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Jianrong Zhang,1,* Yiyu Tang,1 Shaoting Feng,1,* Io Nam Wong,2,* Yue Guo,1 Jun Zhang,1 Jiancong Chen,1 Daya Yang,1 Kunsong Zhang,1 Wenbao Yao,1 Rong Li,1 Yaying Bai,1 Shuqin Ding,1 Ming Kuang,1 Haipeng Xiao,1 Dan Xu1,3,* 1Department of Medical Education, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2General Practice Research, Faculty of Medicine, Macau University of Science & Technology, Taipa, 999078, Macau; 3General Practice Research, Curtin School of Population Health/Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, WA, Australia*These authors contributed equally to this workCorrespondence: Ming Kuang; Shuqin Ding, Email kuangm@mail.sysu.edu.cn; dingshq@mail.sysu.edu.cnIntroduction: The rising demand for knowledge updates and technological innovations in China has made clinical placement teaching challenging. Reforms for innovative teaching models through pilot classes have shown to improve students’ academic performance. This novel integration led to the announcement of healthcare collaboration in the Guangdong-Hong-Kong-Macao Greater Bay Area for projects within China’s “Global-Innovation-Hub” zones. First Affiliated Hospital (FAH) of Sun Yat-sen University (SYSU) in Guangzhou and the Faculty of Medicine (FMD) of Macau University of Science & Technology (MUST) in Macau have developed an inaugural project for FMD/MUST medical students to perform pre-internships at FAH-SYSU. This study aimed to reflect on students’ experiences with collaborative teaching and learning through medical curricular integration in the “Global-Innovation-Hub” zones designed by both institutions for developing integrated curriculum.Methods: FMD/MUST students attended medical clerkships at FAH-SYSU using a system-integrated curriculum in China’s “Global-Innovation-Hub” zones, allowing different education systems at different locations. Post-clerkship surveys ranked teaching models in conjunction with written reflections in response to post-clerkship questionnaires for all participating students. The teaching models were defined by the way supervisors’ interaction with students, and written reflections in response to the post-clerkship questionnaire were descriptively and semantically analysed.Results: The top-ranked teaching models include first “Student-led consultation under supervision in observers’ chair with discussion”, second “Observe consultation and discuss with the teacher in-between patients in observers’ chair” and third “Student-led consultation under supervision in consultants’ chair with discussion”. The post-clerkship questionnaires showed positive outcomes.Conclusion: This study demonstrates the successful delivery of collaborative teaching and learning through medical curricular integration in China’s “Global-Innovation-Hub” zones. This integration enables the development of a consistent and student-preferred teaching model being introduced into clinical placement curriculum. The unique location of China’s “Global-Innovation-Hub” zones in the Guangdong-Hong-Kong-Macao Greater Bay Area allows this integration to significantly improve students’ clinical reasoning learning.Keywords: Guangdong-Hong Kong-Macao Greater Bay Area, Global Innovation Hub, teaching model integration, clinical placement teaching, clinical reasoning learning

Yanling Huang,1,* Bing Li,1,* Suibin Feng,2,* Sifen Jiang,1 Kun Zeng1,3 1School of Nursing, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Pediatric Urology Department, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, People’s Republic of China; 3Science and Education Section, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kun Zeng, School of Nursing, Guangdong Pharmaceutical University, No. 283, Jianghai Avenue, Haizhu District, Guangzhou City, Guangdong Province, 510310, People’s Republic of China, Tel +86 13790300213, Email zengkun660524@163.comPurpose: This study aimed to investigate the current state of empathy for pain among clinical nurses, analyze the relationship between resilience and empathy for pain, and explore the mediating effects of coping styles.Methods: This was a multicenter cross-sectional study conducted among 1601 clinical nurses in Guangdong Province, China. The convenience sampling method was used to collect data from Sociodemographic information, the 14-Item Resilience Scale, the Simplified Coping Style Questionnaire, and the Chinese version of the Empathy for Pain Scale from June to September 2023. To analyze the relationship between resilience, coping styles, and empathy for pain among clinical nurses with descriptive statistics, Spearman correlation analysis, and mediation analysis.Results: The empathy for pain score among Chinese clinical nurses was 2.92 ± 0.79, with the empathy reactions dimension at 3.56 ± 0.74, and the body and mind discomfort reactions dimension at 2.70 ± 0.89. Clinical nurses’ resilience was positively related to the coping styles and the empathy reactions dimension, whereas negatively associated with the body and mind discomfort reactions dimension. Coping styles were negatively related to the empathy for pain and the body and mind discomfort reactions dimension, whereas positive with the empathy reactions dimension. Coping styles partially mediated between resilience and empathy reactions dimension (β=0.127, 95% CI: 0.070~0.183), accounting for 56.19% of the total effect. There were suppressing effects of coping styles between resilience and empathy for pain (β=− 0.157, 95% CI: − 0.189~-0.126), the body and mind discomfort reactions dimension (β=− 0.172, 95% CI: − 0.203~-0.142).Conclusion: The effects of resilience on clinical nurses’ empathy for pain were partially mediated and suppressed by coping styles. During clinical pain management, nursing administrators should focus on developing clinical nurses’ resilience and positive coping strategies to improve nurses’ physical and mental health, optimize pain management, and foster a heightened sense of empathy for pain.Keywords: resilience, coping styles, empathy for pain, mediating effect, suppressing effect

