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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

Ying Pan,1 Mengjie Zhao,1 Tiantian Song,2 Jia Tang,2 Ming Kuang,2 Hongying Liu,2,* Shao Zhong3,* 1Department of General Practice, Kunshan Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, People’s Republic of China; 2Hangzhou Kang Ming Information Technology Co., Ltd, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Endocrinology, Gusu School, Nanjing Medical University, The First People’s Hospital of Kunshan, Kunshan, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shao Zhong, Department of Endocrinology, Gusu School, Nanjing Medical University, the First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China, Tel +86 13328056828, Email drzhong@163.com Hongying Liu, Hangzhou Kang Ming Information Technology Co., Ltd, Hangzhou, 310000, People’s Republic of China, Tel +86 02164045531, Email hongyingliu@91jkys.comAbstract: Insulin resistance (IR) is the major mechanism in the pathogenesis of type 2 diabetes mellitus (T2DM). Early identification of IR is of great significance for preventing the onset of T2DM and delaying the progression of the disease. Previous studies have shown that triglyceride-glucose (TyG) index can be used as an effective surrogate marker for IR. There is a significant correlation between TyG index and T2DM and its common complications. In addition, the predictive efficacy of TyG index is better than that of other IR surrogate indicators. TyG index may not only become an important marker to identify people at high risk of T2DM and its complications, but is also expected to become a strong predictor of the prognosis of these diseases. However, there are still some challenges in the widespread application of TyG index in clinical practice. In the future, more high-quality studies are needed to clarify the assessment methods of TyG index for the prognosis of T2DM and its complications. Further investigations of the relationship between TyG index and T2DM and its complications will be expected to provide new ideas and methods for the prevention and treatment of T2DM and its complications.Keywords: triglyceride-glucose index, type 2 diabetes mellitus, complication, insulin resistance

Zhi-Hang Chen,1,&ast; Qian Zhou,2,&ast; Ze-Bin Chen,1,&ast; Wen-Xuan Xie,1 Zi-Min Song,1 Shui-Rong Lin,1 Wei Wang,3 Shun-Li Shen,1 Ming Kuang1 1Department of Liver Surgery, Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Department of Medical Statistics, Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 3Division of Interventional Ultrasound, Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shun-Li Shen; Ming Kuang, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China, Tel +86 20-87755766, Email shenshli@mail.sysu.edu.cn; kuangm@mail.sysu.edu.cnPurpose: Liver resection and ablation remain the most common therapeutic options for Barcelona Clinic Liver Cancer (BCLC) stage 0-A hepatocellular carcinoma (HCC), but there is a lack of evidence to show which is the most suitable therapy. This study aimed to make concurrent multi-arm comparisons of the short-term and long-term outcomes of percutaneous ablation (PA), open (OLR) or laparoscopic liver resection (LLR) for these patients.Patients and Methods: This was a retrospective observational cohort study. A series of generalized propensity score methods for multiple treatment groups were performed to concurrently compare the clinical outcomes of these three treatment options to balance potential confounders. Regression standardization was used to account for hazard of all-cause mortality and recurrence of intergroup differences.Results: Of the 1778 patients included, 1237, 307 and 234 underwent OLR, LLR and PA, respectively. After overlap weighting, which was the optimal adjustment strategy, patients in the minimally invasive group (LLR and PA groups) had few postoperative complications and short postoperative hospital stays (both P < 0.001). The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate were significantly higher in the LLR group when compared with the OLR and PA groups (RFS: 55.6% vs 48.0% vs 30.2%, P < 0.001; OS: 89.1% vs 79.7% vs 84.0%, P = 0.020). Multivariable Cox analysis and regression standardization showed that LLR was an independent factor for better RFS when compared with OLR and PA. In subgroup analysis, the long-term outcomes of patients with BCLC stage A HCC were consistent with the whole population.Conclusion: In the observational study using various covariate adjustment analysis with excellent balance, LLR is not only minimally invasive, but also provides better RFS and equivalent OS for patients with BCLC stage 0-A HCC when compared with OLR and PA.Keywords: hepatocellular carcinoma, laparoscopic liver resection, generalized propensity score analysis, overlap weighting, clinical outcome

