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The Facility for Rare Isotope Beams (FRIB) began operation with 1 kW beam power for scientific users in May 2022 upon completion of 8 years of project construction. The ramp-up to the ultimate beam power of 400 kW, planned over a 6-year period, will enable the facility to reach its full potential for scientific discovery in isotope science and applications. In December 2023, a record-high beam power of 10.4 kW uranium was delivered to the target. Technological developments and accelerator improvements are being made over the entire facility and are key to completion of the power ramp-up. Major technological developments entail the phased deployment of high-power beam-intercepting systems, including the charge strippers, the charge selection systems, the production target, and the beam dump, along with support systems, including non-conventional utilities (NCU) and remote handling facilities. Major accelerator improvements include renovations to aging legacy systems associated with experimental beam lines and system automation for improved operational efficiency and better machine availability. Experience must be gained to safely handle the increased radiological impacts associated with high beam power; extensive machine studies and advanced beam tuning procedures are needed to minimize uncontrolled beam losses for the desired operating conditions. This paper discusses the technological developments and accelerator improvements with emphasis on major R&D efforts.

Abstract: The flux ratios of gravitationally lensed quasars provide a powerful probe of the nature of dark matter. Importantly, these ratios are sensitive to small-scale structure, irrespective of the presence of baryons. This sensitivity may allow us to study the halo mass function even below the scales where galaxies form observable stars. For accurate measurements, it is essential that the quasar’s light is emitted from a physical region of the quasar with an angular scale of milli-arcseconds or larger; this minimizes microlensing effects by stars within the deflector. The warm dust region of quasars fits this criterion, as it has parsec-size physical scales and dominates the spectral energy distribution of quasars at wavelengths greater than 10μm. The JWST Mid-Infrared Instrument (MIRI) is adept at detecting redshifted light in this wavelength range, offering both the spatial resolution and sensitivity required for accurate gravitational lensing flux ratio measurements. Here, we introduce our survey designed to measure the warm dust flux ratios of 31 lensed quasars. We discuss the flux-ratio measurement technique and present results for the first target, DES J0405-3308. We find that we can measure the quasar warm dust flux ratios with 3 % precision. Our simulations suggest that this precision makes it feasible to detect the presence of 107 M⊙ dark matter halos at cosmological distances. Such halos are expected to be completely dark in Cold Dark Matter models.

Xiaojuan Wu, Guoyue Zhang, Xianzhi Du Department of Respiratory Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaCorrespondence: Xianzhi Du, Department of Respiratory Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China, Tel +86 023 62887761, Email dxzdjy868@sina.comBackground: Chronic obstructive pulmonary disease (COPD) is caused by exposure to noxious external particles, air pollution, and the inhalation of cigarette smoke. Airway mucus hypersecretion particularly mucin5AC (MUC5AC), is a crucial pathological feature of COPD and is associated with its initiation and progression. In this study, we aimed to investigate the effects of cigarette smoke extract (CSE) on MUC5AC expression, particularly the mechanisms by which reactive oxygen species (ROS) induce MUC5AC expression.Methods: The effects of CSE on the expression of MUC5AC and mucin5B (MUC5B) were investigated in vitro in Calu-3 cells. MUC5AC and MUC5B expression levels were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA). Total cellular levels of ROS and Ca2+ were determined using DCFH-DA and Fluo-4 AM. Subsequently, the expression levels of IP3R, IRE1α, p-IRE1α and XBP1s were measured by Western blotting. Gene silencing was achieved by using small-interfering RNAs.Results: Our findings revealed that exposure to CSE increased MUC5AC levels and upregulated ROS, IP3R/Ca2+ and unfolded protein response (UPR)-associated factors. In addition, knockdown of IP3R using siRNA decreased CSE-induced Ca2+ production, UPR-associated factors, and MUC5AC expression. Furthermore, 10 mM N-acetyl-l-cysteine (NAC) treatment suppressed the effects of CSE, including ROS generation, IP3R/ Ca2+, UPR activation, and MUC5AC overexpression.Conclusion: Our results suggest that ROS regulates CSE-induced UPR and MUC5AC overexpression through IP3R/ Ca2+ signaling. Additionally, we identified NAC as a promising therapeutic agent for mitigating CSE-induced MUC5AC overexpression.Keywords: chronic obstructive pulmonary disease, mucin5AC, cigarette smoke extract, reactive oxygen species, unfolded protein response, IP3R, Ca2+