Bo Xu,1 Xudong Zhao,2 Lei Zhang,1 Shouhan Feng,3 Jinxia Li,1 Ye Xu4 1Acupuncture and Rehabilitation Department, Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Huzhou, Zhejiang, People’s Republic of China; 2Physical Therapy Center, Huzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, People’s Republic of China; 3Oncology Department, Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Huzhou, Zhejiang, People’s Republic of China; 4Rehabilitation Department, Huzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Ye Xu, Rehabilitation Department, Huzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, No. 2088 Tiaoxi East Road, Huzhou City, Zhejiang Province, People’s Republic of China, Email 15268277775@163.comPurpose: Pain management for spinal facet joint (SFJ) and sacroiliac joint (SIJ) pain is challenging, often requiring interventions like radiofrequency ablation (RFA) or corticosteroid injections (CI). This study aims to assess and compare the effectiveness of CI and RFA in treating SFJ and SIJ pain. We combine these treatments due to their shared pathophysiology, similar therapeutic interventions, and the necessity for an integrated approach to spinal pain management.Patients and methods: Literature search from PubMed, Scopus, CENTRAL and Google Scholar for published studies upto 31st December 2023, and reporting data of patients who were treated using CI of RFA for SFJ and SIJ pain. Pooled standardized mean difference (SMD) with a 95% Confidence Interval (CI) was calculated.Results: Our meta-analysis incorporated thirteen studies. Overall, patients, treated with CI had a higher pain intensity score compared to patients treated with RFA (SMD=0.92; 95% CI: 0.19 to 1.65) at 3 months, and at 6 months (SMD=1.53; 95% CI: 0.66 to 2.40) after the treatment. No significant association was reported at 12 months (SMD=1.47; 95% CI: − 0.03 to 2.97). Subgroup analysis based on joint types revealed increased pain intensity scores in patients who were treated with CI for SIJ (SMD=1.25; 95% CI: 0.39 to 2.11) and SFJ (SMD=1.33; 95% CI: 0.09 to 2.57) pain. A negative but not significant effect was detected in patients, treated with CI for cervical joint pain (SMD=− 0.40; 95% CI: − 0.90 to 0.10). Patients treated with CI exhibited higher functional disability score compared to patients treated with RFA at 3 months (SMD=1.28; 95% CI: 0.20 to 2.35) post-treatment.Conclusion: This study suggests that RFA may offer superior pain relief with longer duration compared to steroid injections for spinal facet and sacroiliac joint pain. Decision regarding specific interventions should be individualized and consider patient preferences, clinical context, and potential risks.Keywords: radiofrequency ablation, steroid injections, spinal facet pain, sacroiliac joint pain, systematic review, meta-analysis, pain management

Kehua Jiang,1 Qing Wang,1 Xiao-Long Chen,1 Xiaodong Wang,1 Xiaoya Gu,1 Shuangshuang Feng,1 Jian Wu,2 Haojie Shang,2 Xiaozhuo Ba,2 Yanlong Zhang,1 Kun Tang2 1Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 2Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Yanlong Zhang, Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China, Email ylzhang3030@163.com Kun Tang, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Qiaokou District, Wuhan, 430030, People’s Republic of China, Email tangsk1990@163.comAbstract: Tryptophan (Trp) metabolism plays a vital role in cancer immunity. Indoleamine 2.3-dioxygenase 1 (IDO1), is a crucial enzyme in the metabolic pathway by which Trp is degraded to kynurenine (Kyn). IDO1-mediated Trp metabolites can inhibit tumor immunity and facilitate immune evasion by cancer cells; thus, targeting IDO1 is a potential tumor immunotherapy strategy. Recently, numerous IDO1 inhibitors have been introduced into clinical trials as immunotherapeutic agents for cancer treatment. However, drawbacks such as low oral bioavailability, slow onset of action, and high toxicity are associated with these drugs. With the continuous development of nanotechnology, medicine is gradually entering an era of precision healthcare. Nanodrugs carried by inorganic, lipid, and polymer nanoparticles (NPs) have shown great potential for tumor therapy, providing new ways to overcome tumor diversity and improve therapeutic efficacy. Compared to traditional drugs, nanomedicines offer numerous significant advantages, including a prolonged half-life, low toxicity, targeted delivery, and responsive release. Moreover, based on the physicochemical properties of these nanomaterials (eg, photothermal, ultrasonic response, and chemocatalytic properties), various combination therapeutic strategies have been developed to synergize the effects of IDO1 inhibitors and enhance their anticancer efficacy. This review is an overview of the mechanism by which the Trp-IDO1-Kyn pathway acts in tumor immune escape. The classification of IDO1 inhibitors, their clinical applications, and barriers for translational development are discussed, the use of IDO1 inhibitor-based nanodrug delivery systems as combination therapy strategies is summarized, and the issues faced in their clinical application are elucidated. We expect that this review will provide guidance for the development of IDO1 inhibitor-based nanoparticle nanomedicines that can overcome the limitations of current treatments, improve the efficacy of cancer immunotherapy, and lead to new breakthroughs in the field of cancer immunotherapy.Keywords: indoleamine 2, 3-dioxygenase 1, IDO1, IDO1 inhibitors, nanodrugs, nanodelivery, cancer immunotherapy, combination therapy

Kang He,1,* Jie Zang,2,* Tingting Ren,1,* Shaojie Feng,3 Mohan Liu,1 Xude Zhang,3 Wenchang Sun,2 Jinjin Chu,2 Donghua Xu,2 Fengxia Liu3 1Department of Clinical Medicine of Shandong Second Medical University, Weifang, People’s Republic of China; 2Central Laboratory, Weifang People’s Hospital, Shandong Second Medical University/Weifang People’s Hospital, Weifang, People’s Republic of China; 3Department of Allergy, Weifang People’s Hospital, Shandong Second Medical University, Weifang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Donghua Xu; Fengxia Liu, Email flower322@163.com; wf_lfx@163.comAbstract: Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense itchiness that is highly prevalent worldwide.The pathogenesis of AD is complex and closely related to genetic factors, immunopathogenic factors, environmental factors, and skin infections. Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells derived from the mesenchymal stroma. They have anti-inflammatory, anti-apoptotic, and regenerative properties. Numerous studies demonstrate that MSCs can play a therapeutic role in AD by regulating various immune cells, maintaining immune homeostasis, and promoting the repair of damaged tissues. The key mediators for their biological functions are extracellular vesicles (MSC-Evs) and soluble cytokines derived from MSCs. The safety and efficacy of MSCs have been demonstrated in clinical Phase I / IIa trials for AD. This paper provides a comprehensive review of the pathogenesis of AD and the currently published studies on the function of MSCs and MSC-Evs in AD, primarily including the pathogenesis and the immunomodulatory impacts of MSCs and MSC-Evs, along with advancements in clinical studies. It provides insights for comprehending AD pathogenesis and investigating treatments based on MSCs.Keywords: atopic dermatitis, mesenchymal stem cells, Th2-associated immunity, extracellular vesicle

