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The study is carried out in line with one of the important subfield in modern linguistics – pragmatics - and covers lexical and semantic features of advertisements in the tourism sector. The rapid development of tourism in the world market has led to the emergence of new ways and approaches to the implementation of linguistic creativity in tourism advertising. The article attempts to identify and characterize the use of lexical means in a specific communication environment in order to create attractive and effective advertisements. Emphasis is made on the analysis of creative potential of widely used loanwords and specific terminology. The existing potential of proper names, including the names of geographical places, animals as well as loanwords has been revealed in the result of systematization and analysis of advertisements. The use of language items and ways to influence consumer behavior is observed in advertisements of travel agencies and tours. The study is theoretically and practically significant in terms of its contribution to the theory of advertising from a linguistic point of view. It would be useful in further studies of creative potential of the language.

Liu Yang,1 Kaijie Gao,1 Weihua Gong,1 Ci Li,1 Nan Chen,1 Tiewei Li,1 Shan Wang,1 Jiajia Ni,2,3 Junmei Yang1 1Department of Clinical Laboratory, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Zhengzhou, Henan, People’s Republic of China; 2Research and Development Center, Guangdong Meilikang Bio-Science Ltd, Foshan, Guangdong People’s Republic of China; 3Department of Detection and Diagnosis Technology Research, Guangzhou National Laboratory, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Junmei Yang, Email yangjunmei7683@163.comPurpose: Although allergic diseases in children are on the rise, there has been no comprehensive investigation of the allergens affecting children with allergic diseases in central China. Therefore, we aimed to analyze the distribution of serum allergen species among children with allergic conditions in central China to inform the prevention, diagnosis, and treatment of childhood allergies.Patients and Methods: A total of 9213 children (5543 males with 2.88 ± 0.04 years old and 3670 females with 2.91 ± 0.05 years old) underwent allergen screening, and serum allergen-specific IgE (sIgE) antibodies were detected using an automated fluorescent enzyme immunoassay system.Results: Our findings revealed a total sIgE-positive rate (sIgE-PR) of 57.83%, with mixed food (42.10%), egg whites (30.83%), milk (28.97%), mixed dust mites (24.57%), and mixed molds (23.20%) being the most prevalent source of allergens. The sIgE-PR for common sources of allergens exhibited significant sex-based differences, with males having greater susceptibility than females (p< 0.05). Dust mites were the primary source of inhaled allergens, whereas egg white was the predominant source of food allergens. Sources of food allergens were most dominant among infants (0– 3 years old); sIgE-PRs for most source of food allergens decreased with age, whereas those for most source of inhaled allergens increased. The autumn sIgE-PRs for mixed molds, weed pollen combinations, and tree pollen combinations were significantly higher than those found in other seasons (p< 0.05).Conclusion: Our findings suggest that sources of allergens profiles in children with allergies vary across age groups and seasons. Understanding these patterns can improve the effective prevention of childhood allergies.Keywords: allergen, childhood allergies, IgE antibodies, source of food allergens, allergy prevention

Shangjian Li, Xiumei Luo, Zhiqiang Lu, Ning Chen Department of Endocrinology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fudan University, Xiamen, People’s Republic of ChinaCorrespondence: Ning Chen, Department of Endocrinology, Zhongshan Hospital (Xiamen), Fudan University, No. 668 Jinhu Road, Xiamen, 361000, People’s Republic of China, Tel/Fax +86-0592-3569583, Email chen.ning@zsxmhospital.comObjective: To investigate the association of the midnight cortisol level with bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM).Methods: This study included 249 T2DM patients (148 males with an average age of 53.8 years and 101 postmenopausal females with an average age of 63.6 years) admitted to Xiamen Hospital of Zhongshan Hospital Affiliated to Fudan University from January 2018 to April 2020. Baseline data were compared between patients with normal BMD and those with osteoporosis/osteopenia. The patients also were divided into groups according to the tertiles of midnight cortisol levels.Results: Among all T2DM, 178 had osteoporosis/osteopenia, including 98 men and 80 women. The baseline data analysis showed that patients with osteoporosis/osteopenia were more likely to be older, female, and thin, and to have high cortisol. Additionally, elevated estradiol levels had a protective effect on bone; once osteoporosis/osteopenia occurred, the probability of severe osteoporotic fracture was significantly increased. The BMD of the femoral neck, hip joint and lumbar spine decreased with increasing midnight cortisol level in men, postmenopausal women, and all T2DM patients (P< 0.05). Multivariate logistic regression analysis identified body mass index, estradiol level, and midnight cortisol level as independent risk factors for osteoporosis/osteopenia in T2DM patients.Conclusion: Higher midnight cortisol levels are significantly associated with increased risk of osteoporosis/osteopenia in T2DM patients. Thus, the midnight cortisol level represents a valuable marker for assessing osteoporosis/osteopenia risk in these patients.Keywords: type 2 diabetes mellitus, midnight cortisol, bone mineral density, osteoporosis

Meiju Deng, Na Chen, Xiaojie Lao, Xiaolei Wang, Jiantao Fu, Lulu Xing, Hongxin Zhao Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaCorrespondence: Hongxin Zhao, Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, No. 8, Jingshun Dongjie, Chaoyang District, Beijing, 100015, People’s Republic of China, Email drzhao66@ccmu.edu.cnPurpose: The study aimed to explore the reasons, efficacy, and safety of switching to dolutegravir (DTG) based regimens in virologically suppressed people living with HIV (PLWH) in tertiary hospitals in China. Therefore, the study could provide a valuable reference for the rational clinical use of DTG.Methods: PLWH’s basic information, treatment details, and reasons for switching were collected, through the electrical clinical medical record system and telephone follow-up. Data included the proportion of PLWH with HIV RNA < 50 copies/mL, changes in immunological indicators, and metabolic metrics at week 48 and week 96.Results: 319 PLWH were included in the analysis. The three major reasons for switching were neurological toxicity (16.30%), simplification (13.79%), and renal toxicity (11.29%). Our study showed high rates of virologic suppression in the per-protocol analysis (week 48: 99.69%; week 96: 99.29%) after switching to DTG-based regimens. The median CD4+ T cell count increased from 579 cells/μL (IQR 420.5– 758) to 642 cells/μL (IQR 466.5– 854) at week 96 (p< 0.0001). An improvement was observed in liver function (ALT: p< 0.0001; AST: p< 0.0001) and fasting glucose (p< 0.0001). However, there was an elevation in creatinine (Cr) (p< 0.0001) and a slight decrease in the estimated glomerular filtration rate (eGFR) (p< 0.0001). Regarding lipid profile, triglyceride (TG) levels declined, while total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels increased. Further analysis revealed that the increase in TC and LDL-C was associated with the withdrawal of tenofovir disoproxil fumarate (TDF). This observed increase in lipid parameters only concerned the PLWH who switched from a TDF-containing regimen to a non-TDF regimen.Conclusion: This study confirmed the virologic efficacy of switching to DTG-based regimens in virologically suppressed PLWH over a 96-week period. The findings also expanded the evidence of immune reconstitution and metabolic safety associated with this switch.Keywords: HIV, dolutegravir, switching, virologically suppressed, lipids profile

