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Since the first plasma realized in 2020, a series of key systems on HL-3 (known as HL-2M before) tokamak have been equipped/upgraded, including in-vessel components (the first wall, lower divertor, and toroidal cryogenic/water-cooling/baking/glow discharge systems, etc.), auxiliary heating system of 11 MW, and 28 diagnostic systems (to measure the plasma density electron temperature, radiation, magnetic field, etc.). Magnet field systems were commissioned firstly for divertor plasma discharges. During the 2nd experimental campaign of HL-3 tokamak, several great progresses have been achieved. Firstly, the successful operation with plasma current larger than 1 MA was achieved under a divertor configuration. Secondly, the advanced divertor concept with two distinct snowflake configurations was realized. It is found that the distribution of ion saturation current and heat flux on bottom plate becomes wide due to magnetic surface expansion, demonstrating the advantage of such configuration in the heat flux mitigation. In addition, using the combination of NBI, ECRH and LHCD, the standard sawtoothing high confinement mode of megampere plasma was firstly accessed on the HL-3. The successful commissioning of HL-3 is beneficial for the initial operation of ITER.

Minjie Jiang,1,2 Yulong Yang,2 Haoyan Wang1 1Department of Respiratory and Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100032, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Hebei Yanda Hospital, Langfang, Hebei, 065201, People’s Republic of ChinaCorrespondence: Haoyan Wang, Department of Respiratory and Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong’an Road, Xicheng District, Beijing, 100032, People’s Republic of China, Email haoyanw@126.comBackground: More studies have focused on the clinical value of the measurement of the neutrophil-to-lymphocyte ratio (NLR) in acute exacerbations of chronic obstructive pulmonary disease (AECOPD). This study aims to assess the stability of NLR in hospitalized AECOPD patients and its relationship with clinical prognosis.Methods: This retrospective observational study recruited patients hospitalized with AECOPD from January 2020 to December 2023. Using receiver operating characteristic curves, we determined the optimal NLR cutoff, categorizing NLR stability into four groups: persistent high (NLR ≥ 3.8), increased (NLR < 3.8 at admission but ≥ 3.8 at discharge), decreased (NLR ≥ 3.8 at admission but < 3.8 at discharge), and persistent low (NLR < 3.8). Adverse hospital outcomes included hospital mortality, transfer to the intensive care unit (ICU), invasive mechanical ventilation (IMV), and length of hospital stay (LOS) ≥ 14 days. The associations between NLR stability and these outcomes were analyzed using multivariable logistic regression and Cox hazard analysis.Results: Among 841 patients hospitalized for AECOPD, the mean age was 72.1± 9.5 years, with 644 males (76.6%) and 197 females (23.4%). The proportions and distribution for groups: persistent high, decreased, increased, and persistent low groups were 109 (12.9%), 175 (20.8%), 216 (25.7%), and 341 (40.5%), respectively. The persistent high group had the worst outcomes, including higher IMV use, ICU transfer, LOS > 14 days, and hospital cost, compared to the persistent low group. Compared to the persistent high group, the persistent low group (HR: 0.13; 95% CI: 0.10– 0.24) and the decreased group (HR: 0.40; 95% CI: 0.22– 0.73) are statistically significant for the risk of death, while the increased group (HR: 0.63; 95% CI: 0.37– 1.04) does not show a statistically significant difference.Conclusion: AECOPD patients who have persistent low NLR group face a low risk of adverse hospital outcomes and mortality after 6 months after discharge. The stability of NLR may serve as a novel biomarker for identifying AECOPD patients at increased risk of poor hospital outcomes.Keywords: neutrophil-to-lymphocyte ratio, acute exacerbations of chronic obstructive pulmonary disease, outcomes

Changqin Li, Li Zeng, Meiling Jiang Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Li Zeng, Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China, Tel +86-18980607090, Email zengli998@163.comBackground and Objective: Concealed penis (CP) is a condition involving a congenital abnormality of the external genitalia, wherein the penile shaft is partially or completely obscured by surrounding skin tissues, negatively affecting the psychological and physical health of children. The guardians, who are primarily responsible for the daily care of children, play a crucial role in the early detection of this condition. Therefore, this study aims to explore knowledge, attitude, and practices (KAP) toward CP among guardians of young boys; results would provide a theoretical basis for the development of health education programs.Methods: This web-based cross-sectional study was conducted among guardians of boys in the Department of Pediatric Surgery, local hospital between June 2023 and September 2023. A self-designed questionnaire was developed to collect demographic information of the guardians and to assess their knowledge, attitudes and practices toward CP.Results: A total of 394 questionnaires were collected. Among the guardians, 143 (36.29%) of them were male, 375 (95.18%) were the parents of the children, 279 (70.81%) had a junior college or bachelor’s degree, and 46 (11.68%) reported their children had CP. The knowledge, attitudes and practices scores were 4.00± 2.00 (possible range: 0– 7), 35.63± 3.40 (possible range: 9– 45), and 23.03± 6.97 (possible range: 9– 45), respectively. The structural equation model demonstrated that knowledge had direct effects on attitudes (β=0.63, p< 0.001), and practices (β=0.81, p< 0.001). Moreover, attitudes had direct effects on practices (β=0.43, p< 0.001).Conclusion: This study found insufficient knowledge, positive attitudes, but poor practices toward the CP in guardians of boys, especially among participants from rural areas of families with lower income. It is recommended to tailor educational initiatives and implement strategies to bridge the knowledge-practice gap toward concealed penis in boys.Keywords: knowledge. attitudes, practices, concealed penis, cross-sectional study

Zhengdong Yang, Xinyang Wang, Huiying Zhou, Minghan Jiang, Jinghui Wang, Bowen Sui The First Department of Oncology, Heilongjiang University of Chinese Medicine, Heilongjiang, 150040, People’s Republic of ChinaCorrespondence: Bowen Sui, The First Department of Oncology, Heilongjiang University of Chinese Medicine, Heilongjiang, 150001, People’s Republic of China, Email suibowen79@sina.comAbstract: Colorectal cancer (CRC) is a diverse disease entity and a leading cause of cancer-related mortality worldwide. CRC results from the accumulation of multiple genetic and epigenetic alterations. This heterogeneity of CRC underscores the significance of understanding its molecular landscape, as variations in tumor genetics can greatly influence both patient prognosis and therapeutic response. The molecular complexity of CRC is defined by three major carcinogenesis pathways: chromosomal instability (CIN), microsatellite instability (MSI), and the CpG island methylator phenotype (CIMP). These pathways contribute to the onset and progression of CRC through mutations, epigenetic modifications, and dysregulated cellular signalling networks. The heterogeneous nature of CRC continues to pose challenges in identifying universally effective treatments, highlighting the need for personalized approaches. Hence, the present review aims at unravelling the molecular complexity of CRC that is essential for improving diagnosis, prognostication, and treatment. We detail on the current understanding of the molecular framework of CRC, central signalling pathways of CRC associated with its initiation to a malignant phenotype, further invasion, progression, metastases, and response to therapy. Continued research into CRC’s pathways and biomarkers will pave the way for the development of more precise and effective therapeutic strategies, ultimately improving patient outcomes.Keywords: colorectal cancer, molecular mechanisms, pathways, chromosomal instability, adenomatous polyposis coli, biomarkers