Xian Du,1,* Jun Hu,1,* Jianhua Xue,1 Yuan Zhuang,2 Xuefeng Tang,1 Zhiyue Xu1 1Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), Wuxi, People’s Republic of China; 2The Affiliated Hospital of Nantong University, Nantong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiyue Xu; Xuefeng Tang, Health Examination Center, Shanghai Health and Medical Center (Huadong Sanatorium), 67 Dajishan, Wuxi, 214065, People’s Republic of China, Email hepenxiaozi@163.com; 978665164@qq.comPurpose: Fatigue was a common symptom of non-alcoholic fatty liver disease (NAFLD), which seriously affected patients’ quality of life. The aim of this study was to detect fatigue rate and to evaluate factors associated with fatigue in NAFLD patients.Patients and Methods: A cross-sectional study was carried out from the Huadong Sanatorium between April 2022 and May 2023, and 133 NAFLD patients were included in this study. They completed Fatigue Severity Scale to assess fatigue, the Hospital Anxiety and Depression Scale to estimate psychological status, and the Pittsburgh Sleep Quality Index for sleep quality. Data were analyzed by independent samples t-tests, χ 2 tests and logistic regression models.Results: We found that 51.1% of NAFLD patients had fatigue. Exercise, anxiety, depression, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disorders, daytime dysfunction and overall sleep quality were related to fatigue among NAFLD patients. Moreover, logistic regression models indicated anxiety, habitual sleep efficiency and sleep disorders as important predictors of fatigue.Conclusion: This was the first time to explore demographic, clinical, psychological and sleeping correlated factors for fatigue in Chinese NAFLD patients. Our study showed that more than half of NAFLD patients had fatigue, and anxiety, habitual sleep efficiency and sleep disorders were significantly associated with fatigue in NAFLD. The findings indicated that it was very necessary to pay more attention to fatigue of NAFLD patients, especially those with negative emotions and poor sleep quality by favorable intervention to relieve fatigue symptoms, so as to improve quality of life.Keywords: non-alcoholic fatty liver disease, fatigue, exercise, anxiety, sleep

Hang Jin,1,2,* Zhongqiang Yan,3,* Xin Ge,4,* Qi Wang,2 Hui Wang,2 Xinying Du,2 Hongbo Liu,2 Chaojie Yang,2 Ying Xiang,2 Sai Tian,2 Shaofu Qiu,1,2 Yu Zhou5 1School of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Infectious Disease Control and Prevention, Center for Disease Control and Prevention of Chinese PLA, Beijing, People’s Republic of China; 3Department of Disease Prevention and Control, The Second Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 4School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 5Department of Clinical Laboratory, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaofu Qiu, Center for Disease Control and Prevention of Chinese PLA, Beijing, People’s Republic of China, Email qiushf0613@hotmail.com Yu Zhou, Department of Clinical Laboratory, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China, Email zhouy427@163.comPurpose: This study conducted an phenotypic and whole-genome sequencing analysis with Klebsiella aerogenes to elucidate its clinical epidemiological characteristics, antimicrobial resistance (AMR) phenotype, biofilm formation ability and hemolytic activity testing, AMR genes and phylogenetic relationships, so as to provide a further understanding of the intra-hospital strain transmission.Methods: Samples were collected from a hospital in Beijing between 2020 and 2022. All strains underwent bacterial identification, antimicrobial susceptibility testing (AST) using the VITEK-2 compact system. Biofilm formation ability and hemolytic activity were tested. Second-generation sequencing was applied to all strains, with those carrying the blaKPC gene were selected for third-generation sequencing. Whole-genome analysis identified resistance genes, plasmid types, MLST typing, and phylogenetic relationships. Plasmids were assembled to detect plasmid structures and AMR gene location.Results: Among the 42 K. aerogenes isolates, 21 were carbapenem-resistant K. aerogenes (CRKA). All strains exhibited strong biofilm formation and no hemolytic activity. Most were sourced from sputum (83.3%). CRKA demonstrated extensive resistance to antibiotics, particularly β-lactamase inhibitors and Cefotetan. This resistance pattern was closely associated with the presence of an IncFII(pHN7A8) plasmid, which carried multiple resistance genes, including blaKPC-2, blaCTX-M-65, blaTEM-1, rmtB and a large number of mobile elements. The majority of CRKA strains clustered within the same branch of the phylogenetic tree, exhibiting minimal single nucleotide polymorphism (0– 13 SNPs) differences, and they shared the same sequence type (ST292), resistance genes, and plasmids, originating from different departments, suggesting clonal transmission among the hospital.Conclusion: Our research reveals that the clonal transmission of CRKA occurs across various departments within the hospital. The widespread resistance observed in CRKA, attributed to the presence of blaKPC and ESBLs genes, underscores the need for heightened vigilance to prevent the further dissemination of CRKA within the hospital and, potentially, throughout the wider community.Keywords: Klebsiella aerogenes, carbapenem resistance, blaKPC-2, clonal transmission

