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Yanyu Zhong,1,&ast; Nan Wang,1,&ast; Sihui Lu,2 Yaqian Lu,2 Xin Pan,3 Ying Zhou1 1Reproductive Medicine Centre, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Zhou, Reproductive Medicine Centre, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Gusu District, Suzhou, Jiangsu Province, 215008, People’s Republic of China, Tel +86-0512-67973182, Email zhouyingzzzyyy@163.com Xin Pan, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Gusu District, Suzhou, Jiangsu Province, 215008, People’s Republic of China, Tel +86-0512-67973182, Email panxinxin9@outlook.comObjective: This study aimed to analyze uterine artery and spiral artery hemodynamics in patients with unexplained recurrent pregnancy loss (URPL) with varying pregnancy outcomes.Methods: 174 pregnant women with URPL and 144 pregnant women without adverse pregnancy histories were enrolled in this retrospective study. Based on pregnancy outcomes, these patients were divided into two groups: normal pregnancy outcomes (URPL-N, n=138) and adverse pregnancy outcomes (URPL-A, n=36). Control group participants were categorized into normal pregnancy outcomes (CON-N, n=129) and adverse pregnancy outcomes (CON-A, n=15). We compared uterine artery and spiral artery hemodynamics during different stages of gestation and the predictive value of these parameters for pregnancy outcomes.Results: URPL-N group had fewer pregnancy losses and lower BMI compared to URPL-A group (P< 0.05). Spiral artery hemodynamics in URPL-N and CON-N groups were lower than those in URPL-A and CON-A groups during the mid-luteal phase, 11– 13 weeks, 15– 17 weeks, and 19– 21 weeks of gestation, respectively. Uterine artery hemodynamics ((Pulsatility index (mPI), resistive index (mRI), and systolic-to-diastolic ratio (mS/D)) in the mid-luteal period were lower in URPL-N group than URPL-A group. Similarly, in CON-N group were lower than CON-A group. The URPL-A and CON-A groups had higher uterine artery and spiral artery hemodynamics when compared to the URPL-N and CON-N groups. Spiral artery hemodynamics exhibited larger areas under the ROC curve compared to uterine artery parameters.Conclusion: Abnormal hemodynamics in these arteries may contribute to URPL and adverse pregnancy outcomes. Spiral artery hemodynamics are more reliable predictors of pregnancy outcomes than uterine artery parameters.Keywords: unexplained recurrent pregnancy loss, spiral artery, uterine artery, blood flow, pregnancy outcome

Jiamin Yu,1 Yongxia Chen,1 Xiaoyan Pan,1 Ji Chen,1 Zhenhua Mai,1 Yuanli Zhang,1 Xiaoyan Wang,2– 4 Gaosheng Zhou,5 Sayed Adam Bukhari,6 Daqing Ma,6,7 Liehua Deng1 1Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000, People’s Republic of China; 2Doctoral Scientific Research Center, Lianjiang People’s Hospital, Zhanjiang, 524400, People’s Republic of China; 3Affiliated Lianjiang People’s Hospital, Guangdong Medical University, Zhanjiang, 524400, People’s Republic of China; 4Laboratory of Southern Marine Science and Engineering, Zhanjiang, 524023, People’s Republic of China; 5Department of Critical Care Medicine, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People’s Hospital, Yichang, Hubei, 443003, People’s Republic of China; 6Division of Anaesthetics, Pain Medicine & Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, SW10 9NH, UK; 7Perioperative and Systems Medicine Laboratory, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of ChinaCorrespondence: Liehua Deng, Email glinson@126.comPurpose: The early diagnosis of septic cardiomyopathy remains a challenge. The present work aims to evaluate the diagnostic and prognostic value of plasma soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels in septic cardiomyopathy when compared with traditional myocardial biomarkers.Methods: In the 143 sepsis enrolled patients, 67 and 76 patients were classified as non-septic cardiomyopathy and septic cardiomyopathy, respectively. Their blood samples were harvested up to 14th day after hospital admission for measurements of sTREM-1 and other biomarkers, such as N-terminal pronatriuretic peptide (NT-proBNP), highly sensitive troponin (TNT-HS), myoglobin (MYO), creatine kinase isoenzyme (CK-MB), etc. All the data were collected at 8:00 a.m. The area under the receiver operating characteristic curve was obtained to assess the diagnostic accuracy of those biomarkers. The Log rank test was utilized to evaluate the prognostic value of sTREM-1 on septic cardiomyopathy.Results: Circulating sTREM-1 showed a high specificity (88.1%) and moderate sensitivity (64.5%) to distinguish patients with septic cardiomyopathy in the 143 septic patients. The diagnostic efficiency of sTREM-1 was higher than inflammatory biomarkers and traditional myocardial markers. Logistic regression revealed that plasma sTREM-1 was an independent predictor of septic cardiomyopathy. Furthermore, in the whole septic cardiomyopathy cohorts, the sTREM-1 levels in the non-survivors were significantly higher than those of survivors during ICU stay. In addition, the left ventricular systolic dysfunction had a high odds ratio (3.968) to predict 90-day mortality in septic patients with cardiomyopathy.Conclusion: High plasma sTREM-1 level may be a diagnostic marker in predicting ICU poor outcome of patients with septic cardiomyopathy.Keywords: sepsis, septic cardiomyopathy, diagnosis, sTREM-1

Dongmei Huang,1 Caizhong Zhou,2 Caili Li,3 Huiqiao Huang,4 Xiao Pan,3 Yanfei Pan,3 Qini Pan,3 Lichong Lai3 1Department of Rehabilitation Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Internal Medicine, Second People’s Hospital of Teng County, Wuzhou, Guangxi, People’s Republic of China; 3Nursing Department, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Party Committee Office, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Huiqiao Huang, Email hhq@sr.gxmu.edu.cnObjective: To investigate the current status of elderly health services in medical institutions at all levels within Guangxi Province, China.Methods: Using a purposeful sampling method, a questionnaire survey was conducted from July 24, 2023 to October 24, 2023 on the general situation, human resources, rehabilitation medicine, nursing services, and the development of hospice care at 1305 medical institutions in Guangxi.Results: Among the surveyed 1305 medical institutions in Guangxi, 172 (13.18%) had established departments of geriatrics, while 293 (22.45%) boasted departments of rehabilitation medicine. Furthermore, 909 (69.66%) of these institutions offered annual free physical examination services to individuals aged 65 and above. Notably, a total of 362 medical institutions, encompassing both comprehensive hospitals and grassroots hospitals, were recognized as elderly-friendly institutions, accounting for 31.4% of the surveyed sample.The highest demand for talents in medical institutions at all levels included specialized physicians/general practitioners (74.6%), traditional Chinese medicine practitioners (63.1%), rehabilitation therapists (56.1%), and specialized nurses for the elderly (41.7%). A total of 1038 medical institutions conducted popular science activities on elderly health, accounting for 79.5% of the total, focusing mainly on disease prevention (89.21%), nutritional diets (84.68%), rational medication use (79.77%), physical exercise (68.21%), and mental health (60.79%). Only 88 medical institutions provided hospice care services, accounting for 6.7% of the total.Conclusion: Guangxi medical institutions’ elderly services are inadequate. Geriatrics and rehab departments are scarce, talent is lacking, and hospice care is underdeveloped. As aging accelerates, the country and society must support elderly care. Governments should introduce talent incentives, and medical institutions should enhance services, foster a positive work environment, and advance Guangxi’s elderly health agenda.Keywords: medical institutions, elderly health services, elderly care, hospice care, current status

Jun Zheng,1 Xiaohong Pan,2 Yiyun Jiang3 1Department of Rehabilitation, Nanxing Health Service Center, Shangcheng, Hangzhou, Zhejiang, 310000, People’s Republic of China; 2Tuberculosis Care Unit, Hospital of Integrated Traditional Chinese and Western Medicine, Zhejiang, 310003, People’s Republic of China; 3Department of Comprehensive Surgery, Hangzhou Geriatric Hospital, Zhejiang, 310022, People’s Republic of ChinaCorrespondence: Yiyun Jiang, Department of Comprehensive Surgery, Hangzhou Geriatric Hospital, No. 50, Jingxin Road, Hangzhou, Zhejiang, 310022, People’s Republic of China, Tel +8615088664025, Email 458247254@qq.comAbstract: Thrombotic thrombocytopenic purpura is a rare but life-threatening emergency. Tuberculosis can have hematologic complications. However, concurrent tuberculosis and thrombotic thrombocytopenic purpura are extremely rare. In this study, we report a 53-year-old man who was initially treated for pulmonary tuberculosis but later developed weakness and an altered mental status. Laboratory tests revealed evidence of thrombocytopenia, acute renal insufficiency, and microangiopathic hemolytic anemia. Brain imaging identified intracranial hemorrhage. Further testing revealed low ADAMTS13 activity (1.8%) and positive anti-ADAMTS13 antibody, confirming the diagnosis of thrombotic thrombocytopenic purpura. The patient had a full recovery after anti-tuberculosis treatment, plasma exchange, and supportive care. We present this rare case and review previous relevant studies to remind clinicians about the potential connections between tuberculosis and thrombotic thrombocytopenic purpura. In patients with signs of severe thrombocytopenia and microangiopathic hemolysis, necessary diagnostic tests should be performed to eliminate the possibility of thrombotic thrombocytopenic purpura occurring concurrently with tuberculosis.Keywords: Thrombotic thrombocytopenic purpura, tuberculosis, case report, literature review

Jia Song,1 Jiancheng Zhang,2 Jun Shi,2 Xuming Pan,2 Dayu Mo3 1Department of General Practice, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Emergency, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Education, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Dayu Mo, Department of Education, The Second Affiliated Hospital of Zhejiang Chinese Medical University, No. 318 Chaowang Road, Hangzhou, Zhejiang, 310005, People’s Republic of China, Tel +86-13857197190, Email modayu@zcmu.edu.cnBackground: Breviscapine has been demonstrated to have beneficial effects in ameliorating acute lung injury (ALI), yet its potential therapeutic value and molecular mechanisms in sepsis-induced ALI remain unexplored.Methods: We utilized network pharmacology approach to identify the potential targets and mechanisms of breviscapine in treating sepsis-induced ALI. To construct a murine model of sepsis, we performed cecal ligation and puncture (CLP). Hematoxylin and eosin (HE) staining and enzyme-linked immunosorbent assay (ELISA) were employed to respectively determine the pathologic changes and levels of inflammatory factors. Neutrophil count and total protein level in bronchoalveolar lavage fluid (BALF) were detected by corresponding kit. Additionally, we utilized flow cytometry, immunofluorescence, Western blotting, and real-time reverse transcription PCR (qRT-PCR) to detect cell apoptosis, protein expression, and gene expression. Finally, we used ELISA kits to detect the activity of myeloperoxidase (MPO) and caspase-8 (CASP8).Results: Breviscapine was revealed to target 81 potential proteins in the treatment of sepsis-induced ALI, while CASP8 was the most important one as demonstrated by network analysis. In vivo experiments demonstrated that breviscapine effectively reduced the severity of sepsis-induced ALI and inflammation, and significantly suppressed neutrophil infiltration in the lung tissues of CLP mice and promoted neutrophil apoptosis in the peripheral blood. In vitro experiments revealed that lipopolysaccharide (LPS)-induced neutrophil apoptosis was inhibited, and the expression and activity of CASP8 were down-regulated. Breviscapine intervention markedly up-regulated the expression and activity of CASP8, consequently activating neutrophil apoptosis and inhibiting inflammatory response by activating the NF-κB signaling pathway.Conclusion: Breviscapine is remarkably effective in improving sepsis-induced ALI, and its mechanism of action may be to induce neutrophil apoptosis, inhibit inflammatory overreaction and reduce its infiltration in pulmonary tissues by up-regulating the expression and activity of CASP8.Keywords: Breviscapine, acute lung injury, sepsis, network pharmacology, neutrophil

Ningning Wang, Yuanyuan Xu, Guangde Yang, He Chen, Xia Wang, Juanjuan Fu, Li Li, Xiucheng Pan Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Xiucheng Pan, Email xzpxc68@126.comPurpose: There is limited research on whether Proton Pump Inhibitors (PPIs) will affect the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC).This study aimed to determine whether PPIs affect the survival outcomes of patients with HBV-associated advanced HCC receiving combination therapy based on ICIs.Methods: We retrospectively analyzed patients with hepatitis B virus (HBV)-associated advanced HCC who underwent ICIs combination therapy from January 1, 2020, to December 30, 2022. Patients were stratified into PPI and non-PPI groups based on whether they received PPI treatment within 30 days before or after ICIs therapy. Patients’ survival and the risk of PPI-associated mortality was assessed. Adverse events were also evaluated.Results: A total of 183 patients with HBV-associated HCC treated with ICI combination therapy were included. The median survival time (12.5 months vs 13.7 months, P = 0.285) and incidence of adverse events (P = 0.729) did not significantly differ between the PPI and non-PPI groups. Even after propensity score matching, the difference in median overall survival (OS) between the two groups was not significant (10.7 months vs 11.4 months; P = 0.596) and the patient’s OS is not significantly related to the dosage of PPI application (P > 0.05).However, according to our subgroup analysis, among HCC patients with a serum HBV DNA concentration ≥ 200 IU/mL, the use of PPIs significantly increased the risk of mortality in patients receiving ICI combination therapy (P = 0.024).Conclusion: PPIs do not notably influence the survival prognosis of patients receiving ICI combination therapy for HBV-associated advanced HCC. However, among patients with high levels of HBV DNA, PPIs increase the risk of mortality. Therefore, antiviral therapy should be intensified in the patients with HBVDNA > 200 IU/mL. Additionally, PPIs do not impact the incidence of adverse reactions in these patients.Keywords: hepatocellular carcinoma, immune checkpoint inhibitors, proton pump inhibitors, chronic hepatitis B virus infection