Man Zhang,1,2,&ast; Siman Nie,3,&ast; Ziwei Hai,2 Yixin Du,2 Menghan Jiang,4 Chunfeng Cai2 1Department of Oncology, The First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Wuhan University School of Nursing, Wuhan, Hubei, People’s Republic of China; 3Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 4Shandong University of Traditional Chinese Medicine College of Health Sciences, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunfeng Cai, Faculty of Wuhan University School of Nursing, Wuhan, Hubei, People’s Republic of China, Email 1660433132@qq.comAim: Chronic disease self-management is critical to disease prognosis and patient quality of life. Several psychological factors influence this process of self-management. In this background, the present study investigated the impact of illness perceptions and coping style on self-management in people with peritoneal dialysis (PD).Methods: The study is a cross-sectional study. From May 2022 to January 2023, a convenience sampling method was used to recruit 246 peritoneal dialysis patients. General information questionnaire, brief illness perception questionnaire, medical coping style modes questionnaire and the self-management scale for peritoneal dialysis patients were used in this study. We used SPSS 24.0 to analyze the data, and the statistical methods included descriptive analysis, single factor analysis, Pearson correlation analysis and multiple linear regression analysis.Results: A total of 246 patients were included in this study (93.89% response rate). Cognitive representations and emotional representations were 30.40, 14.18, respectively. However, illness comprehensibility was 2.87. Illness perceptions were negative significantly correlated with self-management. With regard to coping style, our patients were more likely to adopt avoidance and resignation coping style. Confrontation and avoidance were positively related to self-management, while acceptance-resignation was negatively related.Conclusion: Self-management of peritoneal dialysis patients needs to be improved. Age, female sex, monthly income, illness perceptions and coping style were independently associated with self-management.Impact: These findings suggest that interventions that improve illness perceptions and coping style should be explored to ultimately improve their self-management. For example, patients can be provided with psychological counseling so that they can face the disease correctly, and we should pay attention to the positive role of social support.Keywords: peritoneal dialysis, illness perception, coping style, self-management

Maomin Jiang,1,&ast; Yisong Yao,2,&ast; Xiaoqian Xia,3,&ast; Yang Kong,4 Nan Zhang5 1School of Public Affairs, Xiamen University, Xiamen, Fujiang, People’s Republic of China; 2School of The Fourth Clinical Medical College, Qingdao University, Yantai, Shangdong, People’s Republic of China; 3Department of Public Health, Environments & Society, London School of Hygiene & Tropical Medicine, London, UK; 4School of Health Management, Binzhou Medical University, Yantai, Shangdong, People’s Republic of China; 5Physical Education Department, Shandong Technology and Business University, Yantai, Shangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nan Zhang, Email zhangnansd@126.comBackground: This study aims to investigate the relationship between older adults’ perceived community services for the elderly (PCSE), life satisfaction (LS), and self-rated health (SRH).Methods: Data from four rounds of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2008 to 2018 were used. A total of 2454 older adults were obtained. Unconditional Least Squares (ULS) was used to measure PCSE, LS, and SRH growth trajectories without covariates. Finally, a mediating latent growth model was constructed using Mplus 8.3 to examine the mediating role of LS in the relationship between PCSE and SRH after adjusting for some demographic characteristics.Results: The results from the ULS method indicate that the intercepts and slopes for PCSE and LS are significantly negatively correlated (β1 = − 0.629, β2 = − 0.579, p < 0.001). Additionally, there is a significant positive correlation between the intercept and slope of health levels (β = 0.774, p < 0.001). Using a parallel growth model, significant regression coefficients were found between the intercept of PCSE and the intercepts of SRH and LS (β1 = − 0.335, β2 = 0.378, p < 0.01). Similarly, the regression coefficients between the slope of PCSE and the slopes of SRH and LS were also significant (β1 = − 0.532, β2 = 0.344, p < 0.01). Furthermore, the regression coefficient between the intercept of LS and the intercept of SRH was significant (β = 0.415, p < 0.001). The regression coefficient between the slope of LS and the slope of SRH was also found to be significant (β = 0.729, p < 0.001).Conclusion: It is essential to ensure adequate supply and accessibility of community services for older adults. LS especially is, and should be a promising target for assessing the quality of life and utilization of PCSE supply.Keywords: perceived community services for elderly, life satisfaction, Self-rated health, Latent growth model, older adults

Cheng Peng,1,2 Shiqi Kang,1,2 Meijun Jiang,1,2 Mingxi Yang,1,2 Xu Gong1,2 1Department of Hand and Podiatric Surgery, Orthopedics Center, The First Hospital of Jilin University, Jilin University, Changchun, 130021, People’s Republic of China; 2Jilin Province Key Laboratory on Tissue Repair, Reconstruction and Regeneration, The First Hospital of Jilin University, Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Xu Gong; Mingxi Yang, Email gongxu@jlu.edu.cn; yangmxchem@jlu.edu.cnBackground: The formation of adhesion after tendon injury represents a major obstacle to tendon repair, and currently there is no effective anti-adhesion method in clinical practice. Oxidative stress, inflammation, and fibrosis can occur in tendon injury and these factors can lead to tendon adhesion. Antioxidant carbon dots and ursolic acid (UA) both possess antioxidant and anti-inflammatory properties. In this experiment, we have for the first time created RCDs/UA@Lipo-HAMA using red fluorescent carbon dots and UA co-encapsulated liposomes composite hyaluronic acid methacryloyl hydrogel. We found that RCDs/UA@Lipo-HAMA could better attenuate adhesion formation and enhance tendon healing in tendon injury.Materials and Methods: RCDs/UA@Lipo-HAMA were prepared and characterized. In vitro experiments on cellular oxidative stress and fibrosis were performed. Reactive oxygen species (ROS), and immunofluorescent staining of collagens type I (COL I), collagens type III (COL III), and α-smooth muscle actin (α-SMA) were used to evaluate anti-oxidative and anti-fibrotic abilities. In vivo models of Achilles tendon injury repair (ATI) and flexor digitorum profundus tendon injury repair (FDPI) were established. The major organs and blood biochemical indicators of rats were tested to determine the toxicity of RCDs/UA@Lipo-HAMA. Biomechanical testing, motor function analysis, immunofluorescence, and immunohistochemical staining were performed to assess the tendon adhesion and repair after tendon injury.Results: In vitro, the RCDs/UA@Lipo group scavenged excessive ROS, stabilized the mitochondrial membrane potential (ΔΨm), and reduced the expression of COL I, COL III, and α-SMA. In vivo, assessment results showed that the RCDs/UA@Lipo-HAMA group improved collagen arrangement and biomechanical properties, reduced tendon adhesion, and promoted motor function after tendon injury. Additionally, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the RCDs/UA@Lipo-HAMA group increased; the levels of cluster of differentiation 68 (CD68), inducible Nitric Oxide Synthase (iNOS), COL III, α-SMA, Vimentin, and matrix metallopeptidase 2 (MMP2) decreased.Conclusion: In this study, the RCDs/UA@Lipo-HAMA alleviated tendon adhesion formation and enhanced tendon healing by attenuating oxidative stress, inflammation, and fibrosis. This study provided a novel therapeutic approach for the clinical treatment of tendon injury.Keywords: tendon adhesion, antioxidant, carbon dots, ursolic acid, liposomes, hydrogel

