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Wenrui Ji,1,* Xiaomin Xie,1,* Guirong Bai,1 Yalei Fan,2 Yanting He,1 Li Zhang,1 Haiyan Zhou,1 Ling Li,1 Dan Qiang,1 Huan Li1 1Department of Endocrinology, the First People’s Hospital of Yinchuan, Yinchuan, 750001, People’s Republic of China; 2The Second Clinical Medical School of Ningxia Medical University, Yinchuan, 750001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaomin Xie, Department of Endocrinology, the First People’s Hospital of Yinchuan, Liqun West Street No. 2, Xingqing District, Yinchuan, Ningxia Hui Autonomous Region, 750001, People’s Republic of China, Tel +8613895189599, Email xxm2324@126.comPurpose: COVID-19 viral infection results in dysregulation of the complement system and a decrease in cortisol and adrenocorticotropin hormone (ACTH) levels. This study aimed to explore the complement system, as well as cortisol and ACTH responses in patients with post-COVID-19 conditions (PCC) and type 2 diabetes mellitus (T2DM).Patients and Methods: This study recruited 31 patients with PCC and T2DM (PCC-T2DM), 19 patients with PCC (PCC), 10 patients with T2DM (T2DM), and 10 healthy participants (control). Cortisol and ACTH in the PCC and PCC-T2DM groups were assessed using the insulin tolerance test. In the fasting state, serum samples were collected for proteomic analyses. Spearman correlation analysis was performed between proteins and cortisol, as well as between proteins and ACTH.Results: Cortisol and ACTH levels were consistently decreased in the PCC and PCC-T2DM groups. Proteomic analyses revealed that most of the differentially abundant proteins (DAPs) in the PCC vs control and PCC-T2DM vs T2DM were involved in the coagulation and complement cascade, and the essential complement C3 was significantly upregulated in the PCC and PCC-T2DM groups when compared to their controls. Additionally, complement-related DAPs in the PCC vs control and PCC-T2DM vs T2DM were significantly correlated with cortisol and ACTH levels. In comparing PCC-T2DM samples with PCC samples, we found that upregulated DAPs were linked to the complement system and other immune system, and most DAPs were negatively correlated with cortisol and ACTH.Conclusion: Our study revealed that T2DM exacerbated dysregulation of the complement system in patients with PCC, and significant correlations were present between complement protein levels and those of cortisol and ACTH. These results provide novel insights into the dysregulation of complement and endocrine hormones in patients with PCC and T2DM.Keywords: post-COVID-19 condition, type 2 diabetes mellitus, complement, cortisol, adrenocorticotropin hormone

Xiao Chen,* Yuanhe Fan,* Hongliang Tu,* Jie Chen Department of Orthopedics, The First People’s Hospital of Neijiang, Neijiang, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao Chen, Department of Orthopedics, The First People’s Hospital of Neijiang, Neijiang, Sichuan, People’s Republic of China, Email 342918992@qq.comObjective: Postoperative delirium (POD) commonly occurs in elderly individuals following hip fracture surgery, with unclear pathophysiological mechanism. Inflammation is a known factor affecting the onset of delirium. The current work aimed to examine the associations of preoperative immune inflammation-related indicators with POD occurrence in elderly cases following hip fracture surgery.Methods: The current retrospective cohort study included 437 elderly cases administered hip fracture surgery from January 2018 to December 2023. The clinicodemographic data and laboratory findings of all cases were retrospectively analyzed. Immune inflammation-related indicators were assessed, eg, MLR, NLR and PLR, as well as SII and SIRI. The bootstrap method was employed to assign cases at 7:3 to the training (48 and 258 cases in the POD and no-POD groups, respectively) and internal validation (13 and 118 cases in the POD and no-POD groups, respectively) cohorts. Next, LASSO, univariable and multivariable logistic regression analyses were applied to determine risk factors in the training cohort, based on which a nomogram model was built. The obtained nomogram was examined for accuracy by calibration plot analysis. Finally, the nomogram’s clinical value was assessed by decision curve analysis (DCA), followed by internal validation based on the training cohort.Results: Of all 437 cases, 61 developed POD, indicating a POD incidence of 13.96%. LASSO regression and multivariable analyses revealed preoperative SIRI independently predicted POD in the training cohort. The developed nomogram had an area under the curve (AUC) of 0.991 (95% CI 0.983~0.998) in the training cohort versus 0.986 (95% CI 0.966~1.000) in the validation cohort. Calibration curve analysis revealed nomogram-predicted and actual probabilities were in line. DCA demonstrated the novel nomogram could confer net benefits for POD prediction in elderly cases administered hip fracture surgery.Conclusion: The immune inflammation-related indicators SIRI could predict POD in elderly cases following hip fracture surgery.Keywords: postoperative delirium, hip fracture, elderly, immune inflammation related indicators, nomogram

Man Huang,1,2,* Yudi Jin,3,* Mengyuan Wang,2 Qiang Song,4 Yanjia Fan,1 Yu Zhang,1 Cheng Tian,1 Chi Zhang,1 Shengchun Liu1 1Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Breast Center, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Central Laboratory, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shengchun Liu, Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email liushengchun1968@163.comBackground: HER2-low breast cancer represents a distinct subgroup with unique clinical characteristics and treatment challenges. Nevertheless, it remains uncertain whether there exists a distinction in δKi67 between patients with HER2-low and HER2-zero statuses, and whether the prognosis varies among patients with differing HER2 statuses and δKi67.Methods: We conducted a multi-center retrospective study to investigate the correlation between alterations in Ki67 index following NAC and the prognosis among patients with HER2-low or HER2-zero breast cancer. 3 distinct cohorts comprising patients with HER2-negative breast cancer who underwent NAC were included. Comprehensive clinicopathological data were documented, with particular emphasis on evaluating changes in Ki67 index from baseline to post-NAC. These changes were then correlated with disease-free survival (DFS) through rigorous analysis.Results: Three cohorts, comprising 403, 315, and 72 patients respectively, were finally included. The study found that δKi67 did not show significant associations with other variables and were not identified as independent risk factors for survival. Nevertheless, across the three cohorts, following NAC, HER2-low breast cancer patients with δKi67 below the cut-off value demonstrated a better prognosis compared to those with δKi67 above the cut-off value. Additionally, their prognosis was also superior to that of HER2-zero breast cancer patients with δKi67 below the cut-off value.Conclusion: Our study demonstrates that HER2-low breast cancer patients with δKi67 values below the cut-off point after NAC are associated with improved prognosis. Monitoring δKi67 index and HER2 status may help identify patients who are likely to benefit from NAC and guide personalized treatment strategies.Keywords: HER2-low breast cancer, neoadjuvant chemotherapy, Ki67 index, prognosis, survival

Jing Su,1,&ast; Lina She,1,&ast; Yang Fan,1 Honghong Wang,2 Qiaorui Zhang,1 Jiao Zhang,1 Hongyun Ma1 1Department of Obstetrics and Gynecology, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Pathology, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongyun Ma, Department of Obstetrics and Gynecology, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, No. 301, Zhengyuan North Street, Jinfeng District, Yinchuan, 750002, Ningxia, People’s Republic of China, Tel +86-15378975354, Email mahongyun2021@163.comBackground: This study retrospectively analyzed the medical records of 200 patients with endometrial hyperplasia to predict the risk of concurrent endometrial cancer.Methods: Patients were categorized into either the endometrial cancer group or the endometrial hyperplasia group based on post-hysterectomy pathology. The investigation compared general information, tumor indices, fertility history, preoperative endometrial sampling methods, comorbidities, and clinical symptoms between the groups to identify risk factors for endometrial hyperplasia complicating endometrial cancer.Results: (1) Of the 200 patients, 68 (34.0%) were diagnosed with concurrent endometrial cancer post-hysterectomy. Among these, 60 (88.24%) had endometrioid adenocarcinoma, while 8 (11.76%) had other types. Stage I was identified in 58 patients (85.29%) and Stage II in 10 patients (14.71%). High differentiation was observed in 57 cases (83.82%), moderate differentiation in 7 cases (10.29%), and poor differentiation in 4 cases (5.89%), indicating that most endometrial cancers complicated by hyperplasia were early-stage, well-differentiated endometrioid carcinomas; (2) Univariate analysis revealed statistically significant differences in age, menopausal status, length of menopause, and preoperative endometrial pathology of severe atypical hyperplasia between the groups; (3) Multivariate analysis indicated significant differences for age ≥ 53.5 years (OR: 4.307, 95% CI: 2.018– 9.192, p < 0.05), menopausal status (OR: 5.250, 95% CI: 2.449– 11.252, p < 0.05), and severe atypical endometrial hyperplasia (OR: 4.817, 95% CI: 1.260– 18.419, p < 0.05); (4) Significant differences were observed among patients with endometrial hyperplasia when stratified by the presence of zero, one, two, or three high-risk factors.Conclusion: In conclusion, patients aged ≥ 53.5 years, those who are menopausal, and those with severe atypical endometrial hyperplasia preoperatively are at higher risk for endometrial cancer. The risk increases with the number of high-risk factors present in patients with atypical endometrial hyperplasia.Keywords: retrospective, endometrial hyperplasia, endometrial cancer, clinical features, high-risk factors, regression

Yuanna Zhou,&ast; Lin Han,&ast; Wuxing Zhang, Yujun Fan, Wenjian Liu, Muzi Liu, Yishan Fan, Xiaoyuan Qu&ast; School of Nursing and Health, Henan University, Kaifeng, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyuan Qu, School of Nursing and Health, Henan University, Jinming Avenue, Kaifeng City, Henan Province, People’s Republic of China, Email quxiaoyuan@henu.edu.cnPurpose: China has made considerable efforts to promote the development of maternal and child health (MCH) care since the new health system reform in 2009. This study aims to evaluate the trend and equity of MCH resources allocation in China from 2008 to 2020 and provide a reference for rational distribution of MCH resources.Methods: Data were collected from the China Health Statistics Yearbook and China Statistics Yearbook. The number of MCH hospitals, licensed (assistant) physicians, registered nurses and beds were selected for the measurement of the equity of MCH resources allocation. The Health Resource Agglomeration Degree and Theil index were used in evaluating MCH resource allocation equity and to compare differences among regions.Results: From 2008 to 2020, the average annual growth rates for MCH hospitals, beds, licensed (assistant) physicians, and registered nurses were 0.72%, 6.95%, 5.04%, and 9.57%, respectively. However, regional disparities in the equity of MCH resource allocation have been identified. Although the western region has shown growth in MCH resource allocation by geography, the agglomeration degree of the four indicators remains less than 1, significantly lower than the average value of greater than 2 in the eastern region. Additionally, the equity of human resource allocation in the western region is lower than the equity in the allocation of institutions. In the densely populated eastern region, the equity of MCH resource allocation by population is decreasing, with the agglomeration degree of all four indicators below 1 in 2020. The disparity in healthcare resource allocation within regions is the main cause of inequitable MCH resource allocation in China.Conclusion: The allocation of MCH resources in China has improved since 2009, however, geographic equity needs further improvement, particularly in densely populated regions. Population and geographic balances should be considered in the development and implementation of MCH resource allocation policies, and improving intraregional equity should be the focus.Keywords: maternal and child health, resources allocation, equity, health resource agglomeration degree, theil index

Zijuan Ma,1,&ast; Yunge Fan,1,&ast; Zhijun Yu,1 Wenxuan Wu,1 Xiangting Zhang,1 Huolian Li,1 Shaochen Zhao,2 Yang Li,3 Yuanyuan Li,4 Dongfang Wang,1 Fang Fan1 1Center for Studies of Psychological Application, School of Psychology, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, People’s Republic of China; 2Research Center for Guangdong-Hong Kong-Macao Policing Model Innovation, China People’s Police University, Guangzhou, People’s Republic of China; 3Department of Educational Psychology, Faculty of Education, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 4Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongfang Wang; Fang Fan, School of Psychology, South China Normal University, Shipai Road, Guangzhou, 510631, People’s Republic of China, Email wdfpsyc@126.com; fangfan@scnu.edu.cnPurpose: Although experimental psychopathology using PET, EEG, and fMRI is at the forefront of understanding the underlying mechanisms of sleep inertia, many questions concerning causality remain unanswerable due to ethical constraints and the use of small and heterogeneous samples in experimental methods. There is a pressing need for a novel perspective in a large and relatively homogeneous population to fully capture and elucidate longitudinal processes and dynamic causality that culminate in episodes of sleep inertia over time. Therefore, this study aimed to reveal the causal relationships between symptoms of sleep inertia across its distinct patterns.Patients and Methods: A total of 1636 intern nurses participated in the first survey (94.1% validity rate), then 1277 intern nurses were followed up (82.9% tracing rate). Symptoms of sleep inertia were self-reported using the Sleep Inertia Questionnaire. The cross-lagged panel network models were used to examine unique longitudinal relationships between symptoms of sleep inertia across distinct trajectories.Results: Four distinct trajectories of sleep inertia were established. Additionally, we found differences in those symptoms with the highest influence on other symptoms at the subsequent point across the networks of four trajectories, particularly, “Difficulty in concentrating” in the persistent-high group and “Feeling tense” in the deteriorating groups.Conclusion: The current study highlights changes in sleep inertia based on the long-term course over time. Notably, symptoms of “Difficulty in concentrating” and “Feeling tense” are imperative to address these specific symptoms within subpopulations.Keywords: sleep inertia, change patterns, network structures, intern nurse, shift work

