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Xueyun Fu,* Xue Tian,* Jing Lin, Qian Wang, Lingwen Gu, Ziyi Wang, Menghui Chi, Bing Yu, Zhuhui Feng, Wenyao Liu, Lina Zhang, Cui Li, Guiqiu Zhao Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cui Li; Guiqiu Zhao, Department of Ophthalmology, Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong, 266003, People’s Republic of China, Email yankelicui@126.com; zhaoguiqiu_good@126.comBackground: Fungal keratitis is a serious blinding eye disease. Traditional drugs used to treat fungal keratitis commonly have the disadvantages of low bioavailability, poor dispersion, and limited permeability.Purpose: To develop a new method for the treatment of fungal keratitis with improved bioavailability, dispersion, and permeability.Methods: Zeolitic Imidazolate Framework-8 (ZIF-8) was formed by zinc ions and 2-methylimidazole linked by coordination bonds and characterized by Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Zeta potential. The safety of ZIF-8 on HCECs and RAW 264.7 cells was detected by Cell Counting Kit-8 (CCK-8). Safety evaluation of ZIF-8 on mice corneal epithelium was conducted using the Draize corneal toxicity test. The effects of ZIF-8 on fungal growth, biofilm formation, and hyphae structure were detected by Minimal inhibit concentration (MIC), crystal violet staining, Propidium Iodide (PI) testing, and calcofluor white staining. The anti-inflammatory effects of ZIF-8 on RAW 246.7 cells were evaluated by Quantitative Real-Time PCR Experiments (qPCR) and Enzyme-linked immunosorbent assay (ELISA). Clinical score, Colony-Forming Units (CFU), Hematoxylin-eosin (HE) staining, and immunofluorescence were conducted to verify the therapeutic effect of ZIF-8 on C57BL/6 female mice with fungal keratitis.Results: In vitro, ZIF-8 showed outstanding antifungal effects, including inhibiting the growth of Aspergillus fumigatus over 90% at 64 μg/mL, restraining the formation of biofilm, and destroying cell membranes. In vivo, treatment with ZIF-8 reduced corneal fungal load and mitigated neutrophil infiltration in fungal keratitis, which effectively reduced the severity of keratitis in mice and alleviated the infiltration of inflammatory factors in the mouse cornea. In addition, ZIF-8 reduces the inflammatory response by downregulating the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β after Aspergillus fumigatus infection in vivo and in vitro.Conclusion: ZIF-8 has a significant anti-inflammatory and antifungal effect, which provides a new solution for the treatment of fungal keratitis.Keywords: fungal keratitis, MOFs, antifungal, anti-inflammatory, ZIF-8

Letao Zhu,1 Yanfeng Li,1 Qingshi Zhao,1 Changyu Li,1 Zongbi Wu,2 Youli Jiang1 1Department of Neurology, People’s Hospital of Longhua, Shenzhen, 518109, People’s Republic of China; 2Nursing Department, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical School of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518033, People’s Republic of ChinaCorrespondence: Youli Jiang, Department of Neurology, People’s Hospital of Longhua, No. 38, Jinglong Jianshe Road, Longhua District, Shenzhen, Tel +8618545403739, Fax +86 27741585-8500, Email h2362120381@163.com Zongbi Wu, Nursing Department, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical School of Guangzhou University of Chinese Medicine, No. 1, Fuhua Road, Futian District, Shenzhen, People’s Republic of China, Tel +8615384435576, Fax +86 0755-88359899, Email wuzongbi2016@126.comBackground: Acute ischemic stroke (AIS) is increasingly affecting younger populations, necessitating prompt thrombolytic therapy within a narrow therapeutic window. Pre-hospital delays are prevalent, particularly in China, yet targeted research on the youth population remains scarce.Methods: In this retrospective cohort study, data from AIS patients aged 18– 50 admitted to Longhua District People’s Hospital, Shenzhen from December 2021 to December 2023 were analyzed using XGBoost and Random Forest machine learning algorithms, coupled with SHAP visualization, to identify factors contributing to pre-hospital delays.Results: Among 1954 AIS patients, 528 young patients were analyzed. The median time to hospital arrival was 8.34 hours, with 82.0% experiencing delays. Analysis of different age subgroups showed that young patients aged 36– 50 years old had a higher delay rate than patients under 36 years old. Machine learning algorithms identified stroke awareness, age, TOAST classification, ambulance arrival, dysarthria, mRS on admission, dizziness, wake-up stroke, etc. as important determinants of delay.Conclusion: This study highlights the necessity of machine learning in identifying delay risk factors in young stroke patients. Enhanced public education, particularly regarding stroke symptoms and the use of emergency services, is crucial for reducing pre-hospital delays and improving patient outcomes.Keywords: acute ischemic stroke, onset-to-door time, young adults, machine learning, emergency medical services