Minmin Jiang,1,&ast; Yongxia Xie,2,&ast; Ping Wang,1 Mengyu Du,3 Ying Wang,4 Shuxun Yan1 1Department of Endocrinology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3The First Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4Department of International Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuxun Yan; Ying Wang, Email ysx982001@163.com; wangying56994@126.comAbstract: Fibrosis leads to organ failure and death, which is the final stage of many chronic diseases. Triptolide (TPL) is a terpenoid extracted from the traditional Chinese medicine Tripterygium wilfordii Hook. F (TwHF). Triptolide and its derivatives (Omtriptolide, Minnelide, (5R)-5-hydroxytriptolide) have been proven to have a variety of pharmacological effects. This study comprehensively reviewed the antifibrotic mechanism of TPL and its derivatives, and discussed the application of advanced nanoparticles (NPs) drug delivery system in the treatment of fibrotic diseases by TPL. The results show that TPL can inhibit immune inflammatory response, relieve oxidative stress and endoplasmic reticulum stress (ERS), regulate collagen deposition and inhibit myofibroblast production to play an anti-fibrosis effect and reduce organ injury. A low dose of TPL has no obvious toxicity. Under pathological conditions, a toxic dose of TPL has a protective effect on organs. The emergence of TPL derivatives (especially Minnelide) and NPs drug delivery systems promotes the anti-fibrosis effect of TPL and reduces its toxicity, which may be the main direction of anti-fibrosis research in the future.Keywords: triptolide, derivatives, anti-fibrosis, nanoparticles

Peijun Li,1,&ast; Yingqi Wang,1,&ast; Yuanyuan Cao,2 Jiacheng Shi,1 Meiling Jiang,2 Xiaoyu Han,2 Linhong Jiang,1 Yidie Bao,1 Weibing Wu,2 Xiaodan Liu1,3,4 1School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Sports Rehabilitation, Shanghai University of Sport, Shanghai, 200438, People’s Republic of China; 3Institute of Rehabilitation Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 4Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodan Liu; Weibing Wu, Email hzhp403@126.com; wwb75@126.comBackground: Exercise is an indispensable component of pulmonary rehabilitation with strong anti-inflammatory effects. However, the mechanisms by which exercise prevents diaphragmatic atrophy in COPD (chronic obstructive pulmonary disease) remain unclear.Methods: Forty male C57BL/6 mice were assigned to the control (n=16) and smoke (n=24) groups. Mice in the smoke group were exposed to the cigarette smoke (CS) for six months. They were then divided into model and exercise training groups for 2 months. Histological changes were observed in lung and diaphragms. Subsequently, agonist U46639 and antagonist Y27632 of RhoA/ROCK were subjected to mechanical stretching in LPS-treated C2C12 myoblasts. The expression levels of Atrogin-1, MuRF-1, MyoD, Myf5, IL-1β, TNF-α, and RhoA/ROCK were determined by Western blotting.Results: Diaphragmatic atrophy and increased RhoA/ROCK expression were observed in COPD mice. Exercise training attenuated diaphragmatic atrophy, decreased the expression of MuRF-1, and increased MyoD expression in COPD diaphragms. Exercise also affects the upregulation of RhoA/ROCK and inflammation-related proteins. In in vitro experiments with C2C12 myoblasts, LPS remarkably increased the level of inflammation and protein degradation, whereas Y27632 or combined with mechanical stretching prevented this phenomenon considerably.Conclusion: RhoA/ROCK plays an important role in the prevention of diaphragmatic atrophy in COPD.Keywords: chronic obstructive pulmonary disease, diaphragmatic atrophy, exercise training, inflammation, RhoA/ROCK signaling

Min Jiang,1,&ast; Hui Zhang,2,&ast; Wenjun Lu,3 Xuedan Qiu,1 Chenyao Lin,1 Rongqing Zhao,1 Qingcao Li,1 Qiaoping Wu1 1Clinical Laboratory, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China; 2Clinical Laboratory, Ninghai County Chengguan Hospital, Ningbo, Zhejiang Province, People’s Republic of China; 3Intensive Care Units, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingcao Li; Qiaoping Wu, The Affiliated LiHuiLi Hospital of Ningbo University, 1111 Jiangnan Road, Ningbo, Zhejiang Province, 315040, People’s Republic of China, Tel +86-574-55835786, Fax +86-574-55835781, Email lqc_lab@163.com; lhlyywqp@163.comBackground: Klebsiella pneumoniae (KP) is a common nosocomial pathogen. Capsules are an important component of KP’s virulence, among which the K1, K2, K5, K20, K54, and K57 serotypes are predominant and exhibit varying degrees of virulence.Methods: The capsule and virulence genes of 150 carbapenem-resistant Klebsiella pneumoniae (CRKP) and 213 carbapenem-sensitive Klebsiella pneumoniae (CSKP) isolates were examined by polymerase chain reaction (PCR). The isolates were tested for hypermucoviscosity by string tests. Phylogenetic relationships between KP isolates were analyzed using multilocus sequence typing (MLST) and a Galleria mellonella infection model confirmed the differences in virulence.Results: A total of 111 of 363 isolates of KP were detected, the highest detected serotypes were K1, K5, and K2, and CSKP was detected more frequently than CRKP. There was a greater prevalence of K1 and K2 serotypes in CSKP, while in CRKP, K5 serotypes were more prevalent. K1 isolates had the highest detection rates for hypermucoviscosity Klebsiella pneumoniae (hmKP) and hypervirulent Klebsiella pneumoniae (hvKP), and carried the most virulence genes. K54 isolates had the lowest detection rate of hmKP while K5 isolates had the lowest detection rate of hvKP and carried the fewest virulence genes. MLST results for serotypes K1, K20, and K57 showed significant homogeneity, while those for serotypes K2, K5, and K54 showed diversity. The Galleria mellonella infection model showed that the K1 serotype was the most virulent and the K54 serotype was the weakest.Conclusion: CSKP isolates were detected more frequently than CRKP isolates for capsular serotype detection. K1 isolates had the most virulence gene and strongest virulence, K5 isolates carried the fewest virulence genes, and K54 isolates had the weakest virulence. Furthermore, significant homogeneity was observed among K1, K20, and K57 isolates.Keywords: Klebsiella pneumoniae, capsular serotypes, virulence, MLST