Lianjie Miao, Songwei Feng, Bo Ding, Ke Zhang, Yue Ding, Yang Shen Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of ChinaCorrespondence: Yang Shen, Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210096, People’s Republic of China, Email shenyang@seu.edu.cnPurpose: The aim of this study was to analyze the survival of patients with endometrial cancer diagnosed after a prior cancer and identify risk factors of endometrial cancer death in this population.Methods: Totally 1371 women diagnosed with second primary endometrial cancer (SPEC) between 2004 and 2015 were identified using the SEER database. Clinicopathological characteristics were collected, and Fine and Gray regression model was employed to assess the impact of treatment for the first primary cancer (FPC) and SPEC on the mortality of endometrial cancer patients. After propensity score matching (PSM), patients diagnosed with single primary endometrial cancer and SPEC between 2004 and 2015 were included as the second cohort. Kaplan-Meier and Cox survival risk models were used to assess the influence of previous cancer history on survival.Results: Patients previously diagnosed as lung cancer exhibited the lowest overall survival (OS). A diagnostic interval of ≥ 3 years was significantly associated with higher mortality from SPEC compared with that < 3 years. Surgical treatment for SPEC was linked to a reduced risk of endometrial cancer-specific mortality (ECSM) and non-ECSM. Conversely, radiotherapy and chemotherapy were associated with an increased risk of ECSM. The 1-, 3-, and 5-year OS rates of patients with SPEC were significantly lower than those with single primary endometrial cancer whether before or after PSM. Univariate and multivariate analyses further demonstrated that endometrial cancer, either as FPC or SPEC, was independently associated with an increased risk for endometrial cancer-specific survival (ECSS) and OS.Conclusion: Chemotherapy and radiotherapy for SPEC can elevate the risk of ECSM. Whether as FPC or SPEC, endometrial cancer is demonstrated to be a significant independent risk factor for ECSS and OS.Keywords: second primary cancer, endometrial cancer, risk factor, overall survival, SEER database

Sitong Feng,1,2,&ast; Ziyao Wu,1,2,&ast; Sisi Zheng,1,2 Linrui Dong,1,2 Hongxiao Jia,1,2 Yanzhe Ning1,2 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanzhe Ning; Hongxiao Jia, Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China, Email ningzy0923@mail.ccmu.edu.cn; jhxlj@ccmu.edu.cnObjective: The thalamus plays a critical role in attentional maintenance. Previous studies have revealed the dysfunction of the thalamus in attention decline after acute sleep deprivation (SD). However, the functional connectivity (FC) between the thalamus subregions and cortical regions underlying attentional impairment after acute SD remains unclear. Here, we aimed to probe the relationship between attentional function and the altered thalamocortical FC after acute SD.Methods: In this study, 25 healthy participants with regular sleep conducted an attentional network test and received a resting-state fMRI scan before and after 24 hours of SD. Then, we analyzed the FC between the thalamus and cerebrum and relationships with attentional function in the enrolled subjects.Results: Our results showed that the participants showed a significantly lower alerting effect, a higher executive effect, and lower accuracy after acute SD. Compared to the rested wakefulness state, we observed decreased FCs between the “somatosensory” thalamic seed and left frontal pole, right frontal pole, left middle temporal gyrus (posterior division), and right middle temporal gyrus (posterior division). Furthermore, the reduced FC between the right middle temporal gyrus and “somatosensory” thalamic seed was negatively associated with the change in orienting effect of the participants.Conclusion: Our findings reveal that the disrupted FC between thalamus subregions and cortical regions may contribute to impaired attention after SD.Keywords: sleep deprivation, fMRI, attention, thalamus, functional connectivity

Zhihong Cheng,1,&ast; Song Feng,1,2,&ast; Linfeng Yang,1 Jing Huang,3 Xilei Chen,4 Yang Guo,1 Yu Xiang,1 Bin Peng1 1Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Department of Neurosurgery, Dazhou Third People’s Hospital, Dazhou, Sichuan, People’s Republic of China; 3Innovation Center for Science and Technology, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 4Department of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Peng, Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, No. 234 Fujiang Road, Shunqing District, Nanchong, Sichuan, People’s Republic of China, Tel/Fax +86-817-2242781, Email binpeng01@sina.comPurpose: The spinal nerve ligation (SNL) model is a typical peripheral neuropathic pain model. During its construction, the removal of paraspinal muscles and transverse processes typically occurs, resulting in additional trauma that may potentially affect the pathophysiologic process of neuropathic pain. This study aimed to investigate the feasibility of establishing a more reliable SNL model using an oblique lateral approach.Methods: 36 adult male Sprague-Dawley rats were randomly divided into three groups: the traditional SNL (T-SNL) group, the new SNL (N-SNL) group (where the left L5 spinal nerve was ligated with a titanium clip via an oblique lateral approach), and the sham-operated (Sham) group. The operation time, Intraoperative bleeding, the number of rats that died, gait behavior, mechanical and cold pain threshold were recorded and measured. Stereology technology was used to calculate the number of microglia in spinal dorsal horn, and the Enzyme-linked immunosorbent assay (ELISA) technology was used to detect the expression of TNF-α and IL-1β in spinal cord as well as C-reactive protein (CRP) in serum in order to assess the effect of surgery on animal inflammation.Results: Compared with the T-SNL group, operative time and intraoperative bleeding were significantly decreased in the N-SNL group. Within 14 days postoperation, one rat in the N-SNL group was died, two rats in the T-SNL group were died. Compared with the Sham group, the N-SNL group showed obvious spontaneous pain behavior, decreased the pain thresholds, the number of microglia and the expression of TNF-α and IL-1β were significantly increased, and there was no significant difference in these indexes compared with T-SNL group. There was no significant difference in serum CRP levels among the three groups.Conclusion: This study suggests that the oblique lateral approach SNL model is a reliable NP model with the advantages of good reproducibility, accessibility, and low trauma.Keywords: animal model, mechanical pain threshold, hyperpathia, microglial, peripheral nerve injury, inflammatory