Changqin Li, Li Zeng, Meiling Jiang Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Li Zeng, Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China, Tel +86-18980607090, Email zengli998@163.comBackground and Objective: Concealed penis (CP) is a condition involving a congenital abnormality of the external genitalia, wherein the penile shaft is partially or completely obscured by surrounding skin tissues, negatively affecting the psychological and physical health of children. The guardians, who are primarily responsible for the daily care of children, play a crucial role in the early detection of this condition. Therefore, this study aims to explore knowledge, attitude, and practices (KAP) toward CP among guardians of young boys; results would provide a theoretical basis for the development of health education programs.Methods: This web-based cross-sectional study was conducted among guardians of boys in the Department of Pediatric Surgery, local hospital between June 2023 and September 2023. A self-designed questionnaire was developed to collect demographic information of the guardians and to assess their knowledge, attitudes and practices toward CP.Results: A total of 394 questionnaires were collected. Among the guardians, 143 (36.29%) of them were male, 375 (95.18%) were the parents of the children, 279 (70.81%) had a junior college or bachelor’s degree, and 46 (11.68%) reported their children had CP. The knowledge, attitudes and practices scores were 4.00± 2.00 (possible range: 0– 7), 35.63± 3.40 (possible range: 9– 45), and 23.03± 6.97 (possible range: 9– 45), respectively. The structural equation model demonstrated that knowledge had direct effects on attitudes (β=0.63, p< 0.001), and practices (β=0.81, p< 0.001). Moreover, attitudes had direct effects on practices (β=0.43, p< 0.001).Conclusion: This study found insufficient knowledge, positive attitudes, but poor practices toward the CP in guardians of boys, especially among participants from rural areas of families with lower income. It is recommended to tailor educational initiatives and implement strategies to bridge the knowledge-practice gap toward concealed penis in boys.Keywords: knowledge. attitudes, practices, concealed penis, cross-sectional study

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

Changqing Li,1 Sha Qu,2 Kai Ren3 1College of Physical Education and Health Science, Chongqing Normal University, Chongqing, 401331, People’s Republic of China; 2College of Sport Science, Beijing Sport University, Beijing, 100084, People’s Republic of China; 3College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua, 321004, People’s Republic of ChinaCorrespondence: Kai Ren, Email Renkai2016@zjnu.edu.cnPurpose: Physical activity has been found to be negatively correlated with academic procrastination. However, the potential mediating variables in this relationship are not well understood. This study aimed to explore the mediating effects of self-esteem and depression in the relationship between physical activity and academic procrastination among Chinese undergraduate students.Patients and Methods: A total of 1233 Chinese undergraduate students participated in the study. The unidimensionality of the self-esteem, depression, and academic procrastination was examined using Confirmatory Factor Analysis (CFA). Serial mediation analysis was conducted using SPSS 25.0 macro-PROCESS 3.3 to examine whether self-esteem and depression jointly mediated the relationship between physical activity and academic procrastination.Results: Self-esteem, depression, and academic procrastination displayed a good-fit to the one-factor model. The results indicated that physical activity indirectly impact academic procrastination through three pathways: (1) self-esteem (β=− 0.011, Boots 95% CI [− 0.021, − 0.001]), which accounted for of 12.09% of the total effect, (2) depression (β=− 0.022, Boots 95% CI [− 0.036, − 0.009]), which accounted for 24.18% of the total effect, and (3) self-esteem and depression (β=− 0.006, Boots 95% CI [− 0.011, − 0.002]), which accounted for 6.59% of the total effect. The total mediating effect was 42.86%.Conclusion: These findings suggest that self-esteem and depression playing a mediating role in the relationship between physical activity and academic procrastination, respectively. Moreover, self-esteem and depression co-mediate this relationship through a serial pathway.Plain Language Summary: This study explores the connection between physical activity and the tendency of undergraduate students in China to delay their academic tasks. Researchers were particularly interested in how feelings of self-worth (self-esteem) and mood (depression) might influence this relationship. We found that students who are more active physically tend to procrastinate less on their study. This effect is partly because physical activity boosts their self-esteem and reduces feelings of depression. Both these factors, individually and together, help explain why active students are more likely to tackle their academic tasks promptly. Basically, being physically active not only helps students feel better about themselves and less depressed but also encourages them to be more diligent with their studies.Keywords: physical activity, self-esteem, depression, academic procrastination

Yunxia Zhu,1 Deng Zhang,1 Liang Wu,1 Xiaoliang Ouyang,2 Shengcai Zhu,1 Xiuping Wang,1 Zhen Xiao,3 Yanping Tan,4 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Plastic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Dermatology, Taiyuan Central Hospital, Taiyuan, Shanxi, People’s Republic of China; 4Department of Dermatology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Chunming Li, Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Tel/Fax +86 79186278821, Email chunminglincu@163.comPurpose: Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant inherited pigmentary dermatosis. The gene responsible for DSH has been identified as adenosine deaminase acting on RNA1 (ADAR1). This study aimed to identify the causative variants in the ADAR1 gene in three Chinese families with DSH.Patients and Methods: Data and blood samples were collected from three Chinese families with DSH. Whole-exome and Sanger sequencing were performed to detect pathogenic gene mutation in the patients. Bioinformatics tools were used to predict the pathogenicity of the variants.Results: Four heterozygous ADAR1 variants were identified, including two novel missense variants c.2369G>C (Arg790Pro), and 503C>T (Pro168Leu), and two previously reported variants: c.3232C>T(R1078C), and c.1472C>G (p.S491X). The novel c.503C>T variant was predicted as “deleterious” (score =− 2.704) by PROVEAN, and “probably damaging” (score = 1) by PolyPhen2. The other novel variant c.2369G>C was also predicted as “deleterious” (score =− 4.167) by PROVEAN, “probably damaging” (score = 1) by PolyPhen2, and “disease-causing” (p = 0.999) by Mutation Taster.Conclusion: Two novel ADAR1 variants were found in Chinese patients with DSH. This research has expanded the ADAR1 gene database for DSH, enhancing our comprehension of the underlying mechanisms.Keywords: dyschromatosis symmetrica hereditaria, adenosine deaminase acting on RNA1, mutation analysis, Chinese