Jiajun Qiu,1– 3,&ast; Xin Huang,1– 3,&ast; Maobin Kuang,1– 3,&ast; Ruijuan Yang,1,4 Jiachong Li,1 Guotai Sheng,5,6 Yang Zou2,3 1Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 2Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 3Jiangxi Cardiovascular Research Institute, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi Province, People’s Republic of China; 4Department of Endocrinology, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 5Jiangxi Provincial Geriatric Hospital, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 6Jiangxi Provincial Geriatric Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guotai Sheng, Jiangxi Provincial Geriatric Hospital, Jiangxi Provincial People’s Hospital, No. 92 Aiguo Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Email tgs200509@163.com Yang Zou, Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, No. 92 Aiguo Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Email jxyxyzy@163.comPurpose: The association between traditional lipid parameters and non-alcoholic fatty liver disease (NAFLD) has been extensively discussed. This study aims to evaluate and compare the lipoprotein combine index (LCI) and traditional lipid parameters [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] to identify NAFLD.Patients and Methods: The analysis included 14,251 participants from the NAfld in the Gifu Area, Longitudinal Analysis (NAGALA). Logistic regression models were employed to calculate standardized odds ratios (ORs) and 95% confidence intervals (CIs) for assessing and comparing the association of LCI and traditional lipid parameters with NAFLD. Additionally, receiver operating characteristic (ROC) curves were used to calculate the area under the curve (AUC) for LCI and traditional lipid parameters in identifying NAFLD.Results: After adjusting for various confounders, we found that LCI was positively associated with NAFLD (OR=2.25, 95% CI 1.92– 2.63), and this association was stronger than that of traditional lipid parameters [OR: TC1.23, TG1.73 LDL-C1.10]. Further subgroup analyses revealed that the association of LCI with NAFLD was stronger than other traditional lipid parameters in all subgroups, including men and women, overweight/obese [body mass index (BMI)≥ 25 kg/m2] and non-obese (BMI< 25 kg/m2), and older (age≥ 45 years) and younger (age< 45 years) participants. Additionally, ROC analysis indicated that LCI (AUC=0.8118) had significantly higher accuracy (All DeLong P< 0.05) in identifying NAFLD compared to traditional lipid parameters (AUC: TC0.6309; TG0.7969; LDL-C0.6941); HDL-C0.7587). Sensitivity analysis further confirmed the robustness of the study findings.Conclusion: This study revealed for the first time a positive correlation between LCI and NAFLD. Compared to traditional lipid parameters, LCI has a higher correlation with NAFLD. Additionally, further ROC analysis demonstrated that LCI had higher accuracy in identifying NAFLD compared to traditional lipid parameters, suggesting that LCI may be a better marker for NAFLD identification than traditional lipid parameters.Keywords: non-alcoholic fatty liver disease, lipoprotein combine index, NAFLD, traditional lipid parameters, LCI

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

Yijie Wang,1,&ast; Weixiang Weng,2,&ast; Ruiming Liang,3,&ast; Qian Zhou,3 Hangtong Hu,4 Mingde Li,4 Lida Chen,4 Shuling Chen,4 Sui Peng,1,3 Ming Kuang,2,4,5 Han Xiao,6 Wei Wang4 1Department of Gastroenterology and Hepatology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 3Clinical Trials Unit, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 4Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 5Cancer Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China; 6Department of Medical Ultrasonics, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Han Xiao, Department of Medical Ultrasonics, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China, Tel/Fax +86-20-87755766-8576, Email xiaoh69@mail.sysu.edu.cn Wei Wang, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China, Tel/Fax +86-20-87755766-8576, Email wangw73@mail.sysu.edu.cnPurpose: The T cell-inflamed gene expression profile (GEP) quantifies 18 genes’ expression indicative of a T-cell immune tumor microenvironment, playing a crucial role in the immunotherapy of hepatocellular carcinoma (HCC). Our study aims to develop a radiomics-based machine learning model using contrast-enhanced ultrasound (CEUS) for predicting T cell-inflamed GEP in HCC.Methods: The primary cohort of HCC patients with preoperative CEUS and RNA sequencing data of tumor tissues at the single center was used to construct the model. A total of 5936 radiomics features were extracted from the regions of interest in representative images of each phase, and the least absolute shrinkage and selection operator and logistic regression were used to construct four models including three phase-specific models and an integrated model. The area under the curve (AUC) was calculated to evaluate the performance of the model. The independent cohort of HCC patients with preoperative CEUS and Immunoscore based on immunohistochemistry and digital pathology was used to validate the correlation between model prediction value and T-cell infiltration.Results: There were 268 patients enrolled in the primary cohort and 46 patients enrolled in the independent cohort. Compared with the other three models, the AP model constructed by 36 arterial phase (AP) features showed good performance with a mean AUC of 0.905 in the 5-fold cross-validation and was easier to apply in the clinical setting. The decision curve and calibration curve confirmed the clinical utility of the model. In the independent cohort, patients with high Immunoscores showed significantly higher GEP prediction values than those with low Immunoscores (t=− 2.359, p=0.029).Conclusion: The CEUS-based model is a reliable predictive tool for T cell-inflamed GEP in HCC, and might facilitate individualized immunotherapy decision-making.Keywords: Radiomics, Contrast-enhanced ultrasound, Hepatocellular carcinoma, T cell-inflamed gene expression profile