Hui Tang,1,&ast; Xiaoxia Ding,2,3,&ast; Youming Huang,2 Danfeng Xu,2 Yibin Fan1,2 1Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, 233030, People’s Republic of China; 2Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 3Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yibin Fan, Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, 233030, People’s Republic of China, Tel +86 18806538451, Email fanyibin@hmc.edu.cnIntroduction: Vitiligo is an acquired skin pigmentation disorder, the cause of which is poorly understood. Researchers in this field are dedicated to exploring novel treatments for achieving re-pigmentation.Methods: Mice were randomly selected and divided into control, model, and model+laser groups. Evaluate the impact of different levels of carbon dioxide laser irradiation on tyrosinase activity, melanocyte viability, and melanin content.Results: In this study, it was found that the cell viability and melanin content were significantly enhanced in human melanocytes after treatment with different energy densities of fractional carbon dioxide laser. In addition, laser-treated vitiligo mouse models showed mild pathological changes.Discussion: Therefore, we believe that fractional carbon dioxide laser may be a potential adjunctive modality for treating vitiligo.Keywords: vitiligo, fractional carbon dioxide laser, melanocytes, melanogenesis, vitiligo mouse models

Bei Li,1,2,&ast; Yuting Luo,1,2,&ast; Geng Liu,1,2 Maling Gou,3 Lei Feng,1,2 Xiwen Ye,1,2 Jianrong Xu,1,2 Yaotian Fan,1,2 Zhen You1,2 1Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 3Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen You, Tel/Fax +86 028 85423823, Email youzhen@wchscu.cnIntroduction: Hepatocellular carcinomas (HCC) have a high morbidity and mortality rate, and is difficult to cure and prone to recurrence when it has already developed. Therefore, early detection and efficient treatment of HCC is necessary.Methods: In this study, we synthesized a novel NDI polymer with uniform size, long-term stability, and high near-infrared two-zone (NIR-II) absorption efficiency, which can greatly enhance the effect of photothermal therapy (PTT) after intravenous injection into Huh-7-tumor bearing mice.Results: The in vitro and in vivo studies showed that NDI polymer exhibited excellent NIR-guided PTT treatment, and the antitumor effect was approximately 88.5%, with obvious antimetastatic effects.Conclusion: This study developed an NDI polymer-mediated integrated diagnostic and therapeutic modality for NIR-II fluorescence imaging and photothermal therapy.Keywords: hepatocellular carcinoma, photothermal therapy, NDI polymer, NIR-II imaging

Mengwen Feng,1 Min Huang,2 Yuanyuan Fan,1 Genyan Liu,3 Suming Zhou,2 Jing Zhou2 1Department of Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Geriatric Intensive Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Jing Zhou, Department of Geriatric Intensive Care Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of China, Email zhoujing1364@jsph.org.cnPurpose: Elizabethkingia spp. infections have recently increased, and they are difficult to treat because of intrinsic antimicrobial resistance. This study aimed to investigate the clinical characteristics of patients with pulmonary infection with Elizabethkingia spp. and reveal the risk factors for infection and death.Patients and Methods: In this retrospective case–control study, patients were divided into infection and control groups based on the bacterial identification results. Patients in the infection group were further divided into survival and death groups according to their hospital outcomes. Clinical characteristics between different groups were compared. We further analyzed antimicrobial susceptibility testing results of the isolated strains.Results: A total of the 316 patients were divided into infection (n = 79), 23 of whom died, and control (n = 237) groups. Multivariate logistic regression analysis showed that glucocorticoid consumption (OR: 2.35; 95% CI: 1.14– 4.81; P = 0.02), endotracheal intubation (OR: 3.74; 95% CI: 1.62– 8.64; P = 0.002), and colistin exposure (OR: 2.50; 95% CI: 1.01– 6.29; P = 0.046) were significantly associated with pulmonary infection with Elizabethkingia spp. Advanced age (OR: 1.07, 95% CI: 1.00– 1.15; P = 0.046), high acute physiology and chronic health evaluation (APACHE) II score (OR: 1.21; 95% CI: 1.01– 1.45; P = 0.037), and low albumin level (OR: 0.73, 95% CI: 0.56– 0.96; P = 0.025) were significantly associated with in-hospital mortality of infected patients. Elizabethkingia spp. was highly resistant to cephalosporins, carbapenems, macrolides, and aminoglycoside, and was sensitive to fluoroquinolones, minocycline, and co-trimoxazole in vitro.Conclusion: Glucocorticoid consumption, tracheal intubation, and colistin exposure were associated with pulmonary infection with Elizabethkingia spp. for critically ill patients. Patients with advanced age, high APACHE II score, and low albumin level had higher risk of death from infection.Keywords: Elizabethkingia spp, intensive care unit, infection, mortality, antimicrobial susceptibility testing

Yihua Fan,1– 3,&ast; Wei Liu,1,2,&ast; Yue Jin,1,2,&ast; Hang Lu,1,2 Chunliu Liu,1,2 Aihua Wang,1,2 Qingxiang Gu,1,2 Yuxiu Ka1,2 1Department of Rheumatism and Immunity, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China; 3Department of Rheumatism and Immunity, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Liu, Email fengshiliuwei@163.comBackground: Acute gouty arthritis (AGA) is characterized by the accumulation of monosodium urate crystals within the joints, leading to inflammation and severe pain. Western medicine treatments have limitations in addressing this condition. Previous studies have shown the efficacy of Qinpi Tongfeng formula (QPTFF) in treating AGA, but further investigation is needed to understand its mechanism of action.Methods: We used ultra-high-performance liquid chromatography tandem Q-Exactive Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-MS) to identify compounds in QPTFF. Target proteins regulated by these compounds were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Chemistry Database, and Swiss Target Prediction Database. AGA-related targets were searched and screened from various databases, including Genecards, PharmGKB, Drugbank, etc. Intersection targets of QPTFF and AGA were analyzed for protein–protein interaction networks, GO function enrichment, and KEGG pathway enrichment. We then verified QPTFF’s mechanism of action using an AGA rat model, assessing pathological changes via H&E staining and target expression via ELISA, RT-qPCR, and Western blot.Results: UHPLC-Q-Orbitrap-MS identified 207 compounds in QPTFF, with 55 selected through network pharmacology. Of 589 compound-regulated targets and 1204 AGA-related targets, 183 potential targets were implicated in QPTFF’s treatment of AGA. Main target proteins included IL-1β, NFKBIA, IL-6, TNF, CXCL8, and MMP9, with the IL-17 signaling pathway primarily regulated by QPTFF. Experimental results showed that medium and high doses of QPTFF significantly reduced serum inflammatory factors and MMP-9 expression, and inhibited IL-17A, IL-6, IKK-β, and NF-κB p65 mRNA and protein expression in AGA rats compared to the model group.Conclusion: Key targets of QPTFF include IL-1β, NFKBIA, IL-6, TNF-α, CXCL8, and MMP9. QPTFF effectively alleviates joint inflammation in AGA rats, with high doses demonstrating no liver or kidney toxicity. Its anti-inflammatory mechanism in treating AGA involves the IL-17A/NF-κB p65 signaling pathway.Keywords: acute gouty arthritis, Qinpi Tongfeng formula, network pharmacology, UHPLC-Q-Orbitrap-MS, IL-17 signaling pathway

Fengxia Zhan,1 Wei Song,2 Yong Fan,3 Fangjian Wang,1 Qian Wang4,5 1Department of Clinical Laboratory, Hospital of Shandong University, Jinan, 250100, People’s Republic of China; 2Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao, 266061, People’s Republic of China; 3Qingdao Mental Health Center, Qingdao University, Qingdao, People’s Republic of China; 4Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, 250012, People’s Republic of China; 5Department of Clinical Laboratory, Qilu Hospital (Qingdao), Shandong University, Qingdao, 266035, People’s Republic of ChinaCorrespondence: Qian Wang, Email wq028038@qlyyqd.comPurpose: Cucurbitacins, which are found in a variety of medicinal plants, vegetables and fruits, were known for their diverse pharmacological and biological activities, including anticancer, anti-oxidative and anti-inflammatory effects. Cucurbitacin E, one of the major cucurbitacins, was recently proved to inhibit inflammatory response.Methods: To explore the therapeutic effects of cucurbitacin E on colitis and the underlying mechanisms, male mice drunk water containing 2.5% dextran sulfate sodium (DSS) to establish colitis model and administrated with cucurbitacin E during and after DSS treatment. The disease activity index was scored and colonic histological damage was observed. Intestinal tight junction and inflammatory response were determined. 16S rRNA and transcriptome sequencing were performed to analyze gut microbiota composition and gene expression, respectively.Results: We found that cucurbitacin E alleviated DSS-induced body weight loss and impaired colonic morphology. Cucurbitacin E decreased the expression of inflammatory cytokines and cell apoptosis, and maintained barrier function. Additionally, cucurbitacin E retrieved DSS-induced alterations in the bacterial community composition. Furthermore, a variety of differentially expressed genes (DEGs) caused by cucurbitacin E were enriched in several pathways including the NFκB and TNF signaling pathways as well as in Th17 cell differentiation. There was a close relationship between DEGs and bacteria such as Escherichia-Shigella and Muribaculaceae.Conclusion: Our results revealed that cucurbitacin E may exert protective effects on colitis via modulating inflammatory response, microbiota composition and host gene expression. Our study supports the therapeutic potential of cucurbitacin E in colitis and indicates that gut microbes are potentially therapeutic targets.Keywords: barrier function, colitis, cucurbitacins, inflammation, microbiota

Jiaman Yang,1,2,&ast; Yulin Xie,1,2,&ast; Zhikuan Xia,1,&ast; Shuaifei Ji,3,&ast; Xin Yang,1 Danxia Yue,1 Yuanyuan Liu,1,3 Rongya Yang,1– 3 Yunlong Fan1,3 1Department of Dermatology, the Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, People’s Republic of China; 2The Second School of Clinical Medicine, SouThern Medical University, Guangzhou, 510599, People’s Republic of China; 3Chinese PLA Medical School, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongya Yang, Department of Dermatology, the Seventh Medical Center of Chinese PLA General Hospital, No. 5, Nanmencang Alley, Dongsi Shitiao, Dongcheng District, Beijing, 100700, People’s Republic of China, Email YangRY301hospital@163.com Yunlong Fan, Department of Dermatology, the Seventh Medical Center of Chinese PLA General Hospital, No. 5, Nanmencang alley, Dongsi Shitiao, Dongcheng District, Beijing, 100700, People’s Republic of China, Email FanYL301hospital@163.comBackground: Neutrophils rapidly accumulate in large numbers at sites of tissue damage, exhibiting not only their well-known bactericidal capabilities but also playing crucial roles in angiogenesis and tissue repair. While exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-Exo) have emerged as a promising therapeutic tool, their exact mechanisms of action remain partly elusive. We hypothesize that HucMSC-Exo treatment may modulate neutrophil phenotypes, thereby significantly influencing wound healing outcomes.Methods: HucMSC-Exo were isolated via ultracentrifugation and subsequently administered through subcutaneous injection into full-thickness cutaneous wounds in mice. To determine the impact of host neutrophils on the healing effects of HucMSC-Exo in skin injuries, strategies including neutrophil depletion and adoptive transfer were employed. Flow cytometry was used to evaluate the proportion of N2 subtype neutrophils in both normal and diabetic wounds, and the effect of HucMSC-Exo on this proportion was assessed. Furthermore, the mitochondrial metabolic reprogramming driven by HucMSC-Exo during N2 polarization was investigated through JC1 staining, ATP quantification, fatty acid uptake assays, and assessment of FAO-related genes (Cpt1b, Acadm, and Acadl).Results: Depleting host neutrophils strikingly dampened prohealing effect of HucMSC-Exo on skin injury, while adoptive transfer of bone marrow neutrophils rescued this process. During normal healing process, some neutrophils expressed N2 markers, in contrast, diabetic wounds exhibited a reduced expression of N2 markers. After treatment with HucMSC-Exo, most neutrophils increased the phosphorylation of STAT6, leading to mitochondrial metabolic reprogramming and thus acquired an N2 phenotype. These N2 neutrophils, polarized by HucMSC-Exo, boosted the release of proangiogenic factors, particularly BV8, a myeloid cell-derived proangiogenic factor, and induced angiogenesis thereby favoring tissue restoration.Conclusion: This research uniquely demonstrates the identification of N2 neutrophils in skin injury and shows that HucMSC-Exo could skew neutrophils toward N2 phenotype, enhancing our insight into how cells react to HucMSC-Exo. Keywords: HucMSC-Exo, neutrophils, phenotype switching, cutaneous wound healing, tissue restoration