Yuxuan Yao,1– 3 Hong Zhao,4 Hua Lu,5 Xiaoli Liu,6 Hui Liu,7 Zhanli Fu,8 Chunyue Li,1 Fude Zhou,1– 3 Wanyin Hou,1– 3 Sufang Shi1– 3 1Department of Nephrology, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, People’s Republic of China; 2Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People’s Republic of China; 3Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, People’s Republic of China; 5Department of Nephrology, Xingtai People’s Hospital, Xingtai, Hebei, People’s Republic of China; 6Department of Pathology, Xingtai People’s Hospital, Xingtai, Hebei, People’s Republic of China; 7Department of Pathology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 8Department of Nuclear Medicine, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Wanyin Hou; Hong Zhao, Peking University First Hospital, Xicheng District, Beijing, People’s Republic of China, Tel +86 10-83575685, Email helenwanyin@bjmu.edu.cn; zhaohong_pufh@bjmu.edu.cnAbstract: Q fever, an infectious zoonotic disease caused by Coxiella burnetii, remains prevalent in China. Systemic infections can result in renal or hepatic complications; however, it is rare for both the kidneys and liver to be simultaneously affected. We present a case of a patient who exhibited fever, rapid deterioration in renal function, thrombocytopenia, and severe ascites. Renal biopsy revealed crescentic glomerulonephritis, while liver biopsy demonstrated non-cirrhotic portal hypertension. Metagenomic next-generation sequencing (mNGS) identified the presence of Coxiella burnetii in both venous blood and liver tissue samples. Notably, the patient’s renal insufficiency and ascites showed a positive response to treatment for chronic Q fever. These findings provide valuable insights into the limited understanding of kidney and liver diseases associated with Q fever. Advanced diagnostic technologies, including mNGS and positron emission tomography/computed tomography (PET/CT), have been employed to identify Coxiella burnetii infection.Keywords: Coxiella burnetii, acute kidney injury, non-cirrhotic portal hypertension, biopsies

Xiaojing Wang, Qinli Guo, Zhaoxiang Liu, Yanlei Wang, Chenxiang Cao, Lixia Jin, Caihong Li, Jianzhong Xiao, Wenhui Zhao Department of Endocrinology, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, People’s Republic of ChinaCorrespondence: Wenhui Zhao, Department of Endocrinology, Beijing Tsinghua Changgung Hospital, LiTang Lu No. 168, Chang Ping District, Beijing, 102218, People’s Republic of China, Tel +86-13810719795, Email zwha01637@btch.edu.cnPurpose: Obesity has become a major public health concern worldwide, increasing the risk of T2DM. Growing evidence indicates gut microbiota dysbiosis is related to metabolic disorders. We aimed to firstly investigate the compositional and functional features of the gut microbiome between obesity with and without T2DM in the Chinese population.Methods: A total of 32 obese individuals accompanied with T2DM and 18 age and gender-matched obesity with normal glucose tolerance (NGT) were enrolled. Fecal samples were collected, and the gut microbiota profile was determined using the Illumina MiSeq platform based on V3-V4 bacterial 16S rRNA gene.Results: Compared with obesity- NGT, obesity-T2DM showed a significantly higher alpha diversity. Principal coordinates analysis based on both Bray-Curtis distance and weighted Unifrac revealed that the global microbial composition was significantly different between the two groups (P = 0.007 and P = 0.005, respectively). At the phylum level, Obesity-T2DM patients exhibited a significant decrease in Bacteroidetes, and a pronounced increase in Firmicutes. Regarding the genus level, Bacteroides and Escherichia-Shigella were found to increase considerably, while Prevotella_9 and Sutterella had an evident decrease in Obesity-T2DM. Furthermore, Spearman correlation analysis revealed that Prevotella_9 and Sutterella were negatively associated with HbA1c and fasting blood glucose.Conclusion: We found clear differences in the gut microbiota composition in obesity-T2DM compared with obesity-NGT. Obesity accompanied with T2DM may aggravate the obesity-associated gut microbiota, and gut microbiota is expected to be a promising novel intervention target for obese management. However, larger sample size and more in-depth taxonomic identification studies are warranted.Keywords: gut microbiota, obesity, type 2 diabetes

