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Jia Deng, Yu-Jian Ye, Qiu-Ping Chen, Yi-Jin Zhang, Ji-Feng Liu Department of Dermatology, Hangzhou Third People’s Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Ji-Feng Liu, Department of Dermatology, Hangzhou Third People’s Hospital, No. 38 of West Lake Road, Shangcheng District, Hangzhou, Zhejiang, 310009, People’s Republic of China, Tel/Fax +86 0571-87827514, Email fliu8166@126.comObjective: To assess the accuracy of HSV1and HSV2 antibody testing in identifying genital herpes infection.Methods: A cohort of 299 patients previously diagnosed with recurrent genital herpes, confirmed via PCR, were tested using ELISA for HSV1 and HSV2 IgM and IgG antibodies. The study compared the accuracy of HSV1 and HSV2 antibody tests in diagnosing genital herpes.Results: Among 299 patients, 14 tested positives for HSV1 DNA. Of these, 9 had HSV1 IgG antibodies, but none had HSV2 IgG antibody. Among 278 patients with HSV2 DNA, 149 had HSV1 IgG, 9 had HSV2 IgG, and 97 had both. Seven patients had both HSV1 and HSV2 DNA; 3 had HSV1 IgG, 1 had HSV2 IgG, and 3 had both. The accuracy of HSV1 IgG for HSV1 infection was 64.2%, and for HSV1 and HSV2 co-infection, 85.7%. The accuracy of HSV2 IgG for HSV2 infection was 38.1%, and for HSV1 and HSV2 co-infection, 57.1%. The combined antibody positivity accuracy was 34.9%.Conclusion: Genital herpes is primarily caused by HSV2 (92.98%). A smaller percentage is HSV1 (4.67%) or co-infection (2.34%). Despite relatively low diagnostic accuracy (34.9– 85.7%) for antibody detection, combined antibody testing is necessary. Herpes DNA testing is recommended for accurate diagnosis. Absence of antibodies does not rule out genital herpes and clinical assessment is essential.Keywords: antibody test, DNA test, genital herpes, HSV-1, HSV-2

Po-Yu Chu,1 Kuan-Po Lien,2,3 Kuan-Cheng Chen,1 Cheng-Yuan Li,4,5 Jai-Sing Yang,6 Tien-Hsiang Wang,1,7 Yu-Jen Chiu1,7,8 1Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, 112201, Taiwan; 2Department of Medicine, Mackay Medical College, New Taipei City, 252005, Taiwan; 3Department of Surgery, Cathay General Hospital, Taipei, 106438, Taiwan; 4Department of Dermatology, Taipei Veterans General Hospital, Taipei, 112201, Taiwan; 5Department of Dermatology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan; 6Department of Medical Research, China Medical University Hospital, China Medical University, Taichung City, 404327, Taiwan; 7Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan; 8Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, 112304, TaiwanCorrespondence: Yu-Jen Chiu, Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, 19/F, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei, 112201, Taiwan, Email chiou70202@gmail.comBackground: Obesity has been identified as a significant risk factor for various diseases, including certain cancers; however, its association with melanoma remains a subject of debate. Despite the increasing incidence of cutaneous melanoma in Taiwan, there has been limited research on its correlation with obesity. This study aims to investigate the relationship between obesity and the prognosis of cutaneous melanoma in Taiwan.Methods: Between January 1, 2000, and December 31, 2022, 201 patients were diagnosed with cutaneous melanoma at our hospital, with 61.69% of them diagnosed with acral melanoma. Data on body weight, height, tumor stages and prognosis were collected and analyzed.Results: The result revealed that older age (≥ 65 years old), male, advanced Breslow thickness stage (T3 and T4) and tumor ulceration were identified as risk factors for worse overall survival in both cutaneous melanoma and acral melanoma. In the adjusted multivariable analysis, being overweight was considered a protective factor in both cutaneous and acral melanoma.Conclusion: Contrary to expectations, it was observed that melanoma patients with obesity exhibited better survival rates compared to those with normal or underweight status. Additionally, no significant differences were found between acral melanoma and non-acral melanoma subtypes regarding the impact of body weight on overall survival.Keywords: melanoma, neoplasms, obesity, obesity paradox, survival analysis

Xiao-Fang Dong,1 Qiang Zhang,2 Jia-Ning Wei,2 Qian-Yu Zhou,3 Fan-Jia-Yi Yang,2 Yan-Jin Liu,4 Yu-Sheng Li,5 Chang-Qing Sun2,3 1Department of Endocrinology and Metabolic Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2School of Nursing and Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Epidemiology and Biostatistics, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 4Department of Nursing, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 5Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Chang-Qing Sun, School of Nursing and Health, Zhengzhou University, NO. 101 Kexue Road, High-Tech Development Zone of District, Zhengzhou, Henan, People’s Republic of China, Email suncq@zzu.edu.cnObjective: Our research explores how leisure-time sedentary behavior (SB) correlates with stroke risk. Additionally, we utilize the isotemporal substitution model (ISM) to examine how replacing brief durations of leisure-time SB with light physical activity (LPA), moderate physical activity (MPA), vigorous physical activity (VPA), and sleep might influence the risk of stroke.Methods: This investigation tracked 478,198 participants from the UK Biobank. Data regarding individual leisure-time SB and PA were collected through a standardized questionnaire. A Cox proportional hazards model, alongside an isotemporal substitution model (ISM), was utilized.Results: We identified 10,003 cases of incident stroke over 12.7 years. When compared to participants who engaged in leisure-time SB for less than 4 hours per day, the hazard ratios (HRs) for stroke incidence increased with more prolonged leisure-time SB: HRs were 1.06 (95% CI: 1.01 to 1.11) for 4– 6 h/d, 1.16 (95% CI: 1.10 to 1.23) for 6– 8 h/d, and 1.24 (95% CI: 1.15 to 1.33) for over 8 h/d. According to the ISM analysis, substituting leisure-time SB with various forms of PA could markedly reduce stroke risk. For individuals sleeping ≤ 8h/d, replacing one hour of leisure-time SB with an equivalent duration of LPA, VPA, or sleep corresponded to a 3.0%, 7.0%, and 22.0% decrease in stroke risk, respectively. Meanwhile, for those already sleeping more than 8h/d, substituting one hour of leisure-time SB with an equivalent duration of LPA or VPA resulted in a notable decrease in the risk of stroke by 6.0% and 18.0%, respectively.Conclusion: The findings demonstrate that leisure-time SB and unhealthy sleep durations are confirmed risk factors for stroke. For individuals sleeping 8 hours or less per day, and for those who sleep more than 8 hours, substituting SB with an adequate amount of sleep or engaging in VPA, respectively, emerges as an effective strategy for reducing stroke risk.Keywords: stroke, isotemporal substitution model, physical activity, sedentary behavior, sleep

Shao-Long Chen,1 Yao-Jie Shen,2 Guo-Zhi Chen1 1Department of Infectious Disease Control and Prevention, Yueqing Center for Disease Control and Prevention, Wenzhou, 325600, People’s Republic of China; 2Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of ChinaCorrespondence: Shao-Long Chen, Yueqing Center for Disease Control and Prevention, Wenzhou, 325600, People’s Republic of China, Email chenshaolong@zjsru.edu.cnPurpose: Worldwide, chronic hepatitis B virus (CHB) infection is a public health concern, ultimately leading to liver cirrhosis and hepatocellular carcinoma. Currently, patients with CHB can be treated using polyethylene glycol (PEG)ylated interferon (PEG-IFN) antiviral therapy, which has both immune modulatory and antiviral properties. This study aimed to reveal the mechanism underlying the effect of PEG-IFN therapy, to rationally optimize this therapeutic option.Patients and Methods: Ten patients with CHB who were positive for the hepatitis B virus e antigen (HBeAg) and were receiving PEG-IFN treatment were enrolled. Clinical and virological parameters were monitored during 48 weeks of treatment. In addition, peripheral blood mononuclear cells (PBMCs) were collected from the 10 patients at 0, 24, and 36 weeks. RNA sequencing technology was used to analyze the RNA expression profile in the PBMC samples.Results: Following PEG-IFN treatment, we identified 217 differentially expressed genes (DEGs), most of which were upregulated. Gene ontology enrichment analysis of the DEGs revealed that they were enriched in 29 clusters, mainly associated with “antiviral defense”, “innate immunity”, “immunity”, “defense response to virus”, “response to virus”, “type I interferon signaling pathway”, “negative regulation of viral genome replication”, “innate immune response”, and “RNA-binding”.Conclusion: After PEG-IFN treatment, a certain mRNA expression profile was observed in patients with CHB, providing further mechanistic insights into the antiviral effect of this therapy.Keywords: Chronic infection, Hepatitis B, PEGylated interferon, RNA sequencing

Yea-Jin Lee,1,2 Namgue Hong,2 Eun Seo Choi,3 Sun-Hyang Choi,2 Eun Young Kim,2 Hyeong Ju Park,4 Jin-Chul Ahn1,2 1Department of Medicine, Dankook University, Cheonan-si, 31116, Republic of Korea; 2Medical Laser Research Center, Graduate School of Medicine, Dankook University, Cheonan-si, 31116, Republic of Korea; 3Department of Physics, Chosun University, Gwangju, 61452, Republic of Korea; 4Bio&Health Photonics Research Center, Korea Photonics Technology Institute, Gwangju, 61007, Republic of KoreaCorrespondence: Hyeong Ju Park; Jin-Chul Ahn, Email phj020603@kopti.re.kr; jcahn@dankook.ac.krPurpose: To evaluate the efficacy and safety of abdominal fat reduction in mini-pigs, utilizing at 1060 nm diode laser with a wavelength of 1060 nm.Patients and Methods: The laser system non-invasively disrupts adipose tissue; its effectiveness and safety were evaluated by ultrasound imaging and histological analysis. Laser irradiation was performed with various powers, and the cooling function was activated to prevent skin surface damage.Results: The dermal tissue temperature increased to at least 43°C during laser exposure, leading to a decrease in abdominal fat thickness after 30 days. Blood tests revealed no significant changes in kidney and liver function but showed increased blood levels of nonessential free acids (NEFAs), likely due to the release of fatty tissue-derived free fatty acids. Histological evaluation demonstrated rapid transformation of adipose tissue into collagen, muscle fibers, and intracellular fibrous tissue.Conclusion: The 1060 nm laser showed promise as a non-invasive and safe tool for reducing abdominal fat.Keywords: diode laser, fat, abdominal, non-invasive, preclinical

Congenital diarrheal disorders (CDD) are a group of rare inherited intestinal disorders, among which CDD7 was recently identified to be associated with only 24 mutations in gene coding for diacylglycerol-acyltransferase 1 (DGAT1).