Yujun He,1,2,&ast; Furui Miao,2,&ast; Cai He,1 Yushan Fan,2 Fangzhi Zhang,2 Pu Yang,3 Miaodong Wang,3 Jiujie He2 1Nancheng Branch Hospital, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning City, People’s Republic of China; 2Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, Nanning City, People’s Republic of China; 3Graduate School of Guangxi University of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cai He, Nancheng Branch Hospital, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, No. 356 Nanmian Street, Xixiangtang District, Nanning City, 530011, People’s Republic of China, Email 578485231@qq.com Yushan Fan, Faculty of acupuncture, moxibustion and tui Na, Guangxi University of Chinese Medicine, 179 Mingxiu East Road, Xi Xiang Tang District, Nanning City, 530001, People’s Republic of China, Email doctorfanyushan@163.comBackground: Carpal tunnel syndrome (CTS) is the most prevalent upper limb compressive neuropathy. A considerable number of clinical trials and meta-analyses have provided evidence supporting the effectiveness of acupuncture in treating CTS. Nevertheless, the ideal choice of acupoints remains ambiguous.Objective: A data mining analysis was conducted with the objective of determining the most effective acupoint combinations and selection for CTS.Methods: A search was conducted across seven Chinese and English electronic bibliographic databases spanning from their inception to March 2023. Selected were clinical trials that evaluated the efficacy of acupuncture therapy for CTS, with or without randomised controlled methods. Data extraction mainly included acupoint prescriptions. Information such as first author, study design and study setting were also extracted. The principal outcomes comprised the clinical manifestations linked to CTS. Statistical descriptions were generated using Excel 2019. The analysis of association rules was conducted using SPSS Modeler 18.0. Using SPSS Statistics 26.0, exploratory factor analysis and cluster analysis were conducted.Results: 142 trials (including 86 RCTs and 56 non RCTs) were identified, and 193 groups of effective prescriptions involving 68 acupoints were extracted. The most frequently used acupoints were Da-ling (PC7), Nei-guan (PC6), He-gu (LI4), Wai-guan (TE5), and Yang-xi (LI5). The most frequently used meridians were the pericardial meridian and the large intestine meridian. The majority of special acupoints used were Five-shu points and Yuan-source points, with acupoints on the upper limbs being the most frequently used. The core acupoint groups were analyzed and 11 groups of association rules, 8 factors, and 5 effective cluster groups were obtained.Conclusion: The evidence-based acupoint selection and combinations of acupuncture therapy for carpal tunnel syndrome were provided by the findings of this study.Keywords: acupuncture, carpal tunnel syndrome, data mining, descriptive statistics, association rule analysis, exploratory factor analysis, cluster analysis

Yanjie Zhu,1,2 Xinkun Zhang,1,2 Guangfei Gu,1,2 Yunshan Fan,1,2 Zhi Zhou,1,2 Chaobo Feng,1,2 Xin Gu,3 Shisheng He1,2 1Department of Orthopedic, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Spinal Pain Research Institute, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Department of Orthopedic Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Shisheng He, Department of Orthopedic, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, People’s Republic of China, Email tjhss7418@tongji.edu.cn Xin Gu, Department of Orthopedic Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 Xianxia Road, Shanghai, 200050, People’s Republic of China, Email guxin2004ty@163.comPurpose: To investigate the clinical outcomes of percutaneous transforaminal endoscopic discectomy assisted with selective nerve root block for treating radicular pain with diagnostic uncertainty in the elderly.Methods: A total number of 36 elderly patients were included in the study. Clinical outcomes collected for analysis include operative time, hospital stay time, Visual Analog Scale, and Oswestry Disability Index before and after the surgery, the global outcome based on the Macnab outcome criteria.Results: Seventeen males and nineteen females with a mean age of 73.72 ± 7.15 were included in this study. Radicular pain was the main complaint of all the patients with the least symptom duration of two months. Radiological findings showed that 80.6% of the patients with multilevel disc herniation, 16.7% received lumbar fusion surgery before, and 8.3% with degenerative scoliosis. Besides, 69.4% of the patients have at least one comorbidity. 85.4% of the patients showed a positive response to selective nerve root block, and 91.6% of the patients reported a favorable outcome at the last follow-up. The mean value of pre-operative leg pain was 7.56 ± 0.74 and dramatically decreased after surgery (2.47 ± 0.81, P < 0.001). Besides, the mean value of Oswestry Disability Index decreased from 43.03 ± 4.43 to 5.92 ± 5.24 (P < 0.001) one year after the surgery.Conclusion: Multilevel degeneration of the lumbar spine is common in elderly patients. Identifying the responsible segment and decompressing the nerve root through minimally invasive surgery can provide a satisfactory clinical outcome for those with radicular pain as their primary complaint. And selective nerve root block is a reliable diagnostic tool for those with an ambiguous diagnosis.Keywords: percutaneous transforaminal endoscopic discectomy, selective nerve root block, radicular pain, elderly, clinical outcome

Xin Yang,1,2,&ast; Zhikuan Xia,1,&ast; Yunlong Fan,1 Yitong Xie,1 Ge Ge,1 Dexiu Lang,3 Junhong Ao,1 Danxia Yue,1 Jiamin Wu,1 Tong Chen,1 Yuekun Zou,1 Mingwang Zhang,4 Rongya Yang1,2 1Department of Dermatology, The Seventh Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 2Department of Dermatology, Yanbian University Hospital, Yanji, People’s Republic of China; 3Department of Dermatology, XingYi People’s Hospital, Xingyi, People’s Republic of China; 4Department of Dermatology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingwang Zhang; Rongya Yang, Email mingwangzhang2@163.com; yangrya@sina.comBackground: Solar lentigines (SLs), serving as a prevalent characteristic of skin photoaging, present as cutaneous aberrant pigmentation. However, the underlying pathogenesis remains unclear and there is a dearth of reliable diagnostic biomarkers.Objective: The aim of this study was to identify diagnostic biomarkers for SLs and reveal its immunological features.Methods: In this study, gene expression profiling datasets (GSE192564 and GSE192565) of SLs were obtained from the GEO database. The GSE192564 was used as the training group for screening of differentially expressed genes (DEGs) and subsequent depth analysis. Gene set enrichment analysis (GSEA) was employed to explore the biological states associated with SLs. The weighted gene co-expression network analysis (WGCNA) was employed to identify the significant modules and hub genes. Then, the feature genes were further screened by the overlapping of hub genes and up-regulated differential genes. Subsequently, an artificial neural network was constructed for identifying SLs samples. The GSE192565 was used as the test group for validation of feature genes expression level and the model’s classification performance. Furthermore, we conducted immune cell infiltration analysis to reveal the immune infiltration landscape of SLs.Results: The 9 feature genes were identified as diagnostic biomarkers for SLs in this study. And an artificial neural network based on diagnostic biomarkers was successfully constructed for identification of SLs. GSEA highlighted potential role of immune system in pathogenesis of SLs. SLs samples had a higher proportion of several immune cells, including activated CD8 T cell, dendritic cell, myeloid-derived suppressor cell and so on. And diagnostic biomarkers exhibited a strong relationship with the infiltration of most immune cells.Conclusion: Our study identified diagnostic biomarkers for SLs and explored its immunological features, enhancing the comprehension of its pathogenesis.Keywords: solar lentigines, photoaging, diagnostic biomarkers, immune infiltration, artificial neural network

Ying Yin,1 Ke Wang,1,2 Yan Xu,2,3 Xin Huang,1 Jinxia Zheng,1 Yuping Fan,1 Jie Bai1 1Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China; 2School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China; 3School of International Medical Technology, Sanda University, Shanghai, 201206, People’s Republic of ChinaCorrespondence: Ke Wang, Email wangkeyfy@126.comObjective: To analyze the mental health and erectile function status of men using sperm donor during pregnancy after ICSI failure in severe oligoasthenospermia and to provide reference for clinical implementation of more targeted psychological intervention and nursing for this group.Methods: A total of 410 sterile men who received assisted pregnancy treatment in our hospital from December 2020 to December 2022 and met the inclusion and exclusion criteria were collected as the study subjects. Among them, 68 patients with severe oligoasthenospermia who used donor assisted pregnancy after ICSI failure were used as the study group. Sixty-eight patients with severe oligoasthenospermia who continued to receive ICSI assisted pregnancy were matched by propensity score 1:1 as control group. General data questionnaire, self-rating Anxiety Scale (SAS), self-rating Depression Scale (SDS), Chinese version of perceived Stress Scale (CPSS) and International Erectile Function Index Rating Scale (IIEF-5) were used to conduct a cross-sectional investigation to compare the mental health and erectile function status of the two groups.Results: There were statistical differences in age and occupational status between the two groups before PSM (P < 0.05), but there was no statistical significance in social demographic data between the two groups after matching (P > 0.05). The incidence of anxiety, depression, stress and erectile dysfunction (ED) in the study group was higher than that in the control group, and there were statistical differences between the two groups (P < 0.05).Conclusion: The use of donor sperm to assist pregnancy has a great impact on the mental health and erectile function of infertile men. Medical personnel should pay attention to the mental health and erectile function of these men, and formulate targeted measures to help these patients actively cope with infertility, so as to improve the life and marriage quality of this group and improve their mental health status.Keywords: sterile male, supply semen, erectile function, mental health, propensity score

Xinhuan Lei,1,&ast; Xiaoting Song,1,&ast; Yongyong Fan,1,&ast; Zhen Chen,1 Liwei Zhang1,2 1Department of Orthopedics, Taizhou Hospital of Zhejiang Province, Zhejiang University, Taizhou, Zhejiang, People’s Republic of China; 2Bone Metabolism and Development Research Center, Taizhou Hospital of Zhejiang Province, Zhejiang University, Taizhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liwei Zhang; Zhen Chen, Email medzlw@sina.com; chenzhen@enzemed.comPurpose: Fibromyalgia (FM) is a syndrome characterized by chronic musculoskeletal pain. Its clinical symptoms include both somatic and psychiatric symptoms, making the treatment of FM extremely challenging. The cause of FM is still unknown, and some patients do not improve their symptoms even after long-term active treatment. Thus, the development of new targeted therapies is important to reduce pain and improve quality of life for FM patients.Methods: In this study, we screened genes and secreted factors that play key roles in FM through bioinformatics and big data analysis. Furthermore, we performed CCK-8, qRT-PCR, glucose, ATP and lactate content testing, dual luciferase reporter gene assay to investigate the potential mechanism of complement factor D in fibromyalgia development.Results: In bioinformatics and big data analysis, we identified CFD was negatively correlated with the pro-inflammatory factor IL-6 and positively correlated with the anti-inflammatory factor IL-4, which suggested that CFD may be an anti-inflammatory factor. Through cellular assays, we verified that CFD reversed the decrease in IL-4 expression and the increase in IL-6 expression in BV2 cells caused by ATP.Conclusion: In summary, based on bioinformatic methods and big data mining we obtained a new target CFD for FM, and further experiments verified that CFD has significant inhibition of ATP-induced neuropathic pain. These findings provide a new theoretical basis for the clinical translation of CFD.Keywords: fibromyalgia, complement factor D, bioinformatics, inflammation

Jie Li,1 Jiangtao Long,1 Zheng Zhao,2 Qianqian Wang,1 Wang Bo,2 Liang Ren,1 Yan Fan,3 Peng Wang,1 Yi Cheng,1 Binbin Liu,1 Xinkui Cheng,1 Hongwei Xi2 1Department of Orthopedics, Children’s Hospital Affiliated to Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of General Surgery, Children’s Hospital Affiliated to Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Burn and Plastic Surgery, Children’s Hospital affiliated to Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Hongwei Xi, Email xihongwei148@sina.comBackground: Multiple stages including hemostasis, inflammation, proliferation, and remodeling were involved in the wound healing process. The increase in nanomaterials in recent years has extended the scope of tools for wound healing; however, it is still difficult to achieve the four multistage procedures simultaneously.Materials and Methods: In this study, graphene-spiky silica heterostructured nanoparticles (GS) were synthesized for the procedural acceleration of the multistage in wound healing process. The nanobridge effect of GS was analyzed through the adhesion of two skins, the antibacterial effect was assessed in Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria, cell proliferation and migration were investigated in mouse embryonic fibroblast (NIH-3T3) cells, and the in vivo wound healing effect was examined in female BALB/c mice with a cutting wound and E. coli or S. aureus bacteria infection on the back.Results: First, GS has a strong nanobridge effect on the rapid closure of wounds because the spiky architecture on the surface of GS facilitates the adhesion of skins, promoting the hemostasis stage. Second, graphene exhibits antimicrobial activities both in chemical and physical interactions, especially under simulated sunlight irradiation. Third, graphene plays an important role in scaffolding function, together with the spiky topographical architecture of GS, accelerating the proliferation and maturation stages.Conclusion: By periodically promoting every stage of wound healing, GS combined with simulated sunlight irradiation could significantly accelerate wound healing. With a simple composition and compact structure but multiple functions, this strategy will be the guideline for the development of ideal wound-healing nanomaterials.Keywords: graphene-spiky silica heterostructured nanoparticles, wound healing, multistage