Xinyong Chen,1,2,&ast; Zhe Chen,3,&ast; Gongchang Ma,2 Jianjun Sha,2 Shan Zhao,2 Zuoqing Liu,2 Nong Chen,2 Huilin Yang1 1Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215000, People’s Republic of China; 2Department of Orthopedics, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 200025, People’s Republic of China; 3Department of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nong Chen, Department of Orthopedics, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 200025, People’s Republic of China, Email chennong1975@126.com Huilin Yang, Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215000, People’s Republic of China, Email orthdoctor@126.comBackground: Dorsal root ganglia (DRGs) contain sensory neurons that innervate intervertebral discs (IVDs) and may play a critical role in mediating low-back pain (LBP), but the potential pathophysiological mechanism needs to be clarified.Methods: A discogenic LBP model in rats was established by penetration of a lumbar IVD. The severity of LBP was evaluated through behavioral analysis, and the gene and protein expression levels of pro-algesic peptide substance P (SP) and calcitonin gene–related peptide (CGRP) in DRGs were quantified. The level of reactive oxygen species (ROS) in bilateral lumbar DRGs was also quantified using dihydroethidium staining. Subsequently, hydrogen peroxide solution or N-acetyl-L-cysteine was injected into DRGs to evaluate the change in LBP, and gene and protein expression levels of transient receptor potential vanilloid-1 (TRPV1) in DRGs were analyzed. Finally, an inhibitor or activator of TRPV1 was injected into DRGs to observe the change in LBP.Results: The rats had remarkable LBP after disc puncture, manifesting as mechanical and cold allodynia and increased expression of the pro-algesic peptides SP and CGRP in DRGs. Furthermore, there was significant overexpression of ROS in bilateral lumbar DRGs, while manipulation of the level of ROS in DRGs attenuated or aggravated LBP in rats. In addition, excessive ROS in DRGs stimulated upregulation of TRPV1 in DRGs. Finally, activation or inhibition of TRPV1 in DRGs resulted in a significant increase or decrease of discogenic LBP, respectively, suggesting that ROS-induced TRPV1 has a strong correlation with discogenic LBP.Conclusion: Increased ROS in DRGs play a primary pathological role in puncture-induced discogenic LBP, and excessive ROS–induced upregulation of TRPV1 in DRGs may be the underlying pathophysiological mechanism to cause nerve sensitization and discogenic LBP. Therapeutic targeting of ROS or TRPV1 in DRGs may provide a promising method for the treatment of discogenic LBP.Keywords: lower back pain, reactive oxygen species, dorsal root ganglion, transient receptor potential vanilloid-1, substance p, calcitonin gene related peptide, intervertebral disc

Meiju Deng,1,2,&ast; Yongqin Zeng,2,3,&ast; Ying Liu,2 Xiaolei Wang,1,2 Na Chen,1,2 Mengyuan Zhang,1,4– 6 Meiqing Jiang,1,4– 6 Hongxin Zhao,2 Juan Du1,4– 6 1Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 3Department of Nephrology, The Affiliated Hospital Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China; 4Beijing Institute of Infectious Diseases, Beijing, 100015, People’s Republic of China; 5National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 6National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing, 100015, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Du; Hongxin Zhao, Email duj656@ccmu.edu.cn; Drzhao66@ccmu.edu.cnBackground: The aging of the immune system is associated with various diseases. It is worth exploring the changes of the immune system in aging. Previous studies have shown that aged T cells have enhanced expression of co-inhibitory molecules. However, it remains unclear whether aged NK cells exhibit similar characteristics to aged T cells. The objective of our research was to clarify this aspect.Patients and Methods: This study included 98 adults aged 24– 90 years (50 males and 48 females). We detected the subset of peripheral blood NK cells and the expression of various receptors on NK cells among donors of different age groups by flow cytometry. Immune subsets were initially defined by forward and side-scatter characteristics and then staining with the appropriate marker.Results: The absolute number and subset distribution of NK cells were not associated with age. However, CD57 expression and CD69 expression were correlated with age. Furthermore, we found that PD-1 was up-regulated on NK cells in older people, associated with aging, while no such change was observed in other co-inhibitory molecules, including 2B4, CTLA-4, TIM-3, BTLA, CD70, CD39, CD160, and TIGIT. PD-1+ NK cells expressed high levels of CD57 and CD69, indicating PD-1+ NK cells displayed a phenotype of over-activation and aging.Discussion: This study indicated that PD-1+ NK cells were one of the characteristics of NK cells in older people.Conclusion: This study indicated that PD-1+ NK cells were one of the characteristics of NK cells in older people. Those findings provided new ideas to explore the underlying drivers of NK aging.Keywords: PD-1, NK cell, aging, co-inhibitory molecules

Cheng Chen,1,&ast; Nandi Chen,2,3,&ast; Yan Qi,1,&ast; Meng Lyu,2 Chaoyan Wu,4,&ast; Conghua Xie,1 Haijun Yu1 1Department of Radiation and Medical Oncology, Hubei Province Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 2Department of Gastrointestinal Surgery & Department of Geriatrics, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020, People’s Republic of China; 3Analysis and Testing Center, Shenzhen Technology University, Shenzhen, 518118, People’s Republic of China; 4Department of Integrated Traditional Chinese Medicine and Western Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haijun Yu; Conghua Xie, Email haijunyu@whu.edu.cn; chxie_65@whu.edu.cnBackground: Radiotherapy is an indispensable part of the multidisciplinary treatment of breast cancer (BC). Due to the potential for serious side effects from ionizing radiation in the treatment of breast cancer, which can adversely affect the patient’s quality of life, the radiation dose is often limited. This limitation can result in an incomplete eradication of tumors.Methods: In this study, biomimetic copper single-atom catalysts (platelet cell membrane camouflaging, PC) were synthesized with the aim of improving the therapeutic outcomes of radiotherapy for BC. Following guidance to the tumor site facilitated by the platelet cell membrane coating, PC releases a copper single-atom nanozyme (SAzyme). This SAzyme enhances therapeutic effects by generating reactive oxygen species from H2O2 and concurrently inhibiting the self-repair mechanisms of cancer cells through the consumption of intracellular glutathione (GSH) within the tumor microenvironment. PC-augmented radiotherapy induces immunogenic cell death, which triggers an immune response to eradicate tumors.Results: With the excellent biocompatibility, PC exhibited precise tumor-targeting capabilities. Furthermore, when employed in conjunction with radiotherapy, PC showed impressive tumor elimination results through immunological activation. Remarkably, the tumor suppression rate achieved with PC-enhanced radiotherapy reached an impressive 93.6%.Conclusion: Therefore, PC presents an innovative approach for designing radiosensitizers with tumor-specific targeting capabilities, aiming to enhance the therapeutic impact of radiotherapy on BC.Keywords: platelet cell membrane, single-atom nanozyme, radiotherapy, radioimmunotherapy, breast cancer