Purpose: To investigate the relationship between prostatic urethral angle (PUA) and the development of surgical capsule calculi (SCC) within the prostate, and to examine the presence and impact of intravesical prostatic protrusion (IPP). Materials and Methods: A retrospective analysis was conducted on 90 patients who underwent radical prostatectomy, with preoperative assessments using both transrectal ultrasound of the prostate (TRUS) and magnetic resonance imaging. Patients were divided into groups with and without SCC and further categorized into type 1 and type 2 stones based on the location and severity of the calculi. Statistical analysis included chi-square and independent sample t-tests, with p

Ji-Hyun Kang,1,2,&ast; Jin-Hyuk Jeong,1,&ast; Yong-Bin Kwon,1 Young-Jin Kim,1 Dae Hwan Shin,1 Yun-Sang Park,3 Soonsil Hyun,1 Dong-Wook Kim,4 Chun-Woong Park1 1College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea; 2School of Pharmacy, Institute of New Drug Development, and Respiratory Drug Development Research Institute, Jeonbuk National University, Jeonju, Republic of Korea; 3Research & Development Center, P2K Bio, Cheongju, Republic of Korea; 4College of Pharmacy, Wonkwang University, Iksan, 54538, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Chun-Woong Park, College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea, Tel +82-43-261-3330, Fax +82-43-268-2732, Email cwpark@cbnu.ac.kr Dong-Wook Kim, College of Pharmacy, Wonkwang University, Iksan, 54538, Republic of Korea, Tel +82-63-229-7130, Fax +82-63-850-7309, Email pharmengin@gmail.comPurpose: Effective mucosal delivery of drugs continues to pose a significant challenge owing to the formidable barrier presented by the respiratory tract mucus, which efficiently traps and clears foreign particulates. The surface characteristics of micelles dictate their ability to penetrate the respiratory tract mucus. In this study, polymeric micelles loaded with insulin (INS) were modified using mucus-penetrative polymers.Methods: We prepared and compared polyethylene glycol (PEG)-coated micelles with micelles where cell-penetrating peptide (CPP) is conjugated to PEG. Systematic investigations of the physicochemical and aerosolization properties, performance, in vitro release, mucus and cell penetration, lung function, and pharmacokinetics/pharmacodynamics (PK/PD) of polymeric micelles were performed to evaluate their interaction with the respiratory tract.Results: The nano-micelles, with a particle size of < 100 nm, exhibited a sustained-release profile. Interestingly, PEG-coated micelles exhibited higher diffusion and deeper penetration across the mucus layer. In addition, CPP-modified micelles showed enhanced in vitro cell penetration. Finally, in the PK/PD studies, the micellar solution demonstrated higher maximum concentration (Cmax) and AUC0-8h values than subcutaneously administered INS solution, along with a sustained blood glucose-lowering effect that lasted for more than 8 h.Conclusion: This study proposes the use of mucus-penetrating micelle formulations as prospective inhalation nano-carriers capable of efficiently transporting peptides to the respiratory tract.Keywords: insulin, polyethylene glycol, cell-penetrating peptide, aerodynamic properties, mucus penetration

Ran Zhang,1,2 Ya-Jie Lei,1,2 Sheng-Yue Wen,1,2 Jian Pang,1,2 Yue-Long Cao,1,2 Min Zhang,1,2 Hong-Sheng Zhan,1,2 Xun Lin,3 Bo Chen1,2 1Shi’s Center of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Institute of Orthopedics and Traumatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Bo Chen; Xun Lin, Tel +86-21-20256519, Email cbm818@shutcm.edu.cn; linxund@163.comPurpose: To prove more accurately that Chinese herbal bath therapy may be a safe, effective, simple alternative treatment modality for knee OA, we designed a randomized, double-blind, placebo-controlled trial to explore the effectiveness of SSBD for the relief of pain, daily activities, and quality of life in patients with knee OA.Patients and Methods: A single-center, 52-week, randomized controlled trial of SSBD versus placebo is being performed. A total of 200 patients with symptomatic knee OA will be randomly allocated to the SSBD treatment or placebo intervention group for 4 weeks. The two groups of patients are allowed to steam and bathe their knees once every other day, using one packet of SSBD each time, for 30 minutes, 3 times a week, for a total of 4 weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale at 4 weeks is the primary outcome measure, and the secondary outcomes include WOMAC stiffness and function scores, the Lysholm knee scale score, quality of life, the Brief Pain Inventory score, the Patient’s Global Impressions of Improvement Scale score and the Clinical Global Impressions of Severity scale score. The safety of the herbal medications will also be evaluated.Conclusion: We will discuss whether SSBD has greater advantages in terms of efficacy, safety, and patient overall perception than does placebo control in middle-aged and elderly patients with knee OA. The findings may provide new and valuable information about the efficacy and safety of Chinese herbal bath therapy in the treatment of knee osteoarthritis.Keywords: balneotherapy, traditional Chinese medicine, complementary and integrative medicine, randomized placebo-controlled trial, knee osteoarthritis

Ying-Chao Ma,1 Ya-Qing Sun,2 Xia Wu,1 Yong-Jing Wang,1 Xiu-Ling Yang,1 Jian-Jun Gu3 1Department of Pharmacy, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050000, People’s Republic of China; 2College of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei Province, 050000, People’s Republic of China; 3Department of Cardiac Surgery, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050000, People’s Republic of ChinaCorrespondence: Jian-Jun Gu, Department of Cardiac Surgery, Second Hospital of Hebei Medical University, No. 215 of Heping West Road, Xinhua District, Shijiazhuang, 050000, Hebei Province, People’s Republic of China, Tel +8631166002991, Email jianjungu62@126.com Xiu-Ling Yang, Department of Pharmacy, Second Hospital of Hebei Medical University, No. 215 of Heping West Road, Xinhua District, Shijiazhuang, Hebei Province, 050000, People’s Republic of China, Tel +8631166002712, Email yangxuilingyxl0d@126.comObjective: To assess the efficacy and safety of colistin sulfate in treating infections caused by carbapenem-resistant organisms (CRO) and to analyze potential factors impacting its effectiveness.Methods: In this retrospective study, medical records of CRO-infected patients from June 2020 to June 2023 were analyzed, divided into effective and ineffective treatment groups, and compared for clinical outcomes and adverse reactions. Multifactorial logistic regression and ROC curve analysis were used to identify influencing factors.Results: The study included 226 patients, with 124 in the effective treatment group and 102 in the ineffective group. A total of 293 CRO strains were cultured. The clinical efficacy rate of colistin sulfate was 54.87%, the microbiological efficacy rate 46.46%, and the hospital mortality rate 20.80%, with nephrotoxicity observed in 11.50% of patients. Multifactorial analysis identified APACHE II scores and vasoactive drug use as independent predictors of ineffective treatment, while treatment duration and albumin levels predicted effective treatment. ROC analysis indicated that albumin levels > 34 g/L, APACHE II scores < 13, and treatment duration > 10 days correlated with better clinical efficacy.Conclusion: Colistin sulfate is both safe and effective in clinical settings. Factors such as treatment duration, albumin levels, APACHE II scores, and vasoactive drug use independently affect its clinical efficacy, providing valuable guidance for its informed clinical application.Keywords: colistin sulphate, carbapenem-resistant organism, clinical efficacy, influencing factors, safety evaluation

Qian-Er Wen,1 Liang Li,1 Rui-Qi Feng,1 De-Hui Li,2 Chang Qiao,1 Xiao-Song Xu,3 Yan-Jing Zhang2 1Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, Hebei Province, People’s Republic of China; 2Oncology Department II, The First Affiliated Hospital of Hebei University of Chinese Medicine (Hebei Province Hospital of Chinese Medicine), Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research, Shijiazhuang, Hebei Province, People’s Republic of China; 3Scientific research Center, The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: De-Hui Li; Yan-Jing Zhang, Email 258289951@qq.com; yanjing198107@163.comAbstract: Breast cancer is one of the most common malignant tumors in women in the world, and its incidence is increasing year by year, which seriously threatens the physical and mental health of women. Triple negative breast cancer (TNBC) is a special molecular type of breast cancer in which estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 are negative. Compared with other molecular types of breast cancer, triple-negative breast cancer (TNBC) has high aggressiveness and metastasis, high recurrence rate, lack of effective therapeutic targets, and usually poor clinical treatment effect. Chemotherapy was the main therapeutic means used in the past. With the advent of the immune era, immunotherapy has made a lot of progress in the treatment of triple-negative breast cancer (TNBC), bringing new therapeutic hope for the treatment of triple-negative breast cancer. This review combines the results of cutting-edge medical research, mainly summarizes the research progress of immunotherapy, and summarizes the main treatment methods of triple-negative breast cancer (TNBC) immunotherapy, including immune checkpoint inhibitors, tumor vaccines, adoptive immunotherapy and the application of traditional Chinese and western medicine. It provides a new idea for the treatment of triple negative breast cancer (TNBC).Keywords: breast cancer, triple negative breast cancer, immunotherapy, immune checkpoint inhibitors, tumor vaccine, adoptive immunotherapy

Tong Guo,1,2 Yuan Feng,1,2 Jingjing Zhou,1,2 Linghui Meng,1,2 Xuequan Zhu,1,2 Xu Chen,1,2 Le Xiao,1,2 Lei Feng,1,2 Ling Zhang,1,2 Yu-Tao Xiang,3,4 Yan-Jie Zhao,1,2 Gang Wang1,2 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 3Unit of Psychiatry, Department of Public Health and Medicinal Administration, Faculty of Health Sciences, Institute of Translational Medicine, University of Macau, Taipa, Macao SAR, People’s Republic of China; 4Centre for Cognitive and Brain Sciences, University of Macau, Taipa Macao SAR, People’s Republic of ChinaCorrespondence: Yan-Jie Zhao; Gang Wang, Email yzhao118@126.com; gangwangdoc@ccmu.edu.cnBackground: Understanding the dynamic relationship between depressive symptoms and quality of life (QOL) is essential in improving long-term outcomes for patients with Major Depressive Disorder (MDD). While previous studies often relied on cross-sectional data, there is a pressing need for stronger evidence based on longitudinal data to better inform the development of effective clinical interventions. By focusing on key depressive symptoms, such interventions have the potential to ultimately enhance QOL in individuals with MDD.Methods: This multi-center prospective study, conducted between 2016 and 2020, enrolled outpatients and inpatients diagnosed with MDD across twelve psychiatric hospitals in China. Longitudinal data on Patient Health Questionnaire – 9 (PHQ-9) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) was analyzed using an Extended Bayesian Information Criterion (EBIC) graphical least absolute shrinkage and selection operator (gLASSO) network model to explore the connections between depressive symptom changes and QOL changes. Flow network was applied to investigate relationships between individual symptom changes and overall QOL score change, as well as daily functional independence.Results: This study included 818 participants with complete data after 8-week antidepressant treatment. Apart from the overlapping items from PHQ-9 and Q-LES-Q-SF, the three edges between “mood” (delta-QLES2) and “anhedonia” (delta-DEP1), between “physical health” (delta-QLES1) and “sleep problems” (delta-DEP3), and between “physical health” (delta-QLES1) and “sad mood” (delta-DEP2) were the most strong bridges between the cluster of depressive symptoms alleviation and the cluster of QOL change. “Anhedonia” (delta-DEP1), “sad mood” (delta-DEP2) and “loss of energy” (delta-DEP4) had the highest bridge strength between the alleviations of depressive symptoms and the total score change of Q-LES-Q-SF. Anhedonia had the greatest connection with participants’ satisfaction with function in daily life.Conclusion: This study highlighted the potential for developing highly effective interventions by targeting on central symptoms, thereby to ultimately improve QOL for patients with MDD.Keywords: network analysis, patients with MDD, acute phase treatment, depressive symptoms, quality of life

Jomana W Alsulaiman,1 Khalid A Kheirallah,2 Ahmad Alrawashdeh,3 Tareq Saleh,4 Maha Obeidat,5 Yareen J Alawneh,2 Ziydoun Abu Sanad,5 Wajdi Amayreh,1 Rama J Alawneh2 1Department of Pediatrics, Faculty of Medicine, Yarmouk University, Irbid, Jordan; 2Department of Public Health and Family Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Allied Medical Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa, Jordan; 5Department of Pediatrics, Princess Rahma Teaching Hospital, Irbid, JordanCorrespondence: Jomana W Alsulaiman, Associate Professor of Pediatrics, Department of Pediatrics, Faculty of Medicine, Yarmouk University, Irbid, 21163, Jordan, Tel + 962 07 9941 2277, Email jomana.a@yu.edu.joBackground: Implementing allergy testing among children with a reported history of penicillin allergy could be challenging, particularly in developing countries with limited resources. This study screened and risk-stratified the likelihood of true penicillin allergy among children labeled with penicillin allergy in Jordan.Methods: A web-based survey, completed by parents, assessed history, type, and severity of penicillin allergic reactions, including age at diagnosis, symptoms, time to the reaction, reaction’s course and resolution, and received medical evaluation/testing. Low-risk allergic symptoms were defined as vomiting, diarrhea, headache, dizziness, itching, rash, cough, or runny nose without evidence of anaphylaxis or severe cutaneous reactions.Results: A total of 530 parents of “penicillin allergy”-labeled children completed the survey. Of these, 86.4% reported allergic reactions to penicillin and 13.6% reported avoidance of penicillin due to family history. Among the former, 52.2% were male, 67.3% were three years old or younger when the reported reaction was established, and 68.3% experienced exclusively low-risk symptoms. Overall, skin rash was the most reported symptom (86.0%). High-risk symptoms were reported in 31.5% of children. About two-thirds (64.0%) of children were reported to have experienced symptoms after the first exposure to penicillin. The most common indication for antibiotic use was a throat infection (63.8%). Asthma comorbidity was significantly higher among high-risk (24.8%) compared low-risk group (11.5%).Conclusion: In Jordan, many parent-reported penicillin allergic reactions seem to be clinically insignificant and unlikely to be verifiable, which can adversely affect patients’ care and antimicrobial stewardship. An appropriate clinical history/evaluation is a key step in identifying true immunoglobulin E-mediated allergic reactions and risk stratifying patients for either de-labeling those with obviously non‐immune–mediated reactions or identifying candidates for direct oral challenge test.Keywords: children, drug hypersensitivity, drug resistance, Jordan, penicillin resistance