Ning Xu,1,&ast; Guanzheng Cui,1,&ast; Shengyin Zhao,1 Yu Li,1 Qian Liu,2 Xuchang Liu,1 Chuanliang Zhao,3 Rongjie Feng,1 Mingjie Kuang,1 Shijie Han1 1Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, 250014, People’s Republic of China; 2Department of Pain, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 3Department of Orthopedic Surgery, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shijie Han; Mingjie Kuang, Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250014, People’s Republic of China, Email hanshijie@sdfmu.edu.cn; doctorkmj@tmu.edu.cnIntroduction: Osteoporosis is a common bone disease in which the bone loses density and strength and is prone to fracture. Bone marrow mesenchymal stem cells (BMSCs) are important in bone-related diseases. Exosomes, as mediators of cell communication, have potential in cell processes. Previous studies have focused on muscle factors’ regulation of bone remodeling, but research on exosomes is lacking.Methods: In order to confirm the therapeutic effect of mechanically stimulated myocytes (C2C12) derived exosomes (Exosome-MS) on the Glucocorticoid-induced osteoporosis(GIOP) compared with unmechanically stimulated myocytes (C2C12) derived exosomes (Exosomes), we established a dexamethasone-induced osteoporosis model in vivo and in vitro. Cell viability and proliferation were assessed using CCK8 and EDU assays. Osteogenic potential was evaluated through Western blotting, real-time PCR, alkaline phosphatase activity assay, and alizarin red staining. Differential expression of miRNAs was determined by high-throughput sequencing. The regulatory mechanism of miR-92a-3p on cell proliferation and osteogenic differentiation via the PTEN/AKT pathway was investigated using real-time PCR, luciferase reporter gene assay, Western blotting, and immunofluorescence. The therapeutic effects of exosomes were evaluated in vivo using microCT, HE staining, Masson staining, and immunohistochemistry.Results: In this study, we found that exosomes derived from mechanical stress had a positive impact on the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). Importantly, we demonstrated that miR-92a-3p mimics could reverse dexamethasone-induced osteoporosis in vitro and in vivo, indicating that mechanical stress-induced mouse myoblast-derived exosomes could promote osteogenesis and prevent the occurrence and progression of osteoporosis in mice through miR-92a-3p/PTEN/AKT signaling pathway.Conclusion: Exosomes derived from mechanical stress-induced myoblasts can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through miR-92a-3p/PTEN/AKT signaling pathway, and can have a therapeutic effect on glucocorticoid-induced osteoporosis in mice in vivo. Keywords: Human bone marrow mesenchymal stem cells, Mechanical stimulation, Exosome, miR-92a-3p, AKT signaling

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

Jia Tang, Tiantian Song, Ming Kuang, Yiping Feng, Guangrong Liu, Hongying Liu Hangzhou Kang Ming Information Technology Co., Ltd, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Hongying Liu, Hangzhou Kang Ming Information Technology Co., Ltd, 401 Building 4, Haichuang Park (across from Taobao City) 998 Wenyi West Road, Yuhang District, Hangzhou, Zhejiang Province, 310000, People’s Republic of China, Tel +86 021 64045531, Email hongyingliu@91jkys.comAbstract: The COVID-19 pandemic is a huge public health crisis in the 21st century. In addition to the acute symptoms, a considerable proportion of patients worldwide have suffered from post-COVID-19 syndrome, commonly known as Long COVID. The impact of Long COVID on individual and public health burden cannot be ignored. According to recent researches, Long COVID has been affecting multiple organ systems throughout the body, with respiratory, mental, nervous and digestive symptoms often seen in Chinese population. Clinical studies have proved that symptoms were alleviated by a variety of treatments, such as physical therapy, rehabilitation training, psychological support, behavioral cognitive therapy, stem cell therapy, etc. Based on the current clinical evidence, it is recommended to strengthen the scientific research on Long COVID and actively carry out early monitoring and intervention in the future, so as to effectively prevent the long-term disease burden and economic pressure.Keywords: Long COVID, post-COVID conditions, China, clinical characteristics, management strategies