Xuan Pan,1,&ast; Ting Han,2,&ast; Zixuan Zhao,3,4 Xiaoming Wang,1 Xiaosan Fang1 1Department of Hepato-Biliary-Pancreatic Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241000, People’s Republic of China; 2Department of Gastroenterology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241000, People’s Republic of China; 3The Translational Research Institute for Neurological Disorders of Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241000, People’s Republic of China; 4The Institute of Brain Science, Wannan Medical College, Wuhu, 241000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaosan Fang; Xiaoming Wang, Department of Hepato-Biliary-Pancreatic Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), 2 West Zheshan Road, Wuhu, 241002, People’s Republic of China, Tel +86-0553-5739219, Email 20142031@wnmc.edu.cn; wxm6901@126.comAbstract: The high malignant degree and poor prognosis of pancreatic cancer (PC) pose severe challenges to the basic research and clinical translation of next-generation therapies. The rise of immunotherapy has improved the treatment of a variety of solid tumors, while the application in PC is highly restricted by the challenge of immunosuppressive tumor microenvironment. The latest progress of nanotechnology as drug delivery platform and immune adjuvant has improved drug delivery in a variety of disease backgrounds and enhanced tumor therapy based on immunotherapy. Based on the immune loop of PC and the status quo of clinical immunotherapy of tumors, this article discussed and critically analyzed the key transformation difficulties of immunotherapy adaptation to the treatment of PC, and then proposed the rational design strategies of new nanocarriers for drug delivery and immune regulation, especially the design of combined immunotherapy. This review also put forward prospective views on future research directions, so as to provide information for the new means of clinical treatment of PC combined with the next generation of nanotechnology and immunotherapy. Keywords: pancreatic cancer, immunotherapy, nanomedicine, immunosuppressive tumor microenvironment regulation, combined drug delivery strategy

Qiang Zhong,&ast; Xin Pan,&ast; Yuhang Chen, Qiang Lian, Jian Gao, Yixin Xu, Jian Wang, Zhanjun Shi, Hao Cheng Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhanjun Shi; Hao Cheng, Nanfang Hospital, Southern Medical University, 1838&num; Guangzhou North Avenue, Guangzhou, People’s Republic of China, Tel +86 2062787924, Email shizhanjun111@gmail.com; haocool317@gmail.comAbstract: The development of metallic joint prostheses has been ongoing for more than a century alongside advancements in hip and knee arthroplasty. Among the materials utilized, the Cobalt-Chromium-Molybdenum (Co-Cr-Mo) and Titanium-Aluminum-Vanadium (Ti-Al-V) alloys are predominant in joint prosthesis construction, predominantly due to their commendable biocompatibility, mechanical strength, and corrosion resistance. Nonetheless, over time, the physical wear, electrochemical corrosion, and inflammation induced by these alloys that occur post-implantation can cause the release of various metallic components. The released metals can then flow and metabolize in vivo, subsequently causing potential local or systemic harm. This review first details joint prosthesis development and acknowledges the release of prosthetic metals. Second, we outline the metallic concentration, biodistribution, and elimination pathways of the released prosthetic metals. Lastly, we discuss the possible organ, cellular, critical biomolecules, and significant signaling pathway toxicities and adverse effects that arise from exposure to these metals. Keywords: metallic joint prostheses, prosthetic metal release, potential toxicity and adverse effects

Juan Zhang,1,&ast; Yinqiao Li,1,2,&ast; Jinju Xia,1 Xingpeng Pan,1 Lun Lu,1 Jiazhao Fu,3 Ningyang Jia1 1Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital of Naval Medical University, Shanghai, China; 2School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China; 3Department of Organ Transplantation, Changhai Hospital, First Affiliated Hospital of Naval Medical University, Shanghai, China&ast;These authors contributed equally to this workCorrespondence: Jiazhao Fu; Ningyang Jia, Email fujiazhao@126.com; ningyangjia@163.comObjective: This study aims to investigate the predictive value of Gadobenate dimeglumine (Gd-BOPTA) enhanced MRI features on microvascular invasion (MVI) and recurrence in patients with Liver Imaging Reporting and Data System (LI-RADS) category 5 hepatocellular carcinoma (HCC).Methods: A total of 132 patients with LI-RADS category 5 HCC who underwent curative resection and Gd-BOPTA enhanced MRI at our hospital between January 2016 and December 2018 were retrospectively analyzed. Qualitative evaluation based on LI-RADS v2018 imaging features was performed. Logistic regression analyses were conducted to assess the predictive significance of these features for MVI, and the Cox proportional hazards model was used to identify postoperative risk factors of recurrence. The recurrence-free survival (RFS) was analyzed by using the Kaplan–Meier curve and Log rank test.Results: Multivariate logistic regression analysis identified that corona enhancement (odds ratio [OR] = 3.217; p < 0.001), internal arteries (OR = 4.147; p = 0.004), and peritumoral hypointensity on hepatobiliary phase (HBP) (OR = 5.165; p < 0.001) were significantly associated with MVI. Among the 132 patients with LR-5 HCC, 62 patients experienced postoperative recurrence. Multivariate Cox regression analysis showed that mosaic architecture (hazard ratio [HR] = 1.982; p = 0.014), corona enhancement (HR = 1.783; p = 0.039), and peritumoral hypointensity on HBP (HR = 2.130; p = 0.009) were risk factors for poor RFS.Conclusion: MRI features based on Gd-BOPTA can be noninvasively and effectively predict MVI and recurrence of LR-5 HCC patients.Keywords: hepatocellular carcinoma, magnetic resonance imaging, microvascular invasion, prognosis

Hui Yao, Bangsheng Jia, Xuelin Pan, Jiayu Sun Department of Radiology, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Jiayu Sun, Department of Radiology, West China Hospital of Sichuan University, Guoxue Xiang No. 37, Chengdu, Sichuan, 610041, People’s Republic of China, Email sunjiayu20232023@163.comPurpose: This study aimed to evaluate the feasibility of ultrafast (2 min) cervical spine MRI protocol using a deep learning-assisted 3D iterative image enhancement (DL-3DIIE) system, compared to a conventional MRI protocol (6 min 14s).Patients and Methods: Fifty-one patients were recruited and underwent cervical spine MRI using conventional and ultrafast protocols. A DL-3DIIE system was applied to the ultrafast protocol to compensate for the spatial resolution and signal-to-noise ratio (SNR) of images. Two radiologists independently assessed and graded the quality of images from the dimensions of artifacts, boundary sharpness, visibility of lesions and overall image quality. We recorded the presence or absence of different pathologies. Moreover, we examined the interchangeability of the two protocols by computing the 95% confidence interval of the individual equivalence index, and also evaluated the inter-protocol intra-observer agreement using Cohen’s weighted kappa.Results: Ultrafast-DL-3DIIE images were significantly better than conventional ones for artifacts and equivalent for other qualitative features. The number of cases with different kinds of pathologies was indistinguishable based on the MR images from ultrafast-DL-3DIIE and conventional protocols. With the exception of disc degeneration, the 95% confidence interval for the individual equivalence index across all variables did not surpass 5%, suggesting that the two protocols are interchangeable. The kappa values of these evaluations by the two radiologists ranged from 0.65 to 0.88, indicating good-to-excellent agreement.Conclusion: The DL-3DIIE system enables 67% spine MRI scan time reduction while obtaining at least equivalent image quality and diagnostic results compared to the conventional protocol, suggesting its potential for clinical utility.Keywords: cervical spine, magnetic resonance imaging, fast imaging, deep learning

Yiyu Chen,1 Chuxuan Fang,1 Jun Luo,1 Xueling Pan,2 Zongyan Gao,3 Shuangyi Tang,1 Meng Li4– 6 1Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Newborn ICU, Guigang Maternal and Child Health Care Hospital, Guigang City, Guangxi, People’s Republic of China; 3Newborn ICU, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 5Key Laboratory of Clinical Laboratory Medicine, Guangxi Department of Education, Nanning, Guangxi, People’s Republic of China; 6Key Laboratory of Fungi and Mycosis Research and Prevention, Guangxi Health Commission, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Meng Li, Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Tel/Fax +8613367809642, Email gxmulimeng@foxmail.comAbstract: The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasing in recent years. Chinese Infectious Disease Surveillance of Pediatrics (ISPED) showed that in 2022, its resistance rate to meropenem was 18.5%. However, there is limited data available on the treatment of CRKP infection in neonates. In this study, we present a case involving a premature infant infected with OXA-48-producing Klebsiella pneumoniae. The combined susceptibility test revealed a significant synergistic effect between ceftazidime–avibactam(CAZ-AVI), and aztreonam(ATM). The infection was successfully treated with a combination of CAZ-AVI, ATM, and fosfomycin. This case represents the first reported instance of sepsis in a premature infant caused by OXA-48-producing Klebsiella pneumoniae in China. The objective of our study is to evaluate the effectiveness and safety of combination therapy in treating CRKP infections in premature infants. We hope that the findings of this study will provide valuable insights for clinicians in their treatment approach.Keywords: OXA-48, Klebsiella pneumoniae, premature infant, ceftazidime–avibactam, aztreonam

Xiaoyu Pan,1,2 Shuqi Wang,1,2 Boying Jia,1,2 Lin Yue,1,3 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Endocrinology, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comBackground: The objective of this investigation was to explore the health status and epidemiological features of civil servants working in Hebei Province, China.Methods: Data was collected through a cross-sectional survey that involved 50,039 adult civil servants in Hebei Province. The research was conducted at the Hebei Provincial Medical Examination Centre and included inquiries about demographics, health behaviours, chronic illnesses, and abnormal check-up indicators. Statistical data were used to determine the prevalence of chronic diseases and abnormal health examination indicators. Subgroup analyses by sex were then conducted to calculate the similarities and differences in health status between men and women.Results: The findings of the survey indicate that 14.2% of individuals who work in civil service suffer from obesity. Additionally, a considerable proportion of this group display poor health behaviours, including smoking and alcohol consumption. Hypertension (21.03%), dyslipidaemia (10.88%), and diabetes mellitus (8.56%) were identified as the top three chronic diseases, while cardiovascular diseases were prevalent at 6.27% among civil servants. Ultrasound showed a high prevalence of fatty liver, non-smooth gallbladder and liver cysts (44.61%, 33.24% and 23.26% respectively). The occurrence of pulmonary nodules was alarmingly high at 88.48%, while thyroid nodules were found in as much as 62.65% of patients. Abnormal E/A values≤ 1, prostate hyperplasia, breast nodules, and carotid plaques were also prevalent, with percentages ranging from 46.76% to 63.04%. In subgroup analyses by gender, the prevalence of chronic diseases and abnormal screening indicators was consistently higher in men than in women, with the exception of thyroid nodules and thyroid surgery.Conclusion: The survey revealed a large proportion of civil servants in Hebei Province, China, suffering from chronic diseases, underscoring the necessity for enhanced attention to chronic disease prevention and management in this group and emphasising the requirement for focused interventions aimed at improving health outcomes.Keywords: civil servants, health status, ultrasound, real-world study, Hebei Province, China

Yu Yang,1,2 Xiaoyu Pan,1,3 Shuchun Chen1,3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel/Fax +86 311 85988406, Email chenshuchunwork88@163.comObjective: This study utilized proteomics to investigate changes in protein expression associated with lung health in obese mice exposed to semaglutide and empagliflozin through a high-fat diet.Methods: Twenty-eight male C57BL/6JC mice were randomly assigned to two groups: a control diet group (n = 7) and a high-fat diet group (n = 21). The HFD group was further divided into three groups: HFD group (n = 7), Sema group (n = 7), and Empa group (n = 7). Post-treatment, mice underwent assessments including glucose tolerance, lipids, oxidative stress markers, body weight, lung weight, and structure. Proteomics identified differentially expressed proteins (DEPs) in lung tissue, and bioinformatics analyzed the biological processes and functions of these proteins.Results: Semaglutide and empagliflozin significantly attenuated obesity-induced hyperglycemia, abnormal lipid metabolism, oxidative stress response, and can decrease alveolar wall thickness, enlarge alveolar lumen, and reduce collagen content in lung tissue. Both medications also attenuated lung elastic fibre cracking and disintegration. In the HFD/NCD group, there were 66 DEPs, comprising 30 proteins that were increased and 36 that were decreased. Twenty-three DEPs overlapped between Sema/HFD and Empa/HFD, with 11 up-regulated and 12 down-regulated simultaneously. After analysing DEPs in different groups, four proteins - LYVE1, BRAF, RGCC, and CHMP5 - were all downregulated in the HFD group and upregulated by semaglutide and empagliflozin treatment.Conclusion: This study demonstrates that obesity induced by a high-fat diet causes a reduction in the expression of LYVE1, BRAF, RGCC, and CHMP5 proteins, potentially affecting lung function and structure in mice. Significantly, the administration of semaglutide and empagliflozin elevates the levels of these proteins, potentially offering therapeutic benefits against lung injury caused by obesity. Merging semaglutide with empagliflozin may exert a more pronounced impact.Keywords: semaglutide, empagliflozin, proteomics, obesity, pulmonary structure