Chenhao Suo,1,&ast; Yiru Gao,2,&ast; Sheng Yang,2 Wanli Zhang,2 Chao Li,3 Lanjing Ma,2 Yingchun Xu,4,5 Jianjun Lei,1 Chen Ding,2 Hailong Li,6 He Zhang,1 Tianshu Sun4,7 1Laboratory Animal Department, Northern Theater General Hospital, Shenyang, Liaoning, 110000, People’s Republic of China; 2College of Life and Health Science, Northeastern University, Shenyang, Liaoning, 110000, People’s Republic of China; 3Department of Emergency Medicine, the Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China; 4Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, 100730, People’s Republic of China; 5Medical Research Centre, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, 100730, People’s Republic of China; 6Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; 7Clinical Biobank, Medical Research Center, National Science and Technology Key Infrastructure on Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianshu Sun; He Zhang, Email sun_tianshu@163.com; alwayszhh@163.comIntroduction: The role of endocytosis in Candida albicans drug-resistance and pathogenicity remains poorly understood, despite its importance as a fundamental component of intracellular trafficking.Objective: In order to understand the role of endocytosis in Candida albicans cell wall integrity, drug resistance, and virulence.Methods: Detection of intracellular endocytosis by FM4-64 staining; Scanning electron microscopy is used to detect cell wall components; Spot assay for detecting drug sensitivity; Co-ip is used to detect protein interactions.Results: In this study, we found the functions of Sla1 in regulating endocytosis is conserved among pathogenic fungi. Our results also revealed that the deletion of the SLA1 gene altered cell wall properties, composition, and gene expression. In addition, we showed that C. albicans Sla1 was responsible for hyphal development in vitro and for fungal pathogenicity in a murine infection model. Intriguingly, sla1∆/∆ mutant demonstrated enhanced drug resistance, and Sla1 was found to interact with the transcription factor Efg1; the relationship between Sla1 and Efg1 impacts the expression of genes encoding components of the ergosterol biosynthesis pathway, including ERG1, EGR11, and ERG25.Discussion: These findings have expanded our knowledge of the capabilities of Sla1 beyond its role as an endocytosis adapter and provided insights into a potential new therapeutic target for the treatment of fungal infections.Keywords: endocytosis, Sla1, cell wall integrity, drug susceptibility, fungal pathogenicity

Renjiao Liu,1 Zhouhuiling Li,2 Yanju Zhang,2 Meiyang Du,2 Xincheng Wang,3 Shi Zhang,3 Chunjun Li1,3 1Graduate School, Tianjin Medical University, Tianjin, People’s Republic of China; 2Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Chunjun Li, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, No. 190 of Jieyuan Road, Hongqiao District, Tianjin, 300121, People’s Republic of China, Tel +86-22-13752090635, Email li_chunjun@126.comBackground: Insulin resistance (IR) is a key feature of type 2 diabetes (T2D) and an independent risk factor for metabolic syndrome. Previous studies have linked elevated serum uric acid (SUA) to an increased risk of T2D.Aim: The purpose of this study was to investigate the relationship between SUA and IR. At the same time, the correlation between New model and SUA compared with other IR alternatives was compared, so as to provide a simple and effective new indicator for early detection and prediction of IR risk and early prevention of T2D.Methods: The first cohort was the Discovery Cohort, which included 318 obese patients. And the second cohort was the Verification Cohort, which included a total of 4333 subjects who underwent a routine health checkup at our hospital. Spearman correlation analysis and binary logistic regression analysis were used to discuss the correlation between SUA and IR.Results: Regardless of sex, fasting insulin (FINS) and IR replacement markers increased with SUA (P< 0.001). In both cohorts, SUA was associated with IR alternatives, especially with New model, and differed between men and women in all correlation analyses. After adjusting for confounding factors, SUA was still associated with IR (P< 0.001).Conclusion: The correlation between SUA and IR was significantly stronger in women than in men. And the correlation between SUA and New model is stronger than other IR replacement models. However, the causal relationship between SUA and IR has not been clearly established.Keywords: insulin resistance, serum uric acid, HDL-c, triglycerides

Xinyang Nie,1– 3,&ast; Jian Liu,1,2,&ast; Daohan Wang,1,2,&ast; Chuan Li,1,2 Yuxin Teng,1,2 Zhufeng Li,1,2 Yangpu Jia,1,2 Peiyao Wang,1,2 Jingyu Deng,2,3 Weidong Li,1,2 Li Lu1,2 1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Lu; Weidong Li, Department of General surgery, Tianjin Medical University General Hospital, 154, Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China, Email luli_1989@126.com; tjmughgs_lwd@163.comBackground: Cisplatin (DDP) resistance in gastric cancer (GC) is likely to come from gastric cancer stem cells (GCSC). It is a new idea to study the mechanism of the DDP-resistance in GCSC from miRNA.Materials and Methods: CD44+ GCSCs and CD44- control cells were constructed based on the HGC27 gastric cancer cell line. DDP sensitivities in CD44+ and CD44- cells were detected via CCK-8 assay. The differential expression of miR-21-5p in these cell lines was detected by RT‒qPCR. The expression levels of downstream TGF-β 2, SMAD2 and SMAD3 were determined through RT‒PCR and Western blotting. A luciferase assay was used to detect the relationship between miR-21-5p and TGFB2, and the TCGA database, clinical data from our centre, and vivo experiment were used for validation. Finally, we knocked down miR-21-5p to detect changes in cisplatin resistance in GCSCs and to verify changes in the levels of downstream pathways in GCSCs.Results: CD44+ GCSCs induced cisplatin resistance compared with CD44- cells. miR-21-5p was highly expressed in GCSCs, and the TGF-β 2/SMAD pathway was also highly expressed. TGFB2 was proven to be a downstream target gene of miR-21-5p and had a positive relationship with it in phenotype. After knockdown of miR-21-5p, the TGF-β 2/SMAD pathway was also inhibited, and the resistance of GCSCs to cisplatin was specifically decreased.Conclusion: MiR-21-5p promotes cisplatin resistance in gastric cancer stem cells by regulating the TGF-β 2/SMAD signalling pathway.Keywords: miR-21-5p, cisplatin resistance, GCSCs, TGF-β 2 pathway