Yong Chen,1 Mang He,1 Si-Jin Zhao,2 Yan-Juan Chen,1 Yong-Qiao Zhang,2 Xiao-Long Chen,2 Chuan-Jie Yang,2 Yu-Zhuo Luo,2 Kutty Selva Nandakumar,3 Zhou-Xiong Xing,4 Mei Tian1 1Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 2Undergraduate Students of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 3Docent, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; 4Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of ChinaCorrespondence: Mei Tian; Zhou-Xiong Xing, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi City, Guizhou Province, People’s Republic of China, Email 348820517@qq.com; xingzhouxiong111@126.comPurpose: To investigate the clinical value of adding Jin-gu-lian (JGL) capsules into rheumatoid arthritis (RA) treatment by examining its impact on disease activity and quality of life (QoL) through a real-world study (RWS).Patients and methods: RWS was conducted to compare the inflammatory markers, including IgM-RF, ESR, and CRP, between RA patients treated with only Western medicine (reference group) and Western medicine plus JGL (study group) during one-year follow-up. The clinical data was acquired from the hospital information system (HIS). Telephone call-based follow-up on QoL (SF-36) and accompanying symptoms, including gastrointestinal complaints, attacks of pneumonia, herpes zoster, URTIs, UTIs, and LTBIs. Finally, the anti-rheumatic drugs given to both groups were also compared. RWS was further validated for its feasibility by performing studies with hydroxychloroquine (HCQ) treatment, which is a commonly used anti-rheumatic drug for RA with mild effect.Results: The study group failed to show a significant effect on inflammatory markers, especially on the CRP levels, indicating no additional clinical value of supplementing with JGL. Similarly, at the endpoint, no significant differences between the two groups on QoL and related symptoms were observed. Our study suggests that the patients in the study group might need more anti-rheumatic drugs to fill the treatment insufficiency, and the application ratio of NSAIDs would be significantly higher than the reference group. By conducting this study on HCQ treatment, the positive aspects of controlling disease activity and reducing NSAIDs application were found, which demonstrates the utility of performing the RWS to evaluate the effect of JGL.Conclusion: Adding JGL did not significantly improve the clinical efficacy of RA treatment by this RWS. Folk herbal prescriptions such as JGL are suggested to underwent strict clinical trials before application.Keywords: real-world study, rheumatoid arthritis, traditional Chinese medicine, disease activity, hydroxychloroquine

Tsen-Pei Chen,1,2 Ying-Jia Lin,3 Yu-Lin Wang,4,5 Li-Min Wu,2,6 Chung-Han Ho3,7,8 1Department of Nursing, Chi Mei Medical Center, Tainan City, Taiwan; 2School of Nursing, Kaohsiung Medical University, Kaohsiung City, Taiwan; 3Department of Medical Research, Chi Mei Medical Center, Tainan City, Taiwan; 4Department of Physical Medicine and Rehabilitation, Chi Mei Medical Center, Tainan City, Taiwan; 5Department of Biomedical Engineering, National Cheng Kung University, Tainan,Taiwan; 6Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan; 7Department of Information Management, Southern Taiwan University of Science and Technology, Tainan City, Taiwan; 8Cancer Center, Taipei Municipal Wanfang Hospital, Taipei Medical University, Taipei, TaiwanCorrespondence: Li-Min Wu, School of Nursing, Department of Medical Research, Kaohsiung Medical University Hospital, No. 100, Shin-Chuan 1st Road., Sanmin District, Kaohsiung City, 807378, Taiwan, Email painting@kmu.edu.tw Chung-Han Ho, Department of Medical Research, Chi Mei Medical Center, No. 901, Chung Hwa Road, Yongkang Dist, Tainan City, 710, Taiwan, Email ho.c.hank@gmail.comBackground: Stroke survivors in post-acute care frequently experience physiological dysfunction and reduced quality of life. This study aims to assess the impact of the Post-Acute Care Interprofessional Collaborative Practice (PAC-IPCP) program across different care settings, and to identify sensitive tools for assessing physiological functions among post-acute stroke survivors.Methods: This retrospective study involved 210 stroke survivors in Taiwan. Participants who self-selection for their preferred between hospital care setting and home care setting under PAC-IPCP. Multiple assessment tools were utilized, including the Barthel Index (BI), Functional Oral Intake Scale (FOIS), Mini Nutritional Assessment (MNA), EQ-5D-3L, and Instrumental Activities of Daily Living (IADL). The logistic regression was used to estimate the odds ratios of various functional assessment tools between hospital and home care settings. Additionally, the area under the ROC curves was used to determine which functional assessment tools had higher accuracy in measuring the association between care settings.Results: Of the study population, 138 stroke survivors (65.71%) selection hospital care setting and 72 stroke survivors (34.29%) selection home care setting. The PAC-IPCP program was equally effective in both care settings for physical function status and quality of life improvements. Specifically, the BI emerged as the most sensitive tool for assessing care settings, with an adjusted OR of 1.04 (95% CI:1.02– 1.07, p < 0.0001; AUC = 0.7557). IPCP-based hospital and home care models are equally effective in facilitating improved functional outcomes in post-acute stroke survivors.Conclusion: The PAC-IPCP program is versatile and effective across care settings. The BI stands out as a robust assessment tool for physiological functions, endorsing its broader clinical application. Future studies should also consider swallowing and nutritional status for a more holistic approach to rehabilitation.Keywords: stroke, neurology, subacute care, recovery of function, health care

Yan-Jun Xiong,&ast; Yu Xiao,&ast; Lei Xie, Lei Gao, Yi Han, Peng-Fei Huang, Shuang Liu, Ya-Xue Liang, Hua Wang Department of Tuberculosis, Anhui Provincial Chest Hospital (Anhui Institute of Tuberculosis Control), Hefei, Anhui, 230022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Wang, Department of Tuberculosis, Anhui Provincial Chest Hospital (Anhui Institute of Tuberculosis Control), No. 392, Jixi Road, Hefei, Anhui, People’s Republic of China, Tel +86 13395694530, Email 1726553540@qq.comBackground: Linezolid (LZD) is a cornerstone medication in the treatment of drug-resistant tuberculosis (DR-TB). However, it frequently triggers adverse effects such as bone marrow suppression, optic neuropathy, and peripheral neuropathy, all of which can impact treatment outcomes and prognosis. Contezolid (CZD), a novel oxazolidinone antibiotic, exhibits comparable antimicrobial efficacy against Mycobacterium tuberculosis as LZD, but with potentially enhanced safety profiles.Case Presentation: This report presents five cases (Cases 1– 5) of LZD intolerance, wherein CZD served as an effective alternative treatment. In Cases 1– 3, LZD administration resulted in bone marrow suppression, primarily manifested as anemia. Transitioning to CZD therapy led to a rise and stabilization of hemoglobin (HGB) levels in Cases 1– 2, and a return to baseline values in Case 3. In Case 4, CZD treatment alleviated symptoms of LZD-induced peripheral neuritis, although complete resolution was not achieved, hinting at potential irreversibility of this type of peripheral neuropathy. In Case 5, direct CZD anti-TB therapy was initiated for recurrent leukopenia and neutropenia, resulting in no further severe myelosuppression and successful recovery.Conclusion: These case studies suggest that CZD could represent an effective and safe option for anti-TB therapy, especially for patients intolerant to LZD.Keywords: contezolid, linezolid, drug-resistant tuberculosis, myelosuppression, peripheral neuropathy

Yuan-Jie Liu,1,&ast; Jing-Xiao Li,1,&ast; Jie-Pin Li,1 Yi-Dou Hu,2 Zhi-Bin Ma,3 Wei Huang,1 Shen-Lin Liu,1 Xi Zou1 1Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, People’s Republic of China; 3Nanjing YOUMENG Biology Science and Technology Co. Ltd, Nanjing, Jiangsu, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi Zou; Shen-lin Liu, Email fsyy00670@njucm.edu.cn; lsljsszyy@126.comBackground: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, underscoring the need for novel therapeutic targets. This study aimed to elucidate the role of endoplasmic reticulum membrane protein complex subunit 1 (EMC1) in HCC progression and its therapeutic potential.Methods: Publicly available sequencing data and biopsy specimens were analyzed to assess EMC’s clinical value and functions in HCC. In vitro experiments validated EMC functions, and multiplex immunofluorescence analysis examined EMC-associated sorafenib resistance mechanisms. EMC1 expression was knocked down in HCC cell lines, followed by cell viability, wound healing, and transwell migration assays. Tumor growth and response to sorafenib treatment were evaluated in mouse models. Metabolomic analysis assessed changes in the TCA cycle.Results: EMC genes were aberrantly expressed in HCC, and high EMC1 expression correlated with poorer survival rates. EMC1 disruption enhanced HCC cells’ sensitivity to sorafenib, reducing cell viability, increasing apoptosis, and decreasing tumor size and weight. EMC1 maintained cancer cell stemness and promoted M2 macrophage infiltration. Metabolomic analysis revealed significant changes in the TCA cycle, indicating EMC1’s role in HCC metabolic reprogramming. Importantly, EMC1 is highly associated with sorafenib resistance, potentially linked to CTNNB1 mutation or activation.Conclusion: EMC1 plays a critical role in regulating the sorafenib resistance in HCC. Targeting EMC1 may improve HCC treatment efficacy.Keywords: endoplasmic reticulum membrane complex subunit 1, catenin beta 1, tumor stemness, M2 macrophage, sorafenib resistance

Xin-Rong Yang,1 Xin-Yi Zhang,1 Yi-Jia Xia,1 Jin Fu,1 Xiao-Xuan Lian,2 Xin-Ru Liang,2 Ying-Qi He,2 Zhuo-Hong Li1 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of ChinaCorrespondence: Zhuo-Hong Li, Email lizhuohong@cdutcm.edu.cnPurpose: Chemotherapy-induced peripheral neuropathy (CIPN) still lacks efficient therapeutic drugs. This study aimed to systematically evaluate the effects of Huangqi Guizhi Wuwu Decoction (HGWD) alone or combined with positive drugs on CIPN prevention and treatment.Methods: The PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure (CNKI), Wan Fang Data, China Science and Technology Journal (VIP) and Chinese Biomedical (CBM) databases were searched for randomized controlled trials (RCTs) of HGWD for CIPN prevention and treatment. The search time ranged from database establishment to October 17, 2023. The Cochrane risk-of-bias assessment tool was used for quality assessment, Review Manager 5.3 and STATA 12.0 were used for meta-analysis, and GRADEprofiler was used for evidence level assessment.Results: A total of 32 RCTs involving 1987 patients were included. The meta-analysis results revealed the following: 1. In terms of the total CIPN incidence, that in the HGWD group was lower than that in the blank control group. The incidence in both the HGWD and HGWD+positive drug groups was lower than that in the monotherapy-positive drug group. 2. In terms of the incidence of severe CIPN, that in the HGWD group was lower than that in the blank control and positive drug groups. There was no statistically significant difference between the HGWD+positive drug and positive drug groups. Sensitivity analysis revealed that the results of severe incidence in the HGWD group was lower than that in the positive drug group were unstable 3. HGWD did not increase the number of chemotherapy-related adverse events.Conclusion: HGWD can safely and effectively prevent CIPN, reduce symptoms, improve quality of life and reduce the impact of chemotherapy drugs on sensory nerve conduction. However, more high-quality RCTs are needed to compare the efficacy of HGWD with that of positive control drugs in preventing severe CIPN.Keywords: huangqi guizhi wuwu decoction, chemotherapy-induced peripheral neuropathy, chemotherapy-induced peripheral neurotoxicity, Chinese medicine, meta-analysis