Fang Wang,1,&ast; Feng-Hua Wang,2,3,&ast; Kaiyu Sun,4,&ast; Chang Jiang,2,5 Sui Peng,6 Li-Xia Xu,1 Ming Kuang,7 Gui-Fang Guo,2,5,8 Shu-Ling Chen9 1Department of Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2State Key Laboratory of Oncology in South China, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Oncology, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 4Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 5Collaborative Innovation Center for Cancer Medicine, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 6Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 7Department of Liver Surgery, Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 8VIP Department, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 9Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shu-Ling Chen; Gui-Fang Guo, Email chenshling@mail.sysu.edu.cn; guogf@sysucc.org.cnIntroduction: Advanced biliary tract carcinoma (BTC) has a poor prognosis and few treatment options. We compared the efficacy of the PD-1 monoclonal antibody (PD-1-mAb) combined regimens with the standard chemotherapy in the first-line and second-line treatment of advanced BTC.Methods: We retrospectively assessed the patients with advanced BTC, who received treatment at the First Affiliated Hospital of Sun Yat-Sen University and the Sun Yat-Sen University Cancer Center. The patients were treated with PD-1-mAb combined regimens or standard chemotherapy at the first line or treated with PD-1-mAb combined regimens or systematic therapy at the second line. Further subgroup analyses were assessed to identify superior regimens.Results: This study included 210 patients. The first-line PD-1-mAb combination group (n = 83) achieved longer median PFS (mPFS) (7.3 vs 5.3 months, p=0.001) and median OS (mOS) (15.6 vs 11.4 months, p=0.002) than the first-line standard chemotherapy group (n=76). Similarly, the second-line PD-1-mAb combination group (n=50) yielded longer mPFS (6.1 vs 2.6 months, p< 0.001) and mOS (11.7 vs 7.2 months, p=0.008) than the second-line systematic therapy group (n=51). Subgroup analyses showed that the PD-1-mAb combined with TKI group achieved better mPFS than the chemotherapy group whether in the first-line (HR = 0.468, p=0.005) or the second-line setting (HR = 0.45, p=0.009), but did not achieve superiority in mOS (both p> 0.05). Compared with the chemotherapy group, the PD-1-mAb combined with chemotherapy group achieved longer mOS (HR = 0.53, p=0.023) in the first-line setting and longer mPFS in the second-line setting (HR = 0.54, p=0.044).Conclusion: The PD-1-mAb combination therapy is superior to the standard chemotherapy in advanced or unresectable BTC, whether as a first-line or second-line treatment. Among the combination therapy, both the PD-1-mAb combined with TKI and combined with standard chemotherapy were promising options for advanced BTC patients.Keywords: biliary tract carcinoma, PD-1-mAb, PD-1 plus anti-angiogenesis TKI, PD-1 plus chemotherapy, the first-line chemotherapy, the second-line chemotherapy

Suipeng Chen,1,&ast; Mengjiao Kuang,1,&ast; Ying Qu,1,2 Shirui Huang,1 Binbin Gong,1 Suzhen Lin,1 Huiyan Wang,1 Guiye Wang,1 Hongqun Tao,1 Jian Yu,1 Zuqin Yang,3 Minghua Jiang,1 Qipeng Xie1 1Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China; 2Department of Clinical Laboratory, Wenzhou People’s Hospital, The Third Affiliated Hospital of Shanghai University, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China; 3Newborn Department of Pediatrics, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qipeng Xie, Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China, Tel +86 15157787159, Email pandon2002@163.comObjective: Sepsis remains a major cause of neonatal death. To better characterize the inflammatory response during neonatal sepsis, we compared the differences in serum cytokines and chemokines between full-term neonates with sepsis and without infection.Methods: We enrolled 40 full-term neonates with sepsis and 26 full-term neonates without infection as controls between October 2016 and June 2018. Forty cytokines /chemokines in serum were analyzed using the Luminex Bead Immunoassay System.Results: Our results showed that serum IL-6, IL-8, TNF-α, IL-1β, MIF, CXCL13, CXCL1, CXCL2, CXCL5, CXCL6, CXCL16, CCL27, CCL2, CCL8, CCL3, CCL20, CCL23, and CX3CL1 levels were significantly increased in neonates with sepsis compared to those in the control group (all p< 0.05). The levels of serum CCL20, and IL-17 were higher in late-onset sepsis (LOS) than those in early-onset sepsis (EOS) (all p< 0.05). Conversely, serum CXCL16 was lower in LOS than that in EOS (p< 0.05).Conclusion: Our findings revealed that excessive pro-inflammatory cytokines might be involved in neonatal sepsis. In addition, chemokines significantly increased the recruitment of immune cells after infection to participate in the anti-infection defense of neonates, but this could lead to damage.Keywords: neonatal sepsis, cytokines, chemokines