Hanwen Cheng,1,&ast; Haoyu Wu,1,&ast; Ni Tan,2,&ast; Zhuojie Liu,1 Ning Wang,1 Ningyi Chen,1 Chunhai Li1,3 1Department of Orthopaedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Cellular and Molecular Diagnostics Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 3Teaching and Research Bureau of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunhai Li, Department of Orthopaedics, Sun Yat-sen Memorial Hospital, Sun Yat‐sen University, Guangzhou, Guangdong Province, 510000, People’s Republic of China, Tel +86-18602079796, Fax +86-(20)81332523, Email lichhai@mail.sysu.edu.cnPurpose: Early diagnosis of spinal infections remains challenging, and emerging metagenomic next-generation sequencing (mNGS) technology holds promise in addressing this issue. The aim of this study is to investigate the diagnostic efficacy of mNGS in spinal infections.Patients and Methods: A total of 78 cases with suspected spinal infections were enrolled in this study, all of whom underwent laboratory, histopathological and mNGS examinations upon admission. Lesion samples were obtained by surgical or C-arm-guided puncture. Sensitivity, specificity, positive predictive value and negative predictive value of culture and mNGS were calculated for statistical analysis.Results: With histopathological results as the reference, the included 78 patients were categorized into 50 cases in the spinal infection group and 28 cases in the aseptic group. The sensitivity (84%) and negative predictive value (77.14%) of mNGS were significantly higher than those of culture (32% and 44.26%, respectively), whereas no significant differences were observed in terms of specificity and positive predictive value. In the subgroup analysis for Mycobacterium tuberculosis, the sensitivity of mNGS (90.91%) and T-spot (90.91%) was significantly higher than that of culture (0). Additionally, mNGS demonstrated markedly higher specificity (100%) compared to T-spot (85.07%).Conclusion: This study underscores the substantial advantages of mNGS in terms of diagnostic accuracy and bacterial coverage for spinal infections. The findings provide compelling clinical evidence that supports the enhanced diagnostic efficacy of mNGS.Keywords: culture, diagnosis, sensitivity, specificity, bacteria, clinical evidence

Na Chen,1,2 Xiaojuan Wang,1,2 Yinyan Li,1,2 Ping Yang,1,2 Mingzhu Huang,1,2 Xiaoyang Lu1,2 1Department of Pharmaceutical, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xiaoyang Lu; Mingzhu Huang, Email luxiaoyang@zju.edu.cn; hmzj2002@zju.edu.cnAbstract: Isavuconazole (ISA) is a second generation broad-spectrum triazole antifungal drug derived from voriconazole structure, and its oral capsules is currently the only oral preparation approved for invasive mucormycosis. In recent years, population pharmacokinetic studies of ISA have been reported continuously. This paper aims to summarize the characteristics of population pharmacokinetic models of ISA in adults, and provide theoretical basis for individualized administration of ISA. We systematically searched PubMed, Embase, CNKI, Wanfang, VIP and other databases to collect population pharmacokinetic models published from the establishment of the database to March 2023. A total of 6 studies were included in this review, including healthy men and women, invasive fungal infections with malignant tumors or neutropenia, solid organ transplantation. The dose of ISA was 40– 400mg for single-dose. The multiple-dose of ISA was 200mg every 8 hours for the first 48 hours and then 200mg once daily. All studies used a two-compartment model, first-order elimination. For oral formulations, except for one study that used first-order absorption, the others used Weibull absorption. Body mass index (BMI) was the most common covariable, followed by total body weight, lean body mass, race, sex, population type (healthy volunteers/patients), and creatinine clearance. These studies included several covariates, and the clearance rate (CL) was similar among populations. In the future, external validation and population pharmacokinetic studies in special populations such as patients with severe liver disease and ECMO support are needed.Keywords: isavuconazonium sulfate, isavuconazole, population pharmacokinetics, covariates

Linqian Lu,1,2,&ast; Lin Mao,3,&ast; Shanshan Yang,3,&ast; Xiangfeng He,1 Zhen Zhang,1 Nan Chen1 1Department of Rehabilitation, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 2The Second Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, People’s Republic of China; 3Department of Rehabilitation, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nan Chen, Department of Rehabilitation, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 202150, People’s Republic of China, Email chennanreh2020@126.comIntroduction: Sarcopenia and depressive symptoms are common disorders in older people; however, there is lacking for studies focus on the association between sarcopenia and depressive symptoms by gender. Thus, we investigate gender differences in the association between sarcopenia and depressive symptoms.Methods: 1119 participants aged ≥ 65 were included in our study. Sarcopenia was defined as no sarcopenia, possible sarcopenia, general sarcopenia, and severe sarcopenia by the Asian Working Group for Sarcopenia 2019 consensus. Depressive symptoms were assessed by the Geriatric Depression Scale-15. The logistic regression analysis was used to identify the association between sarcopenia and depressive symptoms.Results: No sarcopenia and severe sarcopenia were significantly inversely and positively associated with depressive symptoms only in women. In men, low appendicular skeletal muscle mass index was significantly inversely associated with depressive symptoms. In women, low gait speed was significantly inversely associated with depressive symptoms, while poor 5-time chair stand test was significantly positively associated with depressive symptoms.Conclusion: Our study found that sarcopenia and its diagnostic elements were significantly associated with depressive symptoms in men or women. Interventions for muscle mass and physical performance are necessary for sarcopenia to prevent the development of depressive symptoms timely.Keywords: sarcopenia, depressive symptoms, gender difference, suburban area, older people