Yun Wang,1 Jun Chen,1 Zheng-Yu Shen,1 Jie Zhang,2 Yu-Jie Zhu,1 Xu-Qiong Xia1 1Department of Dermatology, Shanghai Ninth People’s Hospital Affiliated Shanghai JiaoTong University School of Medicine, Shanghai, 200080, People’s Republic of China; 2The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaCorrespondence: Yu-Jie Zhu; Xu-Qiong Xia, Email zhuyujie@sh9hospital.org.cn; xiaxuqiong@outlook.comIntroduction: Both rheumatoid arthritis (RA) and rosacea represent common chronic systemic autoimmune conditions. Recent research indicates a heightened RA risk among individuals with rosacea. However, the molecular mechanisms linking these diseases remain largely unknown. This study aims to uncover shared molecular regulatory networks and immune cell infiltration patterns in both rosacea and RA.Methods: The gene expression profiles of RA (GSE12021, GSE55457), and the rosacea gene expression profile (GSE6591), were downloaded from Gene Expression Omnibus (GEO) databases, and obtained to screen differentially expressed genes (DEGs) by using “limma” package in R software. Various analyses including GO, KEGG, protein–protein interaction (PPI) network, and weighted gene co-expression network analyses (WGCNA) were conducted to explore potential biological functions and signaling pathways. CIBERSORT was used to assess the abundance of immune cells. Pearson coefficients were used to calculate the correlations between overlapped genes and the leukocyte gene signature matrix. Flow cytometry (FCM) analysis confirmed the most abundant immune cells detected in rheumatoid arthritis and rosacea. Receiver operator characteristic (ROC) analysis, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR were used to confirm biomarkers and functions.Results: Two hundred seventy-seven co-expressed DEGs were identified from these datasets. Functional enrichment analysis indicated that these DEGs were associated with immune processes and chemokine-mediated signaling pathways. Fourteen and 17 hub genes overlapped between cytoHubba and WGCNA were identified in RA and rosacea, respectively. Macrophages and dendritic cells were RA and rosacea’s most abundant immune cells, respectively. The ROC curves demonstrated potential diagnostic values of CXCL10 and CCL27, showing higher levels in the serum of patients with RA or rosacea, and suggesting possible regulation in the densities and functions of macrophages and dendritic cells from RA and rosacea, which were validated by FCM and qRT-PCR.Conclusion: Importantly, our findings may contribute to the scientific basis for biomarkers and therapeutic targets for patients with RA and rosacea in the future.Keywords: autoimmune disease, immune infiltration, macrophage, chemokine, diagnostic biomarkers

Jin-Wei Lin,1– 3 Pei-Ying Lin,1,2 Tse-Yao Wang,1,2 Ying-Ju Chen,1,2 David Hung-Tsang Yen,1– 5 Hsien-Hao Huang1– 3 1Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2Emergency Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 3Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 4Department of Nursing, Yuanpei University of Medical Technology, Hsinchu, Taiwan; 5Chang Bing Show-Chwan Memorial Hospital, Changhua City, TaiwanCorrespondence: Hsien-Hao Huang, Department of Emergency Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei, 112201, Taiwan, Email hhhuang@vghtpe.gov.twBackground: Frailty epitomizes the most complex consequence of an aging population. This study aimed to evaluate the impact of frailty, measured using the Clinical Frailty Scale (CFS), on outcomes of older people in an emergency department (ED).Methods: We conducted a prospective observational study enrolling patients aged 65 years and older in a medical center of Taiwan between March 8, 2021, and November 30, 2021. The primary outcome was 90-day mortality rate. Individuals were categorized into three groups based on the CFS scores. Logistic regression was employed to examine the influence of frailty on clinical outcomes following covariate adjustment. Survival analysis was conducted using Kaplan–Meier curves and Log rank tests.Results: A total of 473 individuals were included in the study, with a mean age of 82.1 years, and 60.5% of them were males. The 90-day mortality rate was 10.6%. Among these groups, the CFS score 7– 9 group had the highest 90-day mortality rate (15.9%), followed by the CFS score 4– 6 group (8.0%) and the CFS score 1– 3 group (7.1%). The multiple logistic regression analyses demonstrated a significant impact of CFS score on prognosis, with adjusted odd ratios of 1.24 (95% CI 1.06– 1.47) for 90-day mortality, 1.18 (95% CI 1.06– 1.31) for hospitalization, and 1.30 (95% CI 1.12– 1.52) for 180-day mortality. The Kaplan–Meier curves revealed a significantly higher 90-day mortality rate for patients with high CFS scores (Log rank tests, p = 0.019).Conclusion: In the older ED population, the severity of frailty assessed by the CFS emerged as a significant and important prognostic factor for hospitalization, 90-day mortality, and 180-day mortality.Keywords: frailty, emergency service, hospital, triage, mortality

Li-Ping Ou,&ast; Yong-Jian Liu,&ast; Shi-Tong Qiu,&ast; Chen Yang, Ji-Xin Tang, Xiao-Yu Li, Hua-Feng Liu, Zhen-Nan Ye Institute of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, and Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen-Nan Ye; Hua-Feng Liu, Email yezhennan12@mails.ucas.ac.cn; liuhf@gdmu.edu.cnAbstract: Metabolic reprogramming contributes to the progression and prognosis of various kidney diseases. Glutamine is the most abundant free amino acid in the body and participates in more metabolic processes than other amino acids. Altered glutamine metabolism is a prominent feature in different kidney diseases. Glutaminolysis converts glutamine into the TCA cycle metabolite, alpha-ketoglutarate, via a cascade of enzymatic reactions. This metabolic pathway plays pivotal roles in inflammation, maladaptive repair, cell survival and proliferation, redox homeostasis, and immune regulation. Given the crucial role of glutaminolysis in bioenergetics and anaplerotic fluxes in kidney pathogenesis, studies on this cascade could provide a better understanding of kidney diseases, thus inspiring the development of potential methods for targeted therapy. Emerging evidence has shown that targeting glutaminolysis is a promising therapeutic strategy for ameliorating kidney disease. In this narrative review, equation including keywords related to glutamine, glutaminolysis and kidney are subjected to an exhaustive search on Pubmed database, we identified all relevant articles published before 1 April, 2024. Afterwards, we summarize the regulation of glutaminolysis in major kidney diseases and its underlying molecular mechanisms. Furthermore, we highlight therapeutic strategies targeting glutaminolysis and their potential clinical applications.Keywords: glutamine, glutaminolysis, kidney diseases, therapeutic target

Yu-Xiang Deng,1,&ast; Yu-Jie Zhao,2,&ast; Qiao-Hong Nong,3 Hong-Mei Qiu,1 Qiao-Li Guo,1 Hui Hu1 1Department of Thyroid and Breast Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518000, People’s Republic of China; 2Department of Radiotherapy, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518000, People’s Republic of China; 3Department of Oncology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Hu, Department of Thyroid and Breast Surgery, Peking University Shenzhen Hospital, 1120 Lianhua Road, Shenzhen, 518000, People’s Republic of China, Tel +86-755-83923333, Email Sapphiretjmu@163.comBackground: The immune system appears to play a crucial role in how breast cancer responds to chemotherapy. In this study, we investigated a peripheral marker of immune and inflammation named the neutrophil to albumin ratio (NAR) to explore its potential relationship with pathological complete response (pCR) in locally advanced breast cancer patients who underwent neoadjuvant chemotherapy (NAC).Methods: We conducted a retrospective analysis of 212 consecutive breast cancer patients who received NAC. The NAR was calculated by examining the complete blood cell count and albumin level in peripheral blood before starting NAC. Through ROC curve analysis, we determined the optimal cutoff value for NAR as 0.0877. We used Pearson’s chi-square test or Fisher’s exact test to evaluate the relationship between NAR and pCR, as well as other clinical and pathological characteristics. Logistic regression models were employed for univariate and multivariate analyses.Results: The results of both univariate and multivariate logistic regression analyses showed that NAR was associated with tumor pathological regression. The NAR high group had a higher pCR rate compared to the NAR low group (OR 3.127 [95% CI 1.545– 6.328]; p = 0.002).Conclusion: According to this study, it was observed that patients with breast cancer who had high levels of NAR were more likely to achieve pCR when undergoing NAC.Keywords: breast cancer, neoadjuvant chemotherapy, pathological complete response, neutrophil to albumin ratio, predictive factors

Yuan-Kai Fu,1 Chi-chin Sun,2,3 Kuan-Jen Chen,1,3 Yu-Jr Lin,4 Chee-Jen Chang,4– 6 Shu-Chen Chang,4 Ming-Hui Sun1,3 1Department of Ophthalmology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Ophthalmology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 3College of Medicine, Chang Gung University, Taoyuan, Taiwan; 4Research Services Center for Health Information, Chang Gung University, Taoyuan, Taiwan; 5Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan; 6Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan, TaiwanCorrespondence: Ming-Hui Sun, Department of Ophthalmology, Linkou Chang Gung Memorial Hospital, No. 5, Fuxing Street, Guishan District, Taoyuan, 333, Taiwan, Tel +886-3-3281200 ext 8666, Fax +886-3-3287798, Email minghui0215@gmail.comStudy Objectives: To evaluate the association between obstructive sleep apnea (OSA) and dry eye disease (DED) and analyze the impact of Continuous Positive Airway Pressure (CPAP) on DED.Methods: This is a retrospective population-based case-control study. Patients who underwent polysomnography in Taiwan from March 1, 2009, to March 1, 2020, were identified from the database of a sleep center. Patients who were diagnosed with keratoconjunctivitis sicca or tear film insufficiency were included. Patients without data from Schirmer’s test, lacking tear break-up time values, or with a history of refractive surgery, Sjögren’s syndrome, ocular injuries, or a disability in eyelid closure were excluded. All patients with DED enrolled had DED in both eyes. OSA severity between patients with and without DED was compared.Results: In total, 86 patients with DED and 86 age-matched patients without DED were enrolled. Significant differences in apnea-hypopnea index values (patients with DED: 29.1 ± 23.4, patients without DED: 17.9 ± 20.2, P < 0.001), OSA severity (P < 0.001), and lowest oxygen saturation (P = 0.040) between patients with and without DED were observed. A multivariate logistic regression model indicated that the use of CPAP was independently associated with DED after adjustments for OSA severity. Patients undergoing CPAP were at greater risk of developing DED than those not undergoing CPAP (Odds ratio: 3.93, 95% confidence interval: 1.47– 10.49, P = 0.006).Conclusion: OSA severity is associated with DED and might be attributed to the use of CPAP.Keywords: dry eye disease, obstructive sleep apnea, continuous positive airway pressure

Yi-Chun Liu,1 Shuh-Kuan Liau,1 Cheng-Chieh Hung,1 Chao-Yu Chen,1 Yueh-An Lu,1 Yu-Jr Lin,2 Ya-Chung Tian,1 Yung-Chang Chen,1 Fan-Gang Tseng,3,4 Hsiang-Hao Hsu1 1Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Linkou Branch, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2Research Services Center for Health Information, from Chang Gung University, Taoyuan, Taiwan; 3Department of Engineering and System Science, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, Taiwan; 4Institute of Nano Engineering and Microsystems, National Tsing Hua University, Hsinchu, TaiwanCorrespondence: Hsiang-Hao Hsu, Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Linkou Branch, College of Medicine, Chang Gung University, No. 5 Fu-Shin Street, Guishan, Taoyuan, 333, Taiwan, Tel +886-3-328-1200 ext. 8181, Fax +886-3-3282173, Email hsianghao@gmail.comBackground: Listeriosis is caused by the facultative anaerobic bacterium Listeria monocytogenes. Infection from Listeria-contaminated food or water is the main etiology. If Listeria travels outside the intestines, it can cause invasive listeriosis, such as sepsis, meningitis, and meningoencephalitis. Invasive illness is especially dangerous for pregnant women and their newborns, elderly people, and people with compromised immune systems or medical conditions such as end-stage kidney disease (ESKD) patients receiving long-term dialysis.Purpose: Describe the manifestations and hospital outcomes of invasive listeriosis and identify the risk factors for in-hospital and one-year mortality in ESKD patients receiving long-term dialysis.Patients and Methods: This retrospective observational study examined hospitalized patient records at a Taiwanese tertiary medical center from August 1, 2000, to August 31, 2021. ESKD patients on chronic dialysis were identified with invasive listeriosis by blood culture and discharge diagnosis. Over 21 years, we accurately recorded 26 cases.Results: ESKD patients on chronic dialysis with invasive listeriosis have a poor prognosis. Only 53.8% of chronic dialysis patients with invasive listeriosis survived their first hospital episode. 42.3% of hospitalized ESKD patients with invasive listeriosis survived one year later. In univariate analysis, shock, tachypnea (RR ≥ 22), respiratory failure, qSOFA score ≥ 2, and lower initial platelet count were linked to greater in-hospital mortality rates.Conclusion: ESKD patients with invasive listeriosis have a grave prognosis. Our research reveals that an early blood sample for a bacterial culture may identify invasive listeriosis in chronic dialysis patients with fever, nausea or vomiting, confusion, and respiratory distress. This study is the first to identify a lower platelet count and qSOFA score ≥ 2 as markers of high-risk invasive listeriosis in ESKD patients.Keywords: chronic dialysis, ESKD, invasive listeriosis, qSOFA, outcome