Lin Chen,1,&ast; Qini Pan,2,&ast; Xiaohong Li,3 Shuangli Luo,4 Xiao Pan,2 Huiqiao Huang2 1Department of Cardiology, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of nursing, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3College of Life Sciences, Chongqing Normal University, Chongqing, People’s Republic of China; 4Department of nursing, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guxngxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiqiao Huang; Xiao Pan, Email huangedugx@126.com; 1910026304@qq.comPurpose: Practitioners in China who implement hospice care services include doctors, nurses, and care workers. These individuals play an important role in the holistic care of patients at the end of life and their families. This study aimed to provide baseline data to develop hospice care services and improve relevant policies by investigating the knowledge and attitudes of hospice care practitioners (HCPs) and analyzing influencing factors.Methods: This cross-sectional descriptive study used stratified sampling and quota sampling. The HCPs were from nursing homes, medical institutions, integrated medical and nursing institutions, and community health service centers in Guangxi Zhuang Autonomous Region. We examined HCPs’ demographic characteristics and scores on a self-designed Chinese scale to measure their knowledge and attitudes(K&A scale). A total of 1821 HCPs completed surveys from May 2022 to July 2022. The data were analyzed using descriptive statistics, univariate analysis and multiple linear regression.Results: The standard score of the K&A scale of 1821 HCPs was 61.62 (SD=9.78), and the individual mean scores of knowledge and attitudes were 76.42 (SD=28.13) and 58.69 (SD=11.31), respectively. The final multiple linear regression analysis indicated that the main factors that influenced the K&A score were monthly income, job satisfaction, and the hospice care-related system (HCS).Conclusion: The HCPs in this study displayed moderate mean scores for knowledge and a less favorable attitude toward hospice care. Monthly income, job satisfaction and the HCS were the common factors that influenced HCPs’ K&A. The results suggest the need to strengthen targeted and professional training for HCPs, increase their welfare and benefits, and improve indigenous policies of hospice care.Keywords: attitudes, hospice care practitioners, hospice care-related system, knowledge

Jiaming Shen,1,2,&ast; Xia Wang,2,&ast; Guangde Yang,2,&ast; Li Li,2 Juanjuan Fu,2 Wei Xu,3 Qingqiao Zhang,3 Xiucheng Pan2 1Department of Gastroenterology, People’s Hospital of Jingjiang, Taizhou, People’s Republic of China; 2Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Interventional Radiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiucheng Pan, Tel +8618052268129, Email xzpxc68@126.comPurpose: Recently, the triple therapy of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) has become a new treatment option for advanced or unresectable hepatocellular carcinoma (HCC) patients. We aimed to explore the liver injury and its effect on overall survival (OS) in patients treated with this combination therapy.Patients and Methods: Patients with HBV-related HCC who were treated with TACE-TKIs-ICIs from January 2020 to December 2021 were enrolled. Liver injury and survival time were the main endpoints of the study. Logistic regression analysis was used to analyze the factors associated with liver injury. Cox regression and Kaplan–Meier analysis were used to determine prognostic factors for OS.Results: As of March 2022, 52 of the 119 enrolled patients developed any grade hepatotoxicity: 15 cases with grade 1, 19 cases with grade 2, 16 cases with grade 3 and 2 cases with grade 4. Our analysis indicated that lack of antiviral prevention was a risk factor for liver injury (OR = 0.149; 95% CI: 0.050– 0.442; P = 0.001). The findings suggested that liver injury events (HR = 1.912; 95% CI: 1.031– 3.546; P = 0.040) was associated with patient death. The median OS of patients without liver injury, grade 1– 2 and grade 3– 4 liver injury were undefined, 13.7 months and 11.1 months, respectively (log-rank P = 0.034).Conclusion: Liver injury adverse events are common in HBV-related HCC patients treated with TACE-TKIs-ICIs. Patients who developed liver injury had a poor prognosis. For HBV-related HCC patients, effective prophylactic antiviral therapy and regular liver function testing are required before and during this triple therapy. Keywords: HBV-related HCC, TACE, TKI, ICI, liver injury, survival time

Ye Lin, Shuke Luo, Qiang Lu, Xueke Pan Department of Ophthalmology, The Second People’s Hospital of Foshan, Foshan, Guangdong Province, People’s Republic of ChinaCorrespondence: Shuke Luo, Department of Ophthalmology, The Second People’s Hospital of Foshan, Foshan, Guangdong Province, 528000, People’s Republic of China, Tel +86 13679830510, Email 542377993@qq.comPurpose: To investigate the psychological changes in patients pre and post implantable collamer lens (ICL, EVO) implantation surgery in the posterior chamber.Patients and methods: Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to assess the mental states of 43 patients who underwent ICL implantation surgery performed by the same surgeon between January 2021 and December 2022.Results: Comparing the results before and one week after the operation, there is a significant difference in both the SAS scale (P< 0.05) and the SDS scale (P< 0.05). Similarly, when comparing the pre-operation and one-month post-operation results, there is also a significant difference in both the SAS scale (P< 0.05) and the SDS scale (P< 0.05). However, when comparing the one-week post-operation and one-month post-operation results, there is no significant difference in either the SAS scale (P> 0.05) or the SDS scale (P> 0.05). Moving on to the comparison between the pre-operation results and the national norm level, there is a significant difference in both the SAS scale (P< 0.05) and the SDS scale (P< 0.05). When comparing the one-week post-operation results and the national norm level, there is a significant difference in the SAS scale (P< 0.05). Similarly, when comparing the one-month post-operation results and the national norm level, there is a significant difference in the SAS scale (P< 0.05).Conclusion: After undergoing ICL implantation surgery, patients typically experience a notable decrease in anxiety (SAS) and depression (SDS) scales. These improvements gradually stabilize and enhance during the postoperative recovery period. However, it may require a significant amount of time for patients to fully restore their psychological well-being to levels comparable to the national norm, particularly in terms of anxiety levels.Keywords: implantable collamer lens implantation, myopia, mental state, self-rating anxiety scale, self-rating depression scale

Shuqi Wang,1,2 Xiaoyu Pan,1,2 Mengmeng Zhang,1,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comPurpose: We investigate the correlation between glucose and lipid metabolism and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and its diagnostic and predictive value.Patients and Methods: A retrospective analysis involved 620 patients diagnosed with T2DM, categorized into two groups based on fundus examination results: the non-diabetic retinopathy group (NDR, n=340) and the diabetic retinopathy group (DR, n=280). We collected baseline patient data, calculated the ratio of glycated hemoglobin (HbA1c) to high-density lipoprotein cholesterol (HDL-C), and analyzed its association with Type 2 Diabetic Retinopathy.Results: HbA1c/HDL-C in DR group exhibited significantly higher than the NDR group (P< 0.001). Mantel-Haenszel’s chi-square trend analysis indicated a notable linear trend (P< 0.001) between HbA1c/HDL-C and DR. HbA1c/HDL-C revealed moderate positive correlations with DR, r=0.342, P< 0.001. Binary logistic regression analysis showed systolic blood pressure (SBP), diabetes course, fasting blood glucose (FBG) and HbA1c/HDL-C as independent risk factors for DR in T2DM patients. Restrictive cubic spline analysis demonstrated a significant nonlinear relationship between HbA1c/HDL-C and DR (P total trend < 0.001, P nonlinear = 0.0196). ROC curve analysis identified that HbA1c/HDL-C had the highest diagnostic accuracy for DR, with an area under the ROC curve (AUC) of 0.711, 53.2% sensitivity, and 78.2% specificity.Conclusion: Our study shows that HbA1c/HDL-C is an independent risk factor for DR in patients with type 2 diabetes. HbA1c/HDL-C has good diagnostic value for DR and can be used as a biological index for early screening of DR.Keywords: glucose metabolism, lipid metabolism, glycosylated hemoglobin, high density lipoprotein cholesterol, HbA1c/HDL-C, type 2 diabetes, diabetic retinopathy

Yingying Lin,1,&ast; Xiaoyan Xiu,2,&ast; Juan Lin,3 Zhiwei Chen,3 Cui Xian Zheng,3 Xuehong Pan,2 Lihua Lin,1 Jianying Yan3 1Department of Healthcare, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Health Education, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianying Yan, Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China, Tel +86591-86329270, Email fjsfyyan@126.comBackground: The goal is to evaluate the effects of a flipped class strategy on knowledge, self-directed learning ability, learning satisfaction and pregnancy outcomes in primiparas undergoing antenatal education.Methods: A random sampling method was adopted. A total of 600 primiparas who were diagnosed with early pregnancy in a first-class hospital in southeast China and received continuous prenatal health education from May to July 2020 were selected as the research subjects. In order to make the baseline of the two groups of primipara comparable, we divided the two groups in the antenatal education centre according to the odd-even number of the lesson card number. The odd-numbered group was the experimental group, who used the prenatal health education model based on blended learning; the even-numbered group was the control group, who used the traditional mode of prenatal health education. The two groups were compared on the following outcomes: knowledge, self-directed learning ability, learning satisfaction and pregnancy outcomes.Results: Compared with traditional learning, the blended learning approach can effectively controlled the gestational weight gain (GWG), alleviated the anxiety and depression during pregnancy, improved the natural delivery rate of the primipara, shortened the delivery process and reduced the risk of gestational diabetes mellitus (GDM), the difference was statistically significant (all P< 0.05).Conclusion: Blended learning may be an effective strategy because of its validity and practicality in antenatal education.Keywords: health education, flipped classroom, team-based learning, primipara, pregnancy outcomes, blended learning

Xinni Pan,1 Yi Lu,2 Shanshan Fan,1 Hao Tang,2 Haisong Tan,3 Cheng Cao,2 Yingsheng Cheng,1 Yanlei Liu2 1Department of Radiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Instrument Science and Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Urology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Yingsheng Cheng, Department of Radiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200235, People’s Republic of China, Tel +86-021-38297858, Email chengyingsheng@hotmail.com Yanlei Liu, Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People’s Republic of China, Tel +86-18721788078, Email liuyanlei@sjtu.edu.cnBackground: Radiotherapy is one of the main clinical methods for the treatment of malignant tumors at present. However, its application is limited by the radiation resistance of some tumor cells and the irradiation damage to the surrounding normal tissues, and the limitation of radiotherapy dose also affects the therapeutic effect. Therefore, developing diagnostic and therapeutic agents with imaging and radiosensitizing functions is urgently needed to improve the accuracy and efficacy of radiotherapy.Materials and Strategy: Herein, we synthesized multifunctional nanotheranostic FRNPs nanoparticles based on gold nanocages (GNCs) and MnO2 for magnetic resonance (MR)/photoacoustic (PA) imaging and combined photothermal, radiosensitive and chemical therapy. A programmed therapy strategy based on FRNPs is proposed. First, photothermal therapy is applied to ablate large tumors and increase the sensitivity of the tumor tissue to radiotherapy, then X-ray radiation is performed to further reduce the tumor size, and finally chemotherapeutic agents are used to eliminate smaller residual tumors and distant metastases.Results: As revealed by fluorescence, MR and PA imaging, FRNPs achieved efficient aggregation and retention at tumor sites of mice after intravenous injection. In vivo studies have shown that the programmed treatment of FRNPs-injected nude mice which were exposed to X-ray after 808 laser irradiation achieved the greatest inhibition of tumor growth compared with other treatment groups. Moreover, no obvious systemic toxicity was observed in all groups of mice, indicating the good biocompatibility of FRNPs and the safety of the treatment scheme.Conclusion: To sum up, our work not only showed a new radiosensitizer, but also provided a promising theranostic strategy for cancer treatment.Keywords: gold nanoparticles, MnO2, radiosensitizing, multimodal imaging, cancer therapy

Shuqi Wang,1,2 Xiaoyu Pan,1,2 Boying Jia,1,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel/Fax +86 311 85988406, Email chenshuchunwork88@163.comPurpose: Systemic immune inflammation index (SII), systemic inflammatory response index (SIRI) are new inflammation indicators calculated after integrating multiple indicators in blood routine. This study aims to investigate the correlation between the SII, SIRI and type 2 diabetic retinopathy (T2DR) and the diagnostic significance of these indices in T2DR.Patients and Methods: A retrospective analysis involved 500 patients diagnosed with type 2 diabetes (T2DM), categorized into two groups based on fundus examination results: the non-diabetic retinopathy group (NDR, n=256) and the diabetic retinopathy group (DR, n=244). We calculated SII and SIRI, and analyzed their associations with T2DR.Results: The DR group exhibited significantly higher SII and SIRI values compared to the NDR group (P< 0.001). Mantel-Haenszel’s chi-square trend analysis revealed a notable linear trend (P< 0.001) between SII, SIRI, and DR. SII and SIRI exhibited moderate positive correlations with DR, (r=0.354, P< 0.001; r=0.469, P< 0.001), respectively. Binary logistic regression analysis identified SII and SIRI as independent risk factors for DR. Restrictive cubic spline analysis demonstrated a significant linear relationship between SII and DR (P total trend < 0.001, P nonlinear = 0.0657). Stratification by gender indicated that SII is more sensitive to the onset of DR in men. A significant nonlinear relationship was observed between SIRI and DR (P total trend < 0.001, P nonlinear = 0.0025), with no gender-related differences in SIRI’s association with DR. ROC curve analysis demonstrated that the combined use of SII and SIRI achieved the highest diagnostic accuracy for DR, with an AUC of 0.782, 74.6% sensitivity, and 69.9% specificity.Conclusion: Our findings suggested that SII and SIRI as independent risk factors for DR. The high accuracy of SII combined with SIRI in diagnosing DR underscores their potential as early biological indicators for DR diagnosis.Keywords: systemic immune inflammation index, system inflammatory response index, type 2 diabetic retinopathy, Inflammation