Sangsang Xiong,1,&ast; Mingqi Tu,1,&ast; Xiaoting Wu,1 Siying Qu,1 Nisang Chen,1 Junyan Jin,1 Haiqin Rong,1 Shuangyi Pei,2 Jianqiao Fang,1 Xiaomei Shao1 1Key Laboratory for Research of Acupuncture Treatment and Transformation of Emotional Diseases, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaomei Shao; Jianqiao Fang, Zhejiang Chinese Medical University, No. 548, Binwen Road, Binjiang District, Hangzhou City, Zhejiang Province, People’s Republic of China, Tel +86 189 5713 0287, Email shaoxiaomei@zcmu.edu.cn; fangjianqiao7532@163.comBackground: Major depressive disorder (MDD) is highly prevalent, affecting more than 300 million individuals worldwide, and its occurrence may be related to the abnormality of the prefrontal cortex and bilateral temporal cortex. Acupuncture, rooted in the theories of acupoints and meridians, has demonstrated its efficacy in regulating cortical blood flow (CBF) in the brains of MDD patients. As one form of acupuncture, intradermal acupuncture (IA) can alleviate clinical symptoms such as depressive mood and insomnia in MDD patients. However, it remains unknown whether IA will have a specific effect on the prefrontal cortex and bilateral temporal cortex in MDD patients.Methods: In total, 60 participants will be recruited: 20 healthy control participants and 40 MDD patients. All healthy control participants will be allocated to the control group, whereas the 40 MDD patients will be randomly divided into two groups: the gallbladder meridian acupoint (GBA) group and the non-acupoint (NA) group, at a 1:1 allocation ratio. All groups will undergo a one-time IA intervention while their cortical activity is monitored using functional near-infrared spectroscopy (fNIRS). Total hemoglobin, oxygenated hemoglobin, and deoxygenated hemoglobin of the prefrontal and bilateral temporal cortices will be measured by fNIRS during the test procedure.Discussion: This trial aims to use fNIRS to compare real-time hemodynamic changes in the prefrontal and bilateral temporal cortices of healthy individuals and MDD patients during IA. The primary objective is to investigate whether MDD patients exhibit specific real-time responses to IA stimulation in these brain regions. The findings from this study will provide clinical data and a possible theoretical basis for the assumption that stimulation of IA may treat MDD by modulating the relevant brain regions.Trial Registration: The study protocol has been registered in the clinicaltrials.gov with the code NCT05707299.Keywords: major depressive disorder, intradermal acupuncture, functional near-infrared spectroscopy, prefrontal cortex, temporal cortex

Dong Zhang,1,2 Siwei Duan,3 Zhangyou He,4 Zeming Zhu,3 Zhiping Li,3 Qincheng Yi,4 Tiantian Cai,1,2 Juanjuan Li,1,2 Nan Chen,1,2 Shaoju Guo1,2 1Gastrointestinal Ward, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China; 2Gastrointestinal Ward, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, People’s Republic of China; 3Institute of Gastroenterology, Science and Technology Innovation Center of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Institute of Gastroenterology, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Shaoju Guo, Gastrointestinal Ward, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, People’s Republic of China, Tel +86-0755-82571384, Email gsj1080@163.comPurpose: This study was conducted to explore the mechanism of Sijunzi Decoction (SJZ) in the treatment of ulcerative colitis (UC).Methods: The study aimed to investigate the active components and targets of SJZ in the treatment of UC by screening databases such as TCMSP, GeneCards, OMIM, Distinct, TTD, and Drugbank. An online Venn tool, Cytoscape 3.7.2, and Autodock Tools were used to analyze the components and targets. The study also used a mouse model of UC to further investigate the effects of SJZ. HE staining, immunofluorescence, ELISA, qPCR, and Western blot were used to detect various indices.Results: Eighty-three active components and 112 action targets were identified from SJZ, including 67 targets for treating UC-related NETs. The five core targets identified were AKT1, JUN, IL1B, PTGS2, and TNF, and molecular docking studies indicated that the five targets were well-docked with ginsenoside Rh2, isoflavones, and formononetin. Animal experiments demonstrated that SJZ could alleviate various parameters such as weight, colon length, spleen index, disease activity index, and intestinal pathology of the UC mice. Immunofluorescence and Western blot showed that SJZ could reduce the expression of IL1B and TNF in intestinal neutrophils while increasing the expression of Occludin. Cellular immunofluorescence suggests that SJZ can reduce the expression of TNF and IL1B in NETs. The qPCR results also suggested that SJZ could inhibit TNF signal. Furthermore, ELISA results suggested that SJZ could inhibit the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) while promoting the expression of anti-inflammatory cytokines (IL-10, IL-37, TGF-β).Conclusion: SJZ treats UC by reducing the content of intestinal NETs, with primary targets on the NETs being IL1B and TNFand suppress TNF signal. The practical components of SJZ may be ginsenoside Rh2, isoflavones, and formononetin.Graphical Abstract: Keywords: ulcerative colitis, Sijunzi decoction, network pharmacology, IL1B, TNF

Nisang Chen,1,&ast; Xiaoting Wu,1,&ast; Mingqi Tu,1 Sangsang Xiong,1 Junyan Jin,1 Siying Qu,1 Shuangyi Pei,1,2 Jianqiao Fang,1,2 Xiaomei Shao1,2 1Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Key Laboratory for Research of Acupuncture Treatment and Transformation of Emotional Diseases, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaomei Shao; Jianqiao Fang, Zhejiang Chinese Medical University, No. 548, Binwen Road, Binjiang District, Hangzhou City, Zhejiang Province, People’s Republic of China, Email 13185097375@163.com; shaoxiaomei@zcmu.edu.cn; fangjianqiao7532@163.comBackground: Major depressive disorder (MDD) exhibits a pronounced occurrence among adolescents, aligning closely with the lifetime prevalence rate of 16.6% observed in adults. It is difficult to treat and prone to recurrence. Acupuncture has shown potential in enhancing treatment effectiveness. Nonetheless, there is a lack of research on the use of intradermal acupuncture (IA) in treating adolescent MDD.Methods: This study is a double-blind, randomized controlled trial. A cohort of 120 participants will be assigned randomly to three distinct groups, namely a Selective Serotonin Reuptake Inhibitors (SSRIs)-only group, a sham intradermal acupuncture combined with SSRIs (SIA) group, and an active intradermal acupuncture combined with SSRIs (AIA) group. Hamilton Depression Rating Scale will serve as the primary outcome, while Patient Health Questionnaire-9, Self-Rating Depression Scale, Pittsburgh Sleep Quality Index, and Short Form 36 Questionnaire will serve as secondary outcomes in assessing the amelioration of depressive symptoms in patients. These data will be analyzed using SPSS26.0 software.Results: We will assess the efficacy and safety of IA for MDD using commonly employed clinical psychiatric scales.Conclusion: The efficacy of IA in treating adolescent MDD may be demonstrated in this study, suggesting its potential for optimizing MDD treatment schemes.Trial Registration: ClinicalTrials.gov Identifier: NCT 05832619 (April 27, 2023).Keywords: major depressive disorder, intradermal acupuncture, selective serotonin reuptake inhibitors, adolescent, randomized controlled trial, protocol

Wildfire plays an important role in restructuring bacterial and protist taxonomic and functional communities in forest ecosystems. Yet, the recovery of bacterial and protist communities following wildfire has not been rigorously investigated across long-term wildfire chronosequences. We compared changes in bacterial and protist alpha diversity, community composition, co-occurrence networks and determinant edaphic factors between burnt and unburnt (reference) soils at 11 different sites representing a 76-year wildfire chronosequence in Canadian boreal forests. The fire increased bacterial and protist alpha diversity and altered community composition (beta diversity) as compared to the site-specific controls during the early recovery stage (30 years) recovery stages. Bacterial and protist communities showed similar patterns of change across the wildfire chronosequence. The post-fire recovery of bacterial communities was associated with changes in soil chemical properties (e.g., nutrient status and pH) and vegetation succession. The protist community assembly was co-influenced by changes in bacterial communities and vegetation succession/soil properties. The concurrent recovery of bacterial and protist communities, and their influencing factors of vegetation and soil properties, imply the above- and belowground living communities are strongly linked in wildfire-perturbed forest ecosystems.