Ting Liu,1,* Chao Lei,1,* Qinhong Huang,2,* Weiqi Song,3 Chen Li,1 Ning Sun,4,5 Zhihua Liu6 1Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510799, People’s Republic of China; 2The First Clinical College, Guangzhou Medical University, Guangzhou, 511400, People’s Republic of China; 3Department of Public Health, Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Guangzhou 11th People’s Hospital, Guangzhou Cadre and Talent Health Management Center, Guangzhou, 510530, People’s Republic of China; 5The State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, the Hong Kong Polytechnic University, 999077, Hong Kong, China; 6Department of Anorectal Surgery, the Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Dongguan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhihua Liu; Ning Sun, Email liuzhihua83@hotmail.com; ning.sun@connect.polyu.hkIntroduction: Obesity, which is associated with gut microbiota dysbiosis, low-grade chronic inflammation and intestinal barrier dysfunction, can cause a variety of chronic metabolic diseases. Phytochemical flavonoids have a variety of biological activities, among which there may be safe and effective anti-obesity solutions.Methods: We tested a plant-derived flavonoid hesperidin and fecal microbiota transplantation (FMT) to alleviate diet-induced obesity. High-fat diet (HFD)-fed mice were treated with hesperidin (100 and 200 mg/kg BW) and FMT.Results: Results indicated that hesperidin had the effects of reducing obesity as indicated by reduction of body weight, fat accumulation and blood lipids, reducing inflammation as indicated by reduction of pro-inflammation factors including TNFα, IL-6, IL-1βand iNOS, and improving gut integrity as indicated by increasing colon length, reducing plasma gut permeability indicators iFABP and LBP, increased mRNA expression of mucus protein Muc2, tight junction p Claudin 2, Occludin and ZO-1 in the HFD-fed mice. The anti-obesity effects of hesperidin treatment have a dose-dependent manner. In addition, 16S rRNA-based gut microbiota analysis revealed that hesperidin selectively promoted the growth of Lactobacillus salivarius, Staphylococcus sciuri and Desulfovibrio C21_c20 while inhibiting Bifidobacterium pseudolongum, Mucispirillum schaedleri, Helicobacter ganmani and Helicobacter hepaticus in the HFD-fed mice. Horizontal feces transfer from the normal diet (ND)-fed mice to the HFD-fed mice conferred anti-obesity effects and transmitted some of the HFD-modulated microbes.Conclusion: We concluded that hesperidin and FMT both affect the reduction of body weight and improve HFD-related disorders in the HFD-fed mice possibly through modulating the composition of the gut microbiota.Keywords: hesperidin, high-fat diet, obesity, gut microbiota, fecal microbiota transplantation

Chan Li,1,2,&ast; Chen Zhu,3,&ast; Genghong Tu,4,&ast; Zhijie Chen,1 Zhixian Mo,1,5 Chaohua Luo1,5 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 2School of Life Sciences, Guangzhou University, Guangzhou, People’s Republic of China; 3The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 4Department of Sports Medicine, Guangzhou Sport University, Guangzhou, Guangdong, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhixian Mo, Mo; Chaohua, Luo, School of Traditional Chinese Medicine, Southern Medical University, 1023-1063 Shatai South Road, Guangzhou, 510515, People’s Republic of China, Tel +020-61648261 ; +020-61648244, Email cherrymo@fimmu.com; 120557369@qq.comObjects: Ketamine is a drug of abuse worldwide and current treatments for ketamine abuse are inadequate. It is an urgent need to develop novel anti-addictive strategy. Since gut microbiota plays a crucial role in drug abuse, the present study investigates the impact and mechanisms of the gut microbiota in addictive behaviors induced by ketamine addiction.Methods: Conditioned place preference (CPP) was employed to assess addiction, followed by 16S rRNA gene sequencing to elucidate alterations in the gut microbiota. Furthermore, qRT-PCR, ELISA, and immunohistochemistry were conducted to evaluate the expression levels of crucial genes and proteins associated with the gut-brain axis. Additionally, we investigated whether ketamine addiction is regulated through the gut microbiota by orally administering antibiotics to establish pseudo-germ-free mice.Results: We found that repeated ketamine administration (20 mg/kg) induced CPP and significantly altered gut microbiota diversity and composition, as revealed by 16S rRNA gene sequencing. Compared to the control group, ketamine exposure exhibited differences in the relative abundance of 5 microbial families, with 4 (Lachnospiraceae, Ruminococcaceae, Desulfovibrionaceae and Family-XIII) showing increases, while one (Prevotellaceae) displayed a decrease. At the genus level, five genera were upregulated, while one was downregulated. Furthermore, COG analysis revealed significant differences in protein functionality between the two groups. Additionally, axis series studies showed that ketamine dependence reduced levels of tight junction proteins, GABA and GABRA1, while increasing BDNF and 5-HT. Moreover, an oral antibiotic cocktail simulating pseudo germ-free conditions in mice did not enhance the addictive behavior induced by ketamine.Conclusion: Our study supports the hypothesis that ketamine-induced CPP is mediated through the gut microbiota. The present study provides new insights into improvement of efficient strategy for addiction treatment.Keywords: ketamine abuse, BDNF, GABRA1, gut microbiota, gut-brain axis