Zhuoya Jia,1,2 Xiaoyu Pan,1,2 Shuchun Chen2,3 1Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Key Laboratory of Metabolic Diseases of Hebei Province, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comObjective: To explore the association between levels of remnant cholesterol (RC) and the incidence of non-alcoholic fatty liver disease (NAFLD) in the general population, ultimately leading to the assessment of a novel proposed model combining RC and waist circumference (R-W) as a predictor of NAFLD incidence.Methods: A cross-sectional analysis was conducted of 4913 subjects undergoing physical examinations at Hebei General Hospital, with ultrasound findings being used to classify patients into individuals with and without NAFLD. Median RC values were used to separate subjects into those with low and high levels of RC, after which the predictive performance of RC and the novel R-W model when used to assess NAFLD risk was assessed through multifactorial logistic regression analyses and receiver operating characteristic curves.Results: Subjects exhibiting higher RC levels were found to exhibit an elevated risk of NAFLD incidence with or without adjusting for confounding factors. The binary logistic regression analysis-based R-W model may thus offer utility as a tool to gauge the risk of NAFLD in the general population, as it outperformed RC or WC alone, particularly when assessing women or individuals < 45 years of age. The area under the ROC curve for this combined R-W model was 0.813 (0.802, 0.824), with respective sensitivity and specificity values of 83.86% and 63.91%, all of which were significantly higher than corresponding values for RC and WC (P < 0.001).Conclusion: The present supports a strong association between RC levels and NAFLD in the general populace, and the combined R-W model exhibits greater utility as a tool to predict NAFLD incidence relative to RC or WC in isolation, particularly for individuals who are female or < 45 years old.Keywords: residual cholesterol, waist circumference, non-alcoholic fatty liver disease

Jiangli Ban,1,2 Xiaoyu Pan,2,3 Liqun Yang,2 Zhuoya Jia,2,3 Ruoxi Zhen,2,3 Xueqing Zhang,2,4 Shuchun Chen2,3 1Graduate School of Hebei North University, Zhangjiakou, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Graduate School of North China University of Science and Technology, Tangshan, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comPurpose: This study aimed to examine the correlation between fibrinogen/albumin (FAR) and diabetic peripheral neuropathy (DPN).Patients and Methods: A total of 342 patients were included and categorized into either the DPN group or the Non-DPN (NDPN) group based on their DPN status. The FAR index was determined by calculating the ratio of fibrinogen (FIB) to serum albumin (ALB), multiplied by 100. The participants were then divided into a High-FAR group and a Low-FAR group using the median FAR value as the threshold. Neurophysiological data were collected from the participants, which included motor conduction velocity (MCV) and sensory conduction velocity (SCV).Results: The DPN group displayed higher FAR levels [(DPN vs NDPN:6.72 (5.89,7.74) vs 5.94± 1.14], in addition to slower SCV and MCV data compared to the NDPN group. The high FAR group had a higher prevalence of DPN (78.9% vs 55.6%) (P< 0.05). There was a negative correlation between FAR and NCV, including bilateral median nerve SCV, left ulnar nerve SCV, bilateral median nerve MCV, bilateral common peroneal nerve MCV, bilateral tibial nerve MCV, and left ulnar nerve MCV. FAR was revealed to be an independent risk factor for the development of DPN in patients and demonstrated a greater predictive value for DPN development in Type 2 diabetes mellitus (T2DM) compared with FIB, HbA1c.Conclusion: The results suggest that monitoring FAR levels in patients with T2DM could identify those at higher risk for developing DPN, making the FAR index a valuable predictor of DPN development. Furthermore, since FAR has an inverse relationship with NCV, it stands to reason that high FAR levels may indicate nerve damage and slower conduction velocities. Thus, managing FAR could prove beneficial in both preventing and delaying the onset of DPN in T2DM patients.Keywords: type 2 diabetes mellitus, diabetic peripheral neuropathy, fibrinogen/albumin

Mengqi Wang,1 Yunzhen Shi,2 Xinling Pan,3 Bin Wang,4 Bin Lu,2 Jian Ouyang4 1Department of Neurology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang Province, People’s Republic of China; 2Department of Infectious Diseases, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang Province, People’s Republic of China; 3Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, People’s Republic of China; 4Department of Emergency, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang Province, People’s Republic of ChinaCorrespondence: Bin Lu, Department of Infectious Diseases, Affiliated Dongyang Hospital of Wenzhou Medical University, No. 60 Wuningxi Road, Dongyang, People’s Republic of China, Email lubin061@163.com Jian Ouyang, Department of Emergency, Affiliated Dongyang Hospital of Wenzhou Medical University, No. 60 Wuningxi Road, Dongyang, Zhejiang, People’s Republic of China, Email 15215864491@163.comPurpose: We intend to develop a nomogram for predicting the mortality risk of hospitalized septic shock patients.Patients and Methods: Data were collected from patients hospitalized with septic shock in Affiliated Dongyang Hospital of Wenzhou Medical University in China, over 10 years between January 2013 and January 2023. The eligible study participants were divided into modeling and validation groups. Factors independently related to the mortality in the modeling group were obtained by stepwise regression analysis. A logistic regression model and a nomogram were built. The model was evaluated based on the discrimination power (the area under the curve of the receiver operating characteristic, AUC), the calibration degree and decision curve analysis. In the validation group, the discrimination powers of the logistic regression model, the sequential organ failure assessment (SOFA) scoring model and machine learning model were compared.Results: A total of 1253 patients, including 878 patients in the modeling group and 375 patients in the validation group, were included in this study. Age, respiratory failure, serum cholinesterase, lactic acid, blood phosphorus, blood magnesium, total bilirubin, and pH were independent risk factors related to the mortality risk of septic shock. The AUCs of the prediction model for the modeling and validation groups were 0.881 and 0.868, respectively. The models had a good calibration degree and clinical applicability. The AUC of the SOFA model for the validation population was 0.799, significantly lower than that of our model. The AUCs of the random forest and ensemble models were 0.865 and 0.863, respectively, comparable to that of our logistical prediction model.Conclusion: The model established in this study can effectively predict the mortality risk in patients hospitalized with septic shock. Thus, the model could be used clinically to determine the best therapy or management for patients with septic shock.Keywords: septic shock, prediction model, mortality risk, nomogram, SOFA

Shu Niu,1,&ast; Qingjuan Ren,1,&ast; Shuchun Chen,2 Xiaoyu Pan,2,3 Lin Yue,4 Xing Chen,2 Zelin Li,2 Ruoxi Zhen3 1Department of Endocrinology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Endocrinology, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shu Niu, Department of Endocrinology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, People’s Republic of China, Email niushucccc@163.comPurpose: Among chronic liver diseases, non-alcoholic fatty liver disease (NAFLD) is one of the commonest. Although empagliflozin has several therapeutic uses in treating cardiovascular and renal disorders, its impacts and mechanisms on NAFLD are poorly understood. This research aimed to examine the metabolic regulatory mechanism through which empagliflozin protects against NAFLD.Methods: Equal grouping of twenty-seven male C57BL/6J mice into those fed a normal diet (NCD), those fed a high-fat diet (HFD), and those fed an HFD with empagliflozin (Empa) was approached. HE, oil red O staining, and Masson staining were utilized for evaluating the pathological damage to the liver and the mice’s liver and body weights. Lipids, blood glucose, and inflammation index were compared across the three groups. Liquid chromatography/mass spectrometry (LC-MS) has been employed for identifying liver metabolomics.Results: The findings suggested that empagliflozin mitigated the inflammatory and oxidative stress response associated with the buildup of lipids caused by HFD. Differentially expressed metabolites (DEMs) were identified by metabonomics analysis as present in both the HFD/NCD and Empa/HFD groups. These DEMs were primarily found in lipids and organic acids like lysophosphatidylcholine (lysoPC), lecithin (PC), triglyceride (TG), palmitic acid, and L-isoleucine. Among the enriched pathways that were shown to be important were those involved in the metabolism of histidine, arachidonic acid, the control of lipolysis in adipocytes, and insulin resistance. There was a strong correlation between inflammation and oxidative stress in most of the metabolites. The inflammation and oxidative stress unbalance were ameliorated by empagliflozin.Conclusion: NAFLD mice model showed considerable improvement in metabolic abnormalities and liver protection after treatment with empagliflozin. The process may include the overexpression of L-isoleucine and the downregulation of lysoPC, PC, TG, and palmitic acid to reduce liver harm caused by lipotoxicity.Keywords: NAFLD, empagliflozin, metabolomics, differentially expressed metabolites, obesity

Xiaoyu Pan,1,&ast; Huazheng Zhu,2,&ast; Jinglong Du,1 Guangtao Hu,1 Baoru Han,1 Yuanyuan Jia1 1College of Medical Informatics, Chongqing Medical University, Chongqing, People’s Republic of China; 2College of Intelligent Technology and Engineering, Chongqing University of Science and Technology, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanyuan Jia, Email yyjia@cqu.edu.cnAim: The Coronavirus Disease 2019 (COVID-19) pandemic has increased the public health burden and brought profound disaster to humans. For the particularity of the COVID-19 medical images with blurred boundaries, low contrast and different infection sites, some researchers have improved the accuracy by adding more complexity. Also, they overlook the complexity of lesions, which hinder their ability to capture the relationship between segmentation sites and the background, as well as the edge contours and global context. However, increasing the computational complexity, parameters and inference speed is unfavorable for model transfer from laboratory to clinic. A perfect segmentation network needs to balance the above three factors completely. To solve the above issues, this paper propose a symmetric automatic segmentation framework named MS-DCANet. We introduce Tokenized MLP block, a novel attention scheme that uses a shift-window mechanism to conditionally fuse local and global features to get more continuous boundaries and spatial positioning capabilities. It has greater understanding of irregular lesion contours. MS-DCANet also uses several Dual Channel blocks and a Res-ASPP block to improve the ability to recognize small targets. On multi-modality COVID-19 tasks, MS-DCANet achieved state-of-the-art performance compared with other baselines. It can well trade off the accuracy and complexity. To prove the strong generalization ability of our proposed model, we apply it to other tasks (ISIC 2018 and BAA) and achieve satisfactory results.Patients: The X-ray dataset from Qatar University which contains 3379 cases for light, normal and heavy COVID-19 lung infection. The CT dataset contains the scans of 10 patient cases with COVID-19, a total of 1562 CT axial slices. The BAA dataset is obtained from the hospital and includes 387 original images. The ISIC 2018 dataset is from the International Skin Imaging Collaborative (ISIC) containing 2594 original images.Results: The proposed MS-DCANet achieved evaluation metrics (MIOU) of 73.86, 97.26, 89.54, and 79.54 on the four datasets, respectively, far exceeding other current state-of-the art baselines.Conclusion: The proposed MS-DCANet can help clinicians to automate the diagnosis of COVID-19 patients with different symptoms.Keywords: multi-modality COVID-19 lesion segmentations, laboratory to clinic, multi-scale feature learning, depthwise separable convolution