Yan Teng,1,&ast; Mingyang Ren,2,&ast; Yang Ding,1 Xianhong Yang,1 Yibin Fan,1 Xiaohua Tao1 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Graduate School of Clinical Medicine, Bengbu Medical School, Bengbu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohua Tao; Yibin Fan, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang provincial people’s hospital, People’s Hospital of Hangzhou Medical College, Tel +86-13505811700 ; +86-18806538451, Email taoxiaohua@hmc.edu.cn; fanyibin@hmc.edu.cnAbstract: Perioral dermatitis (POD) is a chronic inflammatory skin disease that primarily affects females between the ages of 16 and 45. Conventional therapies face the challenge of limited efficacy and a high recurrence rate. In this report, we present the case of a 26-year-old male patient with POD who was successfully treated using the Janus kinase (JAK) inhibitor, abrocitinib. This treatment exhibited both good efficacy and safety. Abrocitinib, as a JAK inhibitor, holds promise as a potential therapy for cases of POD that might be resistant to conventional therapies.Keywords: JAK inhibitors, abrocitinib, perioral dermatitis

Haoran Chen,1,2,&ast; Zhongyu Han,2,&ast; Yi Wang,1,&ast; Junyan Su,3 Yumeng Lin,4 Xuhua Cheng,1 Wen Liu,1 Jingyu He,5 Yiyue Fan,6 Liuyan Chen,2 Houdong Zuo1 1Department of Orthopaedics, Chengdu Xinhua Hospital, Chengdu, 610000, People’s Republic of China; 2School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, People’s Republic of China; 3Department of Orthopaedics, The First People’s Hospital of Longquanyi District, Chengdu, 610000, People’s Republic of China; 4School of Ophthalmology, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, People’s Republic of China; 5Sichuan Judicial and Police Officers Professional College, Deyang, 618000, People’s Republic of China; 6Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houdong Zuo, Department of Orthopaedics, Chengdu Xinhua Hospital, Chengdu, 610000, People’s Republic of China, Email xhyyzhd@163.com Liuyan Chen, School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, People’s Republic of China, Email Lycheecly@163.comAbstract: Ferroptosis is a new cell fate decision discovered in recent years. Unlike apoptosis, autophagy or pyroptosis, ferroptosis is characterized by iron-dependent lipid peroxidation and mitochondrial morphological changes. Ferroptosis is involved in a variety of physiological and pathological processes. Since its discovery, ferroptosis has been increasingly studied concerning bone-related diseases. In this review, we focus on the latest research progress and prospects, summarize the regulatory mechanisms of ferroptosis, and discuss the role of ferroptosis in the pathogenesis of bone-related diseases, such as osteoporosis (OP), osteoarthritis (OA), rheumatoid arthritis (RA), and osteosarcoma (OS), as well as its therapeutic potential.Keywords: ferroptosis, cell death, iron accumulation, lipid peroxidation, bone-related diseases

Yan Teng,1,&ast; Huiting Zhong,2,&ast; Xianhong Yang,1 Xiaohua Tao,1,&ast; Yibin Fan1,&ast; 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Department of Dermatology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yibin Fan; Xiaohua Tao, Center for plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Tel +86-18806538451 ; +86-13505811700, Email fanyibin@hmc.edu.cn; taoxiaohua@hmc.edu.cnAbstract: Atopic dermatitis (AD) in the elderly has recently emerged as a distinct subgroup of AD, garnering widespread concern due to its increasing global incidence rate. Epidermal barrier dysfunction, inflammatory response, and chronic pruritus interact with each other, contributing to the pathogenesis and pathophysiology of AD in the elderly. Although fundamental medications are essential for managing AD in the elderly, older adults often struggle with regular usage of moisturizing emollients, topical medications, and avoidance of environmental triggers, leading to recurrent or even exacerbated disease progression. Therefore, a systematic medication approach is necessary to control pruritus and skin lesions. Traditional systemic treatments may not adequately meet the treatment needs of moderate and severe AD in the elderly and may even pose certain safety risks. Biologics and Janus kinase (JAK) inhibitors, exhibiting excellent clinical efficacy, have made significant breakthroughs in AD treatment. Existing evidence suggests that dupilumab, a human monoclonal IgG4 antibody, has been confirmed as an effective and safe first-line systematic treatment for moderate to severe AD in the elderly, with no notable differences between adults and the elderly. However, the limited inclusion of elderly patients in related clinical studies hinders the generalizability of these findings. As older patients face a higher risk of adverse events with JAK inhibitors, JAK inhibitors are recommended when no other suitable treatment options are available. Obtaining population-specific data is crucial for making evidence-based treatment choices when managing AD in older adults with JAK inhibitors.Keywords: atopic dermatitis in the elderly, treatments, biologics, JAK inhibitors

Renke Chen,1,&ast; Mengxiao Xie,2,&ast; Shenlong Wang,1 Fei Yu,2– 4 Dan Zhang,2– 4 Lingjun Yuan,2 Jieyuan Zheng,2 Jingchao Wang,2 Jieting Zhou,2 Binxiao Li,2 Shufa Zheng,2– 4 Yongsheng Fan,1 Dongsheng Han2– 4 1The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Key Laboratory of Clinical in vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, People’s Republic of China; 4Institute of Laboratory Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongsheng Han, Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Email hands@zju.edu.cn Yongsheng Fan, School of Basic Medical Sciences, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email fyszjtcm@163.comBackground: Metagenomic next-generation sequencing (mNGS) is a promising tool for improving antimicrobial therapy and infection control decision-making in complex infections. Secondary infection surveillance using mNGS in COVID-19 patients has rarely been reported.Methods: Respiratory pathogen and antibiotic resistance prediction were evaluated by BALF mNGS for 192 hospitalized COVID-19 patients between December 2022 and February 2023.Results: Secondary infection was confirmed in 83.3% (160/192) of the COVID-19 patients, with bacterial infections (45%, 72/160) predominating, followed by mixed bacterial and fungal infections (20%, 32/160), and fungal infections (17.5%, 28/160). The incidence of bacterial or viral secondary infection was significantly higher in patients who were admitted to the ICU, received mechanical ventilation, or developed severe pneumonia (all p< 0.05). Klebsiella pneumoniae (n=30, 8.4%) was the most prevalent pathogen associated with secondary infection followed by Acinetobacter baumannii (n=29, 8.1%), Candida albicans (n=29, 8.1%), Aspergillus fumigatus (n=27, 7.6%), human herpes simplex virus type 1 (n=23, 6.4%), Staphylococcus aureus (n=20, 5.6%) and Pneumocystis jiroveci (n=14, 3.9%). The overall concordance between the resistance genes detected by mNGS and the reported phenotypic resistance in 69 samples containing five clinically important pathogens (ie, K. pneumoniae, A. baumannii, S. aureus, P. aeruginosa and E. coli) that caused secondary infection was 85.5% (59/69).Conclusion: mNGS can detect pathogens causing secondary infection and predict antimicrobial resistance for COVID19 patients. This is crucial for initiating targeted treatment and rapidly detect unsuspected spread of multidrug-resistant pathogens.Keywords: COVID-19, SARS-CoV-2, metagenomic next-generation sequencing, antibiotic resistance

Yujun He,1 Furui Miao,1 Yushan Fan,1 Jiujie He,1 Fangzhi Zhang,1 Zibin Wang,1 Yu Wu,1 Yiping Zhao,1 Pu Yang2 1Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 2Graduate School, Guangxi University of Chinese Medicine, Nanning, People’s Republic of ChinaCorrespondence: Furui Miao; Yushan Fan, Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, 179 Mingxiu East Road, Xi Xiang Tang District, Nanning City, People’s Republic of China, Email snowymiao@163.com; doctorfanyushan@163.comBackground: Piriformis syndrome (PS) is a neuromuscular condition characterized by discomfort in the gluteal region. The efficacy of acupuncture as a treatment modality for PS has been substantiated through a multitude of clinical trials. However, certain queries persist, such as the optimal approach for identifying the most efficacious acupoints. The objective of this study is to perform an initial data mining analysis aimed at identifying the optimal acupoint selection and combinations for the treatment of PS.Methods: We will search 7 electronic bibliographic databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database and Chongqing VIP Database) from inception to June 2023. We will select clinical trials that evaluate the efficacy of acupuncture therapy in the management of PS. Exclusions will be made for reviews, protocols, animal trials, case reports, systematic reviews, and meta-analyses. The primary outcome measure will be clinical outcomes associated with PS. Descriptive statistics will be performed in Excel 2019. Association rule analysis will be performed in SPSS Modeler 18.0. Exploratory factor analysis and cluster analysis will be performed in SPSS Statistics 26.0.Results: This study will investigate the most effective acupoint selection and combinations for patients with PS.Conclusion: Our findings will provide evidence for the effectiveness and potential treatment prescriptions of acupoint application for patients with PS, helping clinicians and patients make a more informed decision together.Keywords: piriformis syndrome, acupuncture, data mining

Yan Teng,1 Yibin Fan,1 Danying Shang,1 Xiaohua Tao,1,&ast; Dongsheng Sun2,&ast; 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Geriatric Medicine Center, Department of Geriatric Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongsheng Sun, Geriatric Medicine Center, Department of Geriatric Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Email sunds@163.com Xiaohua Tao, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China, Email taoxiaohua@hmc.edu.cnAbstract: Drug-induced alopecia areata is a rare adverse event wherein medications such as antimicrobials, anticonvulsants, and biologics, trigger the premature transition of actively growing hairs into the telogen phase. Herein, a unique case of alopecia universalis observed during a clinical trial involving sacubitril/alisartan, a novel angiotensin receptor-neprilysin inhibitor (ARNI) has been reported. This case contributes to the range of cutaneous reactions that might be observed in association with ARNI therapy.Keywords: alopecia universalis, sacubitril/alisartan, angiotensin receptor-neprilysin inhibitor

Yan Teng,1,&ast; Hui Tang,2,&ast; Yong Yu,1 Yibin Fan,1 Xiaohua Tao,1 Danfeng Xu1 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Danfeng Xu; Xiaohua Tao, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, 158 Shangtang Road, Gongshu District, Hangzhou, 310014, People’s Republic of China, Tel +86-13567122384 ; +86-13505811700, Email 3100102508@zju.edu.cn; taoxiaohua@hmc.edu.cnBackground: There is limited literature on AD with a predominant involvement of nipple among the adult male group. SARS-CoV-2 infection might have been an exacerbating factor of AD by initiating the “cytokine storm”. Conventional treatment suffers from a dilemma of poor efficacy and a high recurrence. The JAK inhibitors have been clinically applied to treat the AD with a good outcome.Patients and Methods: We present a case of a 28-year-old male AD patient with a predominant nipple involvement successfully treated with JAK inhibitor abrocitinib, with no adverse affects.Results: The case shows a good clinical efficacy of JAK inhibitor abrocitinib in the treatment of AD with a predominant nipple involvement during the COVID-19 pandemic with a rapid and long-term symptomatic relief.Conclusion: JAK inhibitor abrocitinib might become a promising agent for the treatment with AD with a predominant uncommon region like nipple that might be resistant to conventional therapies during the COVID-19 pandemic.Keywords: atopic dermatitis, nipple and areola, JAK inhibitors, abrocitinib, COVID-19

