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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

Dan Xu,1,2 Shaoting Feng,1 Daya Yang,1 Shuqin Ding,1 Johan B Rosman,2 Ming Kuang,1 Haipeng Xiao1 1First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, AustraliaCorrespondence: Dan Xu; Haipeng Xiao, Email daniel.xu@curtin.edu.au; xiaohp@mail.sysu.edu.cnPurpose: Clinical placement teaching could be challenging due to time constraints, lack of effective teaching models and consensus approaches. Learner-centred approach facilitated deeper learning by demonstrating “seeing-patients-under-supervision” being ideal during Residential-Aged-Care-Facility (RACF)-visit in GP clinical placements. The study aimed to reflect on the students’ experiences in aged-care visits by applying an innovative teaching model of “students-being-the-GP-clinician-in-charge-of-RACF-visit-ward-round-under-the-supervision-of-clinical-supervisor”. Through students’ reflections, this study identified 12 commonly managed RACF problems to be introduced into the curriculum to optimise clinical reasoning learning during RACF-visit.Methods: This qualitative study used online surveys and interviews. All participating students reported all the encountered cases during the RACF visit through an online survey. The participating students acted as GP in charge of all clinical interactions with patients, caregivers, and nurses during RACF visits and final management plan discussions with GP supervisors to ensure clinical-service safety and teaching-and-learning quality. The interview questionnaires applied standard-and-open-ended-questions to examine the impact of this innovative teaching model on clinical-reasoning-learning, clinical-competence-improvement, Objective Structured Clinical Exam (OSCE) preparation, limitations-from-students’-patients’-and-supervisors’ perspectives, and intern readiness.Results: An online survey summarising students’ encountered cases was returned by 30 students. The 12 most commonly-managed problems were tabulated. Falls, urinary tract infections, and behavioural and psychological symptoms of dementia were the three most commonly-managed problems. All thirty students’ reflections indicated the positive impact of the innovative-teaching-models on “Improving-Clinical-Reasoning-Learning”, “Enhancing-Clinical-Competency”, “Enriching-Salient-Learning-Points”, “Facilitating-Feedback-Discussion-with-Supervisor”, “Strengthening-OSCE-exam-preparation”, “Understanding-the-Limitation-from-students’-patients’-and-supervisors’-perspectives”, “Enabling-intern-readiness”. Twelve students’ individual reflections were demonstrated.Conclusion: This qualitative pilot study demonstrated through students’ reflection that “Student-doctor-in-charge-of-nursing-home-round” is an innovative teaching model for clinical reasoning learning. This model extended the concepts of “cognitive-apprenticeship” in the context of modern medical education. Students’ reflections and summary of commonly managed problems indicated the need for further study to verify the feasibility of implementing this teaching model in the formal curriculum and creating a RACF-visit-specific curriculum for students.Keywords: clinical reasoning learning, learner-centred approach, cognitive apprenticeship

Kunlin Guo,&ast; Mingjie Mao,&ast; Susu Zhang, Shiqin Xu, Liping Zhao, Xian Wang, Shanwu Feng Department of Anesthesiology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian Wang; Shanwu Feng, Department of Anesthesiology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, No. 123, Mochou Road, Tianfei Lane, Nanjing, Jiangsu Province, 210004, People’s Republic of China, Tel +86-25-13770723174 ; +86-25-13921426351, Fax +82-25-52226530, Email wangxian2002@126.com; iamfsw@163.comBackground: Allopregnanolone is a kind of neuroactive steroid or neurosteroid in the central nervous system that acts as an endogenenous GABAA receptor positive modulator. However, at present, no comprehensive bibliometric analysis regarding allopregnanolone research is available. In our study, we intend to analyze the research trends and hot spots related to allopregnanolone in the past 20 years.Methods: We searched for allopregnanolone related articles and reviews between 2004 and 2023 from the Web of Science Core Collection database. Then, the bibliometric analysis was conducted using VOSviewer, CiteSpace, Microsoft Excel 2019, as well as the online bibliometric analysis platform (http://bibliometric.com/).Results: A total of 1841 eligible publications were identified. The number of annual publications and citations was generally on the rise. Among countries, the United States ranked first in overall publications, citations, international cooperation, and the number of research institutions. The University of North Carolina was the most active institution, conducting numerous preclinical and clinical work that focusing on allopregnanolone treatment for diverse psychiatric or neurologic disorders. As for authors, Dr. Frye CA, Morrow AL, and Pinna G were identified as the top three prolific scholars due to their great publications and citations. Based on the publication clusters and citation bursts analysis, the keyword co-occurrence network, the strongest citation bursts, and co-cited references analysis, the hot spots in recent years included “depression”, “postpartum depression”, “GABAA receptor”, and so on.Conclusion: Allopregnanolone is still a popular area of research, and the United States leads the way in this area. Dr. Frye CA, Morrow AL, Pinna G, and their teams contributed greatly to the mechanism study and translation study of allopregnanolone. The use of allopregnanolone for the treatment of psychiatric or neurologic disorders, especially postpartum depression, is the current hot spot. However, the underlying mechanisms of anti-depression are still not clear, deserving more in-depth research.Keywords: allopregnanolone, VOSviewer, CiteSpace, bibliometric analysis, research trend

Hui Guo,1 Shuai Feng,1 Zhiqiang Li,1 Yueju Yin,1 Xueying Lin,2 Lingqin Yuan,1 Xiugui Sheng,3 Dapeng Li1 1Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Department of Surgery, Liaocheng Dongchangfu District Maternal and Child Health Hospital, Liaocheng, Shandong, People’s Republic of China; 3Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Dapeng Li, Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440, Jiyan Load, Jinan, Shandong, 250117, People’s Republic of China, Email dpli@sdfmu.edu.cnBackground: Abnormal changes in body composition and systemic inflammation response have been associated with poor survival of cancer patients. Our study was to explore the prognostic value of the association between body composition indicators and systemic inflammation markers among patients with locally advanced cervical cancer (LACC) who underwent concurrent chemoradiotherapy (CCRT).Methods: We retrospectively reviewed medical records of LACC patients treated between 2016 and 2019. Subcutaneous, visceral and intra-muscular adipose index (SAI, VAI and IMAI) and skeletal muscle index (SMI) were derived from computed tomography (CT). Kaplan-Meier analysis and Univariate and multivariate Cox analyses were used to evaluate the survival. A nomogram was constructed to assess the prognostic value.Results: The study included 196 patients treated with CCRT. According to multivariable Cox analyses, IIIC1r (P = 0.045), high systemic immune-inflammation index (SII) (P = 0.004), sarcopenia (P = 0.008), high SAI (P = 0.016) and high VAI (P = 0.001) were significantly risk factors for overall survival (OS). Kaplan-Meier analysis showed that patients with low lymphocyte-to-monocyte ratio (LMR) and sarcopenia had longer OS than those with high LMR and sarcopenia (P = 0.023). The high neutrophil-to-lymphocyte ratio (NLR) in non-sarcopenic patients showed better survival (P = 0.022). Low VAI (P = 0.019) or low IMAI (P = 0.019) combined with low SII had a favorable OS. Low LMR combined with low SAI was associated with longer OS (P = 0.022). The calibration plots of nomogram predicting the 3-year and 5-year OS rates were close to the ideal models.Conclusion: Inflammation factors were closely associated with abnormal muscle and fat distribution. The combined prognostic value of body composition indicators and systemic inflammation markers was reliable in predicting survival for LACC patients.Keywords: body composition, systemic inflammatory markers, cervical cancer, overall survival, nomogram