Wenzhe Yang,1,2,&ast; Xue Pan,2,&ast; Peng Zhang,2 Xue Yang,1,2 Huashi Guan,1,2 Huan Dou,3 Qian Lu1,2 1Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong Province, People’s Republic of China; 2Marine Traditional Chinese Medicine R&D Laboratory, Marine Biomedical Research Institute of Qingdao, Qingdao, Shandong Province, People’s Republic of China; 3Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Lu, Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, Shandong Province, People’s Republic of China, Tel +86 15850672529, Fax +86 532 8506779, Email lq7080@ouc.edu.cn Huan Dou, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu Province, 210093, People’s Republic of China, Tel +86 13913832488, Fax +86 025 83686441, Email douhuan@nju.edu.cnRationale: Reversing the hypoxic and immunosuppressive tumor microenvironment (TME) is crucial for treating malignant melanoma. Seeking a robust platform for the effective reversion of hypoxic and immunosuppressive TME may be an excellent solution to revolutionizing the current landscape of malignant melanoma treatment. Here, we demonstrated a transdermal and intravenous dual-administration paradigm. A tailor-made Ato/cabo@PEG-TK-PLGA NPs were administrated transdermally to melanoma with the help of a gel spray containing a skin-penetrating material borneol. Nanoparticles encased Ato and cabo were released and thereby reversed the hypoxic and immunosuppressive tumor microenvironment (TME).Methods: Ato/cabo@PEG-TK-PLGA NPs were synthesized through a self-assembly emulsion process, and the transdermal ability was assessed using Franz diffusion cell assembly. The inhibition effect on cell respiration was measured by OCR, ATP, and pO2 detection and in vivo photoacoustic (PA) imaging. The reversing of the immunosuppressive was detected through flow cytometry analysis of MDSCs and T cells. At last, the in vivo anti-tumor efficacy and histopathology, immunohistochemical analysis and safety detection were performed using tumor-bearing mice.Results: The transdermally administrated Ato/cabo@PEG-TK-PLGA NPs successfully spread to the skin surface of melanoma and then entered deep inside the tumor with the help of a gel spray and a skin puncturing material borneol. Atovaquone (Ato, a mitochondrial-respiration inhibitor) and cabozantinib (cabo, a MDSCs eliminator) were concurrently released in response to the intratumorally overexpressed H2O2. The released Ato and cabo respectively reversed the hypoxic and immunosuppressive TME. The reversed hypoxic TME offered sufficient O2 for the intravenously administrated indocyanine green (ICG, an FDA-approved photosensitizer) to produce adequate amount of ROS. In contrast, the reversed immunosuppressive TME conferred amplified systemic immune responses.Conclusion: Taken together, we developed a transdermal and intravenous dual-administration paradigm, which effectively reversed the hypoxic and immunosuppressive tumor microenvironment in the treatment of the malignant melanoma. We believe our study will open a new path for the effective elimination of the primary tumors and the real-time control of tumor metastasis.Keywords: melanoma, tumor microenvironment, hypoxia, immunosuppression, transdermal administration

Xian Pan,1,2,&ast; Shao-Jie Wu,1,2,&ast; Yi Tang,1,2,&ast; Yan-Feng Zhou,1,2 Jie-Wei Luo,1,3 Zhu-Ting Fang1,2 1Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Interventional Radiology, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 3Department of Traditional Chinese Medicine, Fujian Provincial Hospital, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie-Wei Luo; Zhu-Ting Fang, Tel +86 59188217540, Email docluo0421@aliyun.com; 470389481@qq.comPurpose: In China, many patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage. Several studies have shown that triple therapy [transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs)] is beneficial for patient survival. In this study, we aimed to evaluate the efficacy of triple therapy (TACE + TKIs + ICIs) for unresectable HCC (uHCC) and the conversion rate of surgical resection (SR). The primary endpoints were objective response rate (ORR) and disease control rate (DCR) based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST v1.1 and adverse events (AEs), while the secondary endpoint was the conversion rate of patients with uHCC treated with triple therapy followed by SR.Patients and Methods: Forty-nine patients with uHCC who received triple therapy at Fujian Provincial Hospital between January 2020 and June 2022 were retrospectively included. The treatment efficacy, SR conversion rate, and associated AEs were recorded.Results: Among the 49 patients enrolled, the ORRs assessed by mRECIST and RECIST v1.1 were 57.1% (24/42) and 14.3% (6/42), respectively, and the DCRs were 92.9% (39/42) and 88.1% (37/42), respectively. Seventeen (34.7%) patients met the criteria for resectable HCC and underwent resection. The median interval between the start of triple therapy and resection was 113.5 days (range 94.75 to 182 d), and the median number of TACE was 2 (range 1 to 2.5). The patients did not achieve median overall survival or median progression-free survival. Treatment-related AEs occurred in 48 (98%) patients, and 18 (36.7%) patients had grade ≥ 3 AEs.Conclusion: Triple combination therapy resulted in a relatively high ORR and conversion resection rate following uHCC treatment.Keywords: TACE, immune checkpoint inhibitors, tyrosine kinase inhibitor, surgical resection

Xiaoyu Pan,1,2 Zhuoya Jia,1,2 Ruoxi Zhen,1,2 Lin Yue,3 Shu Niu,1,4 Jiangli Ban,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Endocrinology, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Endocrinology, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comPurpose: Studies have shown that atherosclerotic plaques are associated with changes in the microbial composition of the intestinal flora and obesity, and that the small intestine plays an irreplaceable role in regulating intestinal flora homeostasis, but the role of the small intestine in the development of obesity-related atherosclerosis remains understudied. Therefore, this study explores the role of the small intestine in obesity-induced atherosclerosis and its molecular mechanisms.Methods: In the GSE59054 data, small intestine tissue samples from 3 normal and 3 obese mice were analyzed using bioinformatics methods. Screening for differentially expressed genes (DEGs) using the GEO2R tool. The DEGs were next processed for bioinformatics analysis. We constructed an obese mouse model and measured aortic arch pulse wave velocity (PWV). Aortic and small intestine tissues were stained with hematoxylin-eosin (HE) to observe pathological changes. Finally, immunohistochemistry was performed to verify the expression of small intestinal proteins.Results: We identified a total of 122 DEGs. Pathway analysis revealed that BMP4, CDH5, IL1A, NQO1, GSTM1, GSTA3, CAV1 and MGST2 were mainly enriched in the Fluid shear stress and atherosclerosis pathway. In addition, BMP4, NQO1 and GSTM1 are closely related to atherosclerosis. Ultrasound and pathological findings suggest the presence of obesity atherosclerosis. Immunohistochemistry verified high expression of BMP4 and low expression of NQO1 and GSTM1 in obese small intestine tissues.Conclusion: The altered expression of BMP4, NQO1 and GSTM1 in small intestine tissues during obesity may be related to atherosclerosis, and Fluid shear stress and atherosclerosis pathway may be the molecular mechanism of their role.Keywords: obesity, differentially expressed genes, atherosclerosis, small intestine, bioinformatics analysis

Xiaoyu Pan,1,2 Xueqing Zhang,2 Jiangli Ban,2 Lin Yue,3 Lin Ren,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Endocrinology, the Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Internal Medicine, Hebei Medical University, People’s Republic of China, Tel +86 31185988406, Email chenshuc2014@163.comBackground: Neutrophils and high-density lipoprotein cholesterol (HDL-C) are significantly linked to cardiovascular disease (CVD). This study investigates the correlation of neutrophil count to HDL-C ratio (NHR) with cardiac ultrasound parameters and cardiovascular risk in healthy populations.Materials and Methods: Firstly, NHR was calculated based on neutrophils and HDL-C. Then, the differences in basic clinical characteristics and cardiac ultrasound parameters were compared between the high and low NHR groups, males and females. Subsequently, cardiovascular risk was predicted according to the Chinese 10-year ischemic cardiovascular disease (ICVD) risk assessment tool for people aged 35– 60 years. Finally, the correlation between NHR and cardiac ultrasound parameters and cardiovascular risk was calculated.Results: A total of 3020 healthy participants, 1879 males and 1141 females, were included. Participants in the high NHR group had significantly increased Aorta (AO), Left Atrium (LA), Right Atrium (RA), Right Ventricle (RV), End Systolic Diameter of Left Ventricle (ESD), End Diastolic Diameter of Left Ventricle (EDD), Main Pulmonary Artery (MPA), Right Ventricular Outflow Tract (RVOT), Interventricular Septum (IVS), Left Ventricular Posterior Wall (LVPW), and cardiovascular risk and decreased E/A values compared to those in the low NHR group. The same results were found in males participants compared to females. A total of 1670 participants underwent ICVD risk assessment tool. Cardiovascular risk was significantly higher in those with high NHR and in males than in those with low NHR and in females. Correlation analysis showed that NHR was positively correlated with AO, LA, RA, RV, ESD, EDD, MPA, RVOT, IVS, LVPW and cardiovascular risk, and negatively correlated with E/A values.Conclusion: Our study demonstrates that NHR is significantly associated with cardiac ultrasound parameters and cardiovascular risk in healthy populations. NHR may serve as a useful indicator for the early diagnosis and treatment of cardiovascular disease among healthy populations.Keywords: neutrophils, high-density lipoprotein cholesterol ratio, cardiovascular risk, cardiac ultrasound, cardiovascular disease

Bin Lu,1 Xinling Pan,2 Bin Wang,3 Chenyuan Jin,1 Chenxin Liu,1 Mengqi Wang,4 Yunzhen Shi1 1Department of Infectious Diseases, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang Province, People’s Republic of China; 2Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, People’s Republic of China; 3Department of Emergency, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang Province, People’s Republic of China; 4Department of Neurology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yunzhen Shi, Department of Infectious Diseases, Affiliated Dongyang Hospital of Wenzhou Medical University, No. 60 Wuningxi Road, Dongyang, People’s Republic of China, Email syzwylwmc@163.comPurpose: We attempted to establish a model for predicting the mortality risk of sepsis patients during hospitalization.Patients and Methods: Data on patients with sepsis were collected from a clinical record mining database, who were hospitalized at the Affiliated Dongyang Hospital of Wenzhou Medical University between January 2013 and August 2022. These included patients were divided into modeling and validation groups. In the modeling group, the independent risk factors of death during hospitalization were determined using univariate and multi-variate regression analyses. After stepwise regression analysis (both directions), a nomogram was drawn. The discrimination ability of the model was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, and the GiViTI calibration chart assessed the model calibration. The Decline Curve Analysis (DCA) was performed to evaluate the clinical effectiveness of the prediction model. Among the validation group, the logistic regression model was compared to the models established by the SOFA scoring system, random forest method, and stacking method.Results: A total of 1740 subjects were included in this study, 1218 in the modeling population and 522 in the validation population. The results revealed that serum cholinesterase, total bilirubin, respiratory failure, lactic acid, creatinine, and pro-brain natriuretic peptide were the independent risk factors of death. The AUC values in the modeling group and validation group were 0.847 and 0.826. The P values of calibration charts in the two population sets were 0.838 and 0.771. The DCA curves were above the two extreme curves. Moreover, the AUC values of the models established by the SOFA scoring system, random forest method, and stacking method in the validation group were 0.777, 0.827, and 0.832, respectively.Conclusion: The nomogram model established by combining multiple risk factors could effectively predict the mortality risk of sepsis patients during hospitalization.Keywords: severe sepsis, mortality risk prediction, nomogram, SOFA, random forest, stacking

Xiaoyu Pan,1,2 Xueqing Zhang,2 Jiangli Ban,2 Lin Yue,3 Lin Ren,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Endocrinology, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China, Tel +86 31185988406, Email chenshuc2014@163.comPurpose: To investigate the effect of high-fat diet on protein expression in mouse heart and aorta using proteomic techniques.Methods: A high-fat diet was used to construct an obese mouse model, and body weight was checked regularly. After the experiment, serum lipid and oxidative stress levels were measured. Proteomic detection of cardiac and aortic protein expression. Cardiac and aortic common differentially expressed proteins (Co-DEPs) were screened based on proteomic results. Subsequently, functional enrichment analysis and screening of key proteins were performed.Results: A high-fat diet significantly increased body weight in mice. Obese mice had considerably higher levels of TC, TG, LDL-C, ROS, and MDA. In the heart and aorta, 17 Co-DEPs were discovered. The results of functional analysis of these proteins indicated that they were mainly related to lipid metabolism. Ech1, Decr1, Hsd17b4, Hsdl2 and Acadvl were screened as key proteins. In mice, a high-fat diet causes lipid metabolism to become disrupted, resulting in higher levels of oxidative stress and lipid peroxidation products.Conclusion: Ech1, Decr1, Hsd17b4, Hsdl2 and Acadvl as cardiac and aortic Co-DEPs are closely related to lipid metabolism and may serve as potential diagnostic and therapeutic targets for obesity-induced cardiovascular disease.Keywords: high-fat diet, obesity, proteomics, cardiovascular disease, lipid

Weiquan Liang,1,&ast; Yiyu Lu,2,&ast; Xingxi Pan,2,&ast; Yunxiang Zeng,1 Weiqiang Zheng,1 Yiran Li,1 Yuanhang Nie,1 Dongbing Li,3 Dongliang Wang3 1Department of Respiratory and Critical Care Medicine, The Second People’s Hospital of Foshan (Affiliated Foshan Hospital of Southern Medical University), Foshan, 528200, People’s Republic of China; 2Department of Oncology, The Sixth Affiliated Hospital, South China University of Technology, Foshan, 528200, People’s Republic of China; 3ChosenMed Technology Beijing Co., Ltd, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiquan Liang, Department of Respiratory and Critical Care Medicine, The Second People’s Hospital of Foshan (Affiliated Foshan Hospital of Southern Medical University), Weiguo Lu 78, Foshan, Guangdong, 528200, People’s Republic of China, Email ribby8@126.comBackground: There is no clear information regarding the role of FAM181A antisense RNA 1 (FAM181A-AS1) in lung adenocarcinoma (LUAD). We explored the relationship between FAM181A-AS1 and LUAD using bioinformatics analysis and experimental validation in this study.Methods: Statistics and databases were used to evaluate the relationship between clinical features in LUAD patients and FAM181A-AS1 expression, prognostic factors, regulation network, and immune infiltration of FAM181A-AS1 in function. LUAD cell lines were tested for FAM181A-AS1 expression using qRT-PCR.Results: FAM181A-AS1 showed significantly low expression in LUAD patients. Low FAM181A-AS1 expression predicted a poorer overall survival (OS) (HR: 0.66; 95% CI: 0.49– 0.88; P=0.005) and disease specific survival (DSS) (HR: 0.64; 95% CI: 0.44– 0.92; P=0.017) of LUAD patients. There was also an independent correlation between low FAM181A-AS1 expression (HR: 0.547; 95% CI: 0.350– 0.857; P=0.008) and OS in LUAD patients. The FAM181A-AS1 high-expression phenotype was differentially enriched for M phase, cellular senescence, cell cycle checkpoints, chromatin modifying enzymes, ESR-mediated signaling, DNA repair, G2/M checkpoints, HCMV infection, and DNA double-strand break repair. A correlation was found between the expression of FAM181A-AS1 and immune infiltrating cells. A significant decrease in FAM181A-AS1 expression was observed in LUAD cell lines compared to Beas-2B.Conclusion: There was a significant association between low FAM181A-AS1 expression in LUAD patients and poor survival and immune infiltration. The FAM181A-AS1 gene may provide a useful biomarker for LUAD prognosis and immunotherapy response.Keywords: lung adenocarcinoma, FAM181A-AS1, prognosis, immune infiltration, biomarker