Yang Xie, Xiangyang Sun, Fubo Xie, Wencheng Jian, Qingliang Wang, Xiaochen Ma, Caixia Li, Kai Zhang Department of Radiology, Qilu Hospital of Shandong University, Shandong, People’s Republic of ChinaCorrespondence: Kai Zhang, Department of Radiology, Qilu Hospital of Shandong University, Shandong, People’s Republic of China, Tel +8618560081593, Email fifa6107@126.comPurpose: To examine the relationship between lactate dehydrogenase (LDH) levels and soluble programmed cell death-ligand 1 (sPD-L1) levels in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE).Methods: A total of 83 hCC patients participated in this study. Patients were categorized into subgroups based on their alpha-fetoprotein (AFP) levels, presence or absence of extrahepatic metastasis, vascular invasion, Barcelona Clinic Liver Cancer (BCLC) stage, tumor response, tumor size, and number LDH and sPD-L1 levels were compared before and after TACE (3, 7, and 30 days post-TACE).Results: LDH and sPD-L1 levels were significantly higher at 3 and 7 days post-TACE than at baseline. Positive correlations were observed between changes in LDH levels and sPD-L1 levels at 3 and 7 days post-TACE. LDH levels were higher in patients with elevated AFP compared to those in the normal AFP group at 3 and 7 days post-TACE, in the stable disease (SD) group compared to complete response (CR) and partial response (PR) groups at 7 days post-TACE, and in those with tumor > 5 cm compared with those with tumor ≤ 5 cm at 3 and 7 days after TACE (all P < 0.05). sPD-L1 levels were higher in patients with vascular invasion than those without vascular invasion at 3 and 7 days post-TACE, in the SD group compared to CR and PR groups at 3 and 7 days post-TACE, and in those with tumor > 5 cm compared to those with tumor < 5 cm at 3 and 7 days after TACE (all P < 0.05).Conclusion: A positive correlation was found between LDH expression and sPD-L1 levels, suggesting LDH as a potential biomarker for assessing immune status in HCC patients following TACE.Keywords: hepatocellular carcinoma, immunotherapy, lactate dehydrogenase, soluble programmed cell death ligand-1, transarterial chemoembolization

Li Ding,1,&ast; Cong Li,1,&ast; Lu Chen,1 Pei-Yu Huang,1 Fei-Fei Bian2 1Emergency Ward, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, People’s Republic of China; 2Department of Surgical, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu, Chen; Pei-Yu Huang, Emergency Ward, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, No. 366 Taihu Road, Taizhou Pharmaceutical High-Tech District, Taizhou, Jiangsu, 225300, People’s Republic of China, Tel +86 13641589385 ; +86 18705267452, Email chenluchen29@126.com; huangpeiyuh@126.comObjective: The objective of this study is to systematically explore and summarize the best evidence on intervention programs for patients with kinesophobia following percutaneous coronary intervention (PCI) to provide a comprehensive reference for clinical practice interventions.Methods: Evidence on interventions for kinesophobia post-PCI was retrieved from Chinese and international integrated databases, treatment guidelines, and websites of professional associations, including systematic reviews and expert consensuses. The evidence considered in this study extends up to May 2022, encompassing information available since the inception of the databases. Two researchers independently evaluated the articles included in the review and extracted and summarized the available evidence.Results: By extracting and integrating data from the 14 articles included in this review, we identified six categories: pre-intervention assessment, psychological intervention, health education, rehabilitation training, social support, and quality control. A total of 21 pieces of evidence were summarized, including mental health assessment, physical fitness evaluation, timing and content of health education, development of personalized exercise prescriptions, and risk control.Conclusion: In clinical settings, using evidence-based practices requires developing feasible intervention programs based on comprehensive consideration of hospital resources, allocation of medical personnel, and consideration of patients’ preferences to reduce the kinesophobia of patients post-PCI and improve their compliance with exercise rehabilitation.Keywords: evidence-based nursing, evidence summary, intervention, kinesophobia, post-PCI