Xian-Lin Wu,1,2,&ast; Hong-Yan Liu,1,&ast; Qiu-Hong Xiang,1 Zhuan Yin,3 Rong Zhou,1 Ye-Juan Wang,1 Bi-Yu Zhou,1 Fang Wang,1 Min Zhao,1 Mei Chen1 1Department of Obstetrics, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, 410007, People’s Republic of China; 2Department of Nursing, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, 410007, People’s Republic of China; 3Department of Neonatology, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, 410007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiu-Hong Xiang, Department of obstetrics, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, No. 416 of Chengnan Dong Lu, Yuhua District, Changsha, 410007, People’s Republic of China, Tel +18684888525, Email xqhong1313@163.comObjective: Labor induction during the late trimester of pregnancy is a common option of terminating pregnancy by inducing uterine contractions through medication or cervical mechanical dilation. However, there are few researches on the factors influencing the effectiveness of cervical ripening balloon combined with oxytocin in inducing labor. To explore factors affecting the efficacy of cervical ripening double balloon combined with oxytocin in labor induction.Methods: Using a convenient sampling method, this study retrospectively collected the clinical data of 230 pregnant women who underwent cervical ripening double balloon combined with oxytocin for labor induction in our hospital from September 2021 to August 2022. The included subjects were divided into a vaginal delivery group (n = 180) and a cesarean section group (n = 50) based on the delivery mode for comparing relevant indicators between the two groups.Results: The presence of acute chorioamnionitis (OR = 1.456, 95% CI: 1.257– 2.112), fetal distress (OR = 1.371, 95% CI: 1.331– 2.633), and the placement of cervical ripening balloon catheter for > 12h (OR = 1.563, 95% CI: 1.231– 3.263) were risk factors for successful application of cervical ripening double balloon combined with oxytocin for labor induction in pregnant women; while multi-gravidity (OR = 0.736, 95% CI: 0.455– 0.875) was a protective factor. In addition, evaluation of the predictive value revealed that acute chorioamnionitis, fetal distress, the placement of cervical ripening balloon catheter for > 12h, and gravidity all had certain predictive value for the failure of cervical ripening double balloon combined with oxytocin for labor induction, with the highest predictive value found through joint predictive (AUC: 0.931, 95% CI: 0.714– 0.811).Conclusion: Cervical ripening double balloon combined with oxytocin for labor induction may have a high success rate in multigravida. Acute chorioamnionitis, fetal distress, and prolonged placement of the balloon may have a negative impact on the success rate of cervical ripening double balloon combined with oxytocin for labor induction.Keywords: cervical ripening balloon, cervical ripening double balloon, labor induction, oxytocin

Sun-Hee Kim,1 Sun Young Jung,1 Yoonjung Kim,2 Yu-Jin Lee1 1College of Nursing, Research Institute of Nursing Science, Daegu Catholic University, Daegu, Republic of Korea; 2College of Nursing, Konyang University, Daejeon, Republic of KoreaCorrespondence: Yoonjung Kim, &num;209 College of Nursing, Konyang University, 158 Gwanjeodong-ro, Seo-gu, Daejeon, 35365, Republic of Korea, Tel +82 42 600 8583, Fax +82 42 600 3277 2850, Email ykim@konyang.ac.krPurpose: This study aimed to develop the Health Belief Model scale for premature birth prevention (HBM-PBP) and evaluated its psychometric properties in women of childbearing age.Methods: This study employed a cross-sectional design and included 724 women of childbearing age with intentions of future childbirth or in their first trimester of pregnancy. An item pool was formulated from the literature and in-depth interviews based on the health belief model. Content validation was conducted by experts and through cognitive interviews with women of childbearing age. Construct and concurrent validity and reliability were evaluated using factor analysis, Pearson’s correlation analysis, and Cronbach’s alpha.Results: The HBM-PBP consisted of 96 items, including perceived susceptibility (21 items, 5 subscales), severity (26 items, 5 subscales), benefits (27 items, 5 subscales), and barriers (22 items, 5 subscales). Convergent and discriminant validity were supported. The Cronbach’s alpha coefficient of the domains ranged from 0.87 to 0.94.Conclusion: The HBM-PBP is a valid and reliable measurement scale with good psychometric properties. It can be used to measure health beliefs in women, either as a whole or in individual domains. Health professionals can leverage the HBM-PBP to discern women’s health beliefs on premature birth, facilitating tailored interventions and educational efforts.Keywords: health belief model, premature birth, reproducibility of results, surveys and questionnaires, women

Yu Chen Xu,1,&ast; Qiu Qin Wang,1,&ast; Meng Yuan Chen,1 Yu Jie Gao,1 Jia Yi Wang,1 Hao Tian Ge,1 Heng Weng,1 Ju Ping Chen,2 Gui Hua Xu1 1School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2Department of Neurology, Changshu Hospital of Traditional Chinese Medicine, Suzhou, 215500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gui Hua Xu, School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Email 7115@njucm.edu.cn Ju Ping Chen, Department of Neurology, Changshu Hospital of Traditional Chinese Medicine, Suzhou, 215500, People’s Republic of China, Email 1523515573@qq.comPurpose: Pain is a common yet undertreated symptom of Parkinson’s disease (PD). This study investigated the effect of Gua Sha therapy on pain in patients with PD.Patients and Methods: A total of 56 PD patients with pain were randomized into either the experimental group (n=28), receiving 12 sessions of Gua Sha therapy, or the control group (n=28) without additional treatment. Participants underwent assessment at baseline, after the twelfth invention, and at the 2-month follow-up timepoints. The primary outcome was KPPS and VAS. Secondary outcomes included UPDRS I–III, PDSS-2, HADS, PDQ-39, and blood biomarkers (5-HT, IL-8, IL-10).Results: The experimental group reported a significant improvement in pain severity, motor functions, affective disorder, and sleep quality (P < 0.05). Furthermore, increasing trends in both 5-HT and IL-10, as well as decreasing trends in IL-8 were observed. No serious adverse events occurred.Conclusion: The preliminary findings suggest that Gua Sha therapy may be effective and safe for alleviating pain and improving other disease-related symptoms in PD patients.Keywords: Parkinson’s disease, pain, Gua Sha therapy, randomized controlled trial

Ting-Yu Hsu,1 Chi-Yung Cheng,1,2,&ast; I-Min Chiu,1,2 Chun-Hung Richard Lin,2 Fu-Jen Cheng,1 Hsiu-Yung Pan,1 Yu-Jih Su,3 Chao-Jui Li1,&ast; 1Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan; 3Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Chi-Yung Cheng; Chao-Jui Li, Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan, Tel +886-7-7317123 ext. 8415, Email qzsecawsxd@gmail.com; chaojui@cgmh.org.twBackground: The global aging population presents a significant challenge, with older adults experiencing declining physical and cognitive abilities and increased vulnerability to chronic diseases and adverse health outcomes. This study aims to develop an interpretable deep learning (DL) model to predict adverse events in geriatric patients within 72 hours of hospitalization.Methods: The study used retrospective data (2017– 2020) from a major medical center in Taiwan. It included non-trauma geriatric patients who visited the emergency department and were admitted to the general ward. Data preprocessing involved collecting prognostic factors like vital signs, lab results, medical history, and clinical management. A deep feedforward neural network was developed, and performance was evaluated using accuracy, sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC). Model interpretation utilized the Shapley Additive Explanation (SHAP) technique.Results: The analysis included 127,268 patients, with 2.6% experiencing imminent intensive care unit transfer, respiratory failure, or death during hospitalization. The DL model achieved AUCs of 0.86 and 0.84 in the validation and test sets, respectively, outperforming the Sequential Organ Failure Assessment (SOFA) score. Sensitivity and specificity values ranged from 0.79 to 0.81. The SHAP technique provided insights into feature importance and interactions.Conclusion: The developed DL model demonstrated high accuracy in predicting serious adverse events in geriatric patients within 72 hours of hospitalization. It outperformed the SOFA score and provided valuable insights into the model’s decision-making process. Keywords: explainable machine learning, deep learning algorithm, adverse events, mortality

Shi-Yuan Fan,1,&ast; Zi-Chi Zhao,1,&ast; Xing-Lv Liu,1 Ying-Gang Peng,1 Hui-Min Zhu,1 Shi-Fan Yan,2 Yan-Juan Liu,2 Qin Xie,2 Yu Jiang,2 Sai-Zhen Zeng1 1The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital), Changsha, Hunan, 410005, People’s Republic of China; 2Department of Emergency, Institute of Emergency Medicine, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, 410005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sai-Zhen Zeng, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital), 61 Jie-Fang West Road, Fu-Rong District, Changsha, Hunan, 410005, People’s Republic of China, Email 55445321@qq.com Yu Jiang, Department of Emergency, Institute of Emergency Medicine, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), 61 Jie-Fang West Road, Fu-Rong District, Changsha, 410005, People’s Republic of China, Email jiangyu@hunnu.edu.cnBackground: Globally, the subsequent complications that accompany sepsis result in remarkable morbidity and mortality rates. The lung is among the vulnerable organs that incur the sepsis-linked inflammatory storm and frequently culminates into ARDS/ALI. The metformin-prescribed anti-diabetic drug has been revealed with anti-inflammatory effects in sepsis, but the underlying mechanisms remain unclear. This study aimed to ascertain metformin’s effects and functions in a young mouse model of sepsis-induced ALI.Methods: Mice were randomly divided into 4 groups: sham, sham+ Met, CLP, and CLP+ Met. CLP was established as the sepsis-induced ALI model accompanied by intraperitoneal metformin treatment. At day 7, the survival state of mice was noted, including survival rate, weight, and M-CASS. Lung histological pathology and injury scores were determined by hematoxylin–eosin staining. The pulmonary coefficient was used to evaluate pulmonary edema. Furthermore, IL-1β, CCL3, CXCL11, S100A8, S100A9 and NLRP3 expression in tissues collected from lungs were determined by qPCR, IL-1β, IL-18, TNF-α by ELISA, caspase-1, ASC, NLRP3, P65, p-P65, GSDMD-F, GSDMD-N, IL-1β and S100A8/A9 by Western blot.Results: The data affirmed that metformin enhanced the survival rate, lessened lung tissue injury, and diminished the expression of inflammatory factors in young mice with sepsis induced by CLP. In contrast to sham mice, the CLP mice were affirmed to manifest ALI-linked pathologies following CLP-induced sepsis. The expressions of pro-inflammatory factors, for instance, IL-1β, IL-18, TNF-α, CXCL11, S100A8, and S100A9 are markedly enhanced by CLP, while metformin abolished this adverse effect. Western blot analyses indicated that metformin inhibited the sepsis-induced activation of GSDMD and the upregulation of S100A8/A9, NLRP3, and ASC.Conclusion: Metformin could improve the survival rate, lessen lung tissue injury, and minimize the expression of inflammatory factors in young mice with sepsis induced by CLP. Metformin reduced sepsis-induced ALI via inhibiting the NF-κB signaling pathway and inhibiting pyroptosis by the S100A8/A9-NLRP3-IL-1β pathway.Keywords: sepsis, pediatric, inflammation, pyroptosis, ALI