Meiling He,1 Chunfeng Liang,1 Yadan Pang,1 Mengjie Jiang,1 Meiying Long,2 Zhongqiang Yao,3 Xiaoting Wang,1 Ruijun Zhang,1 Qiaoyuan Wu,1 Shixiong Liang,1 Jianxu Li1 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of China; 2School of Public Health, Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Department of General Affairs, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of ChinaCorrespondence: Shixiong Liang; Jianxu Li, Tel +86 13917716605 ; +86 18878732921, Email shixliang@sina.com; lijianxu1236@163.comPurpose: The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti-PD1) showed preliminary efficacy in hepatocellular carcinoma (HCC). This study aimed to identify the prognostic factors and construct a nomogram to predict the overall survival (OS) of patients with advanced HCC after treatment with intensity-modulated radiotherapy (IMRT) plus anti-PD1.Patients and Methods: The OS and progression-free survival (PFS) of 102 patients with BCLC stage C HCC was analyzed using the Kaplan-Meier method. Potential independent prognostic factors were determined using univariate and multivariate Cox regression analyses. A nomogram was established to predict prognosis whose accuracy and reliability was verified by a calibration curve and area under the receiver operating characteristic curve (AUROC).Results: The median PFS and OS rates of the 102 patients with advanced HCC were 9.9 months and 14.3 months, respectively. Ninety-three patients were evaluated for efficacy, including five (5.38%) with complete response and 48 (51.61%) with partial response, with an overall response rate of 56.99%. Grade 3 and 4 adverse reactions (AEs) were observed in 32.35% of patients; no grade 5 AEs occurred. Multivariate Cox analysis revealed albumin and alpha-fetoprotein levels, neutrophil counts 3– 4 weeks after IMRT initiation, and platelet-to-lymphocyte ratio 3– 4 weeks after IMRT initiation to be independent prognostic factors. The nomogram model constructed using these factors had good consistency and accuracy with 1– 3 years AUROC of 78.7, 78.6, and 93.5, respectively.Conclusion: IMRT plus anti-PD1 showed promising efficacy and controllable adverse reactions in treating advanced HCC. The nomogram model demonstrated good reliability and clinical applicability.Plain Language Summary: The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti‑PD1) showed preliminary efficacy and manageable safety in HCC. We retrospectively evaluated the efficacy and safety of 102 patients with advanced HCC treated with intensity-modulated radiotherapy (IMRT) plus anti-PD1. The study shows that the combination showed promising efficacy with a median PFS and OS of 9.9 months and 14.3 months, respectively. The adverse reactions were controllable. The novel nomogram model established based on independent prognostic factors including albumin, alpha-fetoprotein, neutrophils count 3– 4 weeks after IMRT initiation and platelet-to-lymphocyte ratio 3– 4 weeks after IMRT initiation demonstrated good reliability.Keywords: hepatocellular carcinoma, advanced, intensity-modulated radiotherapy, antibody against programmed cell death 1, nomogram

Runbing Xu,1,&ast; Changhe Yu,2,&ast; Xinyu Zhang,1 Yipin Zhang,1 Mengfei Li,1 Bei Jia,1 Shiyan Yan,3 Miao Jiang1,4 1Hematology and Oncology Department, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, People’s Republic of China; 2Tuina and Pain Management Department, Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, People’s Republic of China; 3School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4School of Life Science, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Miao Jiang, School of Life Science, Beijing University of Chinese Medicine, Gongchen Street, Beijing, People’s Republic of China, Tel +8613511072205, Email doctorjiang@139.com Shiyan Yan, School of Acupuncture-Moxibustion and Tuina, Gongchen Street, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, Tel +8613521436209, Email yanshiyan0927@sina.comPurpose: To determine the efficacy and safety of a neuromodulation intervention regimen in the treatment of chemotherapy-induced peripheral neuropathy (CIPN).Patients and Methods: Systematic searches were conducted in seven English databases. Randomized controlled trials of all neuromodulation interventions (both invasive and non-invasive) for the treatment of CIPN were selected. Group comparisons of differences between interventions and controls were also made. We divided the outcomes into immediate-term effect (≤ 3 weeks), short-term effect (3 weeks to ≤ 3 months), and long-term effect (> 3 months).Results: Sixteen studies and 946 patients with CIPN were included. Among immediate-term effects, neuromodulation interventions were superior to usual care for improving pain (SMD=− 0.77, 95% CI − 1.07~ 0.47), FACT-Ntx (MD = 5.35, 95% CI 2.84~ 7.87), and QOL (SMD = 0.44, 95% CI 0.09~ 0.79) (moderate certainty); neuromodulation loaded with usual care was superior to usual care for improving pain (SMD=− 0.47, 95% CI − 0.71 ~ − 0.23), and QOL (SMD = 0.40, 95% CI 0.12 ~ 0.69) (moderate certainty). There were no statistically significant differences between the neuromodulation interventions regimen vs usual care in short- and long-term outcomes and neuromodulation vs sham stimulation from any outcome measure. There were mild adverse events such as pain at the site of stimulation and bruising, and no serious adverse events were reported.Conclusion: Neuromodulation interventions had significant immediate-term efficacy in CIPN but had not been shown to be superior to sham stimulation; short-term and long-term efficacy could not be determined because there were too few original RCTs. Moreover, there are no serious adverse effects of this therapy.Keywords: chemotherapy, peripheral neuropathy, neuromodulation, systematic review, meta-analysis

Zeyu Wu,1,&ast; Yan Li,1,&ast; Min Jiang,1 Lixuan Sang,2 Bing Chang1 1Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixuan Sang, Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China, Email sanglixuan2008@163.com Bing Chang, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China, Email cb000216@163.comBackground: Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal inflammatory disease. Selenium has been reported to have therapeutic potential in IBD. Selenium yeast is a common selenium supplement that is convenient to access. This study explored the effect of selenium yeast on dextran sulfate sodium- (DSS-)induced chronic colitis in mice.Methods: Mice were randomly divided into four groups: the control group, selenium yeast group, chronic colitis group, and chronic colitis+selenium yeast group (n=6). Mice were killed on the 26th day. The disease activity index (DAI) score and histological damage score were calculated. Cytokines, serum selenium, colonic tissue selenium, gut microbiota and their metabolites short-chain fatty acids (SCFAs) were evaluated.Results: Selenium yeast lowered IL-1β, IL-6, TNF-α, IL-17A, IL-22 and IFN-γ (P< 0.05). In addition, selenium yeast significantly elevated Turicibacter, Bifidobacterium, Allobaculum, Prevotella, Halomonas, Adlercreutzia (P< 0.05), and butyric acid (P< 0.05).Conclusion: Selenium yeast could improve DSS-induced chronic colitis in mice by regulating cytokines, gut microbiota and their metabolites.Keywords: selenium yeast, chronic colitis, gut microbiota, metabolism