Linxi Zeng,1 Sen Feng,1 Lulu Yao,1 Jiaqing Zhao,1 Guoqiang Zhang1,2 1Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, People’s Republic of China; 2Candidate Branch of National Clinical Research Center for Skin Diseases, Shijiazhuang, People’s Republic of ChinaCorrespondence: Guoqiang Zhang, The First Hospital of Hebei Medical University, 89 Donggang Road, Yuhua District, Shijiazhuang City, Hebei Province, People’s Republic of China, Email zlx090702@163.comAbstract: Herpes zoster is typically a blister rash involving a single skin group, caused by the reactivation of primary varicella zoster virus infection. Disseminated herpes zoster refers to the presence of more than 20 small blisters outside the primary or adjacent skin, which is rare and usually occurs in individuals with weakened immune function. This case described a patient diagnosed with disseminated herpes zoster, with a decrease in CD4 count (379 cells/mm3) and certain skin lesions. He was subsequently screened positive for HIV. Also, we summarized other studies on the CD4 value of HIV patients with herpes zoster. Overall, for herpes zoster patients with decreased CD4 levels and certain skin manifestations, such as diffuse, ulcerative, or pustular lesions, clinicians should be aware of HIV infection.Keywords: disseminated herpes zoster, CD4, HIV infection

Zhiqiang Shi,1 Yu Liu,1,2 Xiaodan Chang,3 Yuan Gao,4 Min Hao,1 Shuo Feng,1 Haoyu Dong1 1Department of Traditional Chinese Medicine Surgery, College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot, People’s Republic of China; 2Department of Integrated Traditional Chinese and Western Medicine Surgery, College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 3Department of Dermatology, Hohhot Second Hospital, Hohhot, People’s Republic of China; 4Department of Anorectal Diseases, Inner Mongolia Hospital of Traditional Chinese Medicine, Hohhot, People’s Republic of ChinaCorrespondence: Yu Liu, Inner Mongolia Medical University, Jinshan Development Zone, Hohhot, Inner Mongolia, People’s Republic of China, Tel +86-153-3471-2606, Email 15074930848@163.comPurpose: This paper aims to investigate the effect of Tounong San (TNS), a well-known traditional Chinese medicine prescription for suppurative infections, on the immune function.Methods: A suppurative infection model was established by injecting Staphylococcus aureus into subcutaneous tissue on the backs of rats. The expressions of CD68, CD163, CD31 and MPO in abscess tissues, phagocytosis rate and reactive oxygen species (ROS) of neutrophils in blood, phagocytosis function of peritoneal macrophages, and proliferation of blood lymphocytes, expression of IL-1, IL-6, CH50, TNF-α, IFN-γ, IgG, IgM in serum were detected at different time points.Results: On the 3rd day of medication, fibrinogen wrapped around the abscesses was visible in TNS groups, with an increase in new blood vessels and the expression of a large number of macrophages and neutrophils. On the 6th day, the pus of TNS groups diminished, and the number of new blood vessels reached its peak. On the 9th day, the abscesses disappeared in TNS groups, fewer new blood vessels, macrophages, and neutrophils were expressed, and more fibrocytes appeared and filled the original pus cavities. On the 3rd and 9th day of medication, the phagocytic rates of neutrophils and macrophages were significantly improved in TNS group, and the ROS content of neutrophils was increased on the 9th day. TNS has no effect on lymphocyte proliferation in vitro, but it can regulate the secretion of IgG and IgM by lymphocytes. TNS increases the level of IL-1, decreases the levels of IL-6 and TNF-α, and regulates the expressions of IFN-γ and CH50 in two ways.Conclusion: TNS can form fibrinogen-wrapped pus to prevent bacterial infection from going deeper, and to improve the phagocytic function of phagocytes, the secretion of lymphocytes, and the defense function of the complement system. Therefore, it is a competitive drug for the treatment of suppurative diseases.Keywords: Tounong San, suppurative infection, immune function, pharmacological mechanism

Sitong Feng,1,2 Linrui Dong,1,2 Bin Yan,3 Sisi Zheng,1,2 Zhengtian Feng,1,2 Xue Li,1,2 Jiajia Li,1,2 Ning Sun,3 Yanzhe Ning,1,2 Hongxiao Jia1,2 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; 3Department of Andrology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Hongxiao Jia; Yanzhe Ning, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Hutong, Xicheng District, Beijing, 100088, People’s Republic of China, Tel +86 010-58303065, Email jhxlj@ccmu.edu.cn; ningzy0923@mail.ccmu.edu.cnPurpose: Several studies have demonstrated that psychogenic erectile dysfunction (pED) patients potentially suffer from cognitive dysfunction. Despite that previous neuroimaging studies have reported abnormal functional connections of brain areas associated with cognitive function in pED, the underlying mechanisms of cognitive dysfunction in pED remain elusive. This study aims to investigate the underlying mechanisms of cognitive dysfunction by analyzing large-scale brain networks.Patients and Methods: A total of 30 patients with pED and 30 matched healthy controls (HCs) were recruited in this study and scanned by resting-state functional magnetic resonance imaging. The Dosenbach Atlas was used to define large-scale networks across the brain. The resting-state functional connectivity (FC) within and between large-scale brain networks was calculated to compare pED patients with HCs. The relationship among cognitive performances and altered FC of large-scale brain networks was further explored in pED patients.Results: Our results showed that the decreased FC within visual network, and between visual network and default mode network, visual network and frontoparietal network, and ventral attention and default mode network were found in pED patients. Furthermore, there was a positive correlation between immediate memory score and FC within visual network. The visuospatial score was negatively correlated with decreased FC between ventral attention network and default mode network.Conclusion: Taken together, our findings revealed the relationship between cognitive impairments and altered FC between large-scale brain networks in pED patients, providing the new evidence about the neural mechanisms of cognitive dysfunction in pED patients.Keywords: large-scale brain network, functional connectivity, cognitive impairment, psychogenic erectile dysfunction

Tianyou Chen,1,&ast; Chong Liu,1 Zide Zhang,2 Tuo Liang,2 Jichong Zhu,1 Chenxing Zhou,1 Shaofeng Wu,1 Yuanlin Yao,1,&ast; Chengqian Huang,1 Bin Zhang,1 Sitan Feng,1 Zequn Wang,1 Shengsheng Huang,1 Xuhua Sun,1 Liyi Chen,1 Xinli Zhan1 1Department of Spine and Osteopathy Ward, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Spine Ward, Liuzhou People’s Hospital, Liuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinli Zhan, Department of Spine and Osteopathy Ward, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email zhanxinli@stu.gxmu.edu.cnObjective: The objective of this study was to utilize machine learning techniques to analyze perioperative factors and identify blood glucose levels that can predict the occurrence of surgical site infection following posterior lumbar spinal surgery.Methods: A total of 4019 patients receiving lumbar internal fixation surgery from an institute were enrolled between June 2012 and February 2021. First, the filtered data were randomized into the test and verification groups. Second, in the test group, specific variables were screened using logistic regression analysis, Lasso regression analysis, support vector machine, and random forest. Specific variables obtained using the four methods were intersected, and a dynamic model was constructed. ROC and calibration curves were constructed to assess model performance. Finally, internal model performance was verified in the verification group using ROC and calibration curves.Results: The data from 4019 patients were collected. In total, 1327 eligible cases were selected. By combining logistic regression analysis with three machine learning algorithms, this study identified four predictors associated with SSI, namely Modic changes, sebum thickness, hemoglobin, and glucose. Using this information, a prediction model was developed and visually represented. Then, we constructed ROC and calibration curves using the test group; the area under the ROC curve was 0.988. Further, calibration curve analysis revealed favorable consistency of nomogram-predicted values compared with real measurements. The C-index of our model was 0.986 (95% CI 0.981– 0.994). Finally, we used the validation group to validate the model internally; the AUC was 0.987. Calibration curve analysis revealed favorable consistency of nomogram-predicted values compared with real measurements. The C-index was 0.982 (95% CI 0.974– 0.999).Conclusion: Logistic regression analysis and machine learning were employed to select four risk factors: Modic changes, sebum thickness, hemoglobin, and glucose. Then, a dynamic prediction model was constructed to help clinicians simplify the monitoring and prevention of SSI.Keywords: surgical site infection, lumbar spine surgery, machine learning, blood glucose, dynamic prediction model