Qiaoting Huang,1 Changzheng Shi,2 Saurabh Sonkusare,3 Congrui Li,1 Valerie Voon,3 Jiyang Pan1 1Department of Psychiatry, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Department of Psychiatry, University of Cambridge, Cambridge, UKCorrespondence: Jiyang Pan, Department of Psychiatry, The First Affiliated Hospital of Jinan University, 613 West Huangpu Avenue, Guangzhou, 510630, People’s Republic of China, Tel +86 20 38688651, Email jiypan@163.com Valerie Voon, Department of Psychiatry, University of Cambridge, Box 189, Level E4, Addenbrooke’s Hospital, Cambridge, CB2 0QQ, UK, Tel +44 1223 765088, Email vv247@cam.ac.ukPurpose: Converging evidence implicates the putamen in sleep-wake regulation. However, its role remains unclear. We hypothesized that metabolic abnormalities in the putamen are linked to insomnia disorder, which has not been previously addressed, and investigated putaminal N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) in patients with insomnia disorder compared to healthy controls.Participants and Methods: In the present study, the concentrations of NAA, Cho, and Cr in the putamen of 23 patients with insomnia disorder and 18 healthy controls were determined using proton magnetic resonance spectroscopy. Sociodemographic, psychometric, and polysomnography data were obtained from all participants.Results: We found that the mean NAA/Cr ratio of the right putamen was significantly greater in the insomnia group compared to the control group and also greater than the left putamen within the insomnia group. The NAA/Cr ratio of the right putamen distinguished insomnia disorder from normal sleep with 78.3% sensitivity and 61.1% specificity. Furthermore, this ratio positively correlated with both objective and subjective insomnia severity and sleep quality.Conclusion: Our findings provide critical evidence for the dysfunctional putaminal metabolism of NAA/Cr in insomnia disorder, suggesting that the abnormal NAA/Cr ratio of the right putamen is linked to wakefulness in patients with insomnia disorder and may serve as a potential biomarker of insomnia disorder.Keywords: insomnia disorder, wakefulness, putamen, proton magnetic resonance spectroscopy, NAA/Cr ratio, polysomnography

Xiang Huo,1 Zhongming Tan,1,2 Huimin Qian,1,2 Yuanfang Qin,1,2 Chen Dong,1,2 Chuchu Li,1,2 Xiaoxiao Kong,1,2 Jie Hong1,2 1National Health Commission (NHC) Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 2Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of ChinaCorrespondence: Jie Hong, Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, 172 Jiangsu Road, Gulou Distrct, Nanjing, People’s Republic of China, Email hongjie@jscdc.cnBackground: Streptococcus pneumoniae is a significant etiological agent of infection and commonly inhabits the human nasopharynx, alongside other potentially pathogenic bacteria. In this study, S. pneumoniae strains were obtained from a community population and subjected to investigation of their phenotypes, genotypes, and vaccine coverage.Methods: S. pneumoniae was isolated from nasopharyngeal swab samples of a healthy population in the Guangfu Community. Capsular serotypes and genotypes were identified using Quellung reaction and multilocus sequence typing (MLST), respectively. The antimicrobial susceptibility was tested using minimum inhibitory concentrations.Results: In total, 500 unvaccinated people were sampled. Ninety-four S. pneumoniae strains were identified. Common serotypes were 19F, 6A, and 9V. The strain coverages of PCV13 and PPV23 were 61.7% and 58.5%, respectively. About 27.6% isolates were non-susceptible to penicillin, and over 80% were resistant to erythromycin and doxycycline. Among 27 novel sequence types (STs) identified in all strains, the most common STs were ST236 (6/94, 6.4%) and ST12669 (6/94, 6.4%). Nearly half of the strains were grouped into four clone complexes (CC12665, CC271, CC6011, and CC180), of which CC271 showed the highest resistance to PEN.Conclusion: In our study, various drug-resistant clone complexes of Streptococcus pneumoniae were found in the healthy population, the elderly, and children. Consequently, pneumococcal vaccines should be included in the national immunization schedule to prevent disease spread.Keywords: vaccine, Streptococcus pneumonia, serotype, antibiotics, STs

Wenyu Zhang,1,&ast; Linquan Li,1,&ast; Yaguang Wu,1 Chengzhilin Li,1 Zi’ang Xu,1 Nianlei Zhang,1 Xinyu Wang,1 Yingchun Zhao,1 Tingjian Zu,1 Qingbin He,1 Jianwei Jiao,2 Runxiao Zheng1 1School of Clinical and Basic Medical Sciences, Medical Science and Technology Innovation Center, Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, People’s Republic of China; 2State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Runxiao Zheng, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, People’s Republic of China, Email zhengrunxiao@sdfmu.edu.cn Jianwei Jiao, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China, Email jwjiao@ioz.ac.cnIntroduction: Immunotherapy has led to a paradigm shift in reinvigorating treatment of cancer. Nevertheless, tumor associated macrophages (TAMs) experience functional polarization on account of the generation of suppressive metabolites, contributing to impaired antitumor immune responses.Methods: Hence, metabolic reprogramming of tumor microenvironment (TME) can synergistically improve the efficacy of anti-tumor immunotherapy. Herein, we engineered an iron-based nanoplatform termed ERFe3O4 NPs. This platform features hollow Fe3O4 nanoparticles loaded with the natural product emodin, the outer layer is coated with red blood cell membrane (mRBCs) inserted with DSPE-PEG2000-galactose. This effectively modulates lactate production, thereby reversing the tumor immune suppressive microenvironment (TIME).Results: The ERFe3O4 NPs actively targeted TAMs on account of their ability to bind to M2-like TAMs with high expression of galectin (Mgl). ERFe3O4 NPs achieved efficient ability to reverse TIME via the production of reducing lactate and prompting enrichment iron of high concentrations. Furthermore, ERFe3O4 NPs resulted in heightened expression of CD16/32 and enhanced TNF-α release, indicating promotion of M1 TAMs polarization. In vitro and in vivo experiments revealed that ERFe3O4 NPs induced significant apoptosis of tumor cells and antitumor immune response.Discussion: This study combines Traditional Chinese Medicine (TCM) with nanomaterials to synergistically reprogram TAMs and reverse TIME, opening up new ideas for improving anti-tumor immunotherapy. Keywords: metabolic immunotherapy, nanoparticles, reprograming, iron oxide, macrophages