Ran Sang,1,2 Manxue Jiang,1,2 Qiuju Zhao,2 Lingti Kong1,2 1Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 2School of Pharmacy, Bengbu Medical University, Bengbu, 233030, People’s Republic of ChinaCorrespondence: Lingti Kong, Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical University, 287 Changhuai Road, Longzihu District, Bengbu, Anhui, 233004, People’s Republic of China, Tel +865523086297, Email konglingtiklt7@126.comBackground: The excessive use of intravenous infusion in China was once a serious problem, but in recent years, attention has been paid to the phenomenon, and the government has implemented several policies to solve the problem, which has been gradually improved.Aim: This study focuses on evaluating the impact of ongoing interventions and improvements in outpatient intravenous infusion therapy.Methods: From January 2016 to December 2022, we conducted a study to gather annual data on intravenous infusion prescriptions. A data questionnaire, encompassing information on departments, clinical diagnosis, and infusion drugs, was developed for this purpose. We analyzed the changing trends of Top 10 clinical departments with higher intravenous infusion usage rates and Top 10 drugs used. We also evaluated the compliance of intravenous infusion prescriptions with management regulations and drug instructions, for further intervention in the future.Results: The analysis of intravenous infusion prescription rates revealed a gradual decrease from 10.89% to 5.63%. This reduction was statistically significant (P < 0.05). High levels of intravenous infusion use were consistently observed in emergency surgery and emergency medicine. Commonly administered drugs via infusion included antibacterial drugs, tumor medications, proton pump inhibitors, and injections of traditional Chinese medicine. Inappropriate prescriptions are often characterized by issues related to drug dosage, usage, indication, and selection. Trend analysis of unreasonable types revealed significant improvements in “Diagnosis incomplete/unwritten”, “Solvent selection”, “Dosing frequency”, and “Treatment without indication” (P < 0.05).Conclusion: The findings of this study indicate a gradual improvement in the situation regarding intravenous infusion. However, there are still prevalent instances of unreasonable practices that need to be addressed.Keywords: cross-sectional study, evaluation, analysis, intravenous infusion prescriptions, outpatient

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

Quantong Wu,1 Fuchao Xu,2 Jie Wang,3 Ming Jiang2 1Department of Anesthesiology, Nanjing Drum Tower Hospital Clinical College, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Emergency Department, Nanjing Drum Tower Hospital Clinical College, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Neurosurgery department, Nanjing Drum Tower Hospital Clinical College, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Ming Jiang, Department of Anesthesiology, Nanjing Drum Tower Hospital Clinical College, Nanjing Medical University, Gulou District, Nanjing, Jiangsu, People’s Republic of China, Email 2021122013@stu.njmu.edu.cnPurpose: To systematically evaluate the effectiveness and safety of ketamine in preventing propofol injection pain (PIP).Patients and Methods: The electronic databases including PubMed, Embase, Web of Science, and Cochrane Library were searched from their inception until 2 August 2023. Randomized controlled trials (RCT) comparing ketamine with placebo or other interventions to alleviate PIP in adults were included. Fixed-effects or random-effects models were used to calculate pooled risk ratios (RR) and corresponding 95% confidence intervals (CI) based on the heterogeneity of the studies included.Results: Thirteen RCTs involving 2105 patients were included. In terms of reducing the incidence of PIP, ketamine is more effective than placebo (RR = 0.43, 95% CI = [0.34, 0.55], P < 0.00001), lidocaine (RR = 0.70, 95% CI = [0.55, 0.90], P = 0.005), dexmedetomidine (RR = 0.52, 95% CI = [0.40, 0.66], P < 0.00001), and thiopental (RR = 0.25, 95% CI = [0.08, 0.83], P = 0.02). In reducing the incidence of severe PIP, ketamine is superior to placebo (RR = 0.12, 95% CI = [0.08, 0.19], P < 0.00001), and lidocaine (RR = 0.34, 95% CI = [0.21, 0.56], P < 0.0001), except dexmedetomidine (RR = 0.20, 95% CI = [0.04, 1.13], P = 0.07), and thiopental (RR = 0.33, 95% CI = [0.04, 3.10], P = 0.33). Compared with mixed injection, separate injection of ketamine and propofol showed no significant difference in the incidence of PIP (RR = 0.96, 95% CI = [0.31, 3.00], P = 0.95) and severe PIP (RR = 1.19, 95% CI = [0.07, 21.29], P = 0.90). Based solely on the reports from the studies included, subanesthetic doses of ketamine are generally safe in preventing PIP.Conclusion: A subanesthetic dose of ketamine can effectively and safely reduce the incidence of PIP and severe PIP in adults, and is more effective than lidocaine, dexmedetomidine, and thiopental.Registration: PROSPERO CRD42023455093.Keywords: ketamine, pain, injection, propofol, meta-analysis

Yin Li,1,&ast; Manling Jiang,2,3,&ast; Yongqi Wei,1,&ast; Xiang He,2 Guoping Li,2,&ast; Chunlai Lu,1 Di Ge1 1Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science & Technology, Taipa, Macao Special Administrative Region of China&ast;These authors contributed equally to this workCorrespondence: Chunlai Lu; Di Ge, Email lu.chunlai@zs-hospital.sh.cn; ge.di@zs-hospital.sh.cnBackground: The pyrimidine salvage pathway plays a critical role in tumor progression and patient outcomes. The roles of pyrimidine salvage pathway-related genes (PSPGs) in cancer, however, are not fully understood. This study aims to depict the characteristics of PSPGs across various cancers.Methods: An integrative pan-cancer analysis of six PSPGs (CDA, UCK1, UCK2, UCKL1, UPP1, and UPP2) was conducted using TCGA data, single-cell RNA sequencing datasets, and patient samples. Single-cell transcriptome analysis and RT-qPCR were used to validate the relation between UPP1 and cytokines. Flow cytometry was performed to validate the role of UPP1 in immune checkpoint regulation. The correlation between UPP1 and tumor associated neutrophils (TAN) were investigated and validated by single-cell transcriptome analysis and tissue microarrays (TMAs).Results: PSPGs showed low mutation rates but significant copy number variations, particularly amplifications in UCKL1, UPP1, and UCK2 across various cancers. DNA methylation patterns varied, with notable negative correlations between methylation and gene expression in UPP1. PSPGs were broadly up-regulated in multiple cancers, with correlations to clinical staging and prognosis. Proteomic data further confirmed these findings. Functional analysis revealed PSPGs’ associations with tumor proliferation, metastasis, and various signaling pathways. UPP1 showed strong correlations with the tumor microenvironment (TME), particularly with cytokines, immune checkpoints, and various immune cells. Single-cell transcriptome analysis confirmed these associations, highlighting UPP1’s influence on cytokine expression and immune checkpoint regulation. In esophageal squamous cell carcinoma (ESCC), UPP1-high tumor cells were significantly associated with immunosuppressive cells in the TME. Spatial analysis using TMAs revealed that UPP1+ tumor cells were predominantly located at the invasive margin and closely associated with neutrophils, correlating with poorer patient prognosis.Conclusion: Our study depicted the multi-dimensional view of PSPGs in cancer, with a particular focus on UPP1’s role in the TME. Targeting UPP1 holds promise as a potential strategy for cancer therapy.Keywords: pyrimidine salvage pathways, UPP1, microenvironment