SiCH and its cation have consistently emerged as predicted species in models of silicon chemistry within the interstellar medium, although they remain unobserved in space. Hindered by their intrinsic instability, no spectroscopic insights have been gleaned concerning the SiCH+ cation. In this study, we present experimental measurements on the SiCH+ cation through single-photon ionization spectroscopy of the SiCH radical within the 8.0–11.0 eV range. Gas-phase SiCH radicals were generated through chemical reactions involving CHx (x = 0–3) and SiHy (y = 0–3) within a microwave discharge flow-tube reactor. Employing a double imaging photoelectron/photoion coincidence spectrometer on the DESIRS beamline at the SOLEIL synchrotron, we recorded mass-selected ion yield and photoelectron spectra. From the analysis of the photoelectron spectrum supported by ab initio calculations and Franck–Condon simulations, the adiabatic ionization energies for the transitions from the X2Π ground electronic state of SiCH toward the X+3Σ− and A+3Π electronic states of SiCH+ have been derived [8.935(6) and 10.664(6) eV, respectively, without spin–orbit correction]. The contribution from the less stable isomer HSiC has been explored in our analysis and ruled out in our experiments. [ABSTRACT FROM AUTHOR]

Yuhao Zeng,1,&ast; Sha Zhu,1,&ast; Zilin Wang,1 Junru Chen,1 Jindong Dai,1 Zhenhua Liu,1 Guangxi Sun,1 Jiayu Liang,1 Xingming Zhang,1 Zhipeng Wang,1 Jinge Zhao,1 Yuchao Ni,1 Jiyu Yang,1 Minghao Wang,1 Qiang Wei,1 Xiang Li,1 Ni Chen,2 Zhiping Li,3 Xin Wang,3 Yali Shen,3 Jin Yao,4 Rui Huang,5 Jiyan Liu,6 Diming Cai,7 Hao Zeng,1 Pengfei Shen1 1Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 6Department of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 7Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengfei Shen; Hao Zeng, Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Email cdhx510@163.com; kucaizeng@163.comPurpose: Multidisciplinary team (MDT) discussion is a widely used model to manage patients diagnosed with cancer. However, there has been no direct evidence to prove its effect on the prognosis of metastatic renal cell carcinoma (mRCC) patients, so this study explored the impact of MDT discussion on mRCC patient survival.Methods: The clinical data of 269 mRCC patients were retrospectively collected from 2012 to 2021. The cases were grouped into the MDT and non-MDT groups, then subgroup analysis was performed according to different histology types, as well as exploring the role of MDT in patients who have undergone multiple-line therapy. Overall survival (OS) and progression free survival (PFS) were set as the study endpoint.Results: Approximately half (48.0%, 129/269) of the patients were in the MDT group, with univariable survival analyses showing these patients had remarkably longer median OS (MDT group: 73.7 months; non-MDT group: 33.2 months, hazard ratio (HR): 0.423 (0.288, 0.622), p< 0.001) and longer median PFS (MDT group: 16.9 months, non-MDT group: 12.7 months, HR: 0.722 (0.542, 0.962), p=0.026). Furthermore, MDT management resulted in longer survival for both ccRCC and non-ccRCC subgroups. Patients in the MDT group were more likely to receive multi-line therapy (MDT group: 79/129, 61.2% vs non-MDT group: 56/140, 40.0%, p< 0.001), and within this patient group, MDT management still resulted in longer OS (MDT group: 94.0 months; non-MDT group: 43.5 months, p=0.009).Conclusion: MDT is associated with prolonged overall survival in mRCC independent of histology, ensuring that patients receive better management and precise treatment.Keywords: mRCC, MDT, overall survival, prognosis, ccRCC, non-ccRCC, multi-line treatment

Weihong Lu,1,2 Silan Zheng,3 Jingqi Zhou,3 Shunfa Huang,4 Ning Chen,3 Zhibin Li5 1Department of Gynecology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, People’s Republic of China; 2Xiamen Clinical Research Center for Cancer Therapy, Xiamen, People’s Republic of China; 3Department of Endocrinology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, People’s Republic of China; 4Department of Radiology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, People’s Republic of China; 5Epidemiology Research Unit, Translational Medicine Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of ChinaCorrespondence: Ning Chen, Department of Endocrinology, Zhongshan Hospital (Xiamen), Fudan University, No. 668 Jinhu Road, Xiamen, 361000, People’s Republic of China, Tel/Fax +86-0592-3569583, Email chen.ning@zsxmhospital.com Zhibin Li, Epidemiology Research Unit, Translational Medicine Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, No. 55 Zhenhai Road, Xiamen, 361003, People’s Republic of China, Tel +86-592-2137364, Fax +86-592-2137557, Email zhibinli33@hotmail.comObjective: This study aimed to examine associations between plasma sex-related hormones with bone mineral density (BMD) and risks of osteoporosis or osteopenia in men and postmenopausal women patients with type 2 diabetes mellitus (T2DM).Methods: Baseline information on an ongoing cohort of 149 men and 102 postmenopausal women with T2DM in Xiamen, China were analyzed. Plasma estradiol (E2), total testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL) were measured. BMD of lumbar spine (L2-4), femoral neck (FN) and total hip (TH) were determined by dual-energy X-ray absorptiometry (DXA). Osteoporosis or osteopenia was defined as the minimum T-scores of BMD of these three different sites of − 1.0 or below.Results: T2DM patients with osteoporosis/osteopenia (66.4% in men and 79.4% in postmenopausal women), compared to those without, showed significantly decreased level of E2 (75.3± 28.9 vs. 107.8± 25.9pmol/L and 18.4 (18.4– 29.5) vs. 22.8 (18.4– 40.5) pmol/L for men and postmenopausal women, respectively, both p-values < 0.05), but not other sex-related hormones (including T, FSH, LH, or PRL). For all T2DM patients together and men separately, multivariable linear regression and logistic regression analyses showed that higher E2 levels were significantly associated with higher BMD T-scores in L2-4, FN, TH and minimum of these three different sites, lower 10-year probability of major osteoporotic fractures (MOF) and hip fractures (HFs) estimated by Fracture Risk Assessment Tool score, as well as decreased risk of osteoporosis/osteopenia. As for postmenopausal women T2DM patients, E2 level was positively associated with BMD T-scores in L2-4 and minimum of three different sites but was not independently associated with risk of osteoporosis/osteopenia.Conclusion: Higher plasma E2 was significantly associated with increased BMD and lower risk of osteoporosis or osteopenia in T2DM patients, especially for men. Screening of BMD and estradiol levels as well as evaluating risks of osteoporosis/osteopenia are important for T2DM patients.Keywords: estradiol, bone mineral density, osteoporosis, osteopenia, diabetes, BMD