Mian Huang,1 Bing-Tao Zhai,1,2 Yu Fan,3 Jing Sun,1 Ya-Jun Shi,1 Xiao-Fei Zhang,1 Jun-Bo Zou,1 Jia-Wen Wang,1 Dong-Yan Guo1,4 1School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China; 2State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China; 3School of Basic Medicine, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China; 4Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of ChinaCorrespondence: Dong-Yan Guo, Email 2051080@sntcm.edu.cnAbstract: Breast cancer (BC) is the most prevalent type of cancer in the world and the main reason women die from cancer. Due to the significant side effects of conventional treatments such as chemotherapy and radiotherapy, the search for supplemental and alternative natural drugs with lower toxicity and side effects is of interest to researchers. Curcumin (CUR) is a natural polyphenol extracted from turmeric. Numerous studies have demonstrated that CUR is an effective anticancer drug that works by modifying different intracellular signaling pathways. CUR’s therapeutic utility is severely constrained by its short half-life in vivo, low water solubility, poor stability, quick metabolism, low oral bioavailability, and potential for gastrointestinal discomfort with high oral doses. One of the most practical solutions to the aforementioned issues is the development of targeted drug delivery systems (TDDSs) based on nanomaterials. To improve drug targeting and efficacy and to serve as a reference for the development and use of CUR TDDSs in the clinical setting, this review describes the physicochemical properties and bioavailability of CUR and its mechanism of action on BC, with emphasis on recent studies on TDDSs for BC in combination with CUR, including passive TDDSs, active TDDSs and physicochemical TDDSs.Keywords: breast cancer, curcumin, targeted drug delivery system, passive targeting, active targeting, physicochemical targeting

Kaichen Zhang,&ast; Yihua Fan,&ast; Kunlan Long, Ying Lan, Peiyang Gao Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peiyang Gao, Email gaopy930@126.comBackground: Interest in the application of deep learning (DL) in critical care medicine (CCM) is growing rapidly. However, comprehensive bibliometric research that analyze and measure the global literature is still lacking.Objective: The present study aimed to systematically evaluate the research hotspots and trends of DL in CCM worldwide based on the output of publications, cooperative relationships of research, citations, and the co-occurrence of keywords.Methods: A total of 1708 articles in all were obtained from Web of Science. Bibliometric analysis was performed by Bibliometrix package in R software (4.2.2), Microsoft Excel 2019, VOSviewer (1.6.18), and CiteSpace (5.8.R3).Results: The annual publications increased steeply in the past five years, accounting for 95.67% (1634/1708) of all the included literature. China and USA contributed to approximately 71.66% (1244/1708) of all publications. Seven of the top ten most productive organizations rank in the top 100 universities globally. Hot spots in research on the application of DL in CCM have focused on classifying disease phenotypes, predicting early signs of clinical deterioration, and forecasting disease progression, prognosis, and death. Convolutional neural networks, long and short-term memory networks, recurrent neural networks, transformer models, and attention mechanisms were all commonly used DL technologies.Conclusion: Hot spots in research on the application of DL in CCM have focused on classifying disease phenotypes, predicting early signs of clinical deterioration, and forecasting disease progression, prognosis, and death. Extensive collaborative research to improve the maturity and robustness of the model remains necessary to make DL-based model applications sufficiently compelling for conventional CCM practice.Keywords: hotspots, trends, deep learning, critical care medicine

Yujun He,1 Furui Miao,1 Yushan Fan,1 Fangzhi Zhang,1 Pu Yang,2 Xinyi Zhao,3 Miaodong Wang,2 Cai He,1 Jiujie He1 1Faculty of Acupuncture, Moxibustion and Tui Na of Guangxi University of Chinese Medicine, Nanning, 530001, People’s Republic of China; 2Graduate School of Guangxi University of Traditional Chinese Medicine, Nanning, 530200, People’s Republic of China; 3Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, 530200, People’s Republic of ChinaCorrespondence: Furui Miao; Yushan Fan, Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, 179 Mingxiu East Road, Xi Xiang Tang District, Nanning, Guangxi, 530001, People’s Republic of China, Email snowymiao@163.com; doctorfanyushan@163.comBackground: Piriformis syndrome (PS) is a common disease that is difficult to clinically treat, which seriously affects people’s health and living quality. Multiple clinical studies have demonstrated that acupuncture therapy is an effective treatment for PS, but the optimal method of various acupuncture methods has remained unknown. The aim of this study protocol is to compare the efficacy and the safety of different acupuncture methods for PS.Methods: We will search seven electronic bibliographic databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, and Chongqing VIP Database) from inception to June 2023. Randomized controlled trials (RCTs) will be selected for assessing the effectiveness of acupuncture therapy on PS. Primary outcome measure for this study is pain intensity, and the secondary outcomes are clinical symptoms and signs, physical activity, effective rate, and adverse events. Study selection, data extraction, and risk of bias assessment will be independently completed by at least two reviewers. Then, standard pairwise meta-analysis and network meta-analysis will be conducted using Revman 5.3, Stata V.15.1 and OpenBUGS V.3.2.3. The heterogeneity will be explored by subgroup, meta-regression, and sensitivity analysis, if applicable. Finally, Grading of Recommendations, Assessment, Development and Evaluation (GRADE) pro system will be used to evaluate the quality of evidence.Results: Our systematic review and network meta-analysis will identify the best acupuncture treatment method for PS patients.Conclusion: The results of our review will help decision-makers make educated choices regarding evidence-based acupuncture management options for PS.Prospero Registration Number: No. CRD42022335028.Keywords: piriformis syndrome, systematic review, network meta-analysis, protocol

Yujun He,1 Furui Miao,1 Yushan Fan,1 Fangzhi Zhang,1 Pu Yang,2 Xinyi Zhao,3 Miaodong Wang,2 Cai He,1 Jiujie He1 1Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 2Graduate School, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 3Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, People’s Republic of ChinaCorrespondence: Yushan Fan, Faculty of Acupuncture, Moxibustion and Tui Na, Guangxi University of Chinese Medicine, 179 Mingxiu East Road, Xi Xiang Tang District, Nanning, People’s Republic of China, Email doctorfanyushan@163.comBackground: Carpal tunnel syndrome (CTS), as the most common compression neuropathy in the upper limb, can lead to upper limb dysfunction in patients. The effectiveness of acupuncture in treating CTS has been validated based on numerous clinical trials and meta-analyses, but questions remain, such as how to select the best acupoints. Our purpose is to conduct the first data mining analysis to identify the most effective acupoint selection and combinations for treating CTS.Methods: We will search 7 electronic bibliographic databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database and Chongqing VIP Database) from inception to March 2023. Clinical trials assessing the effectiveness of acupuncture therapy on the management of CTS will be selected. Reviews, protocols, animal trials, case reports, systematic reviews, and meta-analyses will be excluded. The primary outcome measure will be clinical result associated with CTS. Descriptive statistics will be performed in Excel 2019. Association rule analysis will be performed in SPSS Modeler 18.0. Exploratory factor analysis and cluster analysis will be performed in SPSS Statistics 26.0.Results: This study will investigate the most effective acupoint selection and combinations for patients with CTS.Conclusion: Our findings will provide evidence for the effectiveness and potential treatment prescriptions of acupoint application for patients with CTS, helping clinicians and patients make a more informed decision together.Keywords: acupuncture, carpal tunnel syndrome, data mining, descriptive statistics, association rule analysis, exploratory factor analysis, cluster analysis

En Cao,1,&ast; Jun Xu,1,&ast; Yuanqi Gong,2,&ast; Jingjing Yuan,3 Anbang Chen,1 Jiayi Liu,4 Yunfei Fan,4 Xiangyang Fan,4 Xiaodong Kuang1 1Department of Pathology, Basic Medical College of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Critical Care Medicine/ICU (Intensive Care Unit), Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Physiology, School of Basic Medicine, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4The Basic Medical School of Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodong Kuang, Department of Pathology, Basic Medical College of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email xdssmu2005@163.comBackground: Macrophages are known to play a crucial role in the chronic inflammation associated with Chronic Obstructive Pulmonary Disease (COPD). BML-111, acting as a lipoxin A4 (LXA4) receptor agonist, has shown to be effective in protecting against COPD. However, the precise mechanism by which BML-111 exerts its protective effect remains unclear.Methods: In order to establish a cell model of inflammation, cigarette smoke extract (CSE) was used on the RAW264.7 cell line. Afterwards, an Enzyme-linked immunosorbent assay (ELISA) kit was employed to measure concentrations of tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), interleukin-18 (IL-18), and interleukin-10 (IL-10) in the cell supernatants of the RAW264.7 cells.In this study, we examined the markers of macrophage polarization using two methods: quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Additionally, we detected the expression of Notch-1 and Hes-1 through Western blotting.Results: BML-111 effectively suppressed the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-18, as well as inflammasome factors NLRP3 and Caspase-1, while simultaneously up-regulating the expression of the anti-inflammatory cytokine IL-10 induced by CSE. Moreover, BML-111 reduced the expression of iNOS, which is associated with M1 macrophage polarization, and increased the expression of Arg-1, which is associated with M2 phenotype. Additionally, BML-111 downregulated the expression of Hes-1 and the ratio of activated Notch-1 to Notch-1 induced by CSE. The effect of BML-111 on inflammation and macrophage polarization was reversed upon administration of the Notch-1 signaling pathway agonist Jagged1.Conclusion: BML-111 has the potential to suppress inflammation and modulate M1/M2 macrophage polarization in RAW264.7 cells. The underlying mechanism may involve the Notch-1 signaling pathway.Keywords: BML-111, macrophage polarization, Notch-1 signaling pathway, COPD

Yan Teng,1 Danfeng Xu,1 Xianhong Yang,1 Hui Tang,2 Xiaohua Tao,1 Yibin Fan,1,&ast; Yang Ding1,&ast; 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Ding; Yibin Fan, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China, Tel +86-13732261339 ; +86-13505811700, Email dingyang@hmc.edu.cn; taoxiaohua@hmc.edu.cnAbstract: Unlike apoptosis, pyroptosis, necroptosis, and ferroptosis are recently identified modes of programmed cell death (PCD) with unique molecular pathways. Increasing evidence has indicated that these PCD modes play a crucial role in the pathogenesis of various non-malignant dermatoses (a group of cutaneous disorders), including infective dermatoses, immune-related dermatoses, allergic dermatoses, benign proliferative dermatoses, etc. Moreover, their molecular mechanisms have been suggested as potential therapeutic targets for the prevention and treatment of these dermatoses. In this article, we aim to review and summarize the molecular mechanisms of pyroptosis, necroptosis, and ferroptosis and their roles in the pathogenesis of some non-malignant dermatoses.Keywords: pyroptosis, necroptosis, ferroptosis, molecular mechanisms, non-malignant dermatoses

Yafan Fan,1,&ast; Tongbo Deng,1,&ast; Min Li2 1School of Public Administration, South China University of Technology, Guangzhou, 510640, People’s Republic of China; 2School of Business Administration, South China University of Technology, Guangzhou, 510641, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yafan Fan, School of Public Administration, South China University of Technology, Guangzhou, 510640, People’s Republic of China, Tel +86 13469968950, Email pafanyafan@mail.scut.edu.cnPurpose: Managing workplace deviance has long been a hot topic in the organizational research. However, the mechanisms through which decent work affects workplace deviance have yet to be fully understood. Drawing upon relative deprivation theory, this study examines the relationship between decent work and workplace deviance by focusing on the mediating role of relative deprivation and the moderating role of career calling.Methods: Two waves of data from 307 doctors and 61 supervisors of public hospitals in central China were examined using a the moderated mediation model.Results: Decent work is negatively associated with workplace deviance via the mediation of relative deprivation, and the negative relationship between decent work and relative deprivation is negatively moderated by career calling. The mediating role of relative deprivation is moderated by career calling, and the indirect effect is stronger when career calling is high than when it is low.Conclusion: By focusing on the mediating role of relative deprivation and the moderating role of career calling, this study contributes to the literature by addressing the previously unexamined relationship between decent work and workplace deviance. Moreover, this study responds to calls for research on decent work from the perspective of relative deprivation.Keywords: decent work, workplace deviance, relative deprivation, career calling, physicians

Zhongbao Wang,1 Yunshao Zheng,2 Yunli Fan,2 Yunming Fan,2 Xianbiao Su,2 Bingrui Wang,2 Jing Li,2 Diancai Chen,2 Fengxia Sun,2 Shen Li,2 Jiashu Ma,1 Xianwei Li,2 Ludong Bai,2 Ranran Li2 1Department of Psychiatry, Jining Medical University, Jining, People’s Republic of China; 2Department of Psychiatry, Shandong Mental Health Center, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Ranran Li, Department of Psychiatry, Shandong Mental Health Center, Shandong University, 49 East Wenhua Road, Jinan, Shandong, 250014, People’s Republic of China, Tel +86 18678777190, Email dtlrr113@126.comBackground: Most antipsychotic drugs are dopamine receptor antagonists that usually lead to abnormal increases in prolactin concentrations and the development of hyperprolactinemia (HPRL), which in turn causes sexual dysfunction in patients. Peony-Glycyrrhiza Decoction (PGD) enhanced dopamine D2 receptors (DRD2) and dopamine transporter (DAT) and significantly reversed the expression of DRD2 and DAT. Therefore, we hypothesized that PGD might effectively improve hyperprolactinemia and alleviate sexual dysfunction in patients.Methods: We performed an 8-week randomized controlled study on 62 subjects with schizophrenia who were randomized into two groups. The experimental group was treated with the PGD intervention, and the control group did not receive treatment. The primary outcome indicators were the levels of sex hormones and the total Arizona Sexual Experience Scale (ASEX) score.Results: There was a significant difference in PRL levels between the two groups at weeks 4 and 8. From the beginning to the end of the experiment, there was a significant increase in PRL levels in the control group, while there was no significant change in the experimental group. The ASEX scale assessed sexual function in both groups, and patients in the experimental group showed an improvement in sexual function at week 8. During the experiment, the two groups found no differences between Positive and Negative Syndrome Scale (PANSS) scores and Treatment Emergent Symptom Scale (TESS) scores.Conclusion: PGD significantly improved the patient’s sexual function but was less effective in reducing prolactin levels and may prevent further increases in prolactin levels.Keywords: hyperprolactinemia, antipsychotics, Peony-Glycyrrhiza Decoction, schizophrenia, sexual function, adverse effects