Guancheng Ye,1,&ast; Ruiheng Miao,2,&ast; Jiaqi Chen,3 Jian Huang,4 Min Jiang2 1Department of Rheumatology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of TCM, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Dermatology, Beijing Hospital of Traditional Chinese Medicine, Beijing, People’s Republic of China; 4Department of Acupuncture, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Huang, Department of Acupuncture, Dongfang Hospital, Beijing University of Chinese Medicine, No. 6, Fangxingyuan District 1, Beijing, 100078, People’s Republic of China, Fax +86 10 67689713, Email xiamenhuangjian@sina.com Min Jiang, Department of TCM, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Beijing, 100038, People’s Republic of China, Fax +86 10 63926060, Email jiangmin545@bjsjth.cnObjective: Fibromyalgia (FM) is a prevalent chronic disorder characterized by widespread skeletal muscle pain. In recent years, complementary and alternative medicine (CAM) has increasingly been recognized for its potential in treating FM symptoms. This study aims to assess the efficacy of CAM therapies in mitigating the symptoms of FM.Methods: This systematic review was registered with INPLASY. A thorough search of both English and Chinese databases was undertaken from their inception until April 15, 2023. The search criteria focused on prospective controlled trials examining CAM therapies in FM patients. The statistical analysis employed mean values and standard deviations. Additionally, an evaluation of the literature’s quality and potential biases was conducted.Results: The search yielded 41 articles, encompassing 2877 FM patients and involving 20 different interventions. All studies were randomized controlled trials (RCTs). The results of the network meta-analysis (NMA) indicated that a combination of Acupuncture and Massage therapy, as well as Navel Needling therapy, effectively alleviated pain symptoms in FM patients. Furthermore, Abdominal Acupuncture and Electroacupuncture were found to be beneficial in improving patients’ mood and sleep quality.Conclusion: Acupuncture + Massage and Umbilical Acupuncture emerged as the most efficacious therapies in relieving pain symptoms in FM patients. Abdominal Acupuncture and Electroacupuncture demonstrated their effectiveness in enhancing mood and sleep quality. Overall, CAM therapies exhibited a high safety profile for patients with fibromyalgia.Keywords: complementary and alternative medicine, CAM, fibromyalgia, FM, effectiveness, network meta-analysis, NMA

Yang Liu,1 Xiaoyu Zhang,1 Mengyang Jiang,1 Yiqiang Zhang,1 Chenhui Wang,1 Yongxing Sun,1 Zhonghua Shi,2 Baoguo Wang1 1Department of Anesthesiology, Sanbo Brain Hospital, Capital Medical University, Beijing, 100093, People’s Republic of China; 2Department of Intensive Care Medicine, Sanbo Brain Hospital, Capital Medical University, Beijing, 100093, People’s Republic of ChinaCorrespondence: Baoguo Wang, Department of Anesthesiology, Sanbo Brain Hospital, Capital Medical University, No. 50 Xiangshan Yi-Ke-Song Road, Haidian District, Beijing, 100093, People’s Republic of China, Tel +86 13370185075, Email wangbg@ccmu.edu.cnBackground: Postoperative delirium (POD) is prevalent in craniotomy patients and is associated with high mortality. Sleep disturbances are receiving increasing attention from clinicians as associated risk factors for postoperative complications. This study aimed to determine the impact of preoperative sleep disturbances on POD in craniotomy patients.Methods: We recruited 130 patients undergoing elective craniotomy for intracranial tumors between May 1st and December 30th, 2022. Preoperative subjective sleep disturbances were assessed using the Pittsburgh Sleep Quality Index on the day of admission. We also measured objective perioperative sleep patterns using a dedicated sleep monitoring device 3 days before and 3 days after the surgery. POD was assessed twice daily using the Confusion Assessment Model for the Intensive Care Unit within the first week after craniotomy.Results: Preoperative sleep disturbances were diagnosed in 49% of the study patients, and POD was diagnosed in 22% of all the study patients. Sleep disturbances were an independent risk factor for POD (OR: 2.709, 95% CI: 1.020– 7.192, P = 0.045). Other risk factors for POD were age (OR: 3.038, 95% CI: 1.195– 7.719, P = 0.020) and the duration of urinary catheterization (OR: 1.246, 95% CI: 1.025– 1.513, P = 0.027). Perioperative sleep patterns (including sleep latency, deep sleep duration, frequency of awakenings, apnea-hypopnea index, and sleep efficiency) were significantly associated with POD.Conclusion: This study demonstrated that preoperative sleep disturbances predispose patients undergoing craniotomy to POD, also inferred a correlation between perioperative sleep patterns and POD. The targeted screening and intervention specifically for sleep disturbances during the perioperative period are immensely required.Keywords: postoperative delirium, preoperative sleep disturbances, craniotomy, sleep pattern, confusion assessment model for the intensive care unit, Pittsburgh Sleep Quality Index

Jinbao Huang,1,* Heng Weng,1,* Ling Ye,1 Meiqin Jiang,1 Yangyu Li,2 Hongyan Li3 1Department of Respiratory Medicine, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, People’s Republic of China; 2Department of Clinical Laboratory Medicine, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, People’s Republic of China; 3Department of Critical Care Medicine, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongyan Li, Department of Critical Care Medicine, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, No. 602 Middle 817 Road, Taijiang District, Fuzhou, 350004, People’s Republic of China, Email fjsrmyylhy@163.comBackground: To evaluate the clinical value of metagenomic next-generation sequencing (mNGS) in screening of lower respiratory tract infections (LRTIs) and human tumors.Methods: Human samples included bronchoalveolar lavage fluid (BALF), sputum, lung biopsy tissue, and peripheral blood from 188 patients who were admitted to our hospital between January 2020 and September 2022 were analyzed using mNGS for simultaneous pathogen and chromosome copy number variation (CNV) detection. Traditional microbial culture and comprehensive microbial test (CMT) were also conducted. The diagnostic efficiencies of the three methods (mNGS, traditional culture, and CMT groups) were compared.Results: Among the 188 patients, 149 (79.3%) were in the LRTIs group and 39 (20.7%) were in the non-LRTIs group. The diagnostic sensitivity and accuracy of the mNGS group were higher than those of the traditional culture and CMT groups (P < 0.001; P < 0.001; P < 0.001; P < 0.001), and the specificity was higher than that of the CMT group (P = 0.039) but lower than that of the traditional culture group (P = 0.006). The positive predictive values of the mNGS and traditional culture groups were higher than that of the CMT group (P = 0.004; P = 0.011). The negative predictive value of the mNGS group was higher than that of the CMT group (P = 0.003). In addition, all samples were subjected to simultaneous chromosome CNV detection, and 8% (15/188) were positive for CNV. Of the 15 patients, 10 were initially misdiagnosed as non-neoplastic diseases, with a misdiagnosis rate of 66.7% (10/15). The BALF CNV test was performed on 13 patients diagnosed with primary or metastatic lung cancer, with a positivity rate of 38.5%.Conclusion: The sensitivity and accuracy of pathogen diagnosis using mNGS were better than those of traditional culture and CMT. CNV detection is an important auxiliary diagnostic tool for cancer, particularly for screening occult tumors. Keywords: metagenomics, next-generation sequencing, respiratory infectious diseases, pathogen diagnosis, genomic instability