Xin Liu,1,* Ruofan Xi,1,* Xinran Du,1 Yi Wang,1 Linyan Cheng,1 Ge Yan,1 Hanzhi Lu,1 Te Liu,2 Fulun Li1 1Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Te Liu; Fulun Li, Email liute1979@shutcm.edu.cn; drlifulun@163.comBackground: Psoriasis is a common chronic inflammatory skin condition. The emergence of psoriasis has been linked to dysbiosis of the microbiota on the skin surface and an imbalance in the immunological microenvironment. In this study, we investigated the therapeutic impact of topical thymopentin (TP5) on imiquimod (IMQ)-induced psoriasis in mice, as well as the modulatory influence of TP5 on the skin immune milieu and the skin surface microbiota.Methods: The IMQ-induced psoriasis-like lesion mouse model was used to identify the targets and molecular mechanisms of TP5. Immunofluorescence was employed to identify differences in T-cell subset expression before and after TP5 therapy. Changes in the expression of NF-κB signaling pathway components were assessed using Western blotting (WB). 16S rRNA sequencing and network pharmacology were used to detect changes in the skin flora before and after TP5 administration.Results: In vivo, TP5 reduced IMQ-induced back inflammation in mice. H&E staining revealed decreased epidermal thickness and inflammatory cell infiltration with TP5. Masson staining revealed decreased epidermal and dermal collagen infiltration after TP5 administration. Immunohistochemistry showed that TP5 treatment dramatically reduced IL-17 expression. Results of the immunoinfiltration analyses showed psoriatic lesions with more T-cell subsets. According to the immunofluorescence results, TP5 dramatically declined the proportions of CD4+, Th17, ROR+, and CD8+ T cells. WB revealed that TP5 reduced NF-κB pathway expression in skin tissues from IMQ-induced psoriasis model mice. 16S rRNA sequencing revealed a significant increase in Burkholderia and Pseudomonadaceae_Pseudomonas and a significant decrease in Staphylococcaceae_Staphylococcus, Aquabacterium, Herbaspirillum, and Balneimonas. Firmicutes dominated the skin microbial diversity after TP5 treatment, while Bacteroidetes, Verrucomicrobia, TM7, Proteobacteria, Actinobacteria, Acidobacteria, Gemmatimonadetes, and other species dominated in the IMQ group.Conclusion: TP5 may treat psoriasis by modulating the epidermal flora, reducing NF-κB pathway expression, and influencing T-cell subsets.Keywords: psoriasis, thymopentin, 16S rRNA sequencing, T-cell subsets

Qiwen Yu,1 Chaopeng Mei,1 Mengwei Cui,1 Qianqian He,1 Xudong Liu,2 Xiaoxiao Du2 1Department of Emergency Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of ChinaCorrespondence: Xiaoxiao Du, Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Erqi, Zhengzhou, Henan, People’s Republic of China, Email xiaoxiao5811@126.comBackground: Nepetoidin B (NB) has been reported to possess anti-inflammatory, antibacterial, and antioxidant properties. However, its effects on liver ischemia/reperfusion (I/R) injury remain unclear.Methods: In this study, a mouse liver I/R injury model and a mouse AML12 cell hypoxia reoxygenation (H/R) injury model were used to investigate the potential role of NB. Serum transaminase levels, liver necrotic area, cell viability, oxidative stress, inflammatory response, and apoptosis were evaluated to assess the effects of NB on liver I/R and cell H/R injury. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to measure mRNA and protein expression levels, respectively. Molecular docking was used to predict the binding capacity of NB and mitogen-activated protein kinase phosphatase 5 (MKP5).Results: The results showed that NB significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver necrosis, oxidative stress, reactive oxygen species (ROS) content, inflammatory cytokine content and expression, inflammatory cell infiltration, and apoptosis after liver I/R and AML12 cells H/R injury. Additionally, NB inhibited the JUN protein amino-terminal kinase (JNK)/P38 pathway. Molecular docking results showed good binding between NB and MKP5 proteins, and Western blotting results showed that NB increased the protein expression of MKP5. MKP5 knockout (KO) significantly diminished the protective effects of NB against liver injury and its inhibitory effects on the JNK/P38 pathway.Conclusion: NB exerts hepatoprotective effects against liver I/R injury by regulating the MKP5-mediated P38/JNK signaling pathway.Keywords: liver ischemia/reperfusion injury, nepetoidin B, MKP5, JNK/P38 pathway