Susu Feng,1 Lin Guo,1 Sijing Wang,1 Lijuan Chen,1 Hang Chang,2 Bo Hang,2,3 Jianhua Mao,2 Antoine M Snijders,2 Yibing Lu,1 Dafa Ding1 1Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; 3Department of Biomaterials, Berkeley-Nanjing Research Center, Nanjing, People’s Republic of ChinaCorrespondence: Dafa Ding, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiang Jia Yuan, Nanjing, 210011, People’s Republic of China, Tel +86 15850514014, Email dingdafa@njmu.edu.cnAim: We aimed to identify the ability of serum bile acids (BAs) and unsaturated fatty acids (UFAs) profiles to predict the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) patients.Methods: We first used univariate and multivariate analysis to compare 15 serum BA and 11 UFA levels in healthy control (HC) group (n = 82), T2DM patients with DR (n = 58) and T2DM patients without DR (n = 60). Forty T2DM patients were considered for validation. Then, the receiver operating characteristic curve (ROC) and decision curve analysis were used to assess the diagnostic value and clinical benefit of serum biomarkers alone, clinical variables alone or in combination, and the area under the curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to further assess whether the addition of biomarkers significantly improved the predictive ability of the model.Results: Orthogonal partial least squares-discriminant analysis (OPLS-DA) of serum BAs and UFAs separated the three cohorts including HC, T2DM patients with or without DR. The difference in serum BA and UFA profiles of T2DM patients with or without DR was mainly manifested in the three metabolites of taurolithocholic acid (TLCA), tauroursodeoxycholic acid (TUDCA) and arachidonic acid (AA). Together, they had an AUC of 0.785 (0.918 for validation cohort) for predicting DR in T2DM patients. After adjusting for numerous confounding factors, TLCA, TUDCA, and AA were independent predictors that differentiated T2DM with or without DR. The results of AUC, IDI, and NRI demonstrated that adding these three biomarkers to a model with clinical variables statistically increased their predictive value and were replicated in our independent validation cohort.Conclusion: These findings highlight the association of three metabolites, TLCA, TUDCA and AA, with DR and may indicate their potential value in the pathogenesis of DR.Keywords: type 2 diabetes mellitus, diabetic retinopathy, serum bile acid, unsaturated fatty acid

Shuyan Feng,1,&ast; Chi Zhang,1,&ast; Shanshan Chen,2,&ast; Ruonan He,1,&ast; Guanqun Chao,3 Shuo Zhang4 1Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, People’s Republic of China; 3Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, 310018, People’s Republic of China; 4The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanqun Chao; Shuo Zhang, Email chaoguanqun@zju.edu.cn; zhangshuotcm@126.comAbstract: Toll-like receptor 5 (TLR5) is a pattern recognition receptor that specifically recognizes flagellin and consequently plays a crucial role in the control of intestinal homeostasis by activating innate and adaptive immune responses. TLR5 overexpression, on the other hand, might disrupt the intestinal mucosal barrier, which serves as the first line of defense against harmful microbes. The intestine symbiotic bacteria, mucous layer, intestinal epithelial cells (IECs), adherens junctions (such as tight junctions and peripheral membrane proteins), the intestinal mucosal immune system, and cytokines make up the intestinal mucosal barrier. Impaired barrier function has been linked to intestinal illnesses such as inflammatory bowel disease (IBD). IBD is a persistent non-specific inflammatory illness of the digestive system with an unknown cause. It is now thought to be linked to infection, environment, genes, immune system, and the gut microbiota. The significance of immunological dysfunction in IBD has received more attention in recent years. The purpose of this paper is to explore TLR5’s position in the intestinal mucosal barrier and its relevance to IBD.Keywords: toll-like receptor 5, intestinal mucosal barrier, microbes, intestinal immune, inflammatory bowel disease

Yanpo Si,1,2 Chengcheng Hui,1 Tao Guo,1,2 Mengqi Liu,1 Xiaohui Chen,3 Chunhong Dong,3,4 Shuying Feng5 1Department of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Henan Engineering Research Center of Medicinal and Edible Chinese Medicine, Zhengzhou, People’s Republic of China; 3Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4Henan Key Laboratory of Chinese Medicine for Polysaccharides and Drugs Research, Zhengzhou, People’s Republic of China; 5Medical College, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of ChinaCorrespondence: Tao Guo; Shuying Feng, Henan University of Chinese Medicine, No. 156 JinshuiEast Road, Zhengzhou, 450046, People’s Republic of China, Tel +86 371 65962746 ; +86 371 65934070, Email gt010010@hactcm.edu.cn; fsy@hactcm.edu.cnPurpose: To reveal the potential mechanism of PDA on hepatocellular carcinoma SMMC-7721 cells in vitro.Methods: The cytotoxic activity, colony formation, cell cycle distribution, apoptosis and their associated protein analysis, intracellular reactive oxygen species (ROS) and Ca2+ levels, proteins in Nrf2 and Ntoch pathways and metabolite profiles of PDA against hepatocellular carcinoma were investigated.Results: PDA with cytotoxic activity inhibited cell proliferation and migration, increased intracellular ROS, Ca2+ levels and MCUR1 protein expression in a dose-dependent manner, caused cell cycle arrest in the S phase and induced apoptosis via adjusting the levels of Bcl-2, Bax, and Caspase 3 proteins, and inhibited the activation of Notch1, Jagged, Hes1, Nrf2 and HO-1 proteins. Metabonomics data showed that PDA significantly regulated 144 metabolite levels tend to be normal level, especially carnitine derivatives, bile acid metabolites associated with hepatocellular carcinoma, and mainly enriched in ABC transporter, arginine and proline metabolism, primary bile acid biosynthesis, Notch signaling pathway, etc, and proved that PDA markedly adjusted Notch signaling pathway.Conclusion: PDA exhibited the proliferation inhibition of SMMC-7721 cells by inhibiting ROS/Nrf2/Notch signaling pathway and significantly affected the metabolic profile, suggesting PDA could be a potential therapeutic agent for patients with hepatocellular carcinoma.Keywords: isoquinoline alkaloid, apoptosis, acylcarnitine, bile acids, metabolomics

Yijia He,1 Sen Feng,1 Lulu Yao,1 Guoqiang Zhang1,2 1Department of Dermatology, the First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Candidate Branch of National Clinical Research Center for Skin Diseases, Shijiazhuang, People’s Republic of ChinaCorrespondence: Guoqiang Zhang, Department of Dermatology, the First Hospital of Hebei Medical University, No. 89, Donggang Road, Shijiazhuang, Hebei Province, People’s Republic of China, Email zlx090702@163.comAbstract: We report the case of a patient with Lymphocytic thrombophilic arteritis (LTA) with a history of 67 years. This is a relatively rare disease with no recognised guidelines for diagnosis and treatment. The long medical history from birth of this patient and the lack of positive progression may provide some new ideas for the treatment of this disease.Keywords: lymphocytic thrombophilic arteritis, macular lymphocytic arteritis, vasculitis, treatment, case report