Si-Min Ruan,1,&ast; Mei-Qing Cheng,1,&ast; Hui Huang,1 Hang-Tong Hu,1 Wei Li,1 Xiao-Yan Xie,1 Ming-De Lu,1,2 Ming Kuang,1,2 Man-Xia Lin,1 Wei Wang1 1Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Man-Xia Lin; Wei Wang, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, People’s Republic of China, Tel/Fax +86-20-87765183, Email linmxia@mail.sysu.edu.cn; wangw73@mail.sysu.edu.cnPurpose: The contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (TRA) is still in development. The aim of this study was to explore whether the CT/MRI LI-RADS TRA features were applicable to CEUS in evaluating the liver locoregional therapy (LRT) response.Patients and Methods: This study was a retrospective review of a prospectively maintained database of patients with hepatocellular carcinoma undergoing ablation between July 2017 and December 2018. The standard criteria for a viable lesion were a histopathologically confirmed or typical viable appearance in the follow-up CT/MRI. Performance of the LI-RADS TRA assessing tumor viability was then compared between CEUS and CT/MRI. Inter-reader association was calculated.Results: A total of 244 patients with 389 treated observations (118 viable) were evaluated. The sensitivity and specificity of the CEUS TRA and CT/MRI LI-RADS TRA viable categories for predicting viable lesions were 55.0% (65/118) versus 56.8% (67/118) (P = 0.480) and 99.3% (269/271) versus 96.3% (261/271) (P = 0.013), respectively. The PPV of CEUS was higher than that of CT/MRI (97.0% vs 87.0%). Subgroup analysis showed that the sensitivity was low in the 1-month assessment for both CEUS (38.1%, 16/42) and CT/MR (47.6%, 20/42) and higher in the 2– 6-month assessment for both CEUS (65.7%, 23/35) and CT/MR (62.9%, 22/35). Interobserver agreements were substantial for both CEUS TRA and CT/MRI LI-RADS TRA (κ, 0.74 for both).Conclusion: The CT/MRI LI-RADS TRA features were applicable to CEUS TRA for liver locoregional therapy. The CEUS TRA for liver locoregional therapy has sufficiently high specificity and PPV to diagnose the viability of lesions after ablation.Keywords: contrast-enhanced ultrasound, Liver Imaging Reporting and Data System, treatment response, hepatocellular carcinoma, locoregional therapy

Guotai Sheng,1,&ast; Dingyang Liu,1,&ast; Maobin Kuang,1,&ast; Yanjia Zhong,2 Shuhua Zhang,3 Yang Zou3 1Cardiology Department, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Provincial, 330006, People’s Republic of China; 2Endocrinology Department, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, 330006, People’s Republic of China; 3Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Provincial, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Yang Zou, Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Provincial, People’s Republic of China, Email jxyxyzy@163.comPurpose: Diabetes is one of the most prevalent chronic diseases in the world, and its prevalence is expected to rise further. To help understand the utility of the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) in diabetes prevention, this large-scale longitudinal cohort study aims to explore the association of NHHR with diabetes risk and compare it as a risk predictor with conventional lipid parameters.Patients and Methods: This observational study extracted data from the NAGALA longitudinal cohort study conducted in Japan between 2004 and 2015. Multivariate Cox regression analysis was used to evaluate the association between NHHR and the risk of diabetes. The dose–response relationship was analyzed by restricted cubic spline (RCS) regression and the potential risk threshold was estimated. The receiver operator characteristic curve (ROC) was used to analyze and calculate the predictive value and optimal threshold of NHHR and other conventional lipids for new-onset diabetes.Results: Of the 15,464 people aged 18– 79, 373 (2.41%) were diagnosed with new-onset diabetes during the study period, with a median age of 46 years. The sensitivity analysis based on multivariate adjustment showed that the independent positive correlation between diabetes and NHHR was stable in different populations. RCS and ROC analysis indicated that the association between NHHR and diabetes was non-linear, and the NHHR was a better marker for predicting diabetes risk than other conventional lipid parameters; Additionally, it is worth noting that an NHHR of approximately 2.74 may be the optimal threshold for intervention in diabetes risk.Conclusion: In the general population, NHHR is a better marker for predicting diabetes risk than conventional lipid parameters, and an NHHR of about 2.74 may be the optimal threshold for assessing diabetes risk.Keywords: non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol, diabetes, longitudinal cohort, operator characteristic curve