Liang Wu,1 Yunxia Zhu,1 Shengcai Zhu,1 Deng Zhang,1 Xiuping Wang,1 Zhen Xiao,2 Yanping Tan,3 Xiaoliang Ouyang,4 Chunming Li1 1Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Dermatology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, People’s Republic of China; 4Department of Plastic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Xiaoliang Ouyang, Department of Plastic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email ouliangncu@163.com Chunming Li, Department of Dermatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email chunminglincu@163.comBackground: Acne vulgaris (AV), a chronic inflammatory pilosebaceous disorder, affects 80– 90% of teenagers. This study aimed to discover lipid profiles and biomarkers of the rabbit ear acne model, and investigate the mechanism of isotretinoin in treating acne at the lipid level.Methods: Untargeted lipidomic analysis using ultra-high performance liquid chromatography system (UHPLC) coupled to q-extraction plus was performed to identify skin lipid metabolites in blank control (groups C), model group (group M) and isotretinoin group (group T). Multivariate statistical analysis was used to process the lipidomics data.Results: A total of 43 lipid classes comprising 6989 lipid species were identified from the mass spectrometry data. The orthogonal partial least squares discriminant analysis (OPLS-DA) model demonstrated significant separation in skin lipidomic profiles between group M and group C. With variable influence on projection (VIP) > 1.0 and P-value < 0.05, 299 significantly different lipid metabolites were identified. These lipid metabolites consisted mainly of ceramides (Cer) (53.85%), phosphatidylethanolamines (PE) (9.03%), phosphatidylcholines (PC)(5.35%), and sphingomyelin (SM)(4.01%). Combining with AUC ≥ 0.9 as the elected criteria, Cer (d18;1_24:0), zymosterol (ZyE)(33:5), Cer (t43:1), ZyE (33:6), ZyE (24:7), and ZyE (35:6) have “high” accuracy. Isotretinoin treatment normalized 25 lipid metabolites in the acne model.Conclusion: Our findings provide new insights into the role of lipid metabolism in the pathogenesis of acne and the action mechanism of isotretinoin.Keywords: acne vulgaris, lipidomics, isotretinoin, skin, animal model

Jingying Xu, Yuan Chen, Jianhua Yu, Shourong Liu, Ying Meng, Chaodan Li, Qian Huang, Yunlei Xiao Department of Infectious Diseases, Hangzhou Xixi Hospital, Hangzhou Sixth People’s Hospital, Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Qian Huang; Yunlei Xiao, Department of Infectious Diseases, Hangzhou Xixi Hospital, Hangzhou Sixth People’s Hospital, Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, No. 2, Hengbu Street, Liu Xia Town, Xihu District, Hangzhou, 310023, Zhejiang, People’s Republic of China, Tel +8613575746522 ; +8615258639960, Email tcm99hq@163.com; 15258639960@163.comPurpose: Developing countries, invasive Salmonella infections can cause considerable morbidity and mortality. There is a relative lack of data on coinfection with Salmonella in HIV-infected patients in Hangzhou, China.Patients and Methods: In this study, we manually collected case data of patients aged > 18 years with HIV combined with invasive Salmonella infections admitted to Xixi Hospital in Hangzhou from January 2012 to August 2023 by logging into the Hospital Information System, and identified 26 strains of invasive Salmonella using a fully automated microbiological identification system and mass spectrometer. Serotypes were determined using Salmonella diagnostic sera based on the White-Kauffmann-Le Minor scheme. Drug sensitivity tests were performed using the automated instrumental method of the MIC method.Results: A total of 26 HIV-infected patients with invasive Salmonella coinfections were identified over 11 years; Twenty-five of the 26 patients (96.2%) were males, with a mean age of 33.5 years (26.75, 46.75). The most common type of infection was bloodstream infection (92.3%). One patient also had concomitant meningitis and osteoarthritis, followed by pneumonia (7.7%). The presence of multiple bacterial infections or even multiple opportunistic pathogens was clearly established in 7 (26.9%) patients. Three (11.6%) patients were automatically discharged from the hospital with deterioration of their condition, and one (3.8%) patient died. Salmonella enteritidis was the most common serotype in 6 patients (23.2%), and Salmonella Dublin was the most common serotype in 6 patients (23.2%). Drug sensitivity results revealed multidrug resistance in a total of 8 (30.8%) patients.Conclusion: The clinical presentation of invasive Salmonella infection in HIV patients is nonspecific and easily masked by other mixed infections. A CD4+ count < 100 cells/μL and comorbid intestinal lesions may be important susceptibility factors. Salmonella has a high rate of resistance to common antibiotics, and the risk of multidrug resistance should not be ignored.