Xiyan Zhang,1,2 Hui Chen,1 Shengnan Liu,3 Xijuan Wang,2 Beibei Guo,2 Jingjing Liu,2 Shaojie Feng,2 Fengxia Liu2 1School of Clinical Medicine, Weifang Medical University, Weifang, People’s Republic of China; 2Department of Allergy, Weifang People’s Hospital, Weifang, People’s Republic of China; 3Department of Blood Transfusion, Affiliated Hospital of Weifang Medical University, Weifang, People’s Republic of ChinaCorrespondence: Shaojie Feng; Fengxia Liu, Email fengshaojie2020@163.com; wf_lfx@163.comBackground: Children are the age group with the highest prevalence of allergy diseases. There is currently a lack of knowledge regarding monosensitization and polysensitization characteristics in children. In this study, we investigated the characteristics and differences between monosensitization and polysensitization in children in Weifang, eastern China.Objective: To demonstrate the basic features of monosensitization and polysensitization in children. To explore the inherent and clinical parameter differences between monosensitized and polysensitized children.Material and Methods: A total of 6030 individuals with a physician-determined need for allergy testing were tested for 15 common allergens, including 9 aeroallergens and 6 food allergens. A total of 938 allergen-positive children aged 1 month to 18 years were eventually included in this analysis. Complete blood count results from the same time as the allergen test were derived from the computerized medical records. Intrinsic features such as age, gender, sIgE, T-IgE, and clinical parameters such as eosinophil percentage, eosinophil count, basophil percentage, and basophil count were compared.Results: The results showed that dust mite-related allergens, mould-related allergens, and tree and grass pollen-related allergens were the most prevalent allergens among monosensitized children. Additionally, the results of the combined pattern of polysensitive childhood allergens indicate the most common two allergens that were present together included dust mites and mould-related allergens, dust mite and Artemisia pollens, and dust mite and Humulus scandens pollens. Polysensitization can result in higher sIgE, T-IgE and eosinophil levels.Conclusion: In conclusion, we provide a basic overview of allergens in monosensitized and polysensitized children. These findings provide new insight into the management of allergic diseases, particularly from the standpoint of polysensitization.Keywords: allergic disease, children, monosensitization, polysensitization, eosinophils, T-IgE

Xiaolong Zhang,1,&ast; Zhiyin Lei,2,&ast; Ying Wu,3 Yuanyuan Song,4 Xiaoling Wu,3,5 Bo Yang,2 Jianmei Fan,2 Shixu Feng,2 Liping Wu,2 Lingyan Li,2 Qin Dai,2 Zhen Zeng,2 Mei Feng,3 Tingting Zhang3 1Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Jiajia Central Health Center of Chengdu Eastern New Area, Chengdu Eastern New Area, Sichuan Province, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 4Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 5Department of Nursing, Sanya People’s Hospital/West China (Sanya) Hospital, Sichuan University, Sanya, Hainan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Wu, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel +86-18980606932, Email 358383278@qq.comPurpose: To investigate the prevalence and risk factors for chronic obstructive pulmonary disease (COPD) in a rural area in western China with severe air pollution.Patients and Methods: 10% of local residents aged 40 years and above were included using a convenience sampling method. This was a cross-sectional study. A self-designed questionnaire was used to collect participants’ demographic data. The screening program was comprised of two steps: First, a portable electronic spirometer was used for COPD screening. Those participants with FEV1/FVC ratio < 0.7 were then referred to a confirmatory pulmonary function (PF) test. COPD was confirmed according to the 2020 Global Initiative for Chronic Obstructive Lung Disease criteria.Results: A total of 4577 participants aged 40 years old or above were included in the final analysis. Examination with a mobile spirometer identified 1159 individuals for confirmatory testing; after that, of the 1159 individuals, 889 were diagnosed with COPD by the confirmatory PF test. The prevalence of COPD among the target group was 19.4%. Older age, male sex (odds ratio [OR] = 1.537, 95% confidence interval [CI] 1.246– 1.894), smoking history (OR = 1.338, 95% CI 1.069– 1.675), family history of respiratory disease (OR = 1.625, 95% CI 1.350– 1.957), education level (OR = 0.735, 95% CI 0.617– 0.876), overweight (OR = 0.614, 95% CI 0.517– 0.730) and obesity (OR = 0.572, 95% CI 0.449– 0.721) were identified as independent factors associated with COPD. The screening program helped earlier detection of COPD in 719 participants.Conclusion: COPD was highly prevalent in the rural area studied. Rural residents who were older, current or ever-smokers, male and those who had a lower education level were more vulnerable to developing COPD. The COPD screening program may be helpful for earlier disease detection in rural health-care settings.Keywords: chronic obstructive pulmonary disease, prevalence, primary care, pulmonary function test, risk factors

Shunhang Feng,1,2,&ast; Jiansheng Lin,1,2,&ast; Xiaoyan Zhang,1,2 Xin Hong,1,2 Wanyin Xu,1,2 Yancheng Wen,1,2 Feifei She1,2 1Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of China; 2Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, School for Basic Medical Sciences, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feifei She, Fujian Medical University, Xueyuan Road 1, Minhou County, Fuzhou, Fujian Province, People’s Republic of China, Tel +86-135-1406-3583, Email Shefeifei@yeah.net Yancheng Wen, Fujian Medical University, Xueyuan Road 1, Minhou County, Fuzhou, Fujian Province, People’s Republic of China, Tel +86-157-0593-5209, Email hitwyc@qq.comPurpose: Helicobacter pylori is associated with the development of gastrointestinal diseases. However, its eradication is challenged by an increased rate of drug resistance. AlgC and GalU are important for the synthesis of UDP-glucose, which is a substrate for the synthesis of lipopolysaccharide (LPS) in H. pylori. In this study, we investigated the role of UDP-glucose in the intrinsic drug resistance in H. pylori.Methods: Gene knockout strains or complementation strains, including ΔalgC, ΔgalU, ΔgalE, Δhp0045, ΔalgC/algC&ast; and ΔgalU/galU&ast; were constructed in Hp26695; and ΔalgC and ΔgalU were also constructed in two clinical drug-resistant strains, Hp008 and Hp135. The minimum inhibitory concentrations (MIC) of H. pylori to amoxicillin (AMO), tetracycline (TET), clarithromycin (CLA), metronidazole (MNZ), levofloxacin (LEV), and rifampicin (RIF) were measured using MIC Test Strips. Silver staining was performed to examine the role of AlgC and GalU in LPS synthesis. Ethidium bromide (EB) accumulation assay was performed to assess the outer membrane permeability of H. pylori strains.Results: Knockout of algC and galU in H. pylori resulted in increased drug sensitivity to AMO, MNZ, CLA, LEV, and RIF; whereas knockout of hp0045 and galE, which are involved in GDP-fucose and UDP-galactose synthesis, respectively, did not significantly alter the drug sensitivity of H. pylori. Knockout of algC and galU in clinically drug-resistant strains resulted in significantly increased drug sensitivity to all the antibiotics, except MNZ. The lipid A-core structure was altered in ΔalgC and ΔgalU when their EB accumulation was higher than that in the wild type and complementation strains.Conclusion: UDP-glucose may play an important role in increasing drug resistance to AMO, MNZ, CLA, LEV, TET, and RIF by maintaining the lipid A-core structure and decreasing membrane permeability. AlgC and GalU may serve as potential drug targets for decreasing antibiotic resistance in clinical isolates.Keywords: H. pylori, UDP-glucose, algC, galU, intrinsic multidrug resistance