The 2015/2016 super El Niño event resulted in a positive precipitation anomaly during dry seasons in the Jiulong River watershed, southeast China. Four years (2014–2017) of high frequency, in situ humic-like fluorescent DOM (FDOMH) data in the Jiulong Estuary were coupled with extrapolation to a freshwater end-member FDOMH concentration and river discharge data to estimate riverine FDOMH export. The wetter El Niño dry season was followed by lower FDOMH export during the subsequent wet season. Furthermore, in the dry season after El Niño reached its strongest phase, a 90–187% increase in FDOMH export occurred. If widespread, this pattern suggests El Niño events may enhance export of FDOMH from south China rivers in dry seasons resulting in seasonal and annual shunting of the terrestrial DOM export, modulating coastal carbon cycling. This study highlights the need to incorporate climate-driven regulation patterns on DOM transport across the land-ocean interface.

Drip irrigation under plastic film mulching with applications of the N-fertilizer is an excellent agricultural strategy, resulting in saving irrigation water, improving N use efficiency, and increasing crop yield. However, the film residue and nitrate-nitrogen (NO3-N) losses are the leading cause of non-point pollution in agricultural fields. To promote the development of sustainable agriculture, the HYDRUS (2D/3D) model was first calibrated and then validated using experimental data from 2016 and 2017, respectively, collected in the drip-irrigated sandy field with plastic film mulching (PFM), biodegradable film mulching (BFM), and no film mulching (NFM). Additionally, the NO3-N spatial and temporal distributions, uptake, leaching, and use efficiency (NUE) under PFM, BFM, and NFM with 280 kg ha−1 of the N-fertilizer (the local recommendation) were evaluated using both observed and simulated data. These factors were also assessed under BFM with 210 (75 % of the recommended value) and 140 kg ha-1 (50 % of the recommended value) of the N-fertilizer. The results of numerical simulations were in good agreement with observations, with the RMSE, R2, and NSE during verification being 0.01-0.08 mg cm-3, 0.62-0.87, and 0.68-0.94, respectively. When the same amount of the N-fertilizer (280 kg ha−1) was applied in each treatment, there were no apparent differences in NO3-N concentrations in the soil profile, cumulative NO3-N uptake by corn (CNU), and cumulative NO3-N leaching (CNL) in the 100-cm soil depth between the BFM280 and PFM280 scenarios (the subscript indicates the amount of the N-fertilizer) during the early growing season (Day After Sowing [DAS] of 0–78 in 2016 and DAS of 0–92 in 2017). However, CNU and CNL were higher, and the NO3-N concentrations in the upper soil layer (0−40 cm soil layer) lower in these two scenarios than in the NFM280 scenario. The NO3-N concentrations in the topsoil layer (the 0−20 cm soil layer) in the BFM280 scenario were 3.9 % higher than in the PFM280 scenario during DAS 93–154 in 2017 due to the disintegration of the biodegradable film and 26.3 % lower during DAS 79–155 in 2016 because of intensive rainfall. Additionally, the highest NUE (50.9 kg kg-1, the average value for two years) was found when 75 % of the recommended N-fertilizer (210 kg ha−1) was applied. Therefore, an application of 210 kg ha−1 of the N-fertilizer in the BFM scenario can be recommended for sandy farmland to avoid plastic pollution, increase NUE, and effectively promote the development of sustainable agriculture.

Lucas Kosobuski,1 Carolyn O’Donnell,1 Cynthia P Koh-Knox Sharp,2 Nathaniel Chen,1 Laura Palombi1 1Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota - College of Pharmacy, Duluth, MN, USA; 2Purdue University College of Pharmacy, West Lafayette, IN, USACorrespondence: Laura Palombi, Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota – College of Pharmacy, 1110 Kirby Drive, 232 Life Science, Duluth, MN, 55812, USA, Tel +1 218-726-6000, Fax +1 218-726-6500, Email lpalombi@d.umn.eduIntroduction: The opioid overdose crisis has claimed hundreds of thousands of lives in the United States in the last decade, with overdose numbers continuing to climb. At the same time, the role of the pharmacist in combating the opioid crisis continues to evolve.Methods: A literature search was conducted in Ovid MEDLINE that incorporated both MeSH terms and keywords to describe two concepts: the opioid epidemic and pharmacists/pharmacies. The search was limited to articles published after 2010 through the end of 2021 and returned 196 articles that were analyzed thematically.Results: Thematic analysis revealed the following themes: prevention, interventions, public health role of the pharmacist, pharmacists in multiple roles, barriers, pharmacist and healthcare provider attitudes, educational initiatives for pharmacists and student pharmacists, and future research.Discussion: While a great deal of progress has been made in the role of the pharmacist in supporting individuals with opioid use disorder (OUD) in the last two decades, pharmacists must seek to invest time and resources into practices with a strong evidence base to better mitigate the growing, devastating impact of the opioid crisis. Pharmacists must be willing to embrace new and non-traditional roles in patient care, service and research, and seek to advance evidence-based knowledge and practice.Conclusion: Pharmacy practice has expanded greatly in the past decade with pharmacists taking on new and creative approaches to addressing the opioid crisis. Collaborative and interdisciplinary approaches to addressing the root causes of opioid misuse and opioid overdose are still desperately needed. These include attention to the critical roles of social determinants of health, stigma elimination, legislative advocacy for patients with OUD, and focused education for providers, pharmacists, and the community. Recognition and support of the value of collaboration to both improve public health and individual patient care, continued investments in pharmacy practice advancement in OUD treatment and harm reduction, and the creation of workflows and prescribing algorithms to assist in dosing medications to prevent withdrawal symptoms and achieve improved pain control are desperately needed.Keywords: pharmacist, pharmacy, opioid, overdose, pharmacy practice