Kunping Cui,1 Yi Mao,2 Shuang Feng,3 Haixia Luo,2 Jiao Yang,2 Lang Bai1 1Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Intensive Care Unit, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, 610000, People’s Republic of China; 3Ultrasonic Medicine, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, 610000, People’s Republic of ChinaCorrespondence: Lang Bai, Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-18980602254, Email pangbailang@163.comPurpose: The mortality rate from pulmonary tuberculosis (PTB) complicated by severe community-acquired pneumonia (SCAP) in the intensive care unit (ICU) remains high. We aimed to develop a rapid and simple model for the early assessment and stratification of prognosis in these patients.Patients and Methods: All adult patients with PTB complicated by SCAP admitted to the ICU of a tertiary hospital in Chengdu, Sichuan, China between 2019 and 2021 (development cohort) and 2022 (validation cohort) were retrospectively included. Data on demographics, comorbidities, laboratory values, and interventions were collected. The outcome was the 28-day mortality. Stepwise backward multivariate Cox analysis was used to develop a mortality risk prediction score model. Receiver operating characteristic (ROC) and calibration curves were used to evaluate the model’s predictive efficiency. Decision curve analysis (DCA) was used to validate the model’s clinical value and impact on decision making.Results: Overall, 357 and 168 patients were included in the development and validation cohorts, respectively. The Pulmonary Tuberculosis Severity Index (PTSI) score included long-term use of glucocorticoid, body mass index (BMI) < 18.5 kg/m2, diabetes, blood urea nitrogen (BUN) ≥ 7.14 mmol/L, PO2/FiO2 < 150 mmHg, and vasopressor use. The area under the ROC curve (AUC) values were 0.817 (95% CI: 0.772– 0.863) and 0.814 for the development and validation cohorts, respectively. The PTSI score had a higher AUC than the APACHE II, SOFA, and CURB-65 score. The calibration curves indicated good calibration in both cohorts. The DCA of the PTSI score indicated the high clinical application of the model compared with the APACHE II and SOFA scores.Conclusion: This prognostic tool was designed to rapidly evaluate the 28-day mortality risk in individuals with PTB complicated by SCAP. It can stratify this patient group into relevant risk categories, guide targeted interventions, and enhance clinical decision making, thereby optimizing patient care and improving outcomes.Keywords: pulmonary tuberculosis, severe community-acquired pneumonia, mortality risk prediction, intensive care unit

Qian Chen,1,2 Chengyin Yu,1,2 Qingqing Wu,1,2 Rong Song,1,2 Ye Liu,1,2 Sheng Feng,3 Chen Yu,1,2 Jingying Jia1,2 1Center Laboratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, People’s Republic of China; 3Jiangsu Hengrui Pharmaceuticals Co., Ltd, Lianyungang, Jiangsu, People’s Republic of ChinaCorrespondence: Jingying Jia, Center Laboratory, Shanghai Xuhui Central Hospital, No. 966, Huaihai Road (M), Shanghai, People’s Republic of China, Tel/Fax +86-21-54030254, Email jyjia@shxh-centerlab.comPurpose: Henagliflozin is an original, selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. Hydrochlorothiazide (HCTZ) is a common anti-hypertensive drug. This study aimed to evaluate the potential interaction between henagliflozin and HCTZ.Methods: This was a single-arm, open-label, multi-dose, three-period study that was conducted in healthy Chinese volunteers. Twelve subjects were treated in three periods, period 1: 25 mg HCTZ for four days, period 2: 10 mg henagliflozin for four days and period 3: 25 mg HCTZ + 10 mg henagliflozin for four days. Blood samples and urine samples were collected before and up to 24 hours after drug administrations on day 4, day 10 and day 14. The plasma concentrations of henagliflozin and HCTZ were analyzed using LC-MS/MS. The urine samples were collected for pharmacodynamic glucose and electrolyte analyses. Tolerability was also evaluated.Results: The 90% CI of the ratio of geometric means (combination: monotherapy) for AUCτ,ss of henagliflozin and HCTZ was within the bioequivalence interval of 0.80– 1.25. For henagliflozin, co-administration increased Css, max by 24.32% and the 90% CI of the GMR was (108.34%, 142.65%), and the 24-hour urine volume and glucose excretion decreased by 0.43% and 19.6%, respectively. For HCTZ, co-administration decreased Css, max by 19.41% and the 90% CI of the GMR was (71.60%, 90.72%), and the 24-hour urine volume and urinary calcium, potassium, phosphorus, chloride, and sodium excretion decreased by 11.7%, 20.8%, 11.8%, 11.9%, 22.0% and 15.5%, respectively. All subjects (12/12) reported adverse events (AEs), but the majority of theses AEs were mild and no serious AEs were reported.Conclusion: Although Css,max was affected by the combination of henagliflozin and HCTZ, there was no clinically meaningful safety interaction between them. Given these results, coadministration of HCTZ should not require any adaptation of henagliflozin dosing.Trial Registration: ClinicalTrials.gov NCT06083116.Keywords: henagliflozin, drug-drug interaction, hydrochlorothiazide, pharmacokinetics, tolerability, pharmacodynamics, selective sodium-glucose cotransporter 2