Lini Chen,&ast; Weiyong Qin,&ast; Jiangdong Wu, Guilin Zhao, Xiaoqing Jiang, Minghui Li, Zijin Huang,&ast; Xueke Du&ast; Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zijin Huang; Xueke Du, Department of Anesthesiology, the Second Affiliated Hospital of Guangxi Medical University, No. 166 of Daxue East Road, Nanning, Guangxi, 530007, People’s Republic of China, Tel +86-13768114848 ; Tel +86-17307711159, Email batistuta921@163.com; duxueke@gxmu.edu.cnPurpose: This study aims to evaluate the effect of remimazolam on induction and maintenance of general anesthesia in kidney transplant patients.Methods: 120 patients undergoing kidney transplant were divided into two groups: Propofol group (Group P) and Remimazolam group (Group R). Anesthesia induction: remimazolam had injected IV at a dose of 0.15– 0.35 mg/kg in Group R, while propofol had injected IV at a dose of 2.0– 2.5 mg/kg in Group P. Anesthesia maintenance: remimazolam was injected IV at a dose of 0.3– 1.0 mg·kg− 1·h− 1 and propofol was injected IV at a dose of 1– 12 mg·kg− 1·h− 1 in Group R, propofol was injected IV at a dose of 3– 12 mg·kg− 1·h− 1 in Group P. All patients have the same remaining anesthesia durgs.Results: Compared with Group P, in Group R the time of disappearance of the eyelash reflex and the time to drop to 60 in BIS was longer (P < 0.05), the time of awakening was shorted (P < 0.05), the MAP of T6 was fluctuated less (P < 0.05), the incidence of hypotension and injection pain during induction was reduced (P < 0.001), the incidence of intraoperative bradycardia during operation was reduced (P < 0.05), the dosages of sedatives drug during maintenance was reduced (P < 0.05). There was no statistically significant difference in postoperative renal function between the two groups of patients (P > 0.05).Conclusion: Remimazolam can be safely and effectively used for the induction and maintenance of general anesthesia in kidney transplant patients.Keywords: remimazolam, propofol, general anesthesia, kidney transplant

Enhao Huang,1,2,&ast; Huadao Li,2,3,&ast; Hanghang Han,1,2,&ast; Lianshan Guo,4 Yubing Liang,3 Zijin Huang,1 Ke Qin,5 Xueke Du1 1Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530007, People’s Republic of China; 2Key Laboratory for Basic Science and Prevention of Perioperative Organ Dysfunction, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 3Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 4Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530007, People’s Republic of China; 5Guilin People’s Hospital, Guilin, Guangxi Zhuang Autonomous Region, 541100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Qin; Xueke Du, Email qinke303@163.com; duxueke@gxmu.edu.cnPurpose: The primary objective of this study was to develop an innovative nanomedicine-based therapeutic strategy to alleviate Postoperative Neurocognitive Disorder (PND) in patients undergoing surgery.Patients and Methods: To achieve this goal, polydopamine-coated Kaempferol-loaded Metal-Organic Framework nanoparticles (pDA/KAE@ZIF-8) were synthesized and evaluated. The study involved encapsulating Kaempferol (KAE) within ZIF-8 nanoparticles, followed by coating with polydopamine (PDA) to enhance biocompatibility and targeted delivery. The characterization of these nanoparticles (NPs) was conducted using various techniques including Scanning Electron Microscopy, Fourier-Transform Infrared Spectroscopy, X-ray Diffraction, and Ultraviolet-Visible spectroscopy. The efficacy of pDA/KAE@ZIF-8 NPs was tested in both in vitro and in vivo models, specifically focusing on their ability to penetrate the blood-brain barrier and protect neuronal cells against oxidative stress.Results: The study found that pDA/KAE@ZIF-8 NPs efficiently penetrated the blood-brain barrier and were significantly taken up by neuronal cells. These nanoparticles demonstrated remarkable Reactive Oxygen Species (ROS) scavenging capabilities and stability under physiological conditions. In vitro studies showed that pDA/KAE@ZIF-8 NPs provided protection to HT-22 neuronal cells against H2O2-induced oxidative stress, reduced the levels of pro-inflammatory cytokines, and decreased apoptosis rates. In a PND mouse model, the treatment with pDA/KAE@ZIF-8 NPs significantly improved cognitive functions, surpassing the effects of KAE alone. This improvement was substantiated through behavioral tests and a noted reduction in hippocampal inflammation.Conclusion: The findings from this study underscore the potential of pDA/KAE@ZIF-8 NPs as an effective nanotherapeutic agent for PND. This approach offers a novel direction in the postoperative care of elderly patients, with the potential to transform the therapeutic landscape for neurocognitive disorders following surgery. The application of nanotechnology in this context opens new avenues for more effective and targeted treatments, thereby improving the quality of life for patients suffering from PND.Keywords: nanomedicine, reactive oxygen species, blood-brain barrier