Hui Jing,1 Xinyi Li,1 Naiqi Chen,1,2 Mohamed Oubibi,1,3 Xinyi Mao,1 Weifeng Di1,3 1College of Teacher Education, College of Education and Human Development, Zhejiang Normal University, Jinhua, People’s Republic of China; 2College of Innovation and Entrepreneurship, Zhejiang Normal University, Jinhua, People’s Republic of China; 3Key Laboratory of Intelligent Education Technology and Application of Zhejiang Province, Zhejiang Normal University, Jinhua, People’s Republic of ChinaCorrespondence: Weifeng Di, Email diwf@zjnu.cnBackground: Hengdian drifters refer to outsiders who participate in shooting film and television dramas in Hengdian. It is a special group. Single access to information, precarious nature of work, unequal treatment of gender, constraints on development, and inadequate guarantee mechanisms are all to blame.Purpose: This paper proposes to improve the ecology of the different actor industries by implementing a precise assessme.Patients and methods: This study combines qualitative and quantitative research, adopts the questionnaire survey and semi-structured interview, and carries out fieldwork by personally experiencing the life of extras to study the ecological environment of the different actor industries and the professional mentality of extras. Before participating in the study, every participant would be offered an Informed Consent Form and all particpants were guaranteed anonymity and their response will be used for a specific academic study. The Ethics Committee of the Zhejiang Normal University’s, Specific academic study that will be published online. College of Teacher Education approved the study and participation of concents under 18 and the study followed the Declaration of Helsinki.Results: There are gaps in social support.Little relevant policy support and financial support have not been implemented. Industry assessment criteria are not standardized.The level of digital management is low.It is difficult to guarantee the rights of mass actors.Conclusion: Implement a precise assessment system,develop a refined talent evaluation mechanism,Ensure the accuracy and transparency of the evaluation process.Establish digital service platforms,provide a new channel for the employment of artistic talents.Strengthen media publicity,strengthen policy support,raise social awareness.Keywords: Chinese Hengdian drifters, professional mentality, industry dilemma, digital management

Mengzhu Hou,1,&ast; Nan Chen,2,&ast; Lili Dong,3,&ast; Yulian Fang,1 Rui Pan,2 Wei Wang,1 Lu Wang,1 Jing Ning,3 Hanquan Dong3 1Tianjin Pediatric Research Institute, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, People’s Republic of China; 2Department of Clinical Lab, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, People’s Republic of China; 3Department of Respiratory, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Ning; Hanquan Dong, Department of Respiratory, Tianjin Children’s Hospital (Children’s Hospital of Tianjin University), No. 238 Longyan Road, Beichen District, Tianjin, 300134, People’s Republic of China, Tel +86 13752230008 ; +86 13820476506, Email jingning2022@126.com; mifits@sina.comPurpose: The data on pediatrics with Multidrug-Resistant (MDR) Klebsiella pneumoniae infections are scarce. This study aims to investigate the molecular epidemiology of MDR Klebsiella pneumoniae, detect the mechanism of drug resistance, and determine the clinical risk factors for carbapenem-resistant Klebsiella pneumonia (CRKP) bloodstream infections (BSIs) in a children’s hospital.Methods: A total of 62 strains were collected from Tianjin Children’s Hospital. Carba NP and polymerase chain reactions (PCR) were performed to detect MDR mechanisms. Multilocus sequence typing (MLST) was used for analyzing strain homology. Clinical data were collected and logistic regression was used for BSI risk factors.Results: ST11 was the principal ST among the CRKP isolates clinically, accounting for 56.45% (35/62); there were also 57.14% (20/35) ST11 CRKP strains co-carrying blaNDM-5 and blaKPC-2, which were resistant to most of the tested antibiotics, being susceptible only to cotrimoxazole and tigecycline. The clinical data showed that 72.73% (40/55) of children with CRKP infection had serious underlying diseases; 20.00% (11/55) patients developed BSIs with the potential to cause multiple organ failure, shock and death. The logistic regression showed that the risk of BSIs caused by CRKP strain infections in children with hematological malignancies after chemotherapy was 7 times that of other children (95%Cl: 1.298– 45.415, P=0.025).Conclusion: ST11 was the prevalent clone in our hospital. The emergence of ST11 CRKP co-carrying blaNDM-5 and blaKPC-2 should be a cause for alarm as they were resistant to most of the tested antibiotics. CRKP strain infections are mainly occurring in young immunocompromised patients and the chemotherapy for hematological malignancies is an independent risk factor for BSIs.Keywords: carbapenem-resistantKlebsiella pneumonia, blaKPC-2, blaNDM-5, ST11, children, bloodstream infection

Xiangfeng He,1,2,&ast; Yanping Song,2,&ast; Lin Ma,2,&ast; Barbara E Ainsworth,3 Yu Liu,4 Nan Chen1,2,4 1Department of Rehabilitation, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Rehabilitation, Xinhua Hospital Chongming Branch, Shanghai, People’s Republic of China; 3College of Health Solutions, Arizona State University, Phoenix, AZ, USA; 4School of Kinesiology, Shanghai University of Sport, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Liu, School of kinesiology, Shanghai University of Sport, No. 399 Changhai Road, Yangpu District, Shanghai, People’s Republic of China, Tel +86-21-65507860, Email yuliu@sus.edu.cn Nan Chen, Department of Rehabilitation, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Yangpu District, Shanghai, People’s Republic of China, Email chennanreh2020@126.comObjective: This study aimed to explore the prevalence and impact of related factors for sarcopenia among community-dwelling older people in Chongming district, China, according to the diagnostic criteria of the Asia Working Group for Sarcopenia-2019.Methods: We conducted a cross-sectional study from April 2021 to December 2021. Diagnosis of sarcopenia (non-sarcopenia, possible sarcopenia, sarcopenia, and severe sarcopenia) was based on appendicular skeletal muscle mass index, handgrip strength, gait speed, and the 5-time chair stand test. Staff collected all subjects’ clinical and sociodemographic characteristics, cardiovascular disease (CVD) risk factors, inflammatory markers, physical activity (PA), and daily lifestyle activities to identify sarcopenia-related factors.Results: A total of 1407 older people aged ≥ 65 years were enrolled into the study (58.7% female). The prevalence of confirmed sarcopenia was 19.6% (17.1% in females and 23.1% in males). The prevalence of possible sarcopenia, sarcopenia, and severe sarcopenia were 19.7% (22.2% in females, 16.2% in males), 11.9% (10.1% in females, 14.5% in males), and 7.7% (7% in females, 8.6% in males), respectively. Increasing age, gender, depression status, and high-fat mass were associated with an increased likelihood of sarcopenia in all subjects. In females, living alone, high-fat mass, lower body mass index (BMI), lower body weight, and have no time spent doing housework increased the likelihood of sarcopenia. In males, depression status, high-fat mass, higher neutrophils-to-lymphocytes ratio (NLR), lower BMI, lower body weight increased the likelihood of sarcopenia.Conclusion: Our study showed a high prevalence of sarcopenia among community-dwelling older people in the Chongming district. Detection, prevention, and treatment efforts are needed to reduce the impact of sarcopenia in older, rural communities in China.Keywords: sarcopenia, prevalence, risk factor, older people, rural area