Yaping Yu,1,&ast; Shun Ding,2,&ast; Xiaoqing Xu,1,&ast; Dongming Yan,3 Yonghao Fan,1 Banzhan Ruan,1 Xiaodian Zhang,1 Liping Zheng,1 Wei Jie,1 Shaojiang Zheng1,4 1Department of Oncology of the First Affiliated Hospital & Tumor Institute, Hainan Medical University, Haikou, 570102, People’s Republic of China; 2Department of Otolaryngology, Head and Neck Surgery, the First Affiliated Hospital, Hainan Medical University, Haikou, 570102, People’s Republic of China; 3Department of Neurosurgery, the First Affiliated Hospital of Hainan Medical University, Haikou, 570102, People’s Republic of China; 4Key Laboratory of Emergency and Trauma, Ministry of Education, Hainan Medical University, Haikou, 571199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Jie; Shaojiang Zheng, Department of Oncology of the First Affiliated Hospital & Tumor Institute, Hainan Medical University, Haikou, 570102, People’s Republic of China, Tel +86-898-66968217 ; +86-898-66568158, Email wei_jie@hainmc.edu.cn; zhengsj2008@163.comPurpose: This study aimed to explore the pharmacological mechanism of Dangshen (Codonopsis pilosula) against hepatocellular carcinoma (HCC) based on network pharmacology and bioinformatics, and to verify the anticancer effect of luteolin, the active ingredient of Codonopsis pilosula, on HCC cells.Methods: The effective compounds and potential targets of Codonopsis pilosula were established using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The genes related to HCC were obtained through the GeneCards database. The interactive genes were imported into the Visualization and Integrated Discovery database for Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal enrichment, and the hub genes were screened out. The Cancer Genome Atlas database was used to construct a prognosis model, and the prognosis and clinicopathological correlation were analyzed. In in vitro experiments, we verified the effects of luteolin, an active compound of Codonopsis pilosula, on the proliferation, cell cycle, apoptosis and migration of HCC cells.Results: A total of 21 effective compounds of Codonopsis pilosula and 98 potential downstream target genes were screened through the TCMSP database, and 1406 HCC target genes were obtained through the GeneCards database. Finally, 53 interacting genes between the two databases were obtained, among which, the 10 key node genes were CASP3, TP53, MDM2, AKT1, ESR1, BCL2L1, MCL1, HSP90AA1, CASP9, and CCND1, involving 77 typical GO terms and 72 KEGG signals. The Kaplan–Meier survival curve of the model group showed that the overall survival of the low-risk group was significantly higher than that of the high-risk group. Luteolin significantly inhibited the proliferation and migration of HCC cells, induced apoptosis, and increased the G2/M phase ratio. Mechanistically, luteolin significantly inhibited the phosphorylation of MAPK-JNK and Akt (Thr308) and subsequently led to upregulation of ESR1. Pharmacological inhibition of ESR1 with fulvestrant enhanced cell viability and migration and attenuated apoptosis.Conclusion: Codonopsis pilosula has potential for clinical development due to its anti-HCC properties. Luteolin, the effective component of Codonopsis pilosula, plays anti-HCC role through AKT- or MAPK-JNK signaling mediated ESR1.Keywords: Codonopsis pilosula, network pharmacology, bioinformatics, luteolin, hepatocellular carcinoma

Yuqian Liao,1,&ast; Yulu Liao,2,&ast; Jun Li,2 Yong Li,1 Ying Fan3 1Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 2Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 3Department of Medical Oncology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Fan, Department of Medical Oncology, Cancer institute and hospital, Peking Union Medical college, Chinese Academy of Medical science, No. 17, Nan Li, Panjiayuan, Beijing, 100021, People’s Republic of China, Tel +86 13693656671, Email fymm000@163.com Yong Li, Department of Oncology, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizhengjie, Donghu, Nanchang, 330006, Jiangxi Province, People’s Republic of China, Tel +86 15879155066, Email liyongly2000@163.comObjective: Human-antigen R (HuR) is an RNA-binding protein, which regulates the expression of several oncogenes and tumor suppressor genes through post-transcriptional mechanisms. But the role of HuR in breast cancer remains controversial. The aim of this study was to verify the association between cytoplasmic HuR level and prognosis of breast cancer patients.Methods: Data mining from the Human Protein Atlas (HPA) and Kaplan–Meier Plotter (KMP) databases was performed. Then, 394 patients with stage I–III primary breast cancer were enrolled between January 2005 and December 2016. We investigated the association between cytoplasmic HuR level and clinicopathological characteristics or survival of these patients. Immunohistochemical analysis was performed to determine HuR expression level. SPSS 21.0 statistical software was used for analysis.Results: In the HPA and KMP datasets, HuR protein and mRNA expression level were not significantly associated with overall survival of all breast cancer patients enrolled. Results from our 394 patients indicated that higher expression level of cytoplasmic HuR was associated with larger tumor size, lymph node positive, ER negative and triple-negative subtype. For all patients enrolled, the results indicated that compared with HuR negative patients, the DFS (disease-free survival) of HuR 1+ was longer (60.5% vs 78.8, P=0.053, HR=0.616, 95% CI: 0.378– 1.005), the P value was borderline. In the triple-negative breast cancer (TNBC) subgroup, HuR positive patients had significantly longer DFS than HuR negative patients (65.5% vs 30.8%, P=0.001, HR=0.345, 95% CI: 0.180– 0.658). In the HR+HER2– subgroup, HuR low (0~1+) patients had significantly longer OS than HuR high (2+~3+) patients (97.0% vs 89.5%, P=0.033, HR=2.482, 95% CI: 1.074– 5.736).Conclusion: In conclusion, our results revealed that higher expression level of HuR was related to aggressive biological characteristics which supported the findings from previous researches. In the HR+HER2– subgroup, lower HuR expression level patients had better survival time, while in the TNBC subgroup we got the opposite results. Our work indicated that HuR might play different roles in different breast cancer subtypes.Keywords: human antigen R, breast cancer, immunohistochemistry, clinicopathological parameters, prognosis

Fan Y, Li Z, Wu L, et al. Drug Des Devel Ther. 2021;15:1509–1519. At the author’s request, we, the Editors and Publisher of Drug Design, Development and Therapy, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 2 and 3 with images from other unrelated articles. Specifically, Images for Figure 2D, have been duplicated with images for Figure 6d from Cheng S, Xia B, Li H, et al. RETRACTED ARTICLE: Long non-coding RNA SATB2-AS1 inhibits microRNA-155-3p to suppress breast cancer cell growth by promoting breast cancer metastasis suppressor 1-like. Cancer Cell Int. 2020;20:321. https://doi.org/10.1186/s12935-020-01411-8; Figure 2B from Wei Y, Liao Y, Deng Y, Zu Y, Zhao B, Li F. MicroRNA-503 Inhibits Non-Small Cell Lung Cancer Progression By Targeting PDK1/PI3K/AKT Pathway. Onco Targets Ther. 2019;12:9005–9016. https://doi.org/10.2147/OTT.S213059; Figure 3B from Qiao Z, Tang J, Wu W, et al. Acteoside inhibits inflammatory response via JAK/STAT signaling pathway in osteoarthritic rats. BMC Complement Altern Med. 2019;19:264. https://doi.org/10.1186/s12906-019-2673-7; Figure 6c from Zhong Q, Huang J, Wei J, et al. Circular RNA CDR1as sponges miR-7-5p to enhance E2F3 stability and promote the growth of nasopharyngeal carcinoma. Cancer Cell Int. 2019;19:252. https://doi.org/10.1186/s12935-019-0959-y and Figure 2B from Ma F, Xie Y, Lei Y, et al. The microRNA-130a-5p/RUNX2/STK32A network modulates tumor invasive and metastatic potential in non-small cell lung cancer. BMC Cancer. 2020;20:580. https://doi.org/10.1186/s12885-020-07056-0. Images for Figure 3A and 3B, have been duplicated with images for Figure 2C and Figure 6C from Tantai J, Zhang Y, Zhao H. Heterophyllin B inhibits the adhesion and invasion of ECA‑109 human esophageal carcinoma cells by targeting PI3K/AKT/β‑catenin signaling. Molecular Medicine Reports. 2016;13:1097–1104. https://doi.org/10.3892/mmr.2015.4659 and Figure 5B from Xu G, Lu X, Huang T, Fan J. ARHGAP24 inhibits cell cycle progression, induces apoptosis and suppresses invasion in renal cell carcinoma. Oncotarget. 2016;7:51829–51839. https://www.oncotarget.com/article/10386/text/. The authors were unable to provide an explanation for the duplicated images or provide data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the authors requested to retract the article and the Editor and Publisher agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

The powder of the hematite sample was isothermally reduced with a hydrogen-water vapor gas mixture at 1023K-1273K. The results indicate that the overall reduction process of hematite can be divided into three stages (Fe2O3-Fe3O4-FeO-Fe) each of which should be investigated. At 1023K, the average reaction rate decreased by 53.6% in stage 1 when the water vapor content of the reaction gas increased from 0% to 50%, and it decreased by about 77.2% in stage 2. However, in stage 3, when the water vapor content increased only from 0% to 20%, it decreased by about 78.1%. The results also show that the influence of water vapor on the reduction reaction increases with increasing reaction temperature in all stages of the reduction reaction. The microstructure of the reduction products showed that they still had some holes; that did not seriously block the channel for hydrogen diffusion. Various models were considered to further clarify the influence of water vapor in the reduction stage The range of apparent activation energy of the different stages obtained by the model fitting was about 20-70 kJ/mol, which also confirmed the absence of the solid-state diffusion phenomenon.

Yan Teng,1 Sujing Li,2 Hui Tang,2 Xiaohua Tao,1 Yibin Fan,1,&ast; Youming Huang1,&ast; 1Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 2Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, 233030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youming Huang; Yibin Fan, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Tel +86-18368023136 ; +86-18806538451, Email huangyouming@hmc.edu.cn; fanyibin@hmc.edu.cnAbstract: Skin infections are common diseases for which patients seek inpatient and outpatient medical care. Globally, an increasing number of people are affected by skin infections that could lead to physical and psychological damage. Skin infections always have a broad spectrum of clinical presentations that require physicians to make an aggressive and accurate diagnosis for prescribing the proper symptomatic antimicrobials. In most instances, the treatment for skin infections mainly includes oral or topical anti-infective drugs. However, some of the classical anti-infective drugs have limitations, such as poor water solubility, low bioavailability, and poor targeting efficiency, which can lead to poor efficacy, adverse effects, and drug resistance. Therefore, research priorities should focus on the development of more effective drug delivery systems with new materials. Hydrogels are a highly multifunctional class of medical materials with potential applications in dermatology. Several hydrogel dressings with anti-infective functions have been formulated and demonstrated to improve the efficacy and tolerance of oral or topical classical anti-infective drugs to a certain degree. In this study, the medical applications of hydrogels for the treatment of various skin infections are systematically reviewed to provide an important theoretical reference for future research studies on the treatment options for skin infections.Keywords: hydrogel, dermatology, skin infections, anti-infective agent, drug delivery systems