Zhihao Zhao,1,&ast; Diya Qi,1,&ast; Zeqing Zhang,2,&ast; Xin Du,3 Fengyun Zhang,2 Ruicong Ma,4 Yi Liang,1 Yuewu Zhao,1 Ying Gao,1 Yu Yang2 1Department of Cardiology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China; 2Department of Cardiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Neurology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China; 4Graduate School, Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Gao, Department of Cardiology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China, Tel +86-13951461302, Email xzyygaoying@163.com Yu Yang, Department of Cardiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China, Tel +86-15651359875, Email xuzhouyangyu@163.comPurpose: The aim of this study was to explore the relationship between inflammatory cytokines and the risk of heart failure (HF) readmission in patients with heart failure with preserved ejection fraction (HFpEF).Patients and Methods: We enrolled 429 patients with HFpEF admitted to the cardiology department in our hospital from January 2020 to July 2022. The patients were divided into the readmission or non-readmission groups according to whether they were readmitted for heart failure within 1 year of discharge. The clinical features and laboratory date of the subjects were collected and analyzed. Multivariate cox regression analysis was used to identify predictors of HF readmission. In addition, receiver operating characteristic (ROC) curves were used to determine the prognostic value of each factor.Results: The levels of IL-1β, IL-6, IL-10, IL-17, TNF-α, NT-proBNP, heart rate, total cholesterol and NYHA class were significantly higher in the readmission group than in the non-readmission group (p < 0.05). IL-1β, IL-6, IL-17, TNF-α, NT-proBNP, heart rate and NYHA class were identified as independent predictors of HF readmission.Conclusion: Inflammatory markers, including IL-1β, IL-6, IL-17 and TNF-α were related to the HF readmission in patients with HFpEF.Keywords: heart failure with preserved ejection fraction, inflammation, cytokine, readmission, risk assessment

EuTe4 is a van der Waals material exhibiting a charge density wave (CDW) with a large thermal hysteresis in the resistivity and CDW gap. In this paper, we systematically study the electronic structure and transport properties of EuTe4 using high-resolution angle-resolved photoemission spectroscopy (ARPES), magnetoresistance (MR) measurements, and scanning tunneling microscopy (STM). We observe a CDW gap of ∼200meV at low temperatures that persists up to 400 K, suggesting that the CDW transition occurs at a much higher temperature. The ARPES intensity near the Fermi level shows large thermal hysteretic behavior, consistent with the resistivity measurement. The hysteresis in the resistivity measurement does not change under a magnetic field up to 7 T, excluding the thermal magnetic hysteretic effect. Instead, the surface topography measured with STM shows surface domains with different CDW trimerization directions, which may be important for the thermal hysteretic behavior. Interestingly, we reveal a large negative MR at low temperatures that can be associated with the canting of magnetically ordered Eu spins. Our results shed light on the understanding of magnetic, transport, and electronic properties of EuTe4.

Jiarun Mi, Xinyu Du, Yilixiati Aili, Mingkun Li, Yuanli Liu School of Health Policy and Management, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Yuanli Liu, School of Health Policy and Management, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongdansantiao, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-13522592907, Email liuyuanli_pumc@163.comBackground: Trust is a major factor affecting patient-physician relationship and healthcare quality. However, there has been a lack of comprehensive study on the extent of and major factors affecting patient trust in healthcare providers of China, the world’s largest developing country. The objective of this study is to elucidate the current status of outpatient trust in physicians in China and its influencing factors, providing empirical evidence to enhance doctor-patient trust and improve doctor-patient relationships.Methods: Between December 2017 and January 2018, 28,760 patients seeking care at the outpatient departments of 136 tertiary hospitals were interviewed, where they were asked to rate their trust in physicians. We applied a multilevel logistic regression model to explore the association between patients trust and characteristics of hospitals, physicians and patient characteristics. We conducted a series of sensitivity analysis to check the robustness of our findings.Results: Among 28,760 participants included in this study, 91.54% expressed trust in their physicians, while 7.52% showed moderate trust. Only 0.94% expressly distrusted or strongly distrusted their physicians. Outpatients of hospitals with convenient payment, volunteer guidance and enough seats available in the rest and waiting area showed higher levels of trust. Physicians who had a senior title, showed patience and protection of the patient’s privacy were more likely to be trusted by their patients in the outpatient setting. Compared to their female counterparts, male outpatients showed a higher degree of trust.Conclusion: While this study highlights an overall high level of Trust in physicians (TIP) among patients in China’s tertiary hospitals, it is found to vary with patient demographic factors as well as provider’s attributes. Hospitals with a more keen sense of protecting patients privacy and better meeting patients’ need for efficient and caring service provision process appeared to yield a higher level of trust.Keywords: trust in physicians, national survey, outpatients

