potential biological functions of DEARGs and constructed protein–protein interaction (PPI) networks. Subsequently, correlation analysis and receiver operating characteristic (ROC) curve were used for the DEARGs. In addition, we estimated the proportions of 22 immune cell subsets by using CIBERSORT algorithm. Finally, RNA expression of seven DEARGs were validated by qRT-PCR in blood samples from sepsis-induced ARDS and healthy controls.Results: We identified 28 DEARGs, including 11 up-regulated genes and 17 down-regulated genes, which were primarily involved in autophagy and apoptosis. Seven genes (BAG3, CTSD, ERBB2, MYC, PEA15, RAB24 and SIRT1) with AUC > 0.70 were considered possible to be sepsis-induced ARDS hub genes for ROC curve analysis. CIBERSORT results shown that sepsis-induced ARDS contained a higher proportion of naive CD4+ T cells, gamma delta T cells, monocytes, and neutrophils, and lower levels of CD8+ T cells, memory resting CD4+ T cells, follicular helper T cells were relatively lower. The results of qRT-PCR also demonstrated that the expression levels of BAG3, CTSD, ERBB2, MYC and SIRT1 in sepsis-induced ARDS patients and healthy controls had differences.Conclusion: We identified an association between DEGs and immune infiltration in sepsis-induced ARDS and validated BAG3, CTSD, ERBB2, MYC and SIRT1 that may be have excellent diagnostic performance.Keywords: autophagy, sepsis-induced ARDS, immune infiltration, bioinformatics analysis, Gene Expression Omnibus dataset

Wei Huang,1,2,&ast; Jinyong Zhang,3,&ast; Shiyi Liu,1 Chunxia Hu,1 Min Zhang,1 Shumin Cheng,1 Huijuan Yu,1,2 Manling Zheng,1 Jinsong Wu,2 Yuemei Lu,2 Quanming Zou,3 Ruiqin Cui1 1Bacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China; 2Department of Clinical Microbiology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China; 3National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Quanming Zou; Ruiqin Cui, Email qmzou2007@163.com; screening_sz@163.comBackground: The use of antibiotic adjuvants is a complementary strategy to the development of new antibiotics. The essential role of the ArnA dehydrogenase domain (ArnA_DH) in the addition of 4-amino-L-arabinose (L-Ara4N) to lipid A makes it a potential target in polymyxin adjuvant design.Purpose: This study aimed to identify a dehydrogenase inhibitor that enhances the antibacterial effect of polymyxin B (PB) and to further understand the mechanism of this drug combination.Methods: A susceptible K. pneumoniae strain, ATCC13883, was used to screen a dehydrogenase inhibitor library based on 3-(4,5)-dimethylthiazol(-z-y1)-2,5-diphenyltetrazolium bromide (MTT) and chequerboard assays. The protein- and cell-based effects of disulfiram (DSF) on ArnA activity were assessed, and the transcription levels of genes in the arn operon were evaluated by quantitative real-time polymerase chain reaction (qRT–PCR). Lipid A was isolated, and a structural analysis was performed. The cell wall function was evaluated through membrane integrity and bacterial viability assays. The in vivo antibacterial activity was evaluated using a mouse pulmonary infection model.Results: We screened a dehydrogenase inhibitor library and found that the anti-alcoholism drug DSF significantly enhanced the antibacterial activity of PB in vitro and in vivo. The protein-based enzyme activity assay showed that DSF exerted no direct effect on the dehydrogenase activity of ArnA. Treatment with the combination of DSF and PB but not with PB alone decreased both the transcription level of genes in the arn operon and the modification level of lipid A. DSF also strengthened the disruption of the cell membrane integrity of PB. Moreover, the enhanced PB antibacterial activity was effective against clinical PB-resistant strains.Conclusion: We identified a new drug combination that can be used to reduce the necessary dosage of PB and overcome PB resistance, and this drug combination has good prospects for clinical application.Keywords: polymyxins, antibiotic adjuvants, antibacterial, cell membrane