Xiaoliang Liu,1,&ast; Kecheng Lou,2,&ast; Yunmeng Zhang,3 Chuanxiao Li,1 Shenghong Wei,1 Shangzhi Feng1 1Department of Urology, Jiujiang University Clinic College/Hospital, Jiujiang, Jiangxi, People’s Republic of China; 2Department of Urology, Lanxi People’s Hospital, Jinhua, Zhejiang, People’s Republic of China; 3Department of Anesthesiology, Jiujiang College Hospital, Jiujiang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shangzhi Feng, Email 1131718266@qq.comAbstract: Botanical preparations for herbal medicine have received more and more attention from drug researchers, and the extraction of active ingredients and their successful clinical application have become an important direction of drug research in major pharmaceutical companies, but the complexity of extracts, multiple side effects, and significant individual differences have brought many difficulties to the clinical application of herbal preparations. It is noteworthy that extracellular vesicles as active biomolecules extracted from medicinal plants are believed to be useful for the treatment of a variety of diseases, including cancer, inflammation, regenerative-restorative and degenerative diseases, which may provide a new direction for the clinical utilization of herbal preparations. In this review, we sort out recent advances in medicinal plant extracellular vesicles and discuss their potential as disease therapeutics. Finally, future challenges and research directions for the clinical translation of medicinal plant extracellular vesicles are also discussed, and we expect that continued development based on medicinal plant extracellular vesicles will facilitate the clinical application of herbal preparations.Keywords: plant-derived extracellular vesicles, Chinese medicine preparation, nanoparticle, drug delivery nanoplatforms, nanotherapeutics

Kunping Cui,1,&ast; Yi Mao,2,&ast; Shuang Feng,3 Haixia Luo,2 Jiao Yang,2 Ruyi Xu,1 Lang Bai1 1Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Intensive Care Unit, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, 610000, People’s Republic of China; 3Ultrasonic Medicine, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, 610000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lang Bai, Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-18980602254, Email pangbailang@163.comPurpose: Age is considered a vital factor in intensive care units (ICUs) because of its association with physiological frailty, comorbidities, and immune system function. Previous studies have examined the association between age and prognosis in patients with tuberculosis (TB) or sepsis; however, the association between age and prognosis in ICU patients with TB complicated by sepsis is rare. This study aimed to assess the association between age and the prognosis of patients in the ICU with TB complicated by sepsis.Patients and Methods: Data from the ICU of the Public Health Clinical Center of Chengdu were analyzed using the multivariable Cox regression model, stratified analysis with interaction, restricted cubic spline (RCS), and threshold effect analysis to investigate the association between age and 28-day all-cause mortality in patients with TB complicated by sepsis.Results: In total, 520 patients diagnosed with TB and sepsis were enrolled (120 women [23.1%]; median age, 64 years). The association between age and risk of death exhibited a J-shaped curve on the RCS (P for nonlinearity = 0.001). In the threshold analysis, the hazard ratio for the risk of death was 1.104 (95% confidence interval, 1.05– 1.16) in participants aged ≥ 66.2 years. The risk of death increased by 10.4% with every 1-year increase in age in patients with TB complicated by sepsis. No significant association was found between age and 28-day all-cause mortality in patients aged < 66.2 years.Conclusion: A nonlinear relationship was observed between age and short-term all-cause mortality in patients in the ICU with TB complicated by sepsis. Patients with a higher age at admission may have a higher risk of death and require focused attention, close monitoring, and early treatment to reduce mortality.Keywords: sepsis, tuberculosis, age, 28-day all-cause mortality, intensive care unit

Jia Li,1,2 Wenjing Guo,1,2 Jieru Wang,1,2 Xiaomeng Feng,1,2 Qingsong Lin,1,2,&ast; Yizhou Zheng,1,2 Fengkui Zhang,1,2 Yingchang Mi,1,2 Xiaofan Zhu,1,2 Erlie Jiang,1,2 Zhijian Xiao,1,2 Jianxiang Wang,1,2 Sizhou Feng1,2,&ast; 1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, People’s Republic of China; 2Tianjin Institutes of Health Science, Tianjin, 301600, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sizhou Feng, Hematopoietic Stem Cell Transplantation Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 288 Nanjing Road, Tianjin, 300020, People’s Republic of China, Tel +86-022-23909162, Fax +022-23909047, Email doctor_szhfeng@163.com; szfeng@ihcams.ac.cnObjective: This study aimed to assess the impact of colonization status on the outcomes of Acinetobacter spp. bloodstream infection (BSI) and investigate the homology and within-host evolution between colonizing and bloodstream carbapenem-resistant Acinetobacter spp. (CRA) to inform antibiotic therapeutic decisions.Methods: We analyzed clinical outcomes of 46 hematological patients with Acinetobacter spp. BSI and performed whole-genome sequencing on the remaining CRA isolates.Results: Among the patients, 39.1% (n=18) had prior Acinetobacter spp. colonization. Colonized patients had higher rates of polymicrobial BSI (50.0% vs 21.4%, P=0.044) and CRA BSI (72.2% vs 17.9%, P< 0.001), resulting in elevated inflammatory markers and increased 30-day mortality. Each of the eight pairs of the remaining respiratory colonizing and bloodstream CRA strains belonged to the same genomospecies. Each pair exhibited definitive agreement in at least 21 of the 22 most representative antibiotic susceptibility tests. The minimum spanning tree based on multilocus sequence typing (MLST) and phylogenetic trees based on MLST and single nucleotide polymorphism (SNP) all indicated that each pair shared the same minimum branch. Very few non-synonymous SNPs in genic regions were identified during the transition from respiratory colonization to bloodstream infection, with minimal changes in virulence genes. Homology analysis suggested that CRA BSI originated from colonizing isolates in the respiratory tract.Conclusion: Strict infection control measures are needed to manage Acinetobacter spp. colonisation in hematological patients. Appropriate empirical therapy can be administered for suspected CRA BSI based on the antimicrobial minimum inhibitory concentration of CRA colonising the respiratory tract.Keywords: Acinetobacter, colonization, bloodstream infections, homology, therapy, carbapenem-resistant