Xue Du,1,2 Qi Dong,1,2 Le Sun,1,2 Xiaoyi Chen,1,2 Jun Jiang3 1College of Educational Science, Chongqing Normal University, Chongqing, People’s Republic of China; 2Key Laboratory of Applied Psychology, Chongqing Normal University, Chongqing, People’s Republic of China; 3Department of Basic Psychology, School of Psychology, Third Military Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Xue Du, Tel +86-23-65910354, Email 714789425@qq.com; duxue@cqnu.edu.cnBackground: It is well known that parents play an important role in the family, particularly the mental health literacy of parents is essential for the growth and development of children. As the parents of children with special needs, they are facing more difficulties and psychological pressure, resulted in more mental health problems.Purpose: The current study examined the effect of social support on mental health literacy, and its underlying mechanisms regarding the mediating role of coping styles and moderating role of social comparison.Methods: Using a cross-sectional design, 165 parents of children with special needs (22– 67 years old, M=37.72, SD=8.78) participated in the study. The general information questionnaire, Mental Health Literacy Scale (MHLS), Social Support Rating Scale, Simplified Coping Style Questionnaire, and Social Comparison Orientation Scale were used.Results: We found that objective support positively predicted the mental health literacy, positive coping style played a mediating role between objective support and mental health literacy. In addition, the relationship between objective support and positive coping styles was moderated by social comparisons; for lower levels of opinion social comparison, the effect of objective support on positive coping styles was significantly stronger.Conclusion: We revealed the underlying mechanisms between social support and mental health literacy. The present study has profound implications for mental health literacy services for parents who have children with special needs.Keywords: parents of children with special needs, social support, mental health literacy, coping styles, social comparison orientation

Wenli Liu,&ast; Shuran Zheng,&ast; Xiaogang Du&ast; Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaogang Du, Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Chongqing, 400016, People’s Republic of China, Tel +13452058896, Fax +86 023 89012019, Email dxgcxm@163.comPurpose: To evaluate the association of the systemic immune-inflammatory index (SII) and systemic inflammatory response index (SIRI) with the clinical and pathological features and progression of diabetic kidney disease (DKD).Patients and Methods: We analyzed 303 patients with type 2 diabetes mellitus (T2DM), classifying them into distinct groups: T2DM, early DKD (EDKD), and clinical DKD (Cli-DKD). Variations in SII and SIRI levels across these groups and their association with renal function were assessed. Logistic regression analysis was used to identify independent risk factors for DKD. Additionally, in 43 patients with biopsy-confirmed DKD, we analyzed the relationship between SII, SIRI, and pathological changes. Kaplan–Meier survival analysis and the Cox proportional hazards model were used to assess the influence of SII and SIRI levels on outcomes in patients with DKD.Results: SII and SIRI were significantly higher in the Cli-DKD group than in the T2DM and EDKD groups, and were positively correlated with the urinary albumin-creatinine ratio and negatively correlated with estimated glomerular filtration rate. Notably, SIRI was identified as an independent risk factor for DKD development. Additionally, a lower SII score was associated with a higher cumulative survival rate.Conclusion: This study demonstrates an association between SII, SIRI, and renal function in patients with T2DM. A high SIRI was an independent risk factor for DKD, while an elevated SII was associated with an increased risk of kidney disease progression in biopsy-confirmed DKD cases. Our findings underscore the potential implications of utilizing SII and SIRI as cost-effective and readily available inflammatory indicators for monitoring DKD in primary care settings.Keywords: diabetes, renal complications, inflammatory markers, prognosis, immune response, biomarkers

Fenge Li,1,2,&ast; Yupeng Wang,1,&ast; Jin Yan,1,&ast; Huancheng Wu,3 Xueming Du,1 Weihong Feng,1 Xiaoqing Zhang,4 Yongming Xue,4 Huaqing Wang,5,6 Wenxin Liu7 1Department of Oncology, Tianjin Beichen Hospital Tianjin People’s Republic of China; 2Core Laboratory, Tianjin Beichen Hospital, Tianjin, People’s Republic of China; 3Department of Neurosurgery, Tianjin Beichen Hospital, Tianjin, People’s Republic of China; 4Department of Basic Research, Suzhou Lanma Biotechnology Co, Suzhou, People’s Republic of China; 5Department of Oncology, Tianjin Union Medical Center, Tianjin, People’s Republic of China; 6Department of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, People’s Republic of China; 7Department of Gynecological Oncology, Tianjin Medical Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenxin Liu, Department of Gynecological Oncology, Tianjin Medical Cancer Institute and Hospital, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, People’s Republic of China, Tel +8618622221101, Email wenxin1973@163.com Huaqing Wang, Department of Translational Medicine, Tianjin Union Medical Center of Nankai University, Jieyuan Road No. 190, Nankai District, Tianjin, People’s Republic of China, Tel +8618622221223, Email huaqingw@163.comIntroduction: Tumor-infiltrating lymphocytes (TILs) therapy is one of the most promising adoptive T cell therapies, which has shown great clinical efficacy against several solid malignancies. Nevertheless, clinical response to TILs mono-therapy in Asian patients with recurrent cervical cancer has not been well reported.Case Presentation: Here, we report two patients who were diagnosed with metastatic cervical cancer and tumor progression following multiple conventional treatments. In particular, one of the patients has a history of severe myelosuppression after chemotherapy. The patients received lymphodepletion therapy, which consisted of cyclophosphamide (30mg/kg) for 2 days, followed by Fludarabine (25mg/m2) for 5 days, approximately 24 hr before receiving intravenous autologous TILs infusion. These two patients then received high doses of IL-2 for 10 days with the purpose of maintaining T cell survival and proliferation. Patient 1 experienced clinical partial response (PR) at 6 weeks post TILs infusion and a 33% tumor shrinkage at 12 weeks follow-up, and patient 2 was evaluated as stable disease (SD) at 6 weeks post treatment. Mild and manageable adverse events were observed and soon subsided after the TILs treatment. A time-course study examining the peripheral blood cell count and cytokine secretion demonstrated the persistence of infused TILs and long-term immune response.Conclusion: These results suggest that TILs mono-therapy can be a promising treatment strategy for Asian patients with late-stage metastatic cervical cancer even with severe myelosuppression. TILs infusion can induce persistence and a long-term systematic immune response that reversed peripheral CD4+T and CD8+T percentages implying that TILs infusion increased cytotic T cell responses, which is consistent with clinical responses in these patients. Trial registration number: NCT05366478.Keywords: tumor-infiltrating lymphocytes, clinical response, immune response, metastatic cervical cancer, treatment