Min Jiang,1,&ast; NanNan Pang,2,&ast; Jing Wang,1 Zheng Li,1 Dan Xu,1 Jing Jing,1 Dan Chen,3 Fengsen Li,1 Jianbing Ding,4 Qifeng Li5 1Xinjiang Key Laboratory of Respiratory Disease Research, Traditional Chinese Medical Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830011, Xinjiang, People’s Republic of China; 2CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, People’s Republic of China; 3School of Public Health, Xinjiang Medical University, Urumqi, 830017, Xinjiang, People’s Republic of China; 4Department of Immunology, College of Basic Medicine, Xinjiang Medical University, Urumqi, 830011, Xinjiang, People’s Republic of China; 5Xinjiang Institute of Pediatrics, Xinjiang Hospital of Beijing Children’s Hospital, Children’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830011, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qifeng Li, Xinjiang Institute of Pediatrics, Xinjiang Hospital of Beijing Children’s Hospital, Children’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830054, People’s Republic of China, Tel +86-991 3056239, Fax +86-991 3056237, Email liqiqi521@sina.comBackground: Studying the potential etiology and pathogenesis of tuberculosis-associated chronic obstructive pulmonary disease (TOPD) from an autoimmunity perspective may provide insights into peripheral blood autoantibodies and immune cells, as well as their interactions.Methods: This study examined the serum autoantibody repertoire in healthy individuals, patients with chronic obstructive pulmonary disease (COPD), patients with pulmonary tuberculosis (TB), and TOPD patients using the HuProtTM protein chip. Autoantigens in the peripheral blood of TOPD patients were verified using ELISA assay. Various epitopes and immune simulation were predicted using bioinformatic methods. Flow cytometry was employed to detect macrophages(M&phis;), T cells, and innate lymphoid cells (ILCs) in the peripheral blood.Results: COPD patients displayed distinct alterations in their IgG and IgM autoantibodies compared to the other groups. GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses revealed that these autoantibodies were associated with regulating macrophages, T cells, and B cells. ELISA results confirmed the upregulation of expression of proliferating cell nuclear antigen (PCNA), Mitogen-Activated Protein Kinase 3 antigen (MAPK3), and threonine protein kinase 1 antigen (AKT1) proteins in the peripheral blood of TOPD patients. Bioinformatic analysis predicted multiple potential epitopes in Th, CTL, and B cells. Immune simulation results demonstrated that PCNA, MAPK3, and AKT1 can activate innate and adaptive immune responses and induce the expression of different cytokines, such as IFN-g and IL-2. Furthermore, data obtained from flow cytometry assay revealed an upregulation in the face of Th1 cells in the peripheral blood of TOPD patients.Conclusion: Tuberculosis infection can effectively induce autoimmune responses, contributing to increased expression of Th1 cells and associated cytokines, ultimately leading to immune dysregulation. Furthermore, the accumulation of pulmonary inflammatory response facilitates the progression of TOPD and is helpful for the clinical diagnosis and the development of targeted therapeutic drugs for this disease.Keywords: chronic obstructive pulmonary disease, COPD, autoantibody, autoimmunity, inflammatory phenotype

Mengwei Jiang Department of Anesthesiology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, 310014, People’s Republic of ChinaCorrespondence: Mengwei Jiang, Department of Anesthesiology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +8618767188937, Email Sasuke941@163.com

Jiangqin Tan,1,&ast; Wanxiang Zheng,2,&ast; Chen Xu,3 Xiaolong Qu,2 Jingxing Wu,3 Min Jiang,2 Haiyan Xu4 1Team 17, Group 5, School of Basic Medicine, Army Military Medical University, Chongqing, People’s Republic of China; 2Department of Cardiology, Southwest Hospital, Army Military Medical University, Chongqing, People’s Republic of China; 3Department of Military Psychology, School of Psychology, Army Military Medical University, Chongqing, People’s Republic of China; 4Experimental Research Center for Medical and Psychological Science, School of Psychology, Army Military Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiyan Xu, Army Military Medical University, No. 30, Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Email xhycq007@163.comAbstract: New approaches to medication adherence interventions are needed. This manuscript presents a highly structured protocol of a single-session solution-focused brief therapy (SFBT) for medication adherence intervention (SFBT-MAI) delivered by general providers. It conceptually integrates the procedure of tailored interventions, techniques of SFBT, and the four steps of Qitang Lin’ conceptualization of single-session SFBT. With specific techniques and examples to reduce operational difficulties, the SFBT-MAI includes two parts. The first part focuses on selecting non-adherent patients and clarifying their barriers to medication adherence. The second part focuses on individualized interventions with four steps: closing, hoping, empowering, and changing and acting. It is hoped that this work will improve the effectiveness of medication adherence interventions for patients with coronary heart disease and to promote the use of brief psychological interventions in clinical practice.Keywords: medication adherence, tailored intervention, psychological intervention, solution-focused brief therapy, general provider, coronary heart disease

Ling Qian,1,2,&ast; Wei Hu,3,&ast; Ming Jiang4 1School of Business, Jinhua Polytechnic, Jinhua, Zhejiang Province, People’s Republic of China; 2Jing Hengyi School of Education, Hangzhou Normal University, Hangzhou, Zhejiang Province, People’s Republic of China; 3School Office, Zhejiang Normal University, Jinhua, Zhejiang Province, People’s Republic of China; 4School of Psychology, Zhejiang Normal University, Jinhua, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Qian; Wei Hu, Email 453241285@qq.com; huwei@zjnu.cnPurpose: To examine the influence of social behavior on college students’ life satisfaction and the mediating effects of perceived social support and core self-evaluation.Methods: 779 college students were investigated with the online social behavior scale, life satisfaction scale, core self-evaluation scale and perceived social support scale.Results: Online social behavior significantly positively predicted the perceived social support and life satisfaction; Perceived social support significantly positively predicted the core self-evaluation and life satisfaction; Core self-evaluation significantly positively predicted life satisfaction; Perceived social support and core self-evaluation have a significant chain mediating effect between online social behavior and life satisfaction.Conclusion: This study confirmed the positive effects of online social behavior on college students, through improving college students’ level of perceived social support and core self-evaluation to increase life satisfaction.Keywords: online social behavior, life satisfaction, perceived social support, core self-evaluation