Chen Lin,1 Jing Wang,2 Kexin Cai,2 Yuqing Luo,2 Wensi Wu,1 Siming Lin,2 Zhihong Lin,2 Shaodan Feng2 1Department of Emergency, The Third Affiliated People’s Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, People’s Republic of China; 2Department of Emergency, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of ChinaCorrespondence: Zhihong Lin; Shaodan Feng, Department of Emergency, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China, Tel +86 59187981975, Email fzlinzh@163.com; sdfeng@fjmu.edu.cnPurpose: To address the critical mortality rates among sepsis-associated acute kidney injury (SA-AKI) patients, early prognosis is vital. This study investigates the relationship between coagulation indices and the 28-day mortality rate in patients with SA-AKI.Patients and Methods: This study was a retrospective cohort analysis including patients with SA-AKI admitted to the First Hospital of Fujian Medical University as a training cohort (n = 119) and patients admitted to the Third People’s Hospital of Fujian University of Traditional Chinese Medicine as a validation cohort (n = 51). We examined the relationship between coagulation indices and 28-day mortality in SA-AKI, the cumulative mortality at different activated partial thromboplastin time (APTT) levels, and the nonlinear relationship between APTT and 28-day mortality. Receiver operating characteristic curves were plotted, and the area under the curve was calculated to assess the predictive power of APTT. Finally, subgroup analyses were performed to assess the robustness of the association.Results: Overall, 119 participants with a mean±standard deviation age of 70.47± 15.20 years were included in the training cohort: 54 died, 65 survived. According to univariate and multivariate COX regression analyses, APACHE II score, CRP level, Lac level, and APTT level were independent risk factors for 28-day adverse prognosis. After controlling for some variables, an elevated baseline APTT (≥ 37.7 s) was associated with an elevated risk of 28-day mortality (HR, 1.017; 95% CI, 1.001– 1.032), and Kaplan–Meier analyses further confirmed the increased mortality in the group with a higher APTT. The same results were shown when the validation cohort was analyzed (HR, 1.024; 95% CI, 0.958– 1.096). Subgroup analyses showed the stability of the association between APTT and poor prognosis in SA-AKI.Conclusion: In essence, APTT elevation is synonymous with increased 28-day mortality rates, indicating a poor prognosis in SA-AKI scenarios.Keywords: APTT, prognosis, retrospective studies, critical illness

Sifen Jiang,1,2,&ast; Tingyu Luo,2,&ast; Zhuoqi Zhu,3,&ast; Yanling Huang,2 Haopeng Liu,4 Bing Li,2 Suibin Feng,5 Kun Zeng1 1Science and Education Section, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, People’s Republic of China; 2School of Nursing, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 3School of Public Health, Guangxi Medical University, Guangxi, People’s Republic of China; 4School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 5Surgery Department, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Suibin Feng, Surgery Department, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), No. 68 South West Lake 3 Road, Shilong Town, Dongguan City, Guangdong Province, 523321, People’s Republic of China, Tel +86 13430293807, Email 19526620667@163.com Kun Zeng, Science and Education Section, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), No. 68 South West Lake 3 Road, Shilong Town, Dongguan City, Guangdong Province, 523321, People’s Republic of China, Tel +86 13790300213, Email Zengkun660524@163.comBackground: The treatment of Type 2 Diabetes Mellitus (T2DM) is a protracted and arduous process. Medication, being a universally crucial therapeutic measure, underscores the significance of medication adherence in managing the disease effectively. Medication beliefs have emerged as a significant predictor of adherence, attracting considerable scholarly attention in recent years. However, there remains a paucity of research utilizing individual-centered approaches to explore medication beliefs among the T2DM population during the hospital-home transition, leaving the relationship between these beliefs and medication adherence unclear.Purpose: To investigate latent categories of medication beliefs among patients with T2DM during the transition from hospital to home, and to analyze variations in medication adherence across these categories of patients.Patients and methods: Between August 2022 and September 2023, this study selected 304 patients with a pre-discharge diagnosis of T2DM as study subjects from a tertiary hospital in Dongguan City. The patients’ profiles were assessed comprehensively via the Sociodemographic and Clinical Characteristics Questionnaire, alongside the Chinese version of Beliefs about Medicines Questionnaire-Specific and Morisky Medication Adherence Scale-8. The present study conducted latent profile analysis using Mplus 7.4 software and analyzed the influencing factors of different medication belief categories and their differences in medication adherence using SPSS 26.0 software.Results: The medication beliefs of 304 patients were rated at 3.36± 5.24 points, while medication adherence scored 6.23± 1.56 points. The medication beliefs were classified into four categories: moderate necessity - low to moderate concern group (40.13%), high necessity - low concern group (9.54%), moderate necessity - moderate to high concern group (19.08%), and moderate necessity - high concern group (31.25%). Age, monthly per capita household income, and place of residence emerged as influential factors for the four categories. Moreover, the disparity in medication adherence among these categories demonstrated statistical significance (P < 0.001).Conclusion: The medication beliefs of patients were classified into four distinct categories, and variations in medication adherence were evident across these categories. The high necessity - low concern group demonstrated the highest medication adherence scores, while the moderate necessity - high concern group exhibited the lowest scores. Healthcare providers are advised to tailor personalized medication belief enhancement programs based on patients’ homogeneous beliefs, addressing specific issues encountered by each category. This approach aims to ensure optimal medication adherence across diverse medical and social environments, effectively improving patient prognosis and enhancing quality of life.Keywords: diabetes mellitus, T2DM, medication beliefs, medication adherence, latent profile analysis, influencing factors