Yongjun Liu,1,&ast; Yuee Chen,2,&ast; Jie Chen,3 Yukung Kuang,4 Niandi Tan,5 Ke Jiang,6 Shuihui Peng,7 Chunlin Hu2 1Department of Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Province Guangdong, People’s Republic of China; 2Department of Emergency Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Province Guangdong, People’s Republic of China; 3Department of Critical Care Medicine, Dongguan People’s Hospital, Dongguan, Province Guangdong, 523059, People’s Republic of China; 4Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Province Guangdong, People’s Republic of China; 5Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 6Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 7Department of Pharmacy Intravenous Admixture Services, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Province Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunlin HuDepartment of Emergency Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Province Guangdong, People’s Republic of ChinaEmail huchunl@mail.sysu.edu.cnShuihui PengDepartment of Pharmacy Intravenous Admixture Services, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Province Guangdong, People’s Republic of ChinaEmail pengshh@mail.sysu.edu.cnObjective: To observe hemodynamic characteristics in a series of patients with myocardial injury caused by severe COVID-19-related pneumonia.Materials and Methods: We continuously collected clinical data from severe COVID-19-related pneumonia patients from the West Campus of Union Hospital in Wuhan and Dongguan People’s Hospital in Dongguan to explore the prevalence of myocardial injury and hemodynamic characteristics after circulatory failure. Doppler ultrasound and PiCCO2 were used to evaluate the hemodynamics of each patient, and arterial blood gas analysis was performed at the same time. Pearson correlation analysis was used to clarify the relationship between the parameters.Results: A total of 376 patients were observed during the study period. Eighty-seven patients had myocardial injury after admission, and the mean time of myocardial injury after admission was 6 (2, 30) days, from which 16 patients developed hemodynamic instability and 15 died of cardiogenic shock or combined with MODS. Cardiac echocardiography found that the LVEF of all patients was in the normal range and that diastolic function was slightly to moderately impaired. The PiCCO2 data showed that the GEF was significantly decreased in all patients. The dpmx was in normal range. EVLWI, SVRI and GEDI were significantly increased in most patients. Pearson correlation analysis showed that cTNI was significantly related to BNP at hemodynamic instability (r = 0.662, p = 0.005); GEF was related to EVLWI (r = − 0.572, p = 0.021) and LAC (r = 0.692, p = 0.003); and EVLWI was affected by LVEF (r = − 0.564, p = 0.023), LVDF (r = − 0.734, p = 0.001) and PVPI (r = − 0.524, p = 0.037).Conclusion: Hemodynamic status after myocardial injury and cardiogenic shock caused by severe COVID-19-related pneumonia was characterized by cardiac preload and increased EVLWI, accompanied by a decline in GEF.Keywords: COVID-19, PiCCO2, myocardial injury, hemodynamic instability

Ying Peng,1 Mingyue Ao,1 Baohua Dong,1 Yunxiu Jiang,1 Lingying Yu,1 Zhimin Chen,1 Changjiang Hu,1,2 Runchun Xu1 1State Key Laboratory of Southwestern Chinese Medicine Resources; Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Neo-Green Pharmaceutical Co., Ltd., Chengdu, People’s Republic of ChinaCorrespondence: Zhimin Chen; Changjiang Hu Email chenzhimin@cdutcm.edu.cn; 654460129@qq.comAbstract: Curcumin is a natural compound with great potential for disease treatment. A large number of studies have proved that curcumin has a variety of biological activities, among which anti-inflammatory effect is a significant feature of it. Inflammation is a complex and pervasive physiological and pathological process. The physiological and pathological mechanisms of inflammatory bowel disease, psoriasis, atherosclerosis, COVID-19 and other research focus diseases are not clear yet, and they are considered to be related to inflammation. The anti-inflammatory effect of curcumin can effectively improve the symptoms of these diseases and is expected to be a candidate drug for the treatment of related diseases. This paper mainly reviews the anti-inflammatory effect of curcumin, the inflammatory pathological mechanism of related diseases, the regulatory effect of curcumin on these, and the latest research results on the improvement of curcumin pharmacokinetics. It is beneficial to the further study of curcumin and provides new ideas and insights for the development of curcumin anti-inflammatory preparations.Keywords: anti-inflammatory, osteoarthritis, psoriasis, atherosclerotic, pharmacokinetics, prodrug

Jingbin Huang,&ast; Wenjing Lai,&ast; Qing Wang, Qin Tang, Changpeng Hu, Min Zhou, Fengling Wang, Dandan Xie, Qian Zhang, Wuyi Liu, Zhe Zhang, Rong Zhang Department of Pharmacy, The Second Affiliated Hospital of Army Medical University, ChongQing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong Zhang; Zhe Zhang Email xqpharmacylab@126.com; 15086988023@163.comIntroduction: Triple-negative breast cancer (TNBC) has the high degree of malignancy and aggressiveness. There is no targeted therapy drug. Many studies have shown that RBC membrane-coated nanoparticles achieve biological camouflage. In addition, the RGD module in the iRGD mediates the penetration of the vector across the tumor blood vessels to the tumor tissue space. Therefore, we developed iRGD-RM-(DOX/MSNs) by preparing MSNs loaded with doxorubicin as the core, and coating the surface of the MSNs with iRGD-modified RBC membranes.Methods: iRGD-RM-(DOX/MSNs) were fabricated using physical extrusion. In addition, their physical and chemical characterization, hemolytic properties, in vivo acute toxicity and inflammatory response, in vitro and in vivo safety, and qualitative and quantitative cellular uptake by RAW 264.7 cells and MDA-MB-231 cells were evaluated and compared. Furthermore, we examined the antitumor efficacy of iRGD-RM-(DOX/MSN) nanoparticles in vitro and in vivo.Results: iRGD-RM-(DOX/MSNs) have reasonable physical and chemical properties. iRGD-RM-(DOX/MSNs) escaped the phagocytosis of immune cells and achieved efficient targeting of nanoparticles at the tumor site. The nanoparticles showed excellent antitumor effects in vivo and in vitro.Conclusion: In this study, we successfully developed biomimetic iRGD-RM-(DOX/MSNs) that could effectively target tumors and provide a promising strategy for the effective treatment of TNBC.Keywords: RBC membrane, iRGD peptide, biological camouflage, targeted treatment, Triple-negative breast cancer