Wenhao Liao,1,&ast; Yuchen Li,1,2,&ast; Jing Wang,3,&ast; Maoyuan Zhao,1 Nianzhi Chen,1 Qiao Zheng,1 Lina Wan,1 Yu Mou,1 Jianyuan Tang,1,4 Zhilei Wang1,4 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Department of Obstetrics and Gynecology, Bishan Hospital of Traditional Chinese Medicine, Chongqing, People’s Republic of China; 4TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianyuan Tang; Zhilei Wang, Email tangjy@cdutcm.edu.cn; wangzl1993@outlook.comAbstract: Cancer stem cells (CSCs) lead to the occurrence and progression of cancer due to their strong tumorigenic, self-renewal, and multidirectional differentiation abilities. Existing cancer treatment methods cannot effectively kill or inhibit CSCs but instead enrich them and produce stronger proliferation, invasion, and metastasis capabilities, resulting in cancer recurrence and treatment resistance, which has become a difficult problem in clinical treatment. Therefore, targeting CSCs may be the most promising approach for comprehensive cancer therapy in the future. A variety of natural products (NP) have significant antitumor effects and have been identified to target and inhibit CSCs. However, pharmacokinetic defects and off-target effects have greatly hindered their clinical translation. NP-based nanoformulations (NPNs) have tremendous potential to overcome the disadvantages of NP against CSCs through site-specific delivery and by improving their pharmacokinetic parameters. In this review, we summarize the recent progress of NPNs targeting CSCs in cancer therapy, looking forward to transforming preclinical research results into clinical applications and bringing new prospects for cancer treatment.Keywords: cancer, cancer stem cells, nanoformulations, natural products, targeted therapy

Sha Zhu,1,&ast; Yige Bao,1,&ast; Linmao Zheng,2,&ast; Jinge Zhao,1 Yuntian Chen,3 Rui Huang,4 Guangxi Sun,1 Fengnian Zhao,1 Xingming Zhang,1 Jiayu Liang,1 Junru Chen,1 Zhipeng Wang,1 Yuchao Ni,1 Ni Chen,2 Pengfei Shen,1 Hao Zeng1 1Department of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Pathology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Radiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengfei Shen; Hao Zeng, Department of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Tel +86-18980602129, Fax +86-28-8542-2451, Email cdhx510@163.com; zengh@scu.edu.cn; kucaizeng@163.comAbstract: CDK12 (Cyclin-Dependent Kinase 12)-mutated prostate cancer patients often respond badly to current therapies. Immunotherapy and platinum-based chemotherapy are recommended based on the molecular features of CDK12-mutated tumors, but the reported patient outcomes are still unsatisfying. Here we report a prostate cancer patient with CDK12 somatic mutation who received multiple therapy options, including platinum-based chemotherapy and immunotherapy. His sequential circulating tumor DNA (ctDNA) -based liquid biopsy tests showed that his original CDK12 mutation fell undetectable twice. This phenomenon was observed only when he was responding well to platinum-based chemotherapy. His responses to immunotherapy were not satisfying. This case indicates that platinum-based chemotherapy can be a good option for treating patients with CDK12 mutation. More importantly, dynamic ctDNA-based liquid biopsies to monitor patients’ CDK12 mutation status are critical in evaluating patients’ response and tolerance during platinum-based chemotherapy, therefore may lead to a better overall prognosis. In conclusion, CDK12-mutated prostate cancer patients are likely to benefit from platinum-based chemotherapy, especially with the help of dynamic ctDNA-based liquid biopsies to monitor their CDK12 mutation status.Keywords: CDK12, liquid biopsy, platinum, prostate cancer, case report

Cu2Se thin films provide a promising route toward relatively safe, sustainable and solution processed thermoelectric (TE) modules in contrast to more expensive and toxic materials currently on the market such as Bi2Te3. Cu2Se is known in the TE community for its high performance at high temperature and has recently attracted attention from its large theoretically predicted figure of merit at room temperature. Unfortunately, one of the main limitations encountered so far in Cu2Se thin films is that the carrier concentrations are not optimized for TE operation after solution processing. In this work, we conduct a comprehensive study of the structural, optical, and TE properties of Cu2Se thin films and demonstrate that nonoptimized carrier concentrations in these films lead to observations of poor performance at room temperature. Through a simple soaking procedure in a Cu+ ion solution for only a few minutes, we demonstrate a 200-300% increase in power factor. This soaking process pushes the carrier concentration of the Cu2Se thin film toward its optimal value for TE operation and marks the highest TE performance for any solution processed Cu2Se thin film at room temperature thus far. If the performance can be further optimized at room temperature, Cu2Se thin films will be the material of choice to utilize in TE modules for powering miniature electronics and sensors, which has been an increasingly popular and rapidly expanding market.

Fusang Wang,1,2,* Xiaohan Zheng,1,2,* Juan Zhang,3,* Fuping Jiang,4 Nihong Chen,5 Mengyi Xu,5 Yuezhang Wu,2 Jianjun Zou,2,5 Xiaoli Cui,3 Junshan Zhou6 1School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Department of Clinical Pharmacology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Neurology, Nanjing Yuhua Hospital, Yuhua Branch of Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Geriatrics, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 5Department of Clinical Pharmacology, Nanjing First Hospital, China Pharmaceutical University, Nanjing, People’s Republic of China; 6Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianjun Zou; Xiaoli Cui, Email zoujianjun100@126.com; 849110554@qq.comBackground and Purpose: Predicting poor outcome for stroke patients with chronic kidney disease (CKD) in clinical practice is difficult. There are no tools available to use for predicting poor outcome in these patients. We aimed to construct and validate a dynamic nomogram to identify CKD–stroke patients at high risk of a 3-month poor outcome.Patients and Methods: We used data for 502 CKD patients who had an acute ischemic stroke, from Nanjing First Hospital, between September 2014 and September 2020, to train the nomogram. An additional 108 patients enrolled from October 2020 to May 2021 were used for temporal external validation. The performance of the nomogram was evaluated by the area under the receiver operating characteristics curve (AUC) and a calibration plot. The clinical utility of the nomogram was measured by decision curve analysis (DCA) and the clinical impact curve (CIC).Results: The median age of the cohort was 79 (70– 84) years. Age, urea, premorbid modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS) on admission, hemiplegia, mechanical thrombectomy, early neurological deterioration, and respiratory infection were used as predictors of 3-month poor outcome to develop the nomogram. In the training set, the AUC of the dynamic nomogram was 0.873 and the calibration plot showed good predictive ability, and both DCA and CIC indicated the excellent clinical usefulness and applicability of the nomogram. In the external validation set, the AUC was 0.875 and the calibration plot also showed good agreement.Conclusion: This is the first dynamic nomogram constructed for CKD–stroke patients to precisely and expediently identify patients with a high risk of 3-month poor outcome. The outstanding performance and great clinical predictive utility demonstrated the ability of the dynamic nomogram to help clinicians to deploy preventive interventions.Keywords: dynamic nomogram, stroke, chronic kidney disease, poor outcome, predict