Jia Liu, Haixiao Zhang, Dan Feng, Jiali Wang, Mingyang Wang, Biao Shen, Yigeng Cao, Xiaoyu Zhang, Qingsong Lin, Fengkui Zhang, Yizhou Zheng, Zhijian Xiao, Xiaofan Zhu, Lei Zhang, Jianxiang Wang, Aiming Pang, Mingzhe Han, Sizhou Feng, Erlie Jiang 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, Tianjin, People’s Republic of ChinaCorrespondence: Sizhou Feng; Erlie Jiang, 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, Email szfeng@ihcams.ac.cn; jiangerlie@163.comPurpose: Patients with hematological diseases are at high risk of carbapenem-resistant Enterobacteriaceae (CRE) infection, and CRE-related bloodstream infection (BSI) is associated with high mortality risk. Therefore, developing a predictive risk model for subsequent BSI in hematological patients with CRE isolated from perianal swabs could be used to guide preventive strategies.Methods: This was a single-center retrospective cohort study at a tertiary blood diseases hospital, including all hematological patients hospitalized from 10 October 2017 to 31 July 2021. We developed a predictive model using multivariable logistic regression and internally validated it using enhanced bootstrap resampling.Results: Of 421 included patients with CRE isolated from perianal swabs, BSI due to CRE occurred in 59. According to the multivariate logistic analysis, age (OR[odds ratio]=1.04, 95% CI[confidence interval]: 1.01– 1.06, P=0.004), both meropenem and imipenem minimal inhibitory concentration (MIC) of the isolate from perianal swabs> 8ug/mL (OR=5.34, 95% CI: 2.63– 11.5, P< 0.001), gastrointestinal symptoms (OR=3.67, 95% CI: 1.82– 7.58, P< 0.001), valley absolute neutrophil count (109/L)> 0.025 (OR=0.07, 95% CI: (0.02– 0.19, P< 0.001) and shaking chills at peak temperature (OR=6.94, 95% CI: (2.60– 19.2, P< 0.001) were independently associated with CRE BSI within 30 days and included in the prediction model. At a cut-off of prediction probability ≥ 21.5% the model exhibited a sensitivity, specificity, positive predictive value and negative predictive value of 79.7%, 85.6%, 96.27% and 47.47%. The discrimination and calibration of the prediction model were good on the derivation data (C-statistics=0.8898; Brier score=0.079) and enhanced bootstrapped validation dataset (adjusted C-statistics=0.881; adjusted Brier score=0.083). The risk prediction model is freely available as a mobile application at https://liujia1992.shinyapps.io/dynnomapp/.Conclusion: A prediction model based on age, meropenem and imipenem MIC of isolate, gastrointestinal symptoms, valley absolute neutrophil count and shaking chills may be used to better inform interventions in hematological patients with CRE isolated from perianal swabs.Keywords: carbapenem-resistant Enterobacteriaceae, bloodstream infection, risk prediction model, hematological patients, perianal colonization

Gaili Wang,1 Huizi Tian,2 Kai Kang,2 Shixian Feng,2 Weihao Shao,1 Xiaorui Chen,1 Caifang Zheng,1 Bowen Zhang,1 Pei Pei,3 Weidong Zhang1 1Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 2Henan Provincial Center for Disease Control and Prevention, Zhengzhou, Henan, 450016, People’s Republic of China; 3Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, 100191, People’s Republic of ChinaCorrespondence: Weidong Zhang, Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China, Tel +86-0371-67781964, Email imooni@163.comObjective: Little is known about the effect of age at first childbirth on lung function. We aimed to investigate the association between age at first childbirth and lung function in Chinese women and further test whether this association is mediated by body mass index (BMI).Methods: This cross-sectional study is a partial survey of the China Kadoorie Biobank (CKB) which was conducted in Xinxiang City, Henan Province between 2004 and 2008. A total of 16,584 postmenopausal women aged 30– 79 years were enrolled. Multiple linear and logistic regression were used to investigate the association between age at first childbirth and lung function and overweight/obesity. The mediation analysis was performed using the PROCESS procedure for SPSS.Results: The mean (SD) age at first childbirth was 23.1 (2.7) years. Women with first childbirth aged ≤ 19 years and 20– 22 years had lower lung function than women who gave first childbirth aged 23– 25 years. Per 1-year increase in the age at first childbirth was associated with a 3.31 mL increase in FEV1 (95% CI = 1.27– 5.35), 3.91 mL increase in FVC (95% CI = 1.63– 6.18), 0.15% increase in FEV1, % predicted (95% CI = 0.05– 0.24) and 0.14% increase in FVC, % predicted (95% CI = 0.05– 0.22). There was no clear association between age at first childbirth and FEV1/FVC ratio. BMI played a contribution to the association between age at first childbirth and FEV1 and the proportion was 16.4% (indirect effect: β = 0.65, 95% CI = 0.46– 0.89; total effect: β = 3.96, 95% CI = 1.92– 5.99). Similarly, the proportion to FVC, FEV1, % predicted, and FVC, % predicted was 25.0%, 16.6%, and 25.0%, respectively.Conclusion: Early age at first childbirth was associated with lower lung function and BMI mediated the association. It is important to test lung function and popularize the knowledge of weight control in women who gave first childbirth at an early age.Keywords: first childbirth, lung function, body mass index, mediation, postmenopausal women

Min Wu,1 Shuo Feng,1 Meng Qian,2 Song Wang,3 Kaiguang Zhang1 1Department of Gastroenterology, Affiliated Provincial Hospital, Anhui Medical University, Anhui, People’s Republic of China; 2Graduate School of Bengbu Medical College, Anhui, People’s Republic of China; 3Department of Gastroenterology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, People’s Republic of ChinaCorrespondence: Kaiguang Zhang, Department of Gastroenterology, Affiliated Provincial Hospital, Anhui Medical University, Anhui, People’s Republic of China, Email zhangkaiguang@ustc.edu.cn Song Wang, Department of Gastroenterology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, People’s Republic of China, Email drwangsong@163.comPurpose: Helicobacter pylori (H. pylori) infection is a high-risk factor for gastric cancer (GC). The main aim of this study was to evaluate the effect of H. pylori on gastritis staging systems and the value of H. pylori combined with gastritis staging systems in predicting GC risk.Patients and Methods: This study enrolled 609 patients with gastric atrophy (GA) and 527 patients with gastric intestinal metaplasia (GIM), who were graded by the OLGA and OLGIM staging systems, respectively. Each individual underwent serum pepsinogen (PG) test, H. pylori detection and questionnaire investigation. We did a real-world retrospective follow-up survey for them in April 2022.Results: Compared with H. pylori-negative patients, H. pylori-positive patients had higher serum PGs/gastrin-17 (G-17) levels and lower PGR levels, regardless of OLGA/OLGIM stages I–II or III–IV. Furthermore, eight patients with atrophic gastritis who progressed to GC were previously in OLGA stages III–IV and OLGIM stages II–IV. The average duration of this process was 2.19± 1.03 years. Logistic regression analysis indicated that PGI and H. pylori infection were independent risk factors of individuals with OLGA stages III–IV. Age and PGR were independent risk factors of patients with OLGIM stages III–IV. PGI and PGR had good clinical diagnostic values for OLGA stages III–IV and OLGIM stages III–IV, respectively.Conclusion: Patients with OLGA/OLGIM stages III–IV should undergo endoscopic surveillance regardless of H. pylori infection. H. pylori-positive patients with OLGIM stage II also have a high risk of GC. H. pylori combined with PGI and PGR is helpful to evaluate the severity of chronic gastritis.Keywords: atrophy, metaplasia, Helicobacter pylori, gastric cancer, risk factors

Xiyan Zhang,1 Xude Zhang,1 Shaojie Feng,1 Xijuan Wang,1 Beibei Guo,1 Jingjing Liu,1 Donghua Xu,2,3 Fengxia Liu1 1Department of Allergy, Weifang People’s Hospital, Weifang, People’s Republic of China; 2Clinical Medicine College, Weifang Medical University, Weifang, People’s Republic of China; 3Department of Rheumatology, The First Affiliated Hospital of Weifang Medical University, Weifang, People’s Republic of ChinaCorrespondence: Fengxia Liu; Donghua Xu, Email wf_lfx@163.com; xudh@wfmc.edu.cnBackground: Allergic asthma is the most common type of asthma and often occurs in early life with increasing comorbidities, including atopic dermatitis and allergic rhinitis. MicroRNAs (miRNAs) are involved in the pathogenesis of numerous immune and inflammatory disorders, particularly allergic inflammation. The specific miRNA profiles of children with allergic asthma have not been fully delineated and still require in-depth study.Objective: This study aimed to identify the expression profile of miRNAs and constructed a network of the interactions between differentially expressed miRNAs and target mRNAs to provide novel insights into understanding the pathogenesis of allergic asthma.Materials and Methods: In this study, we performed high-throughput sequencing of peripheral blood mononuclear cells (PBMCs) from children in the acute phase of asthma. Bioinformatics approaches, including miRanda, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, were employed to predict novel therapeutic and diagnostic targets for allergic asthma. Real-time quantitative PCR was conducted to detect the expression of aberrantly expressed miRNAs.Results: One hundred and sixty-one differentially expressed miRNAs were identified in children with allergic asthma, including 140 conserved miRNAs and 21 novel miRNAs. A total of 8929 targeted mRNAs (44,186 transcripts) associated with differentially expressed miRNAs were predicted and significantly enriched in the cGMP-PKG signalling pathway, cholinergic synapse, and salivary secretion. We also found that miRNA-370-3p targeted PKG and MLCP molecules in the cGMP-PKG signalling pathway and was involved in the pathogenesis of allergic asthma.Conclusion: We identified the miRNA profile of PBMCs in children with allergic asthma and also found that miRNA-370-3p targeted PKG and MLCP molecules in the cGMP-PKG signalling pathway, which provides a novel insight into understanding the pathogenesis of allergic asthma and investigating new targets for the treatment of allergic asthma in children.Keywords: allergic asthma, MicroRNAs, inflammation, house dust mite, children