This paper creatively proposes a new process with desulfurization slag leached by ammonium chloride as pretreatment, and the main point of this paper lies in the processing of desulfurization residue leached by ammonium chloride. Through component analysis the formula is adjusted with high aluminum coal ash and glass cullet, making the melting point of the reduction slag around 1200℃, which facilitates the separation of iron and slag. At the same time, the reduction slag is adjusted to the target crystallization phase, so that the high temperature reduction slag after carbon thermal reduction can be used to produce glass-ceramics directly. The results show that iron recovery rate is over 99%, and diopside and nepheline glass-ceramics are produced, which shows that the new process is feasible. However, the crystal growth index is less than 3, which means that the crystallization capacity of the glass-ceramics is low, and nucleating agent is needed in the preparation of glass-ceramics.

Teng Zhou,1,2,* Mengjiao Kuang,1,* Shirui Huang,1 Jizhen Li,1 Qipeng Xie1 1Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qipeng XieDepartment of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of ChinaTel +86 15157787159Email pandon2002@163.comObjective: Central nervous system infections (CNSI) are serious diseases that endanger human health. Identifying pathogens and their susceptibility to antibiotics, and promptly using antibiotics under this guidance is essential for treatment. The purpose of this study is to investigate the pathogen characteristics of CNSI patients, which can help clinicians choose appropriate empiric antibiotic .Methods: We retrospectively collected data on CNSI patients with cerebrospinal fluid (CSF) culture positive from 2012 to 2020, including demographic characteristics, laboratory data, pathogenic bacteria, and antimicrobial susceptibility test results.Results: A total of 166 patients with 168 isolates out of 8188 patients were available for data analysis. Among the isolates, Gram-positive bacteria, Gram-negative bacteria and fungi accounted for 59.5%, 36.3%, and 4.2%, respectively. Among newborns, children under 12, and patients over 12, the most isolated strains were Streptococcus agalactiae (24/46, 52.2%), Streptococcus pneumoniae (21/68, 30.9%) and Staphylococcus epidermidis (10/54, 18.5%), respectively. Streptococcus agalactiae is more sensitive to linezolid and vancomycin. Streptococcus pneumoniae is more sensitive to vancomycin. Staphylococcus epidermidis is more sensitive to clindamycin and rifampicin. The sugar content in the CSF of Gram-negative bacteria of children ≤ 12 years old was significantly lower than that of Gram-positive bacteria (P< 0.05).Conclusion: We comprehensively studied the etiological characteristics and antimicrobial resistance patterns of positive cerebrospinal fluid cultures in Wenzhou City, Zhejiang Province from 2012 to 2020, which can provide valuable strategies for preventing pathogens and improving evidence-based treatment.Keywords: cerebrospinal fluid, bacterial culture, drug resistance, epidemiological characteristics