Ping Luo,1 Ying Fan,2 Yusha Xiong,2 Chunlin Zhang,1 Zhiping Yang,1 Fenglan Sun,1 Bing Mei1 1Department of Laboratory Medicine, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, People’s Republic of China; 2Gongan County Maternal and Child Health Care Hospital, Jingzhou, People’s Republic of ChinaCorrespondence: Bing Mei, Department of Laboratory Medicine, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, People’s Republic of China, Email meibing008@163.comObjective: To describe the metabolic characteristics of gestational diabetes mellitus (GDM) and assess their effects on perinatal outcomes.Methods: A two-center nested case‒control study was designed, including 192 pregnant women with GDM and 191 pregnant women with normal glucose tolerance (NGT). Serum glucose and insulin concentrations based upon the 75 g oral glucose tolerance test (OGTT) were measured. Several indices were calculated to describe the metabolic characteristics of the subjects. The relationship between glucose metabolism parameters and pregnancy outcomes was evaluated using stepwise linear regression and binary logistic regression.Results: Compared with the NGT group, the GDM group showed significantly higher fasting and postprandial glucose parameters but significantly lower fasting and postprandial insulin responses. Meanwhile, the GDM group had significantly lower HOMA-β, DI and ISIMatsuda but comparable HOMA-IR. The IFG subgroup showed significantly lower FINS/FPG only, while the IGT and IFSG subgroups showed deficiency in both fasting and postprandial insulin response. The IFSG subgroup had the highest glucose parameters and the lowest insulin parameters, as well as significantly lower ISIMatsuda and HOMA-β than the NGT group. FPG had a significant effect on infants’ birth weight, and 1hPG and FINS/FPG had a significant effect on delivery gestational age. AUC-INS, IGI60 and DI were related to premature delivery risk after adjusting for confounders. The IFG subgroup of GDM was 2.319 times more likely to be subject to cesarean section than the NGT group. FPG, FINS/FPG, AUC-GLU, AUC-INS/AUC-GLU and HOMA-β were related to macrosomia risk.Conclusion: Beta cell dysfunction rather than insulin resistance determines the occurrence of GDM in the central Chinese population. Women with predominant insulin secretion defects had a similar risk of adverse perinatal outcomes to women with NGT. Our study provided a basis for the selection of glucose metabolism monitoring indicators useful for the prevention of adverse perinatal outcomes.Keywords: insulin resistance, insulin sensitivity, glucose metabolism, perinatal outcomes, type 2 diabetes mellitus

Chen Jiang,1,&ast; Stefanos Mastrotheodoros,2,3 Yihong Zhu,4,&ast; You Yang,5 Souheil Hallit,6– 8 Bing Zhao,4 Yuping Fan,1 Mengyi Huang,1 Cen Chen,1 Haiyan Ma,1,9 Runtang Meng1,9,&ast; 1School of Public Health, Hangzhou Normal University, Hangzhou, People’s Republic of China; 2Department of Psychology, University of Crete, Rethymno, Greece; 3Department of Youth and Family, Utrecht University, Utrecht, the Netherlands; 4The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, People’s Republic of China; 5School of Nursing, Hangzhou Normal University, Hangzhou, People’s Republic of China; 6School of Medicine and Medical Sciences, Holy Spirit University of Kaslik, Jounieh, Lebanon; 7Applied Science Research Center, Applied Science Private University, Amman, Jordan; 8Research Department, Psychiatric Hospital of the Cross, Jal Eddib, Lebanon; 9Engineering Research Center of Mobile Health Management System, Ministry of Education, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Runtang Meng; Haiyan Ma, School of Public Health, Hangzhou Normal University, No. 2318, Yuhangtang Road, Yuhang District, Hangzhou, Zhejiang, 311121, People’s Republic of China, Email mengruntang@hznu.edu.cn; mahaiyan@hznu.edu.cnPurpose: Stress may relate to an increased risk of psychological and physical disorders. Thus, a brief and efficient measurement instrument for researchers to measure stress is essentially needed.Participants and Methods: To assess measurement properties of the validated Chinese version of the Perceived Stress Questionnaire-13 (PSQ-C-13), we conducted a two-wave longitudinal study from September to December, 2021 with a convenient sample of medical students.Results: A two-factor (constraint and imbalance) structure showed good fit indices (Comparative Fit Index [CFI] = 0.972, Tucker-Lewis Index [TLI] = 0.966, Root Mean Square Error of Approximation [RMSEA] = 0.062). Spearman correlations with the Chinese Perceived Stress Scale-10 illustrated that convergent validity of the PSQ-C-13 was relatively satisfactory (r = 0.678 [baseline], 0.753 [follow-up]). Measurement invariance was supported across subgroups (gender, age, home location, single-child status, monthly households’ income, and part-time status) and time points. Internal consistency was sound (Cronbach’s α = 0.908 [baseline], 0.922 [follow-up]; McDonald’s ω = 0.909 [baseline], 0.923 [follow-up]). Stability between time points was good (Intraclass Correlation Coefficient = 0.834).Conclusion: The two factors of the PSQ-C-13 including constraint and imbalance may adequately measure the level of stress on participants. The PSQ-C-13 is a convenient and efficient instrument that contains valid and reliable psychometric properties.Keywords: Perceived Stress Questionnaire, longitudinal survey, medical students, psychometrics

Yingfeng Tu,1,2 Xiaowei Ma,3 Hao Chen,2,4 Yuhua Fan,5 Lei Jiang,2 Ruiping Zhang,2,6 Zhen Cheng2,4 1Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 2Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Stanford, CA, USA; 3Department of Nuclear Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 5College of Pharmacy, Harbin Medical University, Daqing, Heilongjiang, People’s Republic of China; 6The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, People’s Republic of ChinaCorrespondence: Zhen Cheng, Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, 1201 Welch Road, Lucas Expansion, P095, Stanford University, Stanford, CA, 94305, USA, Tel +01-650-723-7866, Email zcheng@simm.ac.cn Ruiping Zhang, Department of Radiology, the Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, 030032, People’s Republic of China, Email 1900547207@qq.comBackground: Matrix metalloproteinases from macrophages are important intraplaque components that play pivotal roles in plaque progression and regression. This study sought to develop a novel multifunctional positron emission tomography (PET) and magnetic resonance imaging (MRI) contrast agents based on MMP-2 cleavable nanoparticles to noninvasive assessment of MMP-2 activity in mouse carotid atherosclerotic plaques.Results: Macrophage-rich vascular lesions were induced by carotid ligation plus high-fat diet and streptozotocin-induced diabetes in CL57/BL6 mice. To render iron oxide nanoparticles (IONP) specific for the extracellular MMP-2, the magnetic nanoparticle base material has been derivatized with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) for the nuclear tracer 64Cu labeling and the MMP-2-cleavable peptide modified with polyethylene glycol 2000, yielding a multi-modality reporter (64Cu-NOTA-IONP@MMP2c-PEG2K, MMP2cNPs) for PET/MR imaging. Small animal PET imaging and biodistribution data revealed that MMP2cNPs exhibited remarkable plaque uptake (3.06 ± 0.87% ID/g and 1.83 ± 0.28% ID/g at 4 and 12 h, respectively). And MMP2cNPs were rapidly cleared from the contralateral normal carotid artery, resulting in excellent plaque-to-normal carotid artery contrasts. Furthermore, in vivo MRI showed a preferential accumulation of MMP2cNPs in atherosclerotic lesions compared with the non-cleavable reference compound, MMP2ncNPs. In addition, histological analyses revealed iron accumulations in the carotid atherosclerotic plaque, in colocalization with MMP-2 expression and macrophages.Conclusion: Using a combination of innovative imaging modalities, in this study, we demonstrate the feasibility of applying the novel smart MMP2cNPs as a PET/MR hybrid imaging contrast agent for detection of MMP-2 in atherosclerotic plaque in vivo.Graphical Abstract: Keywords: atherosclerosis, macrophage, matrix metalloproteinase-2, nanoparticles, magnetic resonance imaging, positron emission tomography

Yuying Xu,1,&ast; Jintao Huang,2,&ast; Yapei Fan,1 Haiyue Long,1 Minting Liang,1 Qunjie Chen,1 Zhiping Wang,2 Chaoxi Wu,1 Yifei Wang1 1Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaoxi Wu; Yifei Wang, Email chaoxiw@gmail.com; twang-yf@163.comAim: This study focuses on constructing of an anti-inflammatory drug delivery system by encapsulation of berberine in the β-glucan nanoparticles and evaluates its effect on treating ulcerative colitis.Methods: β-Glucan and the anti-inflammatory drug berberine (BER) are self-assembled into nanoparticles to construct a drug delivery system (GLC/BER). The interaction between the drug and the carrier was characterized by circular dichroism, ultraviolet-visible spectroscopy, and dynamic light scattering. The anti-inflammatory effect of the GLC/BER was evaluated through a lipopolysaccharide (LPS)-induced RAW264.7 macrophage inflammation model and a sodium sulfate (DSS)-induced C57BL/6 mouse ulcerative colitis model.Results: The GLC/BER nanoparticles have a particle size of 80– 120 nm and a high encapsulation efficiency of 37.8± 4.21%. In the LPS-induced RAW264.7 macrophage inflammation model, GLC/BER significantly promoted the uptake of BER by RAW264.7 cells. RT-PCR and ELISA assay showed that it could significantly inhibit the inflammatory factors including IL-1β, IL-6 and COX-2. Furthermore, GLC/BER shows inhibiting effect on the secretion of pro-inflammatory factors such as IL-1β and IL-6, down-regulating the production of nitrite oxide; in animal studies, GLC/BER was found to exert a relieving effect on mice colitis.Conclusion: The study found that GLC/BER has an anti-inflammatory effect in vitro and in vivo, and the GLC carrier improves the potency and bioavailability of BER, providing a new type of nanomedicine for the treatment of colitis.Keywords: β-glucan, chiral, drug carrier, immunoregulation, anti-inflammation

Sha Peng,1,2 Xiaoya Kong,1,2 Guiyuan Ma,1,2 Jianmei Hou,1 Lingxia Luo,1 Ran Xu,1,2 Yuhua Fan,1 Jinghui Zhang1– 3 1Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Xiangya Nursing School, Central South University, Changsha, Hunan, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Jinghui Zhang, Email zhangjh-1206@163.comPurpose: The present study aims to evaluate the current situation of knowledge, attitude and practice of clinical nurses in catheter-related thrombosis, analyze its influencing factors, enhance the attention of nursing managers and clinical nurses about catheter-related thrombosis, and provide a basis for formulating catheter-related thrombosis training plan.Patients and Methods: The research was conducted from January 1 to February 31, 2022, we recruited 549 nurses from two hospitals in Hunan province in this cross-sectional study using a two-stage random sampling method. We used a self-designed questionnaire with good reliability and validity to measure clinical nurses’ knowledge, attitudes, and practice toward catheter-related thrombosis. We used χ2 test, Welch t-test, and multiple linear regression analysis to analyze the data.Results: The knowledge of clinical nurses about catheter-related thrombosis was insufficient (55.00%), while the attitude was positive (88.49%) and the practice was inadequate (68.62%). Knowledge of clinical nurses was significantly associated with job title (β: 1.069, P< 0.001), educational level (β: 0.094, P< 0.05), and training times (β: 0.085, P< 0.05), which were positive factors while whether they are specialized nurses in intravenous therapy (β: − 0.126, P< 0.05), and hospital level (β: − 0.101, P< 0.05) were negative factors. Training times (β: 0.166, P< 0.001), job title (β: 0.099, P< 0.019), and hospital level (β: 0.090, P< 0.05) were associated factors of attitude. Moreover, training times (β: 0.255, P< 0.001) was the only factor associated with the practice.Conclusion: Although clinical nurses hold a positive attitude towards catheter-related thrombosis, their knowledge level was unsatisfactory and their practice was affected by many factors, suggesting that nursing managers should strengthen the training and skill assessment of catheter-related thrombosis. At the same time, the hospital can formulate relevant rules, regulations, and guidelines to reduce the incidence of catheter-related thrombosis.Keywords: knowledge, attitude, practice, clinical nurses, catheter-related thrombosis

Dan Liu,1,&ast; YiWen Fan,2,&ast; YuGang Zhuang,1 Hu Peng,1 ChengJin Gao,3 YanQing Chen1 1Emergency Department, Shanghai Tenth People’s Hospital, Affiliated with Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pathology and Medical Biology, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 3Emergency Department, Xinhua Hospital, affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: ChengJin Gao, Emergency Department, Xinhua Hospital, Affiliated to the Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Yangpu District, Shanghai, People’s Republic of China, Tel +86 25076045, Email gaochengjin@xinhuamed.com.cn YanQing Chen, Emergency Department, Shanghai Tenth People’s Hospital, affiliated with Tongji University School of Medicine, No. 301, Yanchang Middle Road, Jingan District, Shanghai, People’s Republic of China, Tel +86 18917683768, Email 18917683768@189.cnPurpose: Sepsis-related disseminated intravascular coagulation (DIC) is closely associated with poor prognosis and high mortality. Higher blood glucose (BG) variability indicates an increased risk of mortality in sepsis; however, its relationship with sepsis-related DIC has not been investigated. This study aimed to determine the association between glucose variability and sepsis-related DIC.Patients and Methods: Patients with sepsis admitted to the intensive care unit were enrolled between October 2017 and January 2021. Baseline data and BG records from the first 72 h were collected. We calculated the glucose liability index (GLI), largest amplitude of glucose excursion, BG standard deviation, and coefficient of variation on days 1 and 3. The relationship between GLI and morbidity of sepsis-related DIC was explored using a competing risk model. In subgroup analysis, we divided patients with and without diabetes into three groups according to the BG range.Results: Of the 238 patients enrolled, 28.2% developed DIC during hospitalization (n=67). GLI on day 3 was found to have the closest relationship with DIC incidence as it has the largest area under the ROC curve and the highest associated odds ratio of death per unit change (GLI3-day: AUC=0.891 OR=1.84), also independently increased the occurrence of DIC after adjusting for the competing risk of death (sub-distribution hazard ratios=1.866, p< 0.01). In subgroup analysis, patients with diabetes had worse outcomes under hypoglycemia than under hyperglycemia. Patients without diabetes having stable BG had the best outcomes.Conclusion: Our study suggested that a higher GLI in patients with sepsis at 72 h was independently associated with an increased risk of sepsis-related DIC, which was not associated with pre-existing diabetes.Keywords: blood disorder, glycemic variability, hypoglycemia, sepsis