Ke Zhang,&ast; Songwei Feng,&ast; Yu Ge, Bo Ding, Yang Shen Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Shen, Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China, Email shenyang@seu.edu.cnPurpose: Mucinous ovarian cancer (MOC) is a rare histological type of EOC. In order to guide the clinical diagnosis and management of MOC patients, we constructed and verified a nomogram for the estimation of overall survival in patients with MOC.Patients and Methods: We collected 494 patients with MOC diagnosed from 2010 to 2015 in SEER database, and the following main inclusion criteria were used: (1) patients whose MOC was confirmed by pathology; (2) patients without a history of primary other cancer. Subsequently, we performed randomized grouping (6:4) and Cox hazard regression analysis in the training group. Subsequently, the nomogram was established. A variety of indicators were used to validate the prognosis value of nomogram, including the C-index, area under the receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). Moreover, Kaplan–Meier analysis was used to compare the survival results among different risk subgroups.Results: Cox hazard regression analysis revealed that age, grade, FIGO stage and log odds of positive lymph nodes stage were independent risk factors for patients with MOC. In the training group, the C-index of the nomogram was 0.827 (95% CI: 0.791– 0.863) and the areas under the curve (AUC) predicting the 1-, 3- and 5-year survival rate were 0.853 (95% CI: 0.791– 0.915), 0.886 (95% CI: 0.852– 0.920) and 0.815 (95% CI: 0.766– 0.864), respectively. The calibration curve revealed that the nomogram of the 1-, 3- and 5-year survival rate was consistent with the actual fact. Patients with high risk had a poorer prognosis than those with low risk (P < 0.001). DCA revealed that the nomogram had the best clinical value than other classical prognostic markers. Similarly, nomogram had excellent prognostic ability in the testing group.Conclusion: The nomogram was constructed to predict overall survival in patients with MOC, which had the significance for clinical evaluation.Keywords: mucinous ovarian cancer, SEER database, nomogram, prognosis, log odds of positive lymph nodes (LODDS) stage

Yanzhe Ning,1– 3 Sisi Zheng,1– 3 Sitong Feng,1– 3 Kuangshi Li,4 Hongxiao Jia1– 3 1The Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2The National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 4Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Hongxiao Jia, The Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China, Email jhxlj@ccmu.edu.cn Kuangshi Li, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China, Email likuangshi89@hotmail.comIntroduction: Sleep deprivation (SD) has a detrimental effect on cognitive functions. Numerous studies have indicated the mechanisms underlying cognitive impairments after SD in brain networks. However, the findings based on the functional connectivity (FC) and topological architecture of brain networks are inconsistent.Methods: In this study, we recruited 30 healthy participants with regular sleep (aged 25.20 ± 2.20 years). All participants performed the repeatable battery for the assessment of neuropsychological status and resting-state fMRI scans twice, during the rested wakefulness (RW) state and after 24 h of total SD. Using the Dosenbach atlas, both large-scale FC and topological features of brain networks (ie nodal, global and local efficiency) were calculated for the RW and SD states. Furthermore, the correlation analysis was conducted to explore the relationship between the changes in FC and topological features of brain networks and cognitive performances.Results: Compared to the RW state, the large-scale brain network results showed decreased between-network FC in somatomotor network (SMN)-default mode network (DMN), SMN-frontoparietal network (FPN), and SMN-ventral attention network (VAN), and increased between-network FC in the dorsal attention network (DAN)-VAN, DAN-SMN after SD. The clustering coefficient, characteristic path length and local efficiency decreased after SD. Moreover, the decreased attention score positively correlated with the decreased topological measures and negatively correlated with the FC of DAN-SMN.Conclusion: Our results suggested that the increased FC of DAN-SMN and decreased topological features of brain networks may act as neural indicators for the decrease in attention after SD.Clinical Trial Registration: The study was registered at the Chinese Clinical Trial Registry, registration ID: ChiCTR2000039858, China.Keywords: brain network, functional connectivity, sleep deprivation, cognitive impairment, topological feature

Jing Mao,1,&ast; Ya Li,2– 4,&ast; Qingqing Bian,3 Yinshuang Xuan,3 Jingmei Li,3 Zhikun Wang,3 Suxiang Feng,1,2,4 Xuefang Liu,2,4 Yange Tian,2,4 Suyun Li2– 4 1College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3Institute for Respiratory Diseases, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Disease by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Suyun Li, Email lisuyun2000@126.comPurpose: Bufei Jianpi formula (BJF), a traditional Chinese medicine, is an effective and safe therapeutic formula for chronic obstructive pulmonary disease (COPD). BJF treatment is known to reduce the incidence of loose stools in rats with COPD. It is unclear whether BJF regulates gut microbiota. This study examined whether BJF improved mucosal immune function by remodeling the gut microbiota and modulating metabolites in COPD rats.Methods: Sixty Sprague Dawley (SD) rats were randomized into control, model, BJF, aminophylline (APL), and probiotics (PBT) groups. The stable COPD rat model was duplicated using repeated cigarette smoke inhalation and lipopolysaccharide (LPS) injection. Normal saline, BJF, APL, or PBT were intragastrically administered from weeks eight to twelve, and then the rats were sacrificed at week thirteen. Lung and colon tissues were removed; feces were collected. Pulmonary function, histopathology, levels of inflammatory factors, and activation of NF-κB in the lung tissues were evaluated. Gut microbiota were analyzed using 16S rRNA gene sequencing; fecal short-chain fatty acid (SCFA) concentrations were determined using gas chromatography/mass spectrometry. Mucosal immune response-related genes and proteins were determined using quantitative polymerase chain reaction and Western blotting.Results: BJF improved pulmonary function and reduced lung inflammation. Further, BJF treatment altered the gut microbiota composition and significantly increased the abundance of Firmicutes and the ratio of Firmicutes to Bacteroides, raising SCFA levels, including acetate, butyrate, and propionate levels. However, the abundance of Bacteroidetes, Proteobacteria, Spirochaetes, Clostridiaceae, and Treponema decreased after BJF administration. BJF decreased the gene and protein expression of NLRP3, Caspase-1, IL-8, and IL-1β, and increased GPR43 expression.Conclusion: Overall, BJF administration improved mucosal immune function by remodeling the gut microbiota and suppressing the SCFAs/GPR43/NLRP3 pathway in COPD rats. This study provides evidence for the mechanisms underlying BJF-induced improvements in COPD and supports clinical application of BJF.Keywords: Bufei Jianpi formula, chronic obstructive pulmonary disease, gut microbiota, gut-lung axis, short-chain fatty acids, mucosal immune function