Xian Li,1,&ast; Hong Lai,2,&ast; Peng Wang,3 Shuai Feng,4 Xuexin Feng,4 Chao Kong,3 Dewei Wu,5 Chunlin Yin,5 Jianghua Shen,6 Suying Yan,6 Rui Han,7 Jia Liu,7 Xiaoyi Ren,8 Ying Li,8 Lu Tang,9 Dong Xue,9 Ying Zhao,9 Hao Huang,10 Xiaoying Li,10 Yanhong Zhang,10 Xue Wang,11 Chunxiu Wang,12 Ping Jin,13 Shibao Lu,3 Tianlong Wang,4 Guoguang Zhao,14 Chaodong Wang1 On behalf of the APPLE-MDT Research Team, Xuanwu Hospital, Capital Medical University and National Clinical Research Center for Geriatric Diseases1Department of Neurology & Neurobiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China; 3Department of Orthopedic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 4Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 5Department of Cardiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 6Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 7Department of Gerontology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 8Department of Nutrition, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 9Department of Oral Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 10Department of Medical Administration, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 11Department of Medical Library, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 12Center for Evidence-Based Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 13Center for Medical Information, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 14Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaodong Wang, Department of Neurology, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, No. 45 Changchun Street, Beijing, 100053, People’s Republic of China, Tel/Fax +86-10-8319-8677, Email cdongwang@xwhosp.orgPurpose: We aimed to identify the risk factors for postoperative cognitive decline (POCD) by evaluating the outcomes from preoperative comprehensive geriatric assessment (CGA) and intraoperative anesthetic interventions.Patients and Methods: Data used in the study were obtained from the Aged Patient Perioperative Longitudinal Evaluation–Multidisciplinary Trial (APPLE-MDT) cohort recruited from the Department of Orthopedics in Xuanwu Hospital, Capital Medical University between March, 2019 and June, 2022. All patients accepted preoperative CGA by the multidisciplinary team using 13 common scales across 15 domains reflecting the multi-organ functions. The variables included demographic data, scales in CGA, comorbidities, laboratory tests and intraoperative anesthetic data. Cognitive function was assessed by Montreal Cognitive Assessment scale within 48 hours after admission and after surgery. Dropping of ≥ 1 point between the preoperative and postoperative scale was defined as POCD.Results: We enrolled 119 patients. The median age was 80.00 years [IQR, 77.00, 82.00] and 68 patients (57.1%) were female. Forty-two patients (35.3%) developed POCD. Three cognitive domains including calculation (P = 0.046), recall (P = 0.047) and attention (P = 0.007) were significantly worsened after surgery. Univariate analysis showed that disability of instrumental activity of daily living, incidence rate of postoperative respiratory failure (PRF) ≥ 4.2%, STOP-Bang scale score, Caprini risk scale score and Sufentanil for maintenance of anesthesia were different between the POCD and non-POCD patients. In the multivariable logistic regression analysis, PRF ≥ 4.2% (odds ratio [OR] = 2.343; 95% confidence interval [CI]: 1.028– 5.551; P = 0.046) and Sufentanil for maintenance of anesthesia (OR = 0.260; 95% CI: 0.057– 0.859; P = 0.044) was independently associated with POCD as risk and protective factors, respectively.Conclusion: Our study suggests that POCD is frequent among older patients undergoing elective orthopedic surgery, in which decline of calculation, recall and attention was predominant. Preoperative comprehensive geriatric assessments are important to identify the high-risk individuals of POCD.Keywords: cognitive dysfunction, postoperative cognitive complications, orthopedic surgery, comprehensive geriatric assessment, risk factors

Ying Zhang,&ast; Sainan Liu,&ast; Qi Miao, Xu Zhang, He Wei, Shuang Feng, Xiaofei Li The First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaofei Li, Transplantation and Hepatobiliary Department, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China, Tel +15940564748, Email lixiaofei0603@aliyun.comPurpose: Kidney transplant recipients (KTRs) may experience symptoms that increase their fear of progression (FoP), but a dearth of research examines the issue from a patient-centered perspective. Our study aimed to first determine the category of symptom burden, then to explore the differences in characteristics of patients in different subgroups, and finally to analyze the impact of symptom subgroup on FoP.Patients and Methods: Sociodemographic and Clinical Characteristics, Symptom Experience Scale, and Fear of Progression Questionnaire-Short Form were used. Latent class analysis was used to group KTRs according to the occurrence of symptoms. We used multivariate logistic regression to analyze the predictors of different subgroups. The differences in FoP among symptom burden subgroups were analyzed by hierarchical multiple regression.Results: Three subgroups were identified, designated all-high (20.5%), moderate (39.9%), and all-low (39.6%) according to their symptom occurrence. Multivariate logistic regression showed that gender, post-transplant time, per capita monthly income, and hyperuricemia were the factors that distinguished and predicted the all-high subgroup (P < 0.05). Hierarchical multiple regression showed that symptom burden had a significant effect on FoP (class1 vs class3: β = 0.327, P < 0.001; class2 vs class3: β = 0.104, P = 0.046), explaining the 8.0% variance of FoP (ΔR2 = 0.080).Conclusion: KTRs generally experience moderate or low symptom burden, and symptom burden is an influencing factor in FoP. Identifying the traits of KTRs with high symptom burden can help clinicians develop targeted management strategies and ease FoP of KTRs.Keywords: kidney transplant, symptom burden, fear of progression, latent class analysis

Shaoting Feng,1,&ast; Daya Yang,1,&ast; Kunsong Zhang,1,&ast; Denise Joy Findlay,2 Ming Kuang,1 Haipeng Xiao,2 Dan Xu1,2 1Department of Medical Education, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2General Practice Research, Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, Australia&ast;These authors contributed equally to this workCorrespondence: Dan Xu; Ming Kuang, Email daniel.xu@curtin.edu.au; kuangm@mail.sysu.edu.cnPurpose: Australian general practice training uses external clinical teaching (ECT) visits for formative work-based assessments. ECT visits appoint senior general-practitioners (GPs) observe trainee GPs’ consultations, provide feedback, and make performance-enhancing recommendations. As ECT visits are one of the best assessment tools in Australian GP training, there is limited evidence of its use in undergraduate teaching. This study aims to introduce ECT visits and evaluate assessment tools during senior medical students’ GP placement.Methods: This study included external and internal GP supervisors and twenty-five Chinese and Australian students during GP placements. The supervisors provided structured in-person feedback, while the ECT assessment tool used a standardised, validated feedback platform to assess every component of a consultation. Students’ feedback was recorded and collected by both internal and external supervisors, and then semantically analysed by external supervisors.Results: Twenty-five ECT visit feedbacks were collected and analysed semantically. All participating students rated ECT visits excellently and confirmed the relevance of assessment tools for discussions with supervisors to achieve the designed learning outcomes. Chinese students rated the assessment tools as innovative from a cultural perspective and recommended the ECT visit teaching model and assessment tools to their home university, whereas Australian students suggested more ECT visits during GP placements. Time management was a limitation for both the students and supervisors.Conclusion: ECT visit is an innovative placement teaching model and work-based assessment tool for senior medical students’ GP placements, and is rated as the most preferred formative assessment tool. The limitations of this study include small group of students/supervisors and lack of patient feedback; however, all of these limitations can be overcome by involving multiple GP clinics in ongoing large-scale study. ECT visits can be introduced quantitatively into students’ GP placement curricula to improve clinical reasoning, learning, and quality assurance with assessments during clinical placements.Keywords: external clinical teaching, general practice placement, senior medical students placement learning, clinical reasoning learning, work-based assessment