Yu Liu,1 Shirui Huang,2 Mengjiao Kuang,2 Huiyan Wang,2 Qipeng Xie2 1Department of Cardiothoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of China; 2Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of ChinaCorrespondence: Qipeng XieDepartment of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of ChinaTel +86-15157787159Email pandon2002@163.comBackground: LARGE1 plays a pivotal role in glycosylation of alpha-Dystroglycan (α-DG) and is aberrantly downregulated in cell lines originating from epithelium-derived cancers including lung cancer. However, the expression of LARGE1 and its clinical significance in NSCLC are not clear.Materials and Methods: The data were collected from the TCGA database to investigate LARGE1 expression in stage I–III NSCLC and explore its associations with clinicopathological parameters and overall survival of patients. The prognostic role of LARGE1 was examined in subgroups according to clinical features and treatments. The results were validated in external cohorts from the NCBI GEO database. Gene Set Enrichment Analysis (GSEA) was performed to investigate the potential molecular mechanisms during LARGE1 alteration in NSCLC.Results: LARGE1 was aberrantly downregulated in NSCLC compared with adjacent tissues and normal lung tissues and in tumors with advanced stage compared with early stage. There was only a trend of association between high LARGE1 with OS in multivariate analysis. Surprisingly, high LARGE1 was significantly associated with improved OS in a subgroup of the patients with adjuvant chemotherapy (ACT) and a significant interaction between LARGE1 expression and ACT was found. Improved OS after ACT was also found in patients with high LARGE1 compared to those with low LARGE1. When combining LARGE1 expression and ACT, compared with patients with non-ACT, HR of low LARGE1/ACT was 0.592 (95% CI=0.432– 0.813, P=0.0012), and HR of high LARGE1/ACT was 0.124 (95% CI=0.031– 0.505, P=0.0036). The results were verified in two external cohorts from the GEO database. GSEA indicated that LARGE1 might downregulate cell cycle pathway to improve ACT sensitivity and subsequently the prognosis in NSCLC.Conclusion: High LARGE1 can be used to identify the patients with resected stage I–III NSCLC most likely to benefit from adjuvant chemotherapy.Keywords: NSCLC, LARGE1, mRNA, overall survival, adjuvant chemotherapy, benefit

Lin Zhang,1,2,* Juan Ye,2– 4,* Qiuyun Luo,2 Miaohuan Kuang,1 Minjie Mao,1 Shuqin Dai,1 Xueping Wang1 1Department of Clinical Laboratory, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, People’s Republic of China; 2Department of Experimental Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 4Department of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xueping Wang; Shuqin Dai Tel/ Fax +86 20 8734 3438Email wangxuep@sysucc.org.cn; daishq@sysucc.org.cnBackground and Objective: Tools for the non-invasive assessment of colorectal cancer (CRC) prognosis have profound significance. Although plasma coagulation tests have been investigated in a variety of tumours, the prognostic value of the prothrombin time (PT) and activated partial thromboplastin time (APTT) in CRC has not been discussed. Our study objective was to explore the prognostic significance of preoperative PT and APTT in CRC patients.Patients and Methods: A retrospective analysis of preoperative coagulation indexes including PT, PTA, INR, APTT, FIB, TT, PLT, NLR and PLR in 250 patients with CRC was performed. Kaplan–Meier and multivariate Cox regression analysis were used to demonstrate the prognostic value of these preoperative coagulation indexes.Results: The overall survival (OS, p< 0.05) and disease-free survival (DFS, p< 0.05) of CRC patients with lower PT and APTT levels were significantly prolonged. Based on univariate analysis, PT levels (p< 0.001, p< 0.001), PTA levels (p=0.001, p=0.001), APTT levels (p=0.001, p< 0.001), INR levels (p< 0.001, p< 0.001), fibrinogen levels (p=0.032, p=0.036), tumour status (p=0.005, p=0.003), nodal status (p< 0.001, p< 0.001), metastasis status (p< 0.001, p< 0.001) and TNM stages (p< 0.001, p< 0.001) were remarkably associated with DFS and OS. Multivariate Cox regression analysis suggested that the levels of PT (HR: 2.699, p=0.006) and APTT (HR: 1.942, p=0.015), metastasis status (HR: 2.091, p= 0.015) and TNM stage (HR: 7.086, p=0.006) were independent predictors of survival in CRC. In the whole cohort, the enrolled patients were then divided into three groups according to their PT and APTT levels. The OS and DFS differed notably among the low-risk (PT< 11.85 sec and APTT< 25.85 sec), medium-risk (PT≥ 11.85 sec or APTT≥ 25.85 sec), and high-risk (PT≥ 11.85 sec and APTT≥ 25.85 sec) groups.Conclusion: Elevated levels of preoperative PT and APTT were predictors of poor outcomes in CRC patients. Moreover, the combination of preoperative PT and APTT can be a new prognostic stratification approach for more precise clinical staging of CRC.Keywords: PT, APTT, CRC, prognosis