Feng Wang,1 Wenyao Zhang,1 Hao Li,1 Xiaonan Chen,1 Sining Feng,1 Ziqing Mei2 1Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing, 100081, People’s Republic of China; 2School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 100083, People’s Republic of ChinaCorrespondence: Ziqing Mei, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 100083, People’s Republic of China, Email Marina1977@163.comAbstract: Chronic wound caused by diabetes is an important cause of disability and seriously affects the quality of life of patients. Therefore, it is of great clinical significance to develop a wound dressing that can accelerate the healing of diabetic wounds. Nanoparticles have great advantages in promoting diabetic wound healing due to their antibacterial properties, low cytotoxicity, good biocompatibility and drug delivery ability. Adding nanoparticles to the dressing matrix and using nanoparticles to deliver drugs and cytokines to promote wound healing has proven to be effective. This review will focus on the effects of diabetes on wound healing, introduce the properties, preparation methods and action mechanism of nanoparticles in wound healing, and describe the effects and application status of various nanoparticle-loaded dressings in diabetes-related chronic wound healing.Keywords: diabetic wound healing, nanoparticles, antibacterial, low cytotoxicity, good biocompatibility, drug delivery

Xiaolong Ma,1,&ast; Xiaodong Lv,1,&ast; Sihan Feng,1 Ruishan Liu,2,3 Hao Fu,2 Feng Gao,1 Hao Xu2 1Department of Respiratory Medicine, the First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), Jiaxing, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Laboratory Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Feng Gao, Department of Respiratory Medicine, the First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), No. 1882 South Zhonghuan Road, Jiaxing, 314000, People’s Republic of China, Tel +86 573 825 198 70, Fax +86 573 820 830 06, Email guti-gf@163.com Hao Xu, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qing chun Road, Hangzhou, 310003, People’s Republic of China, Tel +86 571 872 364 23, Fax +86 571 872 364 21, Email xuhao0523@zju.edu.cnPurpose: To investigate the phenotypic and genomic characteristics of the multi-drug resistant and hypervirulent Klebsiella pneumoniae strain recovered from bacteremia.Methods: Antimicrobial susceptibility testing (AST) was performed by the microdilution method. Antimicrobial resistance genes, virulence-associated genes, multilocus sequence typing (MLST), and plasmid replicon were characterized by next-generation sequencing (NGS) and nanopore sequencing. S1 nuclease-pulsed field gel electrophoresis (S1-PFGE) and Southern blotting were performed to characterize the plasmid profile.Results: The hypervirulent colistin- and carbapenem-resistant K. pneumoniae strain DY2009 was identified as ST5571, co-carrying mcr-1, blaNDM-1, and blaOXA-10. In silico analysis found that it was K2 serotype. AST results revealed that DY2009 was resistant to carbapenems, cephalosporins, ciprofloxacin, chloramphenicol, and colistin but remained susceptible to aztreonam, gentamicin, amikacin, and tigecycline. Through the whole-genome analysis, a variety of virulence determinants were identified, including rmpA. Plasmid analysis confirmed that the mcr-1 and blaNDM-1 gene harbored a ∼ 33 kb IncX4 plasmid and a ∼ 44 kb IncX3 plasmid. In contrast, blaOXA-10 was encoded by chromosome.Conclusion: To the best of our knowledge, we first report the clinical hypervirulent K. pneumoniae isolate co-producing MCR-1, NDM-1, and OXA-10 causing bacteremia. We found that mcr-1 and blaNDM-1 genes were located on two self-conjugative epidemic plasmids, contributing to the widespread MCR-1 and NDM-1 in China. The results of this work improve our understanding of the genetic background of colistin- and carbapenem-resistant K. pneumoniae isolate from bacteremia and the resistance mechanisms. Our findings highlight the urgent need for infection control of such strain to prevent it from becoming an extensive-drug resistant clone.Keywords: Klebsiella pneumoniae, NDM-1, MCR-1, OXA-10, rmpA, bacteremia

Xianhua Liao,1 Qianqian Ma,1 Tingfeng Wu,1 Congxiang Shao,1 Yansong Lin,1 Yanhong Sun,2 Shiting Feng,3 Wei Wang,4 Junzhao Ye,1 Bihui Zhong1 1Department of Gastroenterology of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Laboratory of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Radiology of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Department of Medical Ultrasonics of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Bihui Zhong; Junzhao Ye, Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, People’s Republic of China, Tel +86 135 0307 9262 ; +86 135 0151 9252, Email zhongbh@mail.sysu.edu.cn; yejzh@mail2.sysu.edu.cnPurpose: Effective treatment of dyslipidemia with lipid-lowering agents is pivotal in the management of metabolic-associated fatty liver disease (MAFLD) for preventing cardiovascular complications. We explored the associations between improvements in liver injuries indicated by changes in transaminases and a reduction in lipid levels in MAFLD patients with dyslipidemia and elevated transaminases during lipid-lowering therapies.Methods: This prospective, cohort study enrolled consecutive MAFLD patients with hyperlipidemia and elevated transaminases. Patients were divided into a group receiving lipid-lowering agents and an age-, sex- and baseline lipid level-matched control group without receiving lipid-lowering agents. Clinical visits were performed at the 1st month and then every 3 months for 1 year.Results: This study included 541 MAFLD patients (lipid-lowering group: 325 patients; control group: 216 patients). Compared with controls, there was a substantially greater reduction in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) in the lipid-lowering group after 12 months (all P < 0.05). The decrease in ALT was positively correlated with the decrease in TC (r = 0.332), TG (r = 0.180), LDL-c (r = 0.253) and apolipoprotein E (ApoE) (r = 0.119), while the decrease in AST was positively correlated with the decrease in TC (r = 0.228) and LDL-c (r = 0.192) (all P< 0.05). The greater range of reduction in blood lipids (TC/TG/LDL-c), the higher the transaminase and GGT normalization rate (all P< 0.05). Multivariate analysis confirmed that a TG decrease of over 50% remained an independent predictor of transaminase and GGT normalization (OR 2.07, 95% CI 1.12– 3.84, P=0.020).Conclusion: Lipid-lowering to target levels might be beneficial to liver injury improvements in MAFLD patients with dyslipidemia when receiving lipid-lowering agents.Keywords: dyslipidemia, metabolic dysfunction-associated fatty liver disease, alanine aminotransferase, triglyceride, gamma glutamyl transpeptidase, statins

Xingming Xie,1,2 Chaochun Chen,1,2 Shu Feng,1,3 Shi Zuo,2 Xueke Zhao,3 Haiyang Li1,2 1School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of ChinaCorrespondence: Haiyang LiDepartment of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, 28 Guiyi Street, Guiyang, Guizhou, People’s Republic of ChinaTel/Fax +86 851-6855119Email lihaiyang@gmc.edu.cnPurpose: Acyl-CoA thioesterase 7(ACOT7) plays an important role in the metabolism of fatty acids. Hepatocellular carcinoma (HCC) has an abnormal lipid profile, and the role of ACOT7 in hepatocellular carcinoma has not been detailedly elucidated. Therefore, we conducted the study to explore the role of ACOT7 in HCC.Materials and Methods: The ACOT7 and Krüppel-like factor 13 (KLF13) mRNA expression levels were obtained from The Cancer Genome Atlas (TCGA) database. Bioinformatics analysis identified the underlying upstream regulator of ACOT7. Quantitative real-time PCR was used to detect the expression of mRNA, and immunohistochemical staining and Western blotting were used to detect the expression of protein. Cell Counting Kit-8 and EdU assays were employed to assess the proliferation of HCC cells. Wound-healing and Transwell migration assays were utilized to test the migration ability of HCC cells. Dual-luciferase reporter assay and ChIP assay were used to explore the potential mechanism. Gas chromatography-mass spectrometer was used to analyze the content of free fatty acids. Xenograft tumour growth was used to evaluate the effect of ACOT7 in vivo.Results: According to The Cancer Genome Atlas (TCGA) database, ACOT7 mRNA was found to be upregulated and predicted the poor prognosis. Overexpression of ACOT7 enhanced the proliferation, migration and invasion abilities of HCC cells in vitro, as well as the HCC cells proliferation in vivo. Moreover, ACOT7 overexpression increased the yield of the monounsaturated fatty acid Oleic acid (C18:1), which strengthened the proliferation and migration abilities of HCC cells. Mechanistically, KLF13 transcriptionally promoted ACOT7 expression. Further, KLF13 was also overexpressed in HCC tissues and facilitated HCC progression.Conclusion: Acyl-CoA thioesterase 7 is transcriptionally activated by Krüppel-like factor 13 and promotes the progression of hepatocellular carcinoma.Keywords: acyl-CoA thioesterase 7, Krüppel-like factor 13, hepatocellular carcinoma, unsaturated fatty acid, prognosis