Xiaoyu Pan,1,2 Lin Yue,1,2 Jiangli Ban,2 Lin Ren,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel +86 31185988406, Fax +86 31185988406, Email chenshuc2014@163.comPurpose: Using proteomics to study the effect of semaglutide on cardiac protein expression in obese mice. Assessment of the effect of semaglutide on cardiac function in obese mice.Materials and Methods: The mice were randomly divided into three groups: the control group (WC), the high-fat group (WF), and the high-fat diet with semaglutide intervention group (WS). Serum samples were collected, and lipids, blood glucose, inflammatory and oxidative stress markers, and cardiac ultrasound, were examined. The cardiac weight of each group of mice was measured, and pathological alterations were examined. Inflammation and oxidative stress levels in heart tissue were evaluated. The labeling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform was used to find differentially expressed proteins (DEPs) and screen for related pathways and key proteins in a proteomics study.Results: Semaglutide greatly alleviated obesity-induced lipid metabolism abnormalities, improved cardiac ventricular wall thickening, and significantly reduced myocardial collagen content in obese mice. Semaglutide significantly reduces obesity-induced inflammation and oxidative stress. There were 64 DEPs in the WF/WC group, with 39 upregulated proteins and 25 downregulated proteins. The WS/WC group, on the other hand, had 83 DEPs, including 57 upregulated and 26 downregulated proteins. Following functional analysis, DEPs were shown to be largely associated with lipid metabolism and peroxisomes. Apolipoprotein A-II, catalase, diazepam-binding inhibitor, paraoxonase-1, and hydroxysteroid 17-dehydrogenase-4 were all upregulated in the WF group but significantly downregulated in the WS group. A high-fat diet increases the expression of lipid synthesis and transport proteins while increasing inflammation and oxidative stress damage.Conclusion: Semaglutide decreases lipid synthesis alleviates inflammation and oxidative stress and prevents lipid peroxidation and cardiac impairment.Keywords: semaglutide, lipid metabolism, DEPs, obesity, inflammation, oxidative stress

Xiaoyu Pan,1,2 Lin Yue,3 Lin Ren,2 Jiangli Ban,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Endocrinology, the Third Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Internal Medicine, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, Hebei, 050017, People’s Republic of China, Tel +86 31185988406, Email chenshuc2014@163.comPurpose: To investigate the correlation between Triglyceride-glucose (TyG) index and liver function parameters in healthy obese civil servants in Shijiazhuang, China.Materials and Methods: This was an outpatient-based cross-sectional study in which 6452 participants were recruited. A total of 784 participants were analyzed according to inclusion and exclusion criteria. A TyG index was calculated based on fasting glucose and triglycerides. All patients were divided into a high TyG index group and a low TyG index group, using the median TyG index as a cut-off. Finally, patients were further divided into two subgroups: males and females.Results: While AST/ALT and direct bilirubin levels were lower in the high TyG index group compared to the low TyG index group, ALT, AST, total protein, and albumin levels were greater. Particularly in male participants, TyG index was inversely connected with AST/ALT and direct bilirubin levels and favorably correlated with ALT, AST, total protein, and albumin levels. These connections persisted in the multilinear regression study even after adjusting for confounding variables.Conclusion: This study describes the correlation between TyG index and liver function parameters in obese populations without co-morbid diseases, providing a new idea for early interventional treatment in this group.Keywords: TyG index, obesity, NAFLD, ALT, AST

Xing Chen,1 Shuchun Chen,2,3 Qingjuan Ren,3 Shu Niu,3 Xiaoyu Pan,3 Lin Yue,3 Zelin Li,3 Ruiyi Zhu,3 Zhuoya Jia,3 Xiaoyi Chen,3 Ruoxi Zhen,3 Jiangli Ban3 1Department of Nephrology, Hebei General Hospital, Shijiazhuang, 050051, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050051, People’s Republic of China; 3Department of Internal Medicine, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel/Fax +86 311 85988406, Email chenshuchunwork88@163.comPurpose: Semaglutide, a new long-acting glucagon-like peptide-1 analogue, has shown benefits for renal diseases, but its direct role on kidney metabolism under obesity remains unclear. The study aims to elucidate the protective effect and metabolic modulation mechanism of semaglutide on obesity-related kidney injury.Methods: Male C57BL/6J mice were divided into control and obesity groups. Mice in the obesity group had a high-fat diet and were treated with or without semaglutide (30nmol/kg/day). The study assayed blood biochemistry and then evaluated renal pathological injury through Periodic Acid-Schiff staining and electron microscopy. Metabolomics was utilized to analyze obesity-related metabolites in kidney samples.Results: Semaglutide significantly improved glucose homeostasis, insulin resistance, and kidney injury in obese mice. We successfully identified 377 altered metabolites (P< 0.05). It was suggested that semaglutide directly improved oxidative stress and inflammation-related metabolites such as nicotinamide adenine dinucleotide (NAD+) and adenosine in the kidney of obese mice, which have not been documented in obesity-related kidney injury. Relevant enriched pathways were included phospholipids and lysophospholipids metabolism, purine metabolism, NAD+ metabolism, and insulin resistance-related metabolism. They could serve as potential targets for intervention of obesity-related kidney injury.Conclusion: Our study revealed the metabolomics-based renoprotective mechanism of semaglutide in obese mice for the first time. The innovation lied in the identified metabolites such as NAD+ and adenosine targeted by semaglutide, which have not been documented in obesity-related kidney injury. Semaglutide may be a promising therapy for obesity-related kidney diseases.Keywords: semaglutide, glucagon-like peptide-1, metabolomics, obesity, kidney

Bin Lu,1 Yunzhen Shi,1 Yangxiao Zhou,2 Fenhua Zhao,3 Mengqi Wang,4 Xinling Pan5 1Department of Infectious Diseases, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, People’s Republic of China; 2Department of Clinical Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, People’s Republic of China; 3Department of Radiology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, People’s Republic of China; 4Department of Neurology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, People’s Republic of China; 5Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, People’s Republic of ChinaCorrespondence: Xinling Pan, Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, No. 60 Wuningxi Road, Dongyang, Zhejiang, People’s Republic of China, Tel +86-0579-86859825, Fax +86-0579-86856878, Email panfengyuwuzu@163.comAbstract: Aggregatibacter aphrophilus is part of the normal flora in the oropharynx and upper respiratory tract, which causes invasive bacteremia in rare cases. However, the culture and identification of Aggregatibacter aphrophilus are challenging, hence easily misdiagnosed or undetected in clinical practice. In this case, a 73-year-old male patient was admitted to the hospital with a fever and right hip pain. Routine blood and C-reactive protein tests showed abnormal inflammatory markers. Positive blood culture revealed the presence of Aggregatibacter aphrophilus through mass spectrometry. The computed tomography examination further revealed the presence of psoas abscess, pulmonary infection, and pleural effusion, which was relieved by ceftriaxone combined with levofloxacin therapy, the drainage of psoas abscess and pleural effusion. Therefore, since multiple anatomic sites infection, including bloodstream, psoas abscess and pulmonary infection caused by Aggregatibacter aphrophilus, is rare, sufficient attention should be paid to its clinical diagnosis and treatment.Keywords: Aggregatibacter aphrophilus, blood stream, psoas abscess, pulmonary infection

Qingjuan Ren,1,2 Shuchun Chen,1,3 Xing Chen,1 Shu Niu,4 Lin Yue,5 Xiaoyu Pan,1 Zelin Li,1 Xiaoyi Chen1 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 2Department of Geriatrics, Shijiazhuang People’s Hospital, Shijiazhuang, 050000, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050000, People’s Republic of China; 4Department of Endocrinology, Shijiazhuang People’s Hospital, Shijiazhuang, 050000, People’s Republic of China; 5Department of Endocrinology, The Third Hospital of Shijiazhuang, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, No. 348, Heping West Road, Shijiazhuang, 050000, People’s Republic of China, Tel +86-13833166283, Email chenshuchunwork88@163.comPurpose: This study aimed to investigate the effect of Semaglutide on skeletal muscle and its metabolomics.Methods: A total of 18 male C57BL/6 mice were randomly divided into normal control (NC) group, high-fat diet (HFD) group and HFD+Semaglutide group, and were given standard diet, HFD diet, HFD diet plus Semaglutide, respectively. The body weight, gastrocnemius weight, serum lipid, blood glucose and inflammatory index levels of mice in each group were observed and compared, and the morphological and structural changes of gastrocnemius were also analyzed. Meanwhile, gastrocnemius metabolite changes were analyzed by untargeted metabolomics.Results: After Semaglutide treatment, the food intake and body weight of mice were evidently decreased, while the relative gastrocnemius weight ratio were conversely increased. Meanwhile, the levels of TG, CHO, LDL, HDL, TNF-α, IL-6, IL-1β and HOMA-IR were all observed to decrease remarkably after Semaglutide intervention. Histological analysis showed that Semaglutide significantly improved the pathological changes of gastrocnemius, manifested as increased type I/type II muscle fiber ratio, total muscle fiber area, muscle fiber density, sarcomere length, mitochondrial number and mitochondrial area. Furthermore, metabolic changes of gastrocnemius after Semaglutide intervention were analyzed, and 141 kinds of differential metabolites were screened out, mainly embodied in lipids and organic acids, and enriched in 9 metabolic pathways including a variety of amino acids.Conclusion: Semaglutide can significantly reduce the body weight and the accumulation of intramuscular fat, promote muscle protein synthesis, increase the relative proportion of skeletal muscle, and improve muscle function of obese mice, possibly by altering the metabolism of muscle lipids and organic acids.Keywords: sarcopenic obesity, sarcopenia, glucagon-like peptide-1 receptor agonists, Semaglutide, metabonomics

Xiaoyu Pan,1,2 Xiaoyi Chen,2 Lin Ren,2 Zelin Li,1,2 Shuchun Chen1,2 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comPurpose: To study the effects of obesity and overweight on carotid vascular function among healthy populations by carotid ultrasound (CAU) and transcranial Doppler (TCD).Materials and Methods: Basic clinical characteristics, CAU and TCD parameters were collected from recruited healthy individuals. Firstly, all participants were divided into three groups: normal, overweight and obese. Then, the variability of basic clinical characteristics and lipids between the three groups was calculated. Subsequently, CAU and TCD parameters were compared between the three groups. Finally, the correlation between body mass index (BMI) and neck vascular function was analyzed.Results: A total of 613 healthy participants were included, of whom 241 were normal, 264 were overweight, and 108 were obese. Overweight and obesity significantly decreased systolic, diastolic and mean flow velocities in the basilar, vertebral and internal carotid arteries, but had no effect on pulsatility index. In addition, BMI was significantly negatively correlated with systolic, diastolic, and mean flow velocities in the basilar, vertebral, and internal carotid arteries, and remained correlated after adjusting for other factors. There was no effect of overweight and obesity on carotid plaques.Conclusion: Our study revealed that overweight and obesity decreased carotid vascular flow velocity and showed a decreasing trend in vascular flow velocity with increasing BMI. Overweight and obesity appear to have no effect on carotid plaques.Keywords: obesity, overweight, basilar artery, vertebral artery, internal carotid artery