Wen Jing Sun,1,2 Yu Jin Liu1 1Department of Nursing Welfare, Changchun Humanities and Sciences College, Changchun, Jilin, 130117, People’s Republic of China; 2Department of Counseling Psychology, Dongshin University, Naju-si, Jeollanam, Republic of KoreaCorrespondence: Wen Jing Sun, Department of Nursing Welfare, Changchun Humanities and Sciences College, No. 1488, Boshuo Road, Jingyue National High-Tech Industrial Development Zone, Changchun City, Jilin, 130117, People’s Republic of China, Tel +8615904405614, Email 179403066@qq.comPurpose: The aim of this study was to investigate the sleep quality as well as the influence of social support on the sleep quality of elderly people in nursing homes in northeast China, and analyze the chain-mediating role of psychological adjustment and coping styles in social support and sleep quality, thereby to provide a scientific basis for the development of effective intervention measures in this direction.Patients and Methods: This study was conducted during January–March 2023 and adopted a cluster sampling method to select 5 elderly care institutions from across the Jilin, Liaoning, and Heilongjiang provinces in Northeast China. A questionnaire survey was conducted using the Self-mate General Situation Questionnaire, Pittsburgh Sleep Quality Index, Nursing Home Adjustment Scale for the Elderly, Social Support Rating Scale, and Medical Coping Modes Questionnaire. Statistical analysis methods, including ANOVA, logistic multi-factor regression, and Pearson’s correlation were employed in SPSS 26.0, while Amos 26.0 was used to build a structural equation model to analyze the interaction path and the mediating role between the variables.Results: The sleep quality of elderly individuals in elderly care institutions was relatively low 8.43(3.456). Social support of elderly individuals in elderly care institutions affected their sleep quality through i) both psychological adjustment and face-to-face coping style (B = 0.493, P < 0.001, 95% CI = 0.050– 0.122) and ii) both psychological adjustment and avoidance coping style (B = − 0.302, P < 0.001, 95% CI = − 0.119 to − 0.048). Psychological adjustment, confrontation coping, and avoidance coping played a mediating role in the sequential relationship between social support and the sleep quality of elderly individuals in elderly care institutions.Conclusion: Psychological adjustment and coping styles have a chain-mediating effect between social support and sleep quality of the elderly in northeast China’s elderly care institutions.Keywords: elderly care institutions, elderly people, sleep quality, psychological adjustment, social support, nursing

Ling Tang,1 Yu-Jia Wang,2 Yuan-Yuan Wang,2 Shu-Tong Li,3 Liang Kong,3 Xue-Tao Li,3 Ling-Ling Ma,1 Xiu-Xiu Liu1 1Department of Obstetrics and Gynecology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 2Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 3School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People’s Republic of ChinaCorrespondence: Ling-Ling Ma; Xiu-Xiu Liu, Department of Obstetrics and Gynecology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China, Email 826269013@qq.com; 1225949002@qq.comPurpose: Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration.Methods and Results: PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects.Conclusion: The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.Keywords: ovarian cancer, functional liposomes, paclitaxel, diosgenin, ROS-response, HA

Jin Wan, Yu Jie Liu, Wen Jun Zhou, Si Yuan Wu School of Economics and Management, East China Jiaotong University, Nanchang, Jiangxi, 330013, People’s Republic of ChinaCorrespondence: Jin Wan, Email 244022935@qq.comIntroduction: To investigate the impact of interpersonal sensitivity on the subjective well-being of accompanying children of migrant workers and the role of perception of exclusion and peer support in the process.Methods: A questionnaire survey was conducted among 304 migrant workers’ accompanying children and 501 urban children in grades 4– 9 in seven schools in Jiangxi Province, China. Hierarchical regression and bootstrap analysis were used.Results: Interpersonal sensitivity not only had a significant direct negative effect on the subjective well-being of migrant workers’ accompanying children (β= − 0.27, 95% CI = [− 0.37, − 0.17]), but also had an indirect effect through perception of exclusion (β= − 0.06, 95% CI = [− 0.11, − 0.03]). Peer support negatively moderated the relationship between interpersonal sensitivity and perception of exclusion (β= − 0.18, 95% CI = [− 0.28, − 0.08]) and the mediating effect of perceptions of exclusion between interpersonal sensitivity and subjective well-being (β = 0.06, CI = [0.02, 0.11]).Conclusion: The subjective well-being of migrant children is indeed lower than that of urban children, and one of the most important reasons is their higher interpersonal sensitivity. Interpersonal sensitivity not only directly reduces their subjective well-being, but also reduces it by triggering their perception of exclusion, while peer support can effectively mitigate this negative effect. Therefore, one way to improve the subjective well-being of these children is to reduce their excessive interpersonal sensitivity. Their parents should help them to adapt to urban life, to develop correct professional values and to deal correctly with “occupational stigma”, to overcome feelings of inferiority, while communities can create specialized activity centers to provide more social opportunities and psychological counseling services for these children.Keywords: migrant workers’ accompanying children, interpersonal sensitivity, perception of exclusion, peer support, subjective well-being

Xin-Mei Hu,1,&ast; Can-Can Wang,1,&ast; Yu Xiao,1 Yu Liu,1 Hong-Ri Huang,2 Peng Jiang,1 Ying-Kai Wang,1 Yun-Jin Lin,1 Liang-Cheng Li,3 Zhong-Quan Qi1 1Medical College, Guangxi University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Research and Development, Guangxi Taimei Rensheng Biotechnology Co., Ltd, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhong-Quan Qi, Guangxi University, Da-Xue-Dong Road No. 100, Xixiangtang District, Nanning, Guangxi Zhuang Autonomous Region, 530004, People’s Republic of China, Tel +8613806001271, Email yxyyz@gxu.edu.cn Liang-Cheng Li, Xiamen University, No. 4221-115, Rm 355, Xiang’an District, Xiang’an, Xiamen Fujian Province, 361102, People’s Republic of China, Tel +8618359206906, Email lchli2013@xmu.edu.cnPurpose: In recent years, exosomes have been proved to be used to treat many diseases. However, due to the lack of uniform quality control standards for exosomes, the safety of exosomes is still a problem to be solved, especially now more and more exosomes are used in clinical trials, and its non-clinical safety evaluation is particularly important. However, there is no safety evaluation standard for exosomes at present. Therefore, this study will refer to the evaluation criteria of therapeutic biological products, adopt non-human primates to evaluate the non-clinical safety of human umbilical cord mesenchymal stem cell exosomes from the general pharmacology and immunotoxicity, aiming at establishing a safety evaluation system of exosomes and providing reference for the clinical application of exosomes in the future.Methods: 3.85 × 1012 exosomes derived from human umbilical cord mesenchymal stem cells were injected into cynomolgus monkeys intravenously. The changes of general clinical conditions, hematology, immunoglobulin, Th1/Th2 cytokines, T lymphocytes and B lymphocytes, and immune organs were observed before and within 14 days after injection.Results: The results showed that exosomes did not have obvious pathological effects on the general clinical conditions, blood, coagulation function, organ coefficient, immunoglobulin, Th1/Th2 cytokines, lymphocytes, major organs, and major immune organs (spleen, thymus, bone marrow) of cynomolgus monkeys. However, the number of granulocyte-macrophage colonies in exosomes group was significantly higher than that in control group.Conclusion: To sum up, the general pharmacological results and immunotoxicity results showed that the injection of 3.85 × 1012 exosomes may have no obvious adverse reactions to cynomolgus monkeys. This dose of exosomes is relatively safe for treatment, which provides basis research for non-clinical safety evaluation of exosomes and provides reliable research basis for future clinical application of exosomes.Keywords: exosomes, cynomolgus monkeys, safety, immunotoxicity

Seunghee Bae,1 Sowon Bae,1 Hee Su Kim,1 Ye Jin Lim,1 Gyeongmi Kim,2 In-Chul Park,2 Kyeong A So,3 Tae Jin Kim,3 Jae Ho Lee1 1Department of Cosmetics Engineering, Konkuk University, Seoul, 05029, Republic of Korea; 2Division of Fusion Radiology Research, Korea Institute of Radiological & Medical Sciences, Seoul, 01812, Republic of Korea; 3Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul, 05030, Republic of KoreaCorrespondence: Jae Ho Lee, Department of Cosmetics Engineering, Konkuk University, Seoul, 05029, Republic of Korea, Email jaeho390@konkuk.ac.krBackground: Ovarian cancer is one of women’s malignancies with the highest mortality among gynecological cancers. Paclitaxel is used in first-line ovarian cancer chemotherapy. Research on paclitaxel-resistant ovarian cancer holds significant clinical importance.Methods: Cell viability and flow cytometric assays were conducted at different time and concentration points of deguelin and paclitaxel treatment. Immunoblotting was performed to assess the activation status of key signaling molecules important for cell survival and proliferation following treatment with deguelin and paclitaxel. The fluo-3 acetoxymethyl assay for P-glycoprotein transport activity assay and cell viability assay in the presence of N-acetyl-L-cysteine were also conducted.Results: Cell viability and flow cytometric assays demonstrated that deguelin resensitized paclitaxel in a dose- and time-dependent manner. Cotreatment with deguelin and paclitaxel inhibited EGFR and its downstream signaling molecules, including AKT, ERK, STAT3, and p38 MAPK, in SKOV3-TR cells. Interestingly, cotreatment with deguelin and paclitaxel suppressed the expression level of EGFR via the lysosomal degradation pathway. Cotreatment did not affect the expression and function of P-glycoprotein. N-acetyl-L-cysteine failed to restore cell cytotoxicity when used in combination with deguelin and paclitaxel in SKOV3-TR cells. The expression of BCL-2, MCL-1, and the phosphorylation of the S155 residue of BAD were downregulated. Moreover, inhibition of paclitaxel resistance by deguelin was also observed in HeyA8-MDR cells.Conclusion: Our research showed that deguelin effectively suppresses paclitaxel resistance in SKOV3-TR ovarian cancer cells by downregulating the EGFR and its downstream signaling pathway and modulating the BCL-2 family proteins. Furthermore, deguelin exhibits inhibitory effects on paclitaxel resistance in HeyA8-MDR ovarian cancer cells, suggesting a potential mechanism for paclitaxel resensitization that may not be cell-specific. These findings suggest that deguelin holds promise as an anticancer therapeutic agent for overcoming chemoresistance in ovarian cancer. Keywords: ovarian cancer, paclitaxel-resistance, deguelin, EGFR, AKT

Xiaomei Cui,1,2 Ting Zhang,2 Tao Xie,2 Fang-xi Guo,2 Yu-ying Zhang,2 Yuan-jia Deng,2 Qi Wang,1,2 Yi-xing Guo,1,2 Ming-hua Dong,1,2 Xiao-ting Luo1,3 1Key Laboratory of Cardio Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China; 2School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China; 3School of General Medicine, Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Xiao-ting Luo, Golden Campus of Gannan Medical University, Zhanggong District, Ganzhou City, Jiangxi Province, People’s Republic of China, Tel +86 13677975578, Email xtluo76@163.comAbstract: Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut–brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations. Keywords: blood pressure, metabolites, gut-brain, treatment

Yan-jiao Zhang,1 Chao Huang,2 Xiu-guang Zu,1 Jin-ming Liu,1 Yong-jun Li1 1Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 2Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, People’s Republic of ChinaCorrespondence: Yong-jun Li, Department of Cardiology, The Second Hospital of Hebei Medical University, Heping West Road No. 215, Shijiazhuang, 050000, People’s Republic of China, Tel +86 15803210938, Email liyongjunbgr@126.comObjective: Immunogenic cell death (ICD) is part of the immune system’s response to coronary artery disease (CAD). In this study, we bioinformatically evaluated the diagnostic and therapeutic utility of immunogenic cell death-related genes (IRGs) and their relationship with immune infiltration features in CAD.Methods: We acquired the CAD-related datasets GSE12288, GSE71226, and GSE120521 from the Gene Expression Omnibus (GEO) database and the IRGs from the GeneCards database. After identifying the immune cell death-related differentially expressed genes (IRDEGs), we developed a risk model and detected immune subtypes in CAD. IRDEGs were identified using least absolute shrinkage and selection operator (LASSO) analysis. Using a nomogram, we confirmed that both the LASSO model and ICD signature genes had good diagnostic performance.Results: There was a high degree of coincidence and immune representativeness between two CAD groups based on characteristic genes and hub genes. Hub genes were associated with the interaction of neuroactive ligands with receptors and cell adhesion receptors. The two groups differed in terms of adipogenesis, allograft rejection, and apoptosis, as well as the ICD signature and hub gene expression levels. The two CAD-ICD subtypes differed in terms of immune infiltration.Conclusion: Quantitative real-time PCR (qRT-PCR) correlated CAD with the expression of OAS3, ITGAV, and PIBF1. The ICD signature genes are candidate biomarkers and reference standards for immune grouping in CAD and can be beneficial in precise immune-targeted therapy.Keywords: bioinformatics, gene signature, immune infiltration, hub genes, immune grouping, immune-targeted therapy