Jing Liao,1,2 Mengyao Jiang,1,2 Jiaxiu Liu,1,2 Xiaoyu Zhou,1,2 Zuyue Zhang,3 Qingmao Rao,4 Li Bai,5 Xiaorong Hou1,2 1College of Medical Informatics, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Medical Data Science Academy, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Chengdu Blood Center, Chengdu, 610041, People’s Republic of China; 4Educational Affairs Office, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610065, People’s Republic of China; 5Hospital of Zigong Mental Health Central, Zigong, Sichuan, People’s Republic of ChinaCorrespondence: Xiaorong Hou, Email xiaoronghou@cqmu.edu.cnBackground: E-consultation medical services have become popular globally, which offers patients more options, regardless of time or location. However, research indicates a prevalent issue with the communication quality in e-consultations, leading to sub-optimal patient experiences.Objective: This study aims to design an evaluation system for e-consultation quality. The developed scale guides operators in improving services and users in assessing their experience. It aids in selecting e-consultation services, saving costs, and assisting doctors in making informed decisions.Methods: This study combines existing scales, literature analysis, and expert consultation to form preliminary evaluation indicators. Fourteen experts were invited using stratified purposive sampling. Two rounds of Delphi method were conducted to exclude indicators that did not meet basic conditions. The final evaluation system was determined through expert discussions and revisions. The Analytic Hierarchy Process (AHP) quantified indicator weights.Results: Both rounds of the questionnaire saw compelling response rates of 100% (14 out of 14) and 92.86% (13 out of 14), respectively. Meanwhile, the Expert Authority Coefficient (Cr) was recorded at 0.89 and 0.88, respectively, while the Kendall Consistency Coefficient (Kendall W) for all level indicators fluctuated between 0.133 and 0.37 (P< 0.05). The ultimate indicator system formulated includes three primary indicators, ten secondary indicators, and thirty-two tertiary indicators. The highest to lowest weighted first-level indicators were ‘Joint Decision-Making between Doctors and Patients’ (0.6232), ‘Patient Responsiveness’ (0.2395), and “Interpersonal Relationship between Doctors and Patients” (0.1373). Weights for the second-level and third-level indicators were also determined.Conclusion: A scientific scale for e-consultation quality evaluation has been created, which effectively captures the essence of online medical communication and patient experiences. It enriches the theoretical framework for evaluating e-consultation quality, broadens perspectives in Internet medicine, provides practical guidance for network medical service managers and users and the development of the “Internet + medical health” service model.Keywords: e-consultation, quality assessment scale, doctor-patient relationship, medical staff, user perception

Tingting Hu,1,&ast; Nannan Pang,2,&ast; Zheng Li,1 Dan Xu,1 Jing Jing,1 Fengsen Li,1 Jianbing Ding,3 Jing Wang,1 Min Jiang1 1Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, 830000, People’s Republic of China; 2CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, People’s Republic of China; 3Department of Immunology, College of Basic Medicine, Xinjiang Medical University, Urumqi, 830000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wang; Min Jiang, Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, People’s Republic of China, Tel +86-13999908413 ; +86-13999162873, Email jingw_xj@163.com; 250579087@qq.comBackground: Excessive activation of M1 macrophages affects the chronic inflammatory response of the airways and leads to the development of chronic obstructive pulmonary disease (COPD). Therefore, it needs to be closely monitored and investigated. MAPK signaling pathway is involved in the activation of M1 macrophages, and N6-methyladenosine (m6A) is involved in the pathogenesis of COPD. However, it is unknown whether activation of the MAPK signaling pathway is mediated by m6A in M1 macrophages in COPD.Methods: The GEO data were analyzed using bioinformatics techniques to assess the differences between COPD and healthy individuals in the levels of M1 macrophages, their secreted cytokines, and m6A regulators. The MAPK signaling pathway was significantly enriched in the list of differentially regulated genes between COPD and healthy individuals. We further analyzed the correlation between M1 macrophages, m6A, and the MAPK signaling pathway. Next, blood samples from COPD and healthy individuals were collected and analyzed by using flow cytometry, ELISA, and RT-PCR. Western blotting was performed using CSE-induced THP-1 cells. COPD and healthy mice were used for Me-RIP sequencing and flow cytometry experiments. Validation of the results of the above bioinformatics analysis by molecular biology experiments and sequencing techniques.Results: We found that GEO data and blood specimens from COPD patients showed increased M1 macrophages, higher levels of IL-6 and TNF-α, and higher mRNA expression of key mediators of the MAPK signaling pathway (p38, ERK, and JNK). Western blotting showed increased expression of p38, ERK, and JNK in the CSE group. In contrast, the expression of m6A regulators was low. Also, M1 macrophages in COPD mice were hyperactivated and had reduced m6A modifications of p38, ERK, and JNK compared with control.Conclusion: m6A may be involved in M1 macrophage hyperactivation by regulating the MAPK signaling pathway, thereby influencing the development of COPD.Keywords: chronic obstructive pulmonary disease, COPD, N6-methyladenosine, m6A, M1 macrophages, mitogen-activated protein kinase signaling pathway, MAPK signaling pathway

Yan Sun,1,&ast; Jiayu Song,2,&ast; Xue Lan,1 Fei Ma,2 Mingyu Jiang,3 Chunming Jiang1,2 1Department of Neonatology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China; 2Department of Neonatology, Zhuhai Women and Children’s Hospital, Zhuhai, Guangdong, 519060, People’s Republic of China; 3Department of Pediatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunming Jiang, Department of Neonatology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, People’s Republic of China, Tel +86-13303601657, Fax +86 0451-53670428, Email chunming0451@163.comPurpose: The calcium-sensing receptor (CaSR) acts as a major modulator of tissue responses related to calcium homeostasis and expresses highly in the mammalian intestine. Endotoxemia tends to impair intestinal barrier function and poses significant obstacles in clinical treatment. This work is designed to decipher whether CaSR can protect lipopolysaccharide (LPS)-induced intestinal barrier dysfunction in neonatal rats by targeting intestinal metabolites.Patient and Methods: In this study, we utilized gas chromatography (GC) combined with liquid chromatography-mass spectrometry (LC-MS) to quantitatively analyze SCFAs and metabolites in fecal samples of 24 neonatal rats with LPS induced endotoxemia.Results: Our results showed that CaSR alleviated endotoxin damage to the intestinal tight junction structure and upregulated the levels of butyric acid, propionic acid, valeric acid, and isovaleric acid in short-chain fatty acids (SCFAs). Non-targeted metabolomics analysis indicated that CaSR improved intestinal metabolic disorders by regulating glycerophospholipid metabolism, α-linolenic acid metabolism, as well as sphingolipids metabolism.Conclusion: CaSR can alter intestinal microbiota metabolites, especially SCFAs, and improve intestinal barrier damage in neonatal rat endotoxemia.Keywords: calcium-sensing receptor, lipopolysaccharide, endotoxemia, short chain fatty acids, metabolomics