Xinran Li,&ast; Jiamin Zheng,&ast; Min Yan, Ye Lu, Xiangtao Pan Department of Hematology and Oncology, Suzhou Medical College of Soochow University, Taicang Hospital Affiliated of Soochow University, Taicang City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye Lu; Xiangtao Pan, Department of Hematology and Oncology, Suzhou Medical College of Soochow University, Taicang Hospital Affiliated of Soochow University, Taicang City, 215400, People’s Republic of China, Tel +86 18915768046 ; +86 18915768003, Email tcyyluye@163.com; panxiangtao@csco.ac.cnObjective: To investigate the significance of fibrinogen (Fib) in combination with the neutrophil to lymphocyte ratio (NLR) in predicting the prognosis of patients with gastric cancer.Methods: The preoperative peripheral blood-related indicators of 281 gastric cancer patients were reviewed retrospectively, and the differences in relationship indicators between the survival and death groups were compared and analyzed. The COX regression analysis and Kaplan–Meier Curve (K-M) were used to assess the prognostic significance of Fib combined with NLR in patients with gastric cancer.Results: ① The difference between the survival and death groups of patients with gastric cancer was statistically significant in the high and low Fib and NLR levels (X2=6.868 and 17.051, respectively, all P < 0.01).② The correlation between Fib and NLR was remarkable (r=0.266, P=0.000).③ The F-NLR classifications showed statistically significant difference between the survival and death groups for gastric cancer patients (X2=20.200, P=0.000).④ Except for Fib and the middle/low classification of F-NLR, which was P< 0.05, and the rest were all P< 0.01. There was a substantial statistical difference between F-NLR classifications, Fib and NLR.⑤ F-NLR was found to be a predictive factor of death in patients with gastric cancer in COX regression analysis (P=0.000).⑥Patients with F-NLR scores of “ 0”, “ 1” and “ 2” had 5-year survival rates of 92.6%, 64.0% and 47.2%, respectively, and 3-year survival rates of 92.6%, 74.3% and 51.9%, respectively (all P=0.000).Conclusion: The combination of Fib and NLR (F-NLR) improves the accuracy of prognosis in patients with gastric cancer.Keywords: fibrinogen, neutrophil to lymphocyte ratio, F-NLR, gastric cancer, prognosis

Jian Lin,1 Yize Huang,1 Li Qian,2 Xiaolong Pan,3 Youliang Song1 1Department of Infectious Diseases, Tongling People’s Hospital, Tongling, Anhui, 244000, People’s Republic of China; 2Department of Ophthalmology, Tongling People’s Hospital, Tongling, Anhui, 244000, People’s Republic of China; 3Medical Laboratories, Tongling People’s Hospital, Tongling, Anhui, 244000, People’s Republic of ChinaCorrespondence: Youliang Song, Tel +86 13956250358, Email 316656399@qq.comAbstract: At present, invasive syndrome caused by hypervirulent Klebsiella pneumoniae (HvKp) is a widespread concern, and HvKp strains of different genotypes have been isolated. Here, we report a case of community-acquired liver abscess and endogenous endophthalmitis caused by a genotype ST25 serotype K2 (ST25-K2) HvKp strain in China. A 51-year-old man with diabetes was transferred to our hospital from a local community hospital with persistent fever for > 20 days and blurred vision in his left eye. A detailed examination revealed a liver abscess, endogenous endophthalmitis, and pneumonia. Bacterial cultures of pus from the liver abscess and the vitreous abscess of the left eye yielded Klebsiella pneumoniae (Kp), which was sensitive to the recommended drugs. In addition to positive string tests, a genetic analysis showed that the strain belonged to sequence type 25 (ST25) and serotype K2, and carried already-reported virulence genes, including iucA, rmpA2, rmpA, aerobactin, and entB. The pathogenic agent isolated from this patient was identified as HvKp. The patient’s general condition improved after a combination of treatments, including antimicrobial therapy, abscess drainage, and nutritional support. Unfortunately, the patient lost the vision in his left eye and developed secondary glaucoma, resulting in inevitable enucleation. Sequence 25 serotype K2 HvKp strains have been previously associated with nosocomial infections, but none associated with community-acquired liver abscess combined with endogenous endophthalmitis has yet been reported. Clinicians must be alert to the possibility of genotype ST25-K2 HvKp infection in patients with community-acquired liver abscess combined with an invasive infection, such as ocular discomfort.Keywords: hypervirulent Klebsiella pneumoniae, liver abscess, endogenous endophthalmitis, sequence type 25, serotype K2

Xinran Li,&ast; Jiamin Zheng,&ast; Ye Lu, Xiangtao Pan Department of Hematology and Oncology, Suzhou Medical College of Soochow University, Taicang Hospital Affiliated of Soochow University, Taicang City, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangtao Pan, Department of Hematology and Oncology, Suzhou Medical College of Soochow University, Taicang Hospital Affiliated of Soochow University, Taicang City, Jiangsu Province, 215400, People’s Republic of China, Tel +86 18915768003, Email panxiangtao@csco.ac.cnObjective: To investigate the risk of death in patients with tumor-related PTE (pulmonary thromboembolism) detected by CAR (C-reactive protein/albumin ratio) combined with DD (D-dimer).Methods: The peripheral hematology and coagulation-related indexes of 109 patients with tumor-related PTE diagnosed by PTCA were retrospectively analyzed, and the differences in relationship indexes between tumor-related PTE patients with good prognosis and poor prognosis were compared and analyzed. The receiver operating characteristic curve (ROC) was used to analyze the risk of death in patients with tumor-related PTE by CAR and DD.Results: ① The values of CAR and DD in the poor prognosis group were 3.90 ± 2.69 and 21.25 ± 21.20, respectively, which were significantly higher than those in the good prognosis group (1.66 ± 1.77, 9.53 ± 3.57) (P all < 0.01). ② WBC, NE and SII in tumor-related PTE patients with poor prognosis were significantly higher than those in patients with good prognosis, while Hb in patients with poor prognosis was significantly lower than that in patients with good prognosis. ③ There was a significant positive correlation between CAR and DD (P=0.018). ④ The values of CAR and DD in the death group were 4.07 ± 2.42 and 19.65 ± 20.48, respectively, which were significantly higher than those in the survival group (1.94 ± 2.12, 11.52 ± 15.84) (P all< 0.05). ⑤ The results of logistic regression analysis showed that both CAR (P=0.000) and DD (P=0.031) were independent prognostic factors in patients with tumor-related PTE. ⑥ CAR combined with DD had high sensitivity (77.8%) and specificity (83.5%), and the Youden index was 0.613. ⑦ The area under the receiver operating characteristic curve of CAR combined with DD was the largest (up to 0.806).Conclusion: CAR and DD were highly expressed in patients with poor prognosis of tumor-related PTE. CAR combined with DD detection is helpful to improve the correct assessment of the risk of death in patients with tumor-related PTE.Keywords: pulmonary thromboembolism, neutrophil/lymphocyte, C-reactive protein, albumin, C-reactive protein/albumin ratio, plasma D-dimer, risk assessment of death

Jinjian Li,1,&ast; Kun Yang,2,&ast; Xinghui Pan,1 Hui Peng,1 Chenting Hou,1 Jie Xiao,1 Qing Wang1 1Ophthalmology, Affiliated Hospital of Qingdao University, Qingdao, 266500, People’s Republic of China; 2Medical Research Center, Affiliated Hospital of Qingdao University, Qingdao, 266500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Wang, Ophthalmology, Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266500, People’s Republic of China, Tel +86 17853290636, Fax +86 532 82911747, Email wangqing6836@sina.comPurpose: The biological role and mechanism of long noncoding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) in dry eye remain to be illustrated. Pyroptosis is a noticeable form of inflammatory activation, which is characteristic of gasdermin D (GSDMD)-driven cell death. The present study was designed to explore the role of MIAT in pyroptosis and apoptosis induced by hyperosmolarity stress (HS) in human corneal epithelial cells (HCECs).Methods: HCECs were cultured in 70– 120 mM hyperosmotic medium for 24 h to create a dry eye model in vitro. The level of the pyroptosis marker GSDMD was measured, and the cell inflammatory response was evaluated by detecting IL-1β and IL-18 levels. Exogenous caspase-1 inhibitor Ac-YVAD-CHO was used. The pyroptosis in HCECs was examined by caspase-1 activity, immunofluorescent staining, and Western blotting. Flow cytometry was performed to test the apoptosis rate of HCECs. Cell migration and proliferation were detected. The expression of the lncRNA MIAT in HCECs was detected by quantitative real-time PCR. MIAT was knocked down by small interfering RNA (siRNA) transfection. The effects of caspase-1 inhibition on pyroptosis, apoptosis, migration, and proliferation were observed.Results: HS promoted pyroptosis in HCECs by elevating caspase-1, GSDMD, and the active cleavage of GSDMD (N-terminal domain, N-GSDMD), and increased the release of IL-1β, IL-18, LDH and the rate of apoptosis, with reduced cell migration. These changes were prevented by the inhibition of caspase-1. The expression of MIAT was significantly increased in HCECs exposed to a hyperosmotic medium. Silencing MIAT increased the expression of GSDMD, caspase-1, and inflammatory chemokines IL-1β and IL-18, and promoted apoptosis while inhibiting migration and proliferation in HCECs.Conclusion: The lncRNA MIAT is involved in HS-induced pyroptosis and apoptosis and the inflammatory response of HCECs and provides a new understanding of the pathogenesis of dry eye.Keywords: myocardial infarction-associated transcript, dry eye, pyroptosis, apoptosis

Xing Chen,1 Shuchun Chen,1,2 Zelin Li,1 Xiaoyu Pan,1 Yujiao Jia,1 Zhijuan Hu,3 Kai Niu,3 Bing Liu,3 Qingjuan Ren1 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Department of Nephrology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel/Fax +86 311 85988406, Email chenshuchunwork88@163.comObjective: To investigate the association between body mass index (BMI) and clinicopathologic parameters in patients with idiopathic membranous nephropathy (IMN).Methods: This study was retrospective and included patients with biopsy-proven IMN from 2018 to 2021 in Hebei General Hospital. Patients were categorized into two groups based on BMI. Clinical and histopathologic data were analyzed at the time of renal biopsy. Pathological data included immunofluorescence staining, glomerulosclerosis (GS, 0– 2), mesangial cell proliferation (MCP, 0– 1), tubular atrophy (TA, 0– 1), interstitial fibrosis (IF, 0– 1), vascular wall thickness (VWT, 0– 1) and a combination score (GMTIV) graded from 0 to 5.Results: Our study revealed that the obese group had a higher prevalence of hypertension and diabetes than the overweight/normal weight group (P=0.001, P=0.002). Systolic blood pressure (P=0.005), diastolic blood pressure (P< 0.001), haemoglobin (P=0.006), triglycerides (P< 0.001), serum uric acid (P=0.05), 24 h urine proteinuria concentration (UP) (P=0.012), MCP (P=0.042), IF (P=0.033), and GMITV (P=0.033) score were higher in obese group compared to the other group, while the high-density lipoprotein-cholesterol (P=0.034) and immunoglobulin A deposition score (P=0.005) were lower. Factors significantly associated with UP were the ratio of lymphocyte count to white blood cell count, serum pre-albumin, immunoglobulin G, microscopic hematuria, anti-phospholipase A2 receptor (anti-PLA2R), C3 deposit on multivariable analysis (adjusted R2=0.343). Binary logistic regression analysis illustrated that MCP was correlated to BMI (OR=2.528, P=0.036). Ordinal logistic regression analysis demonstrated that GMTIV was associated with BMI (OR=1.114, P=0.010) and C3 deposit (OR=1.655, P=0.001).Conclusion: High BMI was associated with MCP and GMTIV score in IMN patients. Obesity may play an essential role in mesangial lesions of IMN. This study emphasized the relation between BMI and histological parameters under the universal usage of anti-PLA2R antibodies for diagnosis and prognosis in IMN.Keywords: obesity, body mass index, idiopathic membranous nephropathy

Deshan Yao,1,2 Bo Shi,3 Sichuan Wang,1,2 Liuxiang Bao,1,2 Meng Tan,1,2 Hui Shen,1,2 Zhengang Zhang,1,2 Xin Pan,1,2 Yi Yang,1,2 Yong Wu,1,2 Kaizheng Gong1,2 1Department of Cardiology, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225001, People’s Republic of China; 2Jiangsu Key Laboratory of Integrative Medicine for the Control of Geriatrics and Institute of Cardiovascular Disease, Yangzhou University, Yangzhou, 225001, People’s Republic of China; 3School of Life Science, Liaoning Normal University, Dalian, 116081, People’s Republic of ChinaCorrespondence: Kaizheng Gong; Yong Wu, Department of Cardiology, the Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Middle Road, Yangzhou, 225001, People’s Republic of China, Tel +86-514-82981199, Email yungkzh@163.com; 154629676@qq.comBackground: Oxidative stress and inflammatory reaction play critical roles in acute myocardial infarction (AMI). Isoliquiritigenin (ISL), a flavonoid monomer extracted from licorice, has been found to have antioxidant and anti-inflammatory effects in cancer studies. Here, we tested the effect and underlying mechanisms of ISL on ischemia-induced myocardial injury in a mouse AMI model.Methods: Adult C57BL/6 mice were pre-treated by intraperitoneal injection of ISL and/or a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor ML385 for 3 days, respectively. Then, the AMI model was established by ligating the anterior descending branch of the left coronary artery. Myocardial oxidative stress status, inflammatory response, cardiac function and infarction size were assessed after 7th day of surgery.Results: Compared with sham group, the reactive oxygen species (ROS) and malondialdehyde (MDA) level in AMI group were significantly increased. However, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) level were dramatically decreased. ISL treatment significantly reduced the myocardial infarction area, improved cardiac function, inhibited the production of ROS and MDA and reduced the consumption of SOD and GSH-Px. Interestingly, ISL could significantly increase nuclear Nrf2 and cytosolic heme oxygenase 1 (HO-1) level in the infarcted myocardium and reduce the oxidative stress after AMI. Also, ISL treatment dramatically inhibited the activation of myocardial NF-κB pathway and reduced the expression of pro-inflammatory factors in the AMI group. However, the administration of ML385 not only suppressed the Nrf2/HO-1 activation, the anti-oxidant and anti-inflammatory effects induced by ISL, but also attenuated the beneficial role of ISL on reducing infarct size and improving cardiac function in the mouse with AMI.Conclusion: The results suggested that activation of Nrf2/HO-1 pathway has an essential role in ISL-induced cardiac protection by alleviating myocardial oxidative stress and inflammation response in mice with AMI.Keywords: isoliquiritigenin, acute myocardial infarction, oxidative stress, Nrf2, NF-κB