Xiaoning Cen,1,&ast; Yunmei Huang,2,&ast; Zhuangnian Lu,3,&ast; Wenjun Shao,4 Chenyi Zhuo,1 Chongchan Bao,5 Shi Feng,5 Cheng Wei,5 Xiqiang Tang,5 Lijun Cen,5 Wenwen Guo,5 Xinru Tian,5 Qianli Tang,5 Xusen Huang1 1General Surgery, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 3Department of Pediatrics, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 4Medical college of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 5YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianli TangYouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of ChinaEmail htmgx@163.comXusen HuangGeneral Surgery, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of ChinaEmail hxsfy@163.comBackground: LncRNAs play an important role in tumor initiation and development. However, the underlying involvement of lncRNA expression in colorectal carcinoma remains to be clarified.Methods: All analyses were performed in R software v4.0, SPSS v13.0, and GraphPad Prism 8. The “limma” package was used to identify differentially expressed lncRNAs between two groups with the threshold of |logFC| > 1 and P < 0.05. The “Survival” package was used to conduct survival analysis. HCT8 and SE480 cell lines were used to conduct further phenotype experiments, including transwell, wound-healing, CCK8 and colony formation assay. Gene set enrichment analysis was used to explore the biological pathway difference in high and low IGFL2-AS1 patients.Results: The lncRNA IGFL2-AS1 was highly expressed in colon adenocarcinoma (COAD) tissue and cell lines (HCT116, HCT8, HCT129, and SW480). The COAD patients with high IGFL2-AS1 were associated with a worse prognosis. Meanwhile, the knockdown of IGFL2-AS1 could significantly suppress the proliferation and invasion of COAD cells. Gene set enrichment analysis showed that the top five biological pathways involving IGFL2-AS1 were angiogenesis, epithelial–mesenchymal transition, KRAS signaling, myogenesis, and coagulation. Western blot results showed that the inhibition of IGFL2-AS1 could significantly reduce the N-cadherin, HIF1A and KRAS protein expression, yet increase the E-cadherin protein level. IGFL2-AS1 was also positively correlated with M0 macrophages, M2 macrophages, and neutrophils but negatively correlated with CD4+ memory T cells and CD8+ T cells.Conclusion: IGFL1-AS1 could seriously worsen patient outcomes and facilitate COAD progression, thus serving as an independent tumor marker.Keywords: IGFL2-AS1, lncRNA, colon cancer, immune

Yanxiang Shao,1,&ast; Thongher Lia,1,&ast; Yaohui Wang,1,&ast; Kan Wu,1 Xu Hu,1 Yang Liu,1 Shuyang Feng,1 Shangqing Ren,1,2 Zhen Yang,1,3 Sanchao Xiong,1 Weixiao Yang,1 Qiang Wei,1 Hao Zeng,1 Xiang Li1 1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Robotic Minimally Invasive Surgery Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, 610072, People’s Republic of China; 3Department of Urology, Chengdu Second People’s Hospital, Chengdu, 610021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang LiDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, 37 GuoXueXiang, Chengdu, 610041, People’s Republic of ChinaEmail xiangli87@hotmail.comObjective: To evaluate the prognostic factors of penile cancer and the utility of prognostic models.Methods: We analyzed postoperatively collected data of 311 patients diagnosed with penile cancer. Survival analysis (Kaplan–Meier and cox regression methods) was performed on this cohort. The c-index was used to determine the predictive accuracies of potential prognostic factors. The accuracies of four prognostic models were also evaluated, which were AJCC prognostic stage group for three recent editions, and four nomograms constructed by the Surveillance, Epidemiology, and End Results program (SEER). Two novel nomograms using our data were created and AUC of 2-year survival were determined to compare existing and newly established models.Results: Tumor site, T and N stages, nuclear grade and lymph vascular invasion (LVI) significantly influenced prognosis. The 8th T and N stages had better c-indexes than former editions, while no improvement was seen in the 8thAJCC stage group. 6th AJCC+grade nomogram had a higher c-index than other three nomograms (SEER+grade, 6th TNM+grade, and 6th T1-3N0-3+grade nomograms; c-index: 0.831 vs 0.738, 0.792 and 0.781). New nomogram 1 included the 8th T and N stages, tumor site, nuclear grade, and LVI, with a c-index of 0.870. Novel nomogram 2 replaced the T and N stages with the AJCC stage group, which had a lower c-index of 0.855. The order of prediction accuracy of 2-year survival in the old and new models is consistent with the c-index results.Conclusion: Tumor site, stages, grade, and LVI play important roles in predicting survival of penile cancer. The 8th stages have better predictive accuracy than former editions. We proposed two models with better predictive accuracy than former models; specifically, nomogram 1 may be a more precise and convenient tool for predicting penile cancer outcomes.Keywords: penile cancer, TNM stage, survival, nomogram, external validation

Jin Peng,1 Ruiying Dong,1 Jianfen Jiao,1 Min Liu,1 Xi Zhang,1 Hualei Bu,1 Ping Dong,2 Shasha Zhao,3 Naidong Xing,4 Shuai Feng,5 Xingsheng Yang,1 Beihua Kong1 1Department of Obstetrics and Gynecology, Qilu hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 3Department of Clinical Nutrition, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 4Department of Urology, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 5Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaCorrespondence: Xingsheng YangDepartment of Obstetrics and Gynecology, Qilu Hospital, Shandong University, No. 107 West Wenhua Road, Jinan, 250001, People’s Republic of ChinaEmail xingshengyang@sdu.edu.cnObjective: Enhanced recovery after surgery (ERAS) protocol has widely gained acceptance in gynecological surgery. Its safety and efficacy should be evaluated fully via well-designed, randomized, control trials. The main objective of our study is to compare the ERAS protocol with the conventional perioperative care program after gynecological oncology. Furthermore, the secondary objectives of our study are the identification of markers that allow us to evaluate the effectiveness of the application of ERAS elements in the modulation of the body’s response to surgical stress.Methods: Patients with gynecological tumors indicated for surgery were randomly assigned to either the ERAS group or the conventional group. The ERAS protocol included short fasting time, fluid restriction, early oral feeding, reduced opioid consumption and immediate mobilization after surgery. The primary endpoint was the reduction of hospital stay in the ERAS group. The day of first flatus, postoperative nausea and vomiting (PONV), maximum pain score by the visual analogue scale (VAS) and complication, readmission rate, reoperation rate, postoperative mortality, total hospital cost and systemic inflammatory response (SIR) were secondary endpoints.Results: A total of 130 patients in gynecological tumor surgery were enrolled (ERAS = 65, conventional = 65). The ERAS group had faster bowel function recovery, significantly less pain, less PONV, shorter hospital stay, and less total hospital costs. SIR markers were estimated and screened out that postoperative platelet, neutrophil-lymphocyte-ratio (NLR) and platelet-lymphocyte-ratio (PLR) were significantly lower in ERAS groups compared to conventional groups.Conclusion: The implementation of ERAS protocol is safe and enhances postoperative recovery after gynecological oncology surgery. We firstly reveal the beneficial effect of ERAS protocols on the alleviation of postoperative SIR, which is a reflection of the magnitude of surgical trauma. Postoperative platelet, NLR or PLR could be the novel and inexpensive markers to assess how ERAS protocols modulate gynecological oncology surgery.Trial Registration: The trial was registered in ClinicalTrials.gov (NCT03629626).Keywords: ERAS, enhanced recovery after surgery, systemic inflammatory response, gynecological oncology surgery, NLR, neutrophil-lymphocyte-ratio, PLR, platelet-lymphocyte-ratio