Ke Zhang,1 Songwei Feng,1 Yan Wang,1 Wen Feng,2 Yang Shen1,3 1Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Department of Gynecology, The First People’s Hospital of Lianyungang, Lianyungang, 222000, People’s Republic of China; 3Institute of Sports and Health, Nanjing, People’s Republic of ChinaCorrespondence: Wen Feng, Department of Gynecology, The First People’s Hospital of Lianyungang, Lianyungang, 222000, People’s Republic of China, Tel +86-0518-85452253, Fax +86-0518-85456700, Email fengw125@126.com Yang Shen, Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210096, People’s Republic of China, Email shenyang@seu.edu.cnObjective: The objective of this research was to determine the age cut-off for worse prognosis and investigate age-related differentially expressed genes (DEGs) in patients with advanced ovarian serous cystadenocarcinoma (AOSC).Methods: In this research, we included a cohort of 20,846 patients diagnosed with AOSC, along with RNA-seq data from 374 patients in publicly available databases. Then we used the X-tile software to determine the age cut-off and stratified the patients into young and old groups. We utilized propensity score matching (PSM) to balance baseline between the young and old groups. Furthermore, we conducted an enrichment analysis of DEGs between the two age groups using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO) to identify dysregulated pathways. To evaluate the potential prognostic value of the DEGs, we performed survival analysis, such as Kaplan-Meier analysis and Log rank test.Results: We stratified the patients into young group (n=16,336) and old group (n=4510) based on the cut-off age of 73 years by X-tile software. Age over 73 years was identified as an independent risk factor for overall survival (OS) and cancer-specific survival (CSS). Next, we identified 436 DEGs and found that the neurotrophin signaling pathway and translation factor activity were associated with prognosis outcomes. Among the top 10 hub genes (RELA, NFKBIA, TRAF6, IRAK2, TAB3, AKT1, TBP, EIF2S2, MAPK10, and SUPT3H), RELA, TAB3, AKT1, TBP, and SUPT3H were found to be significantly associated with poor prognosis in old patients with AOSC.Conclusion: Our study determined 73 years as the cutoff value for age in patients with AOSC. RELA, TAB3, AKT1, TBP, and SUPT3H were identified as age-related DEGs that could contribute to the poor prognosis of older patients with AOSC.Keywords: advanced ovarian serous cystadenocarcinoma, propensity score matching, prognosis, real-world study, age

Ming Zhang,1,&ast; Feng Chen,2,&ast; Shaoguang Feng,3,&ast; Xu Liu,4 Zhen Wang,5 Nan Shen,6 Lingjian Meng,7 Dongsheng Zhu,1 Zhitao Zhu8 1Department of Pediatric Surgery, The First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 2Department of Pediatric, Luodian Hospital, Shanghai, People’s Republic of China; 3Department of Pediatric Surgery, The Children’s Hospital of Hangzhou, Hangzhou, People’s Republic of China; 4Department of Pediatric Surgery, The Children’s Hospital of Xuzhou, Xuzhou, People’s Republic of China; 5Department of Pediatric, the Maternal and Child Health Hospital of Zibo, Zibo, People’s Republic of China; 6Department of Pediatrics, Suqian Hospital Affiliated to Xuzhou Medical University, Suqian, People’s Republic of China; 7Department of Pediatrics, Hospital Affiliated to Xuzhou Medical University, Xuzhou, People’s Republic of China; 8Department of Radiology, The Second People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhitao Zhu; Dongsheng Zhu, Email zhuzhitao621@126.com; zhudongsheng@tmu.edu.cnObjective: To investigate the role of FBLN5in renal clear cell carcinoma (KIRC), in particular on the tumor’s immune microenvironment, including children and young adults.Methods: FBLN5 expression in tumor and normal samples was explored using SangerBox, TIMER2.0, GEPIA, UALCAN, HPA databases. The Linkedomics database was used to obtain FBLN5 co-expressed genes in KIRC tissue. SangerBox was also used to estimate immune infiltration of FBLN5 in KIRC. The Kaplan-Meier plotter was used to investigate the survival effects of FBLN5 expression in the presence of immune infiltration. We then collected 48 cases from 7 hospitals over a-20 year period to calculate the impact of FBLN5 on the prognosis of children and young adults with KIRC.Results: FBLN5 expression was significantly reduced in KIRC tissue compared to normal adjacent tissue. FBLN5 was potentially involved in the immune-related biological processes. In addition, FBLN5 expression has been linked to a number of immune checkpoints, cytokines, chemokines and chemokine receptors in KIRC. At the same time, the expression of FBLN5 affected the survival rates differently in KIRC patients with high or low levels of immune infiltration. High expression of FBLN5 in children and young adults with KIRC was associated with a favorable prognosis.Conclusion: This study shed light on the potential of FBLN5 as a prognostic marker in children and young adults with KIRC and as an immune-related target for clinical treatment.Keywords: FBLN5, immune microenvironment, prognostic biomarker, kidney cancer, children