Lu Zhu,1,&ast; Jing Li,1,&ast; Zhao-Qin Wang,1,2,&ast; Yun-Jia Gu,1 Guo-Na Li,3 Wen-Jia Wang,1 Guang-Bin Pen,1 Qi Li,1 Meng-Die Wu,1 Hui-Rong Liu,1,2 Yan Huang,1,2 Lu-Yi Wu1 1Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3School of Acupuncture, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu-Yi Wu, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Hongkou District, Shanghai City, 200437, People’s Republic of China, Email luyitcm@163.com Yan Huang, Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, No. 650 Wanping South Road, Xuhui District, Shanghai City, 200030, People’s Republic of China, Email huangyan@shutcm.edu.cnObjective: Moderate-to-severe pain is the most common clinical symptom in patients with hepatocellular carcinoma (HCC).This trial aimed to analyze the clinical efficacy of Transcutaneous electrical acupoint stimulation (TEAS) in patients of HCC with severe pain and provide a reliable reference for optimizing the clinical diagnostic and therapeutic strategies of HCC.Methods: A total of 104 eligible patients were randomly allocated to experimental and control groups in a ratio of 1:1.The treatment was administered for 1 week continuously. Patients in both groups were followed up 1 week after the end of the treatment.The primary outcome measure was the Numerical Rating Scale (NRS) score, whereas the secondary outcome measures included Brief Pain Inventory BPI-Q3, Q4, Q5 scores, analgesic dose, frequency of opioid-induced gastrointestinal side effects, Karnofsky Performance Status (KPS), Quality of Life Scale - Liver Cancer (QOL-LC), and Brief Fatigue Inventory (BFI) scores.Results: The NRS scores of experimental group was significantly lower after treatment and at the follow-up than baseline (average P< 0.01), there were also statistical differences between the groups at the above time points (average P< 0.01). BPI-Q3, -Q4, and -Q5 scores in the experimental group were decreased after treatment when compared with those before treatment (average P< 0.01). Furthermore, there were significant improvements of gastrointestinal side effects, KPS, QOL-LC and BPI in the experimental group after treatment, and the above results were statistically significant compared to the control group.Conclusion: 7-day TEAS treatment can significantly enhance the analgesic effect and maintain for the following week, also reduce the incidence of gastrointestinal side effects caused by opioids, and improve the quality of life of patients with moderate-to-severe HCC-related pain, which has reliable safety and certain clinical promotion value.Keywords: hepatocellular carcinoma pain, transcutaneous electrical acupoint stimulation, cancer pain, randomized controlled trial

Sheng-Kai Wang,1 Jia-Wei Cai,2 Yu Zhang,3 Ya-Jing Lin,4 Yi-Hui Yang2 1Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, People’s Republic of China; 2Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China; 3Department of Pathology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Clinical Laboratory, the First People’s Hospital of Wenling, Affiliated to Wenzhou Medical University, Taizhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yi-Hui Yang, Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, No. 365, Renmin East Road, Jinhua, 321000, People’s Republic of China, Tel/Fax +86 139 5848 5323, Email aoliao0211@163.comAbstract: Squamous cell carcinoma (SCC) in situ can occur on any skin or mucus surface and is more commonly found in elderly patients on areas of skin that have been sunburnt. Most previous case reports are from dermatologists, with few published reports from pathologists. In this study, three patients underwent pathological routine and auxiliary immunohistochemical (IHC) examination and were ultimately diagnosed with pagetoid SCC in situ – a different diagnosis from the initial clinical assessment. All three patients received a complete resection of the skin mass. After follow-up, as of June 2023, the patients had no tumour recurrence or metastasis. Pagetoid SCC in situ is a particular type of SCC in situ that has no specific features in clinical manifestations, gross diagnosis or histopathological sections. The final diagnosis depends on IHC staining. Pagetoid SCC in situ expresses EMA, CK5/6 and p63 but not CEA, CK8 or S-100, which are expressed in extramammary Paget’s disease. Pagetoid SCC in situ is usually only locally invasive, and the main treatment is complete surgical resection. The prognosis is related to human papillomavirus infection, surgical margin closure, disease location, tumour thickness and other factors.Keywords: pagetoid, pagetoid squamous cell carcinoma in situ

Yul Hee Kim,1 Han-Seul Kim,1 Hyeung Kyoo Kim,2 Soo Young Kim,2 Jeonghun Lee,2 You Chan Kim,1 Young Joon Park1 1Department of Dermatology, Ajou University School of Medicine, Suwon, Republic of Korea; 2Department of Surgery, Ajou University School of Medicine, Suwon, Republic of KoreaCorrespondence: Young Joon Park, Department of Dermatology, Ajou University Hospital, 164, World Cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-Do, Suwon, Republic of Korea, Tel +82-31-219-5187, Email aro@ajou.ac.krPurpose: Early intervention of surgical scars with a pulsed dye laser is known to effectively prevent pathologic scars. Despite multiple reports on the effectiveness of the treatment, very few studies have demonstrated its appropriate initiation timing. In this study, our objective was to determine the optimal timing for initiating laser treatment following thyroidectomy.Methods: This study retrospectively analyzed 91 patients undergoing pulsed dye laser treatment post-thyroidectomy, grouping them by treatment initiation timing. The patients underwent treatment at intervals of 3– 4 weeks with at least five sessions. Those with a high pliability score were injected with intralesional corticosteroids. The Antera 3D® skin imaging analyzer was used to assess biophysical parameters.Results: The total Vancouver Scar Scale score significantly reduced after treatment in all groups. The Vancouver Scar Scale score reduction rate was significantly higher after treatment in the group for which the treatment was initiated within 3 weeks of surgery. The pigmentation and erythema score analyzed by Antera 3D® was also lower in this group.Conclusion: Early intervention using a pulsed dye laser within 3 weeks of thyroidectomy can substantially inhibit pathological scar development, providing physicians with a guide for optimal treatment commencement.Keywords: hypertrophic scars, laser treatment of scar, scar, pulsed dye laser

Meng-Ru Zhang,1,2,&ast; Lin-Lin Fang,3,&ast; Yang Guo,1 Qin Wang,1 You-Jie Li,1 Hong-Fang Sun,1 Shu-Yang Xie,1 Yan Liang1 1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China; 2Department of Clinical Medicine, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China; 3RemeGen Co., Ltd, YanTai, ShanDong, 264000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Liang; Shu-Yang Xie, Department of Biochemistry and Molecular Biology, School of Basic Medicine, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China, Tel/Fax +86 535 6913335 ; +86 535 6913166, Email 18766567201@163.com; xieshuyang@bzmc.edu.cnAbstract: Cancer immunotherapy has emerged as a novel therapeutic approach against tumors, with immune checkpoint inhibitors (ICIs) making significant clinical practice. The traditional ICIs, PD-1 and PD-L1, augment the cytotoxic function of T cells through the inhibition of tumor immune evasion pathways, ultimately leading to the initiation of an antitumor immune response. However, the clinical implementation of ICIs encounters obstacles stemming from the existence of an immunosuppressive tumor microenvironment and inadequate infiltration of CD8+T cells. Considerable attention has been directed towards advancing immunogenic cell death (ICD) as a potential solution to counteract tumor cell infiltration and the immunosuppressive tumor microenvironment. This approach holds promise in transforming “cold” tumors into “hot” tumors that exhibit responsiveness to antitumor. By combining ICD with ICIs, a synergistic immune response against tumors can be achieved. However, the combination of ICD inducers and PD-1/PD-L1 inhibitors is hindered by issues such as poor targeting and uncontrolled drug release. An advantageous solution presented by stimulus-responsive nanocarrier is integrating the physicochemical properties of ICD inducers and PD-1/PD-L1 inhibitors, facilitating precise delivery to specific tissues for optimal combination therapy. Moreover, these nanocarriers leverage the distinct features of the tumor microenvironment to accomplish controlled drug release and regulate the kinetics of drug delivery. This article aims to investigate the advancement of stimulus-responsive co-delivery nanocarriers utilizing ICD and PD-1/PD-L1 inhibitors. Special focus is dedicated to exploring the advantages and recent advancements of this system in enabling the combination of ICIs and ICD inducers. The molecular mechanisms of ICD and ICIs are concisely summarized. In conclusion, we examine the potential research prospects and challenges that could greatly enhance immunotherapeutic approaches for cancer treatment.Keywords: antitumor therapy, immunogenic cell death, co-delivery, immune-checkpoint inhibitors, stimulus-responsive nanocarriers

Yu-Jie Jiang,1,2 Ye-Ming Cao,1 Yong-Bing Cao,1 Tian-Hua Yan,2 Cheng-Lin Jia,1 Ping He1 1Institute of Vascular Anomalies, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 200082, People’s Republic of China; 2Department of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211100, People’s Republic of ChinaCorrespondence: Cheng-Lin Jia; Ping He, Institute of Vascular Anomalies, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 200082, People’s Republic of China, Tel/Fax +1 522 136 9352 ; +1 301 693 1191, Email jiachengling0716@126.com; 3322092025@stu.cpu.edu.cnAbstract: Alcoholic fatty liver disease (FALD) and non-alcoholic fatty liver disease (NAFLD) have similar pathological spectra, both of which are associated with a series of symptoms, including steatosis, inflammation, and fibrosis. These clinical manifestations are caused by hepatic lipid synthesis and metabolism dysregulation and affect human health. Despite having been studied extensively, targeted therapies remain elusive. The Cytochrome P450 (CYP450) family is the most important drug-metabolising enzyme in the body, primarily in the liver. It is responsible for the metabolism of endogenous and exogenous compounds, completing biological transformation. This process is relevant to the occurrence and development of AFLD and NAFLD. In this review, the correlation between CYP450 and liver lipid metabolic diseases is summarised, providing new insights for the treatment of AFLD and NAFLD.Keywords: CYP450, liver metabolism, lipid accumulation, monooxygenases, alcoholic fatty liver disease, non-alcoholic fatty liver disease

Yen-Jen Chen,1,2,&ast; Ming-Che Chang,3,&ast; Kai-Ming Jhang,4,&ast; Wen-Fu Wang,4,&ast; Yi-Cheng Liao1 1Department of Psychiatry, Changhua Christian Hospital, Changhua, Taiwan; 2Department of Psychiatry, Yuanlin Christian Hospital, Changhua, Taiwan; 3Department of Nuclear Medicine, Changhua Christian Hospital, Changhua, Taiwan; 4Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan&ast;These authors contributed equally to this workCorrespondence: Yi-Cheng Liao, Department of Psychiatry, Changhua Christian Hospital, 135, Nan-Xiao St, Changhua, 500, Taiwan, Tel +886 4 7238595 ext. 7160, Fax +886 4-7251004, Email 40202@cch.org.twBackground: To compare short-term cognitive outcomes among groups with and without neuropsychiatric symptoms (NPSs) or antipsychotic prescription and to determine which disease status or treatment modality is associated with relatively faster cognitive decline.Methods: We retrospectively analyzed a prospective cohort of patients diagnosed with dementia and mild cognitive impairment. All participants were evaluated using the Cognitive Abilities Screening Instrument (CASI) during their initial clinical assessments and at the annual follow-up. The dependent variable was annual delta CASI. Multivariate linear regression analysis was used to assess the degree of association between NPS, antipsychotic use, and cognitive decline after adjusting for confounding factors. Neuropsychiatric symptoms were examined individually to determine their predictive value for cognitive decline.Results: A total of 407 (N = 407) patients were included in the study. NPSs, rather than antipsychotic use, led to faster cognitive decline. A higher baseline NPI total score predicted a significantly faster decline in CASI scores (1-year delta CASI = − 0.22, 95% CI = − 0.38~ − 0.05, p = 0.010). Specific items (delusions, agitation, depression, anxiety, euphoria, and apathy) in the NPS significantly increased cognitive decline.Conclusion: Certain neuropsychiatric symptoms, rather than antipsychotic use, lead to faster cognitive decline in a dementia collaborative care model. Checking for and providing appropriate interventions for NPS in people with dementia and their caregivers are highlighted.Keywords: neuropsychiatric symptoms, antipsychotics, cognitive decline, cognitive abilities screening instrument, dementia collaborative care