Chunting Liang &ast;, Tongtong Huang &ast;, Xiaofeng Zhang, Huaqing Rao, Zhiru Jin, Xiaoxiong Pan, Jingtao Li, Yingying Mo, Yongzhi Cai, Ji Wu Department of Ultrasonic Medicine, The First Hospital Affiliated to Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ji Wu, Department of Ultrasonic Medicine, The First Hospital Affiliated to Guangxi Medical University, Nanning, 530021, People’s Republic of China, Email gxnnwuji@126.comPurpose: To study the thrombolytic effect and safety of cRGD urokinase liposomes (cRGD-UK-LIP) in rats with acute pulmonary microthromboembolism (APMTE), and explore the application value of echocardiography (ECHO) in animal models.Patients and Methods: Ninety-six SD rats were randomized into 6 groups (16/group): normal control, sham operation, APMTE, normal saline (NS), free urokinase (UK), cRGD-UK-LIP. Four groups (APMTE, NS, UK, cRGD-UK-LIP) of rats were injected with autologous thrombus to induce APMTE. Samples were injected into 3 groups (NS, UK, cRGD-UK-LIP) of rats after modeling. Echocardiography was used to assess right ventricle (RV) function and morphology in rats. Six rats in each group were randomly selected and pulmonary artery pressure (PAP) of them was measured through ECHO-guided transthoracic puncture. Finally, the rats were killed and their tissues were taken for pathological examination.Results: Compared with normal control or sham operation group, rats in APMTE group had enlarged RV, decreased RV function, increased PAP, and lung tissue of them showed postthromboembolic appearance. There was no significant difference between NS group and APMTE group. RV morphology and function of rats in the UK group and cRGD-UK-LIP group were better and vessels with residual thrombus in these 2 groups were less than APMTE group, especially in the cRGD-UK-LIP group. In terms of PAP, only cRGD-UK-LIP group was significantly lower than APMTE group. No hyperemia, bleeding and swelling were observed in heart, liver and kidney of rats in each group.Conclusion: A rat model of APMTE was successfully established. cRGD-UK-LIP has better thrombolytic effect than free urokinase and it is safe. Echocardiography is not merely an important way to evaluate the morphology and function of RV, transthoracic puncture measurement under the guidance of it can be an effective way to monitor PAP in animal models.Keywords: cRGD urokinase liposomes, acute pulmonary microthromboembolism, targeted thrombolysis, right ventricle, echocardiography, pulmonary artery pressure

Tingyu Ou,1,2 Yousheng Wei,1 Ying Long,1 Xinbin Pan,3 Desheng Yao1 1Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China; 2Department of Gynecology, The Third Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Desheng Yao, Email yaodesheng@gxmu.edu.cnPurpose: Pyroptosis has vital roles in tumorigenesis and cancer development; however, its relationship with cervical squamous cell cancer (CSCC) remains unexplored. In this study, we aimed to develop a CSCC prediction signature related to pyroptosis.Patients and Methods: Consensus clustering analysis was conducted to detect pyroptosis-related subclusters for CSCC. Next, differentially expressed genes (DEGs) between subclusters were identified. Univariate, least absolute shrinkage and selection operator, and stepwise multivariate Cox regression analyses were applied to establish a prognostic model and a nomogram drawn. Additionally, functional enrichment analysis, tumor mutation burden, and immune characteristics associated with this signature were investigated.Results: We constructed a seven-gene signature that functions as an independent predictor of prognosis in CSCC using data from The Cancer Genome Atlas. Patients with CSCC were divided into two groups based on median risk score, and patients in the low-risk group had significantly longer survival time than those in the high-risk group. Our findings were validated using Gene Expression Omnibus cohort data. We also established a nomogram, to expand the clinical applicability of our findings. The seven gene signature was associated with various molecular pathways, tumor mutation status, and immune microenvironment.Conclusion: The pyroptosis-related risk signature consisting of seven genes developed here represents a potential robust biomarker for predicting prognosis and immunotherapy response in patients with CSCC.Keywords: pyroptosis, cervical squamous cell carcinoma, prognosis, immune microenvironment, nomogram

Tiantian Shan,&ast; Xinran Li,&ast; Min Yan, Xiangtao Pan Department of Hematology, Taicang Hospital Affiliated to Soochow University, Taicang City, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangtao Pan Tel +86 18915768003Email drpanxiangtao@163.comObjective: To investigate the relationship between neutrophil/lymphocyte ratio, C-reactive protein/albumin ratio, plasma D-dimer and prognosis in patients with pulmonary thromboembolism, and to evaluate the risk of death.Methods: We retrospectively analyzed peripheral hematology and coagulation-related indicators of 362 pulmonary thromboembolism patients and 32 normal people, and the differences between the patients and control group and between good and poor prognosis groups were compared. And we analyzed and compared separate detection and combined detection of neutrophil/lymphocyte ratio, C-reactive protein/albumin ratio and D-dimer on the efficiency of risk of death in patients.Results: ① Neutrophil/lymphocyte ratio of pulmonary thromboembolism patients was 8.96± 1.94, significantly higher than that of control group 1.76± 0.53 (t=2.4281, P< 0.05). C-reactive protein/albumin ratio was 2.13± 2.08, significantly higher than 0.03± 0.01 in control group (t=20.7736, P< 0.01). D-dimer was 9.69± 8.61mg/L, significantly higher than 0.20± 0.11mg/L in control group (t=3.0066, P< 0.01). ② Hemoglobin, lymphocyte, albumin and lymphocyte/monocyte ratio in patients with good prognosis were significantly lower than those in poor prognosis group, while white blood cell, C-creative protein, neutrophil, C-reactive protein/albumin ratio, neutrophil/lymphocyte ratio and D-dimer were significantly lower than those in poor prognosis group (P all < 0.05). ③ Regression analysis showed that neutrophil/lymphocyte ratio (P=0.007), C-reactive protein/albumin ratio (P=0.010) and D-dimer (P=0.003) were independent prognostic factors for pulmonary thromboembolism. ④ In assessing the risk of death of patients, D-dimer alone had the highest sensitivity (93.1%), and C-reactive protein/albumin ratio alone had the highest specificity (68.8%). The combined detection of these three indicators had higher sensitivity (86.2%) and higher specificity (67.6%) at the same time. ⑤ The area under receiver operating characteristic curve for combined detection of neutrophil/lymphocyte ratio, C-reactive protein/albumin ratio and D-dimer was the largest (up to 0.821).Conclusion: Patients with pulmonary thromboembolism highly expressed in neutrophil/lymphocyte ratio, C-reactive protein/albumin ratio and D-dimer. The combined detection of these three indicators can improve the assessment efficacy of the risk of death in patients with pulmonary thromboembolism.Keywords: pulmonary thromboembolism, neutrophil to lymphocyte ratio, C-reactive protein/albumin ratio, plasma D-dimer, risk assessment of death, prognosis

Jianwei Wang,1,2,&ast; Lili Yu,1,3,&ast; Yulong Sun,4,&ast; Liangming Zhang,1,3 Mingshu Tu,1,3 Liqing Cai,1,3 Xiaoqing Yin,3,5 Xiaojie Pan,1,6 Tao Wang,4 Yi Huang1,3,7,8 1Provincial Clinical College, Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 2Department of Clinical Laboratory, Fujian Provincial Hospital South Branch, Fuzhou, 350008, People’s Republic of China; 3Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 4Shanghai Liangrun Biomedicine Technology Limited Company, Shanghai, 200000, People’s Republic of China; 5Integrated Chinese and Western Medicine College, Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, People’s Republic of China; 6Department of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 7Central Laboratory, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China; 8Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fuzhou, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Huang; Tao Wang Email hyi8070@126.com; wangtao@microdiag.comPurpose: Our pilot study has shown that cystatin SN (CST1) protein is highly expressed in esophageal squamous cell carcinoma (ESCC) tissues. We intend to develop a chemiluminescent enzyme immunoassay (CLEIA) available for serum CST1 detection and define the diagnostic value of CST1 detection for early ESCC patients, and establish a panel of CST1 with traditional tumor markers to improve the diagnostic sensitivity for early ESCC.Methods: Detection performance of CLEIA for CST1 was evaluated by linearity, detection limit, accuracy, precision, anti-interference and stability. Diagnostic performance of CST1 for early ESCC was evaluated by detecting CST1 of 112 early ESCC, 107 esophageal benign lesions (EBL), and 151 healthy controls (HC). CEA, CYFRA21-1 and SCC-Ag were detected by chemiluminescence immunoassay (CLIA).Results: The linear range and detection limit of CLEIA for CST1 were 6.25– 400 pg/mL and 1.35 pg/mL, respectively; the average recovery rate was 102.65%; CVs of intra-batch precision and inter-batch precision were < 1/4 TEa and < 1/3 TEa, respectively; 8 interferents including 7 common interferents and CST4 had no interference on CST1 detection; stability evaluation showed good sample and reagent stability. The level and positive rate of CST1 in early ESCC group were significantly higher than those in EBL/HC groups (P< 0.05). The diagnostic sensitivity of CST1 for early ESCC was 31.25% (specificity 92.64%, AUC 0.654). The diagnostic sensitivity of traditional tumor markers ranged from 16.07% to 28.57%, at > 93.0% specificity, and SCC-Ag showed the highest AUC (0.709). Combination of CST1 and CEA, SCC-Ag exhibited the highest AUC up to 0.736 (sensitivity 49.11%, specificity 89.53%).Conclusion: CLEIA has excellent detection performance for CST1. CST1 might be a prospective serological biomarker for early diagnosis of ESCC, while combination of CST1 and CEA, SCC-Ag might improve the early diagnostic performance.Keywords: esophageal squamous cell carcinoma, cystatin SN, chemiluminescence enzyme immunoassay, methodological evaluation, early diagnosis

Luna Sun,1,2,&ast; Bin Yi,3,&ast; Xiao Pan,4,&ast; Lili Wu,1,2,&ast; Zhilei Shang,1,2,&ast; Yanpu Jia,1,2 Xiandong Tao,3 Feng Zhao,5 Weifen Xie,6 Zhuoer Sun,1,2 Yonghai Bai,4 Weizhi Liu1,2 1Lab for Post-Traumatic Stress Disorder, Faculty of Psychology and Mental Health, Naval Medical University, Shanghai, 200433, People’s Republic of China; 2The Emotion & Cognition Lab, Faculty of Psychology and Mental Health, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Eastern Hepatobiliary Surgery Hospital, Shanghai; Department II of Infectious Disease, Huoshenshan Hospital, Wuhan, 430100, People’s Republic of China; 4Department of Medical Psychology, Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of China; 5Hongkou District of Changhai Hospital, Naval Medical University, Shanghai, 200081, People’s Republic of China; 6Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weizhi LiuLab for Post-Traumatic Stress Disorder, Faculty of Psychology and Mental Health, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, People’s Republic of ChinaTel/Fax +86-21-81871671Email 13024141970@163.comYonghai BaiDepartment of Medical Psychology, Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of ChinaTel/Fax +86-21-81885057Email baiyonghai179@126.comBackground: The outbreak of COVID-19 has developed into a pandemic. Data are required that specifically address the psychological consequences in COVID-19 confirmed patients. This study mainly aimed to examine posttraumatic stress disorder (PTSD) symptoms and sleep quality among COVID-19 confirmed patients during hospitalization.Methods: An observational study was conducted in two designated hospitals in Wuhan, China. Data were collected from 190 patients hospitalized with laboratory-confirmed COVID-19 infection between February 10, 2020 and March 13, 2020.Results: The mean age of the 190 confirmed patients was 55.7 years (SD = 13.7), of which 96 (50.5%) were female and 88 (46.3%) had family members or acquaintances infected with COVID-19. Lymphocytopenia was presented in 62 (32.6%) patients and 25 (13.2%) patients showed oxygen desaturation. The prevalence of high PTSD symptoms was 22.6% among the 190 patients. The median time from symptom onset to first medical visit and hospitalization was 2 days (IQR, 1– 5) and 16 days (IQR, 10– 27), respectively. Patients’ PTSD symptoms were positively related to the time from symptom onset to first medical visit (r = 0.156, p < 0.05) and hospitalization (r = 0.181, p < 0.01). There were significant correlations between sleep quality and PTSD symptoms (r = 0.312– 0.547, p < 0.01).Conclusion: The prevalence of high PTSD symptoms was 22.6% among hospitalized COVID-19 patients. Early diagnosis and treatment of COVID-19 symptoms are beneficial to infected patients both physically and psychologically. With the recovery of physical symptoms, psychological intervention is desired to promote the trauma recovery in COVID-19 patients.Keywords: COVID-19, patients, psychological, PTSD, sleep quality