Zhiyuan Yang,1,2,&ast; Siyu Zhang,1,2,&ast; Tian Xia,1,2,&ast; Yue Fan,1,2 Ying Shan,1,2 Kaiwen Zhang,1,2 Jiayan Xiong,1,2 Miao Gu,1,2 Bo You1,2 1Department of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, People’s Republic of China; 2Institute of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo You; Miao Gu, Email youbo19891014@163.com; 13862932120@163.comAbstract: RNA modifications occur through the whole process of gene expression regulation, including transcription, translation, and post-translational processes. They are closely associated with gene expression, RNA stability, and cell cycle. RNA modifications in tumor cells play a vital role in tumor development and metastasis, changes in the tumor microenvironment, drug resistance in tumors, construction of tumor cell-cell “internet”, etc. Several types of RNA modifications have been identified to date and have various effects on the biological characteristics of different tumors. In this review, we discussed the function of RNA modifications, including N6-methyladenine (m6A), 5-methylcytosine (m5C), N7-methyladenosine (m7G), N1-methyladenosine (m1A), pseudouridine (Ψ), and adenosine-to-inosine (A-to-I), in the microenvironment and therapy of solid and liquid tumors.Keywords: tumor, RNA modification, non-coding RNA, tumor microenvironment, tumor therapy

Yan Teng, Youming Huang, Xu Danfeng, Xiaohua Tao,* Yibin Fan* Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yibin Fan; Xiaohua Tao, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Tel +86-18806538451 ; Tel +86-13505811700, Email fanyibin@hmc.edu.cn; txhtxh@sina.comAbstract: Solar ultraviolet radiation (UVR) is the primary pathogenetic factor in skin photoaging. It can disrupt cellular homeostasis by damaging DNA, inducing an inflammatory cascade, immunosuppression, and extracellular matrix (ECM) remodeling, resulting in a variety of dermatologic conditions. The skin microbiome plays an important role in the homeostasis and maintenance of healthy skin. Emerging evidence has indicated that highly diverse gut microbiome may also have an impact on the skin health, referred to as the gut-skin axis (GSA). Oral and topical probiotics through modulating the skin microbiome and gut-skin microbial interactions could serve as potential management to prevent and treat the skin photoaging by multiple pathways including reducing oxidative stress, inhibiting ECM remodeling, inhibiting the inflammatory cascade reaction, and maintaining immune homeostasis. In this review, the effects of oral and topical probiotics in skin photoaging and related mechanisms are both described systematically and comprehensively.Keywords: probiotics, skin photoaging, skin microbiome, gut-skin axis, ultraviolet radiation, reactive oxygen species, extracellular matrix

Shan Huang,1 Bingtao Zhai,1 Yu Fan,2 Jing Sun,1 Jiangxue Cheng,1 Junbo Zou,1 Xiaofei Zhang,1 Yajun Shi,1 Dongyan Guo1 1Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, People’s Republic of China; 2School of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang, 712046, People’s Republic of ChinaCorrespondence: Dongyan Guo, Tel +86-029-38185180, Email xmc2051080@163.comBackground: Ulcerative colitis (UC) is one of the intractable diseases recognized by the World Health Organization, and paeonol has been proven to have therapeutic effects. However, the low solubility of paeonol limits its clinical application. To prepare and optimize paeonol liposome, study its absorption mechanism and the anti-inflammatory activity in vitro and in vivo, in order to provide experimental basis for the further development of paeonol into an anti-inflammatory drug in the future.Methods: Paeonol loaded liposomes were prepared and optimized by thin film dispersion-ultrasonic method. The absorption mechanism of paeonol-loaded liposomes was studied by pharmacokinetics, in situ single-pass intestinal perfusion and Caco-2 cell monolayer model, the anti-inflammatory activity was studied in a mouse ulcerative model.Results: Box-Behnken response surface methodology permits to screen the best formulations. The structural and morphological characterization showed that paeonol was entrapped inside the bilayer in liposomes. Pharmacokinetic studies found that the AUC0-t of Pae-Lips was 2.78 times than that of paeonol suspension, indicating that Pae-Lips significantly improved the absorption of paeonol. In situ single intestinal perfusion and Caco-2 monolayer cell model results showed that paeonol was passively transported and absorbed, and was the substrate of P-gp, MRP2 and BCRP, and the Papp value of Pae-Lips was significantly higher than that of paeonol. In vitro and in vivo anti-inflammatory experiments showed that compared with paeonol, Pae-Lips exhibited excellent anti-inflammatory activity.Conclusion: In this study, Pae-Lips were successfully prepared to improve the oral absorption of paeonol. Absorption may involve passive diffusion and efflux transporters. Moreover, Pae-Lips have excellent anti-inflammatory activity in vitro and in vivo, which preliminarily clarifies the feasibility of further development of Pae-Lips into oral anti-inflammatory drugs.Keywords: paeonol liposomes, intestinal absorption, Caco-2 monolayer cell model, absorption mechanism, anti-inflammatory activity

Lei Lei,1 Yihua Bai,1 Yang Fan,1 Yaling Li,1 Hongying Jiang,1 Jiaping Wang2 1Department of Nephrology, The Second Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Department of Radiology, The Second Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, People’s Republic of ChinaCorrespondence: Yihua Bai, Department of Nephrology, The Second Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, People’s Republic of China, Email baiyihua@kmmu.edu.cnBackground: Diabetic nephropathy (DN) is a primary driver of end-stage renal disease. Given the heterogeneity of renal lesions and the complex mechanisms of DN, the present-day diagnostic approach remains highly controversial. We aimed to design a diagnostic model by bioinformatics methods for discriminating DN patients from normal subjects.Methods: In this study, transcriptome sequencing was performed on 6 clinical samples (3 from DN patients and 3 from healthy volunteers) from the Second Affiliated Hospital of Kunming Medical University. Construction of a competing endogenous RNA (ceRNA) network based on differentially expressed (DE)-mRNAs and -long noncoding RNAs (lncRNAs). Subsequently, the CytoHubba plugin was used to identify hub genes from DE-mRNAs in the ceRNA network and to perform functional enrichment analysis on them. The least absolute shrinkage and selection operator (LASSO) regression analysis was responsible for screening the diagnostic biomarkers from hub genes and assessing their diagnostic power using ROC curves. The pathways involved in hub genes were revealed by single-gene Gene Set Enrichment Analysis (GSEA). Moreover, we verified the expression levels of diagnostic biomarkers by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot.Results: A total of 10 hub genes were screened from the ceRNA network, which appeared to be associated with the viral infection, kidney development, and regulation of immune and inflammatory responses. Subsequently, LASSO regression analysis established a diagnostic model consisting of DDX58, SAMD9L, and TLR6 with a robust diagnostic potency (AUC = 1). Similarly, single-gene GSEA showed a strong association of these diagnostic biomarkers with the viral infection. Furthermore, PCR and Western blot demonstrated showed that DDX58, SAMD9L, and TLR6 were upregulated in DN patients at both transcriptome and protein levels compared to healthy controls.Conclusion: We confirmed that differentially expressed hub genes may be novel diagnostic biomarkers in DN.Keywords: diabetic nephropathy, DN, diagnosis, ceRNA, biomarker

Peng Wang,1,2,&ast; Yueying Fan,2,&ast; Wenqin Lian,2,&ast; Yingjun Su,3 Hou’an Xiao,1 Chiyu Jia2 1Department of Burns and Plastic and Cosmetic Surgery, Xi’an Ninth Hospital, Xi’an, People’s Republic of China; 2Department of Burns and Plastic and Wound Repair Surgery, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 3Department of Burns and Plastic Surgery, Plastic Surgery Hospital, Xi’an International Medical Center, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chiyu Jia, Department of Burns and Plastic and Wound Repair Surgery, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China, Email jiachiyu@qq.com Hou’an Xiao, Department of Burns and Plastic and Cosmetic Surgery, Xi’an Ninth Hospital, Xi’an, People’s Republic of China, Email xiaohouan@163.comObjective: To investigate the application of local rotation flaps for reconstruction of divided nevi of the penises in young male patients.Methods: A group of 8 patients of divided nevi of the penises who underwent wound reconstruction with local rotation flaps after surgical lesion removal was enrolled in a retrospective clinical study. Postoperative complication, sexual function and psychological traits were evaluated during the follow-up.Results: All patients, with ages ranged from 16 to 32 years (mean 23.25 years), were followed up for 6 to 48 months (mean 19.86 months). The patient’s average length of hospital stay was 7.85 day (7 to 15 days). The average dimension of the lesions was (2.31± 0.44) × (1.46± 0.48) cm2 on the glans and (1.38± 0.40) × (1.01± 0.46) cm2 on the inner prepuce plate. All patients had no postoperative infection and were satisfied with the postoperative outcome upon discharge. Five cases of benign intradermal nevi and 3 cases of compound nevi without malignant transformation were confirmed by pathological evaluation on the removed samples. The sexual function of all patients was unaffected postoperatively by male sexual function scale (BMSFI and IIEF-5) evaluation. The psychological status of depression, anxiety and stress was all improved after the surgical reconstruction confirmed by the psychological traits scale (DASS) evaluation.Conclusion: Reconstruction with the local rotation flap is a simple, safe and appropriate surgical procedure, achieves satisfactory cosmetic outcome, and maintains intact male sexual function when used for the repair of defect after removal of divided nevi of the penises.Keywords: divided nevi, local rotation flap, genital plastic surgery, postoperative, follow-up

Xinwei Li,1,&ast; Yongfei Fan,2,&ast; Mingyue Tang,1 Huiyuan Li,1 Yue Zhang,1 Jiaqi Mi,1 Yanyan Wang,1 Menglin Zhao,1 Zishu Wang,1 Fang Su1 1Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, People’s Republic of China; 2Department of Thoracic Surgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Su; Zishu Wang, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People’s Republic of China, Tel +86 13605523272; +86 13955254185, Email sufang@bbmc.edu.cn; wzshahbb@163.comBackground: Research has revealed that Plexin domain containing 1 (PLXDC1) is correlated with the prognosis of a variety of tumors, but its role in the tumor microenvironment (TME) of gastric cancer has not been reported.Methods: In this study, we analyzed PLXDC1 expression in gastric cancer using the Oncomine and the Cancer Genome Atlas (TCGA) databases and immunohistochemical staining experiments, and performed prognostic assessment with data from the TCGA and Kaplan–Meier Plotter databases. The immunomodulatory role of PLXDC1 in the gastric cancer TME was analyzed by signaling pathway enrichment, immune cell correlation analysis, immunomodulator risk model construction and immunohistochemical staining experiments of immune cells.Results: The results indicated that PLXDC1 was overexpressed in gastric cancer and that its overexpression was associated with poor prognosis. Multivariate Cox analysis revealed that PLXDC1 could be an independent biomarker of the risk of gastric cancer. Signaling pathway enrichment revealed that high PLXDC1 expression was involved in signaling pathways related to immune activation and stromal activation, and Tumor Immune Dysfunction and Exclusion (TIDE) assessment indicated that high PLXDC1 expression was associated with a significantly higher risk of immune evasion than low PLXDC1 expression. A Cox risk model based on PLXDC1-associated immunomodulators also presented poor prognosis, and immune evasion was significantly higher in the high-risk group than in the low-risk group. In addition, immunohistochemical staining of CD8/CD3/CD4+ T cells in the high and low PLXDC1 expression groups also observed immune cell distribution characteristics of immune evasion.Conclusion: This study analyzed PLXDC1 from multiple biological perspectives and revealed that PLXDC1 can be a biomarker for poor prognosis and immune evasion in gastric cancer.Graphical Abstract: Keywords: PLXDC1, biomarker, tumor microenvironment, immune evasion, prognosis, immunotherapy