Jian Zhou,1 Ya-Jie Li,2 Xiao-Dong Zhou,3 Li-Juan Wang1 1Department of Cardiology, The Heart Center, Zhe Jiang Hospital, Hangzhou, 310012, People’s Republic of China; 2Psychiatry Department, Fuyang District Third People’s Hospital, Hangzhou, 311400, People’s Republic of China; 3Department of Cardiology, The Heart Center, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325000, People’s Republic of ChinaCorrespondence: Jian Zhou, Department of Cardiology, Zhe Jiang Hospital, 12 Lingyin Road, Xihu Qu, Hangzhou, 310012, People’s Republic of China, Tel +86-517-8798-7373, Email zhoujian202211@163.comBackground: Rate-pressure product (RPP) calculated by multiplying heart rate by systolic blood pressure, is a convenient indicator closely associated with cardiac work or myocardial oxygen consumption. It has been reported to relate strongly to important indices of cardiovascular risk in patients with myocardial ischemia. However, its relationship with short- and long-term mortality in patients with acute coronary syndrome (ACS) undergoing primary PCI/immediate invasive strategy has not been defined.Methods: This study analyzed 1301 consecutive ACS patients who had undergone primary PCI, between January 2018 and September 2021. Patients with systolic BP < 90 mmHg were excluded to avoid the confounding effect of cardiogenic shock. RPP values were collected on admission and were divided into four groups: RPP ≤ 7.4, 7.4 ≤ 8.8, 8.8 < 8.8 < RPP8, and RPP > 10.8. Clinical endpoints were in-hospital cardiac and long-term all-cause mortality. The predictive performance was assessed by C-statistic, multivariate analysis and survival analysis.Results: Multivariate analysis showed that these in the highest vs lowest category of RPP (> 10.8 vs ≤ 7.4) had OR of 4.33 (95% CI=1.10 − 17.01; P = 0.036) in in-hospital cardiac mortality and 3.15 (95% CI=1.24 − 8.00; P = 0.016) in long-term all-cause mortality. In C-statistic analyses, RPP was a strong predictor in ACS, STEMI or UA/NSTEMI group for in-hospital cardiac mortality (AUC = 0.746, 95% CI = 0.722– 0.770, p < 0.001) and long-term all-cause mortality (AUC = 0.701, 95% CI = 0.675– 0.725, p < 0.001). The Kaplan–Meier event rate for long-term survival of RPP > 10.8 was significantly lower than that of RPP ≤ 10.8.Conclusion: RPP showed a positive association with in-hospital cardiac or long-term all-cause mortality in ACS patients undergoing primary PCI/immediate invasive strategy, and RPP > 10.8 can be as an independent predictor.Keywords: rate-pressure product, acute coronary syndrome, short-and long-term mortality

Huan-Huan Shen,1,2,&ast; Jie-Fei Peng,1,3,&ast; Ran-Ran Wang,4,&ast; Ping-Yu Wang,1,5 Jia-Xiang Zhang,1 Hong-Fang Sun,1 Yan Liang,1 Yan-Mei Li,6 Jiang-Nan Xue,7 You-Jie Li,1 Guang-Bin Sun,1,&ast; Shu-Yang Xie1,2,&ast; 1Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, 264003, People’s Republic of China; 2Shandong Laboratory of Advanced Materials and Green Manufacturing, Yantai, Shandong, 264000, People’s Republic of China; 3Department of Clinical Laboratory, the Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, People’s Republic of China; 4Institute of Rehabilitation Medicine, School of Rehabilitation Medicine, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China; 5Department of Epidemiology, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China; 6Department of Immune Rheumatism, Yantaishan Hospital, Yantai, Shandong, 264000, People’s Republic of China; 7Department of Immunology, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shu-Yang Xie; Guang-Bin Sun, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, 264003, People’s Republic of China, Tel +86 535 6913010 ; +86 535 6913335, Fax +86 535 6913163, Email xieshuyang@bzmc.edu.cn; bingo@bzmc.edu.cnPurpose: The drug resistance and low response rates of immunotherapy limit its application. This study aimed to construct a new nanoparticle (CaCO3-polydopamine-polyethylenimine, CPP) to effectively deliver interleukin-12 (IL-12) and suppress cancer progress through immunotherapy.Methods: The size distribution of CPP and its zeta potential were measured using a Malvern Zetasizer Nano-ZS90. The morphology and electrophoresis tentative delay of CPP were analyzed using a JEM-1400 transmission electron microscope and an ultraviolet spectrophotometer, respectively. Cell proliferation was analyzed by MTT assay. Proteins were analyzed by Western blot. IL-12 and HMGB1 levels were estimated by ELISA kits. Live/dead staining assay was performed using a Calcein-AM/PI kit. ATP production was detected using an ATP assay kit. The xenografts in vivo were estimated in C57BL/6 mice. The levels of CD80+/CD86+, CD3+/CD4+ and CD3+/CD8+ were analyzed by flow cytometry.Results: CPP could effectively express EGFP or IL-12 and increase ROS levels. Laser treatment promoted CPP-IL-12 induced the number of dead or apoptotic cell. CPP-IL-12 and laser could further enhance CALR levels and extracellular HMGB1 levels and decrease intracellular HMGB1 and ATP levels, indicating that it may induce immunogenic cell death (ICD). The tumors and weights of xenografts in CPP-IL-12 or laser-treated mice were significantly reduced than in controls. The IL-12 expression, the CD80+/CD86+ expression of DC from lymph glands, and the number of CD3+/CD8+T or CD3+/CD4+T cells from the spleen increased in CPP-IL-12-treated or laser-treated xenografts compared with controls. The levels of granzyme B, IFN-γ, and TNF-α in the serum of CPP-IL-12-treated mice increased. Interestingly, CPP-IL-12 treatment in local xenografts in the back of mice could effectively inhibit the growth of the distant untreated tumor.Conclusion: The novel CPP-IL-12 could overexpress IL-12 in melanoma cells and achieve immunotherapy to melanoma through inducing ICD, activating CD4+ T cell, and enhancing the function of tumor-reactive CD8+ T cells.Keywords: cancer immunotherapy, CaCO3 nanoparticle, interleukin-12, immunogenic cell death, tumor therapy

Xiao-Yu Xu,1,&ast; Yang Gao,2,&ast; Chuang-Shi Yue,3,&ast; Yu-Jia Tang,4,&ast; Zhao-Jin Zhang,5 Feng-Jie Xie,6 Hong Zhang,6 Yu-Cheng Zhu,7 Yan Zhang,7 Qi-Qi Lai,4 Xin-Tong Wang,4 Jia-Xi Xu,4 Jia-Ning Zhang,4 Bo-Wen Liu,4 Jian-Nan Zhang,4 Kai Kang4 1Department of Critical Care Medicine, The Second People’s Hospital of Beihai, Beihai, People’s Republic of China; 2Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 3Department of Critical Care Medicine, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 4Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 5Department of Critical Care Medicine, The Yichun Central Hospital, Yichun, People’s Republic of China; 6Department of Critical Care Medicine, The Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 7Department of Critical Care Medicine, The Hongxinglong Hospital of Beidahuang Group, Shuangyashan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian-Nan Zhang; Kai Kang, Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, People’s Republic of China, Tel +86-13836119816 ; +86-13904618016, Email zhangjiannan@hrbmu.edu.cn; janekk79@126.comPurpose: In this study, our objective was to investigate the potential utility of lymphocyte-C-reactive protein ratio (LCR) as a predictor of disease progression and a screening tool for intensive care unit (ICU) admission in adult patients with acute pancreatitis (AP).Methods: We included a total of 217 adult patients with AP who were admitted to the First Affiliated Hospital of Harbin Medical University between July 2019 and June 2022. These patients were categorized into three groups: mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP), based on the presence and duration of organ dysfunction. Various demographic and clinical data were collected and compared among different disease severity groups.Results: Height, diabetes, lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet count (PLT), D-Dimer, albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), glucose (GLU), calcium ion (Ca2+), C-reactive protein (CRP), procalcitonin (PCT), hospitalization duration, ICU admission, need for BP, LCR, sequential organ failure assessment (SOFA) score, bedside index for severity in AP (BISAP) score, and modified Marshall score showed significant differences across different disease severity groups upon hospitalization. Notably, there were significant differences in LCR between the MAP group and the MSAP and SAP combined group, and the MAP and MSAP combined group and the SAP group, and adult AP patients with ICU admission and those without ICU admission upon hospitalization.Conclusion: In summary, LCR upon hospitalization can be utilized as a simple and reliable predictor of disease progression and a screening tool for ICU admission in adult patients with AP.Keywords: lymphocyte-C-reactive protein ratio, acute pancreatitis, lymphocyte count, C-reaction protein, disease progression, ICU admission, screening tool

Min Liu, Yun-Jiao Duan, Ye Zhang, Jun Yang, Bing Wei, Junyu Wang Emergency Medicine Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, & Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Clinical Center for Medicine in Acute Infection, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Bing Wei; Junyu Wang, Email dr_weibing@126.com; wangjunyu_cyyy@126.comObjective: This study examines the effectiveness of MIP-3alpha and severity scores in determining the prognosis of elderly sepsis patients.Methods: From October 2020 to April 2021, a total of 171 elderly sepsis patients were admitted to the Emergency Department of the Shijingshan Branch of Beijing Chaoyang Hospital, Capital Medical University. According to the 28-day mortality rate, they were divided into two groups: survivors (48 cases) and deaths (123 cases). At admission, severity scores which are the Sequential Organ Failure Assessment (SOFA) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) were calculated. The logistic regression was used to analyze the independent risk factors associated with 28-day mortality in elderly sepsis patients. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the value of MIP-3alpha, SOFA, and APACHE II in the evaluation of 28-day mortality in elderly sepsis patients.Results: MIP-3alpha, SOFA and APACHE II of the death group were significantly higher than those of the survival group (P < 0.05). Multivariate logistic regression analysis showed that MIP-3alpha, SOFA, APACHE II, and systolic blood pressure (SBP) were independent risk factors for 28-day mortality of senile sepsis (P < 0.05). Analysis of the ROC curve revealed that MIP-3alpha, SOFA, APACHE II had predictive value for the 28-day prognosis of senile sepsis (all P < 0.01). Combing with MIP-3alpha and SOFA showed better predictive ability (Z1 = 3.733, Z2 = 2.996, both P < 0.01), compared to detecting MIP-3alpha and SOFA alone.Conclusion: In senile sepsis, MIP-3alpha, SOFA, APACHE II and SBP are independent risk factors for 28-day mortality. The combination of MIP-3alpha and SOFA can further enhance the predictive value of 28-day mortality in patients with senile sepsis and provide some reference value for the evaluation and treatment of senile sepsis.Keywords: sepsis, the elderly, MIP-3alpha, prognosis

Hsin-Ying Lin,1 Chung-Han Ho,2,3 Yu-Shiuan Lin,1 Shu-Chun Kuo,1,4 Yi-Chen Chen,2 Yung-Jen Cheng5 1Department of Ophthalmology, Chi Mei Medical Center, Tainan, Taiwan; 2Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; 3Department of Information Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 4Department of Optometry, Chung Hwa University of Medical Technology, Tainan, Taiwan; 5Department of Radiation Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanCorrespondence: Yung-Jen Cheng, Department of Radiation Oncology, National Cheng Kung University Hospital, No. 138, Sheng Li Road, Tainan, 704, Taiwan, Email n052337@mail.hosp.ncku.edu.twPurpose: Continuous advancements in medical diagnostic technology and the growing availability of resources suggest a potential for fluctuations in the incidence rate of retinoblastoma (Rb). This study aimed to analyze incidence data of Rb patients in Taiwan from 1999 to 2018, utilizing the nationwide Taiwan Cancer Registry (TCR) database. Additionally, we investigated the treatment modalities used for these Rb patients and compared them with those observed in other countries.Patients and Methods: We conducted a retrospective cohort study utilizing data from the TCR database. The study cohort comprised individuals who were newly diagnosed with Rb between 1999 and 2018. The incidence of Rb was calculated as the number of patients with Rb per million live births, both for the entire population and for different gender groups and time periods. The trends in Rb incidence from 1999 to 2018 across various age groups and sexes were presented with the linear trend test.Results: From 1999 to 2018, a total of 248 cases of Rb were identified. The overall incidence rate over this 20-year period was 60.20 cases per million live births, corresponding to 1 case per 16,611 live births. Incidence rates for each 5-year period between 1999 and 2018 exhibited no significant differences. The study cohort was predominantly male, with 134 cases (54.03%) being males and 114 cases (45.97%) being females, resulting in an overall male-to-female sex ratio of 1.18. Females had lower relative risk than males (RR: 0.92, 95% CI: 0.72– 1.19). Primary surgical intervention was the preferred treatment modality for over 75% of the cases.Conclusion: This retrospective epidemiology study, using TCR from 1999 to 2018, indicated that no discernible trend of retinoblastoma incidence in Taiwan. Nevertheless, continuous monitoring of incidence rates and exploration of treatment strategies for retinoblastoma within the Taiwanese population are important to address potential changes in developing medical practices.Keywords: retinoblastoma, incidence rate, treatment outcome, Taiwan cancer registry