Zheng Wang,1,2 Xin Du,1 Jianzeng Dong1 1Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital, Beijing, 100029, People’s Republic of China; 2Department of Intensive Care Unit, Peking University International Hospital, Beijing, 102206, People’s Republic of ChinaCorrespondence: Jianzeng Dong; Xin Du, Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital, No. 2 of Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 13911828375 ; +86 13370103558, Fax +86 1084005363, Email jz_dong@126.com; duxinheart@sina.comObjective: To describe the effects of various fluid strategies on mechanical ventilation time and other outcomes in patients with diastolic dysfunction undergoing non-cardiac surgery.Methods: After evaluation, 192 Intensive Care patients met the inclusion criteria. Based on infusion volume and fluid balance, we categorized patients into quartiles using two grouping methodologies. The first quartiles for total infusion volume on day one of ICU admission after surgery were as follows: Q1 ≤ 2.02 mL/kg/h; Q2 > 2.02 to 2.69 mL/kg/h; Q3 > 2.69 to 3.86 mL/kg/h; Q4 > 3.86 mL/kg/h. The second quartiles for fluid balance divided by actual body weight multiplied by the corresponding number of hours were as follows: G1 ≤ − 0.07 mL/kg/h; G2 > − 0.07 to 0.56 mL/kg/h; G3 > 0.56 to 1.54 mL/kg/h; G4> 1.54 mL/kg/h. The primary outcome was mechanical ventilation time. The research utilized both univariate and multivariate negative binomial regression models.Results: The fourth group (Q4 and G4) had a significant impact on mechanical ventilation time(P< 0.05).There were also significant differences between Q4 or G4 and some other groups in terms of ICU time, ICU cost, total hospital time, and total hospital cost (P < 0.05).After negative binomial regression analysis,Q2 and Q4 were approximately 2.406 times (95% CI 1.153– 5.017, P = 0.019) and 3.532 times (95% CI 1.812– 6.883, P < 0.01) longer than Q1 respectively, when grouped by infusion volume, but there was no significant difference between G groups. And Q4 or G4 also differed significantly from other parameters of clinical outcomes (P < 0.05).Conclusion: For patients admitted to the ICU following non-cardiac surgery with left ventricular diastolic dysfunction, the greater the fluid infusion or fluid balance, the greater the mechanical ventilation time, ICU or hospital time, and cost.Keywords: fluid strategies, left ventricular diastolic dysfunction, non-cardiac surgery, mechanical ventilation time, perioperative period

Yan Fang,1,2,&ast; Chuang Xiao,1,&ast; Lueli Wang,1,&ast; Youlan Wang,3 Jun Zeng,1 Yaping Liang,1 Rong Huang,1 Yunke Shi,2 Sha Wu,1 Xiaohua Du,2 Shibo Sun,2 Min Li,2 Yuanyuan Zheng,2 Hongxiang Wu,1 Qiuzhe Guo,4 Weimin Yang1 1School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, People’s Republic of China; 2The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Kunming Institute of Medical Sciences, Kunming, People’s Republic of China; 4Fuwai Yunnan Cardiovascular Hospital, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuzhe Guo; Weimin Yang, Email drguoqz@163.com; ywmbessie@yeah.netBackground: Sepsis is initiated by the dysfunctional response of the host immune system to infection. Septic shock and acute lung injury (ALI) are the main etiology of death caused by sepsis. Glucocorticoids, which are commonly used in clinic to antagonize the inflammatory response of sepsis, may cause serious side effects. Isoforskolin (ISOF) from the plant Coleus forskohlii stimulates adenylyl cyclase, increases the cAMP level and inhibits inflammatory response. The aim of this study was to investigate the synergistic effect of ISOF with dexamethasone (DEX) to prevent and ameliorate septic inflammation.Methods: Lipopolysaccharide (LPS) of 30 and 5 mg/kg (iv.) was used to induce sepsis and ALI mice model respectively in vivo. BEAS-2B cells stimulated by LPS were applied as cell model in vitro. The cumulative survival of mice with LPS-induced sepsis and the histopathological changes of lungs in mice with acute lung injury were observed, and the secretion of pro-inflammatory cytokines was analyzed by ELISA. The expression of RGS2 in BEAS-2B cells was detected by immunoblotting assay and PCR.Results: In the sepsis mice model, ISOF (10 mg/kg) combined with DEX (10 mg/kg.) (ip.) pretreatment significantly increased mice survival rate from 33.3% to 58.3%, which was significantly higher than that of ISOF or DEX treated alone. In the ALI mice model, ISOF, DEX pretreatment alone and combined application attenuated pulmonary pathological changes in ALI mice. Furthermore, ISOF, DEX alone or combined administration decreased MPO, MDA, IL-6, and IL-8 levels, while significantly synergistic effects were observed in the combined treatment group compared with ISOF or DEX alone. In BEAS-2B cells, combined pretreatment with ISOF and DEX significantly decreased the expression of IL-8 and increased the expression of RGS2.Conclusion: The results indicated that ISOF in combination with DEX synergistically improves survival rate and attenuates ALI in mice model through anti-inflammatory and antioxidant effects.Keywords: isoforskolin, sepsis, acute lung injury, pulmonary inflammation, glucocorticoids, regulator of G-protein signaling 2

Ming-Yue Zhu,&ast; Rong Li,&ast; Jie Xu, Fei She, Xin Du, Wei Zhang Department of Emergency Medicine, the Fourth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Zhang, Department of Emergency Medicine, the Fourth Medical Center, Chinese PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing, 100048, People’s Republic of China, Tel +86 010-66867373, Email zhangw8642@126.comObjective: To clarify variations of diagnosis and treatment in the emergency care of critically ill patients not infected with novel coronavirus (COVID-19) prior to and amidst the COVID-19 pandemic.Methods: A retrospective cohort study was conducted to compare and analyze the diagnosis and treatment data of critically ill patients with non-COVID-19 infection who were admitted to the emergency department of the Fourth Medical Center of Chinese PLA General Hospital from January 2019 to November 2022. The variations in emergency care of the pandemic were summarized, and the influence of the pandemic on emergency care was assessed.Results: A total of 6634 critically ill patients with non-COVID-19 infection were included in this study. These patients were elderly, high incidence of chronic diseases, and extended emergency duration during the pandemic. Notably, the proportion of patients requiring intensive care was twofold higher compared to the period before the pandemic. Throughout the pandemic, patients experienced prolonged emergency durations, increased overall costs and daily expenses per patient. Further investigation revealed that elderly patients exhibited worse medical conditions, requiring lengthier emergency treatment and incurring escalated healthcare expenses. However, the presence of pre-existing chronic diseases did not appear to influence disease severity, nor extended emergency durations or heightened healthcare expenditures. Irrespective of the pandemic phase—be it short-term, medium-term, or long-term emergency care—greater healthcare spending was necessary.Conclusion: There was no difference in the disease spectrum of emergency critical ill patients with non-COVID-19 infection prior to and amidst the COVID-19 pandemic, nor the duration and expenditure in prior chronic illness patients. However, the disease severity and emergency duration have led to an increase in the total cost and economic intensity of emergency care for all patients during the epidemic. Especially, elderly patients required longer emergency duration, greater healthcare spending, and more inpatient medical resources than usual.Keywords: novel coronavirus epidemic, emergency, elderly

Crystal geometry can greatly influence the emergent properties of quantum materials. As an example, the kagome lattice is an ideal platform to study the rich interplay between topology, magnetism, and electronic correlation. In this work, combining high-resolution angle-resolved photoemission spectroscopy and ab initio calculation, we systematically investigate the electronic structure of XMn6Sn6 (X=Dy,Tb,Gd,Y) family compounds. We observe the Dirac fermion and the flat band arising from the magnetic kagome lattice of Mn atoms. Interestingly, the flat band locates in the same energy region in all compounds studied, regardless of their different magnetic ground states and 4f electronic configurations. These observations suggest a robust Mn magnetic kagome lattice across the XMn6Sn6 family, thus providing an ideal platform for the search for, and investigation of, new emergent phenomena in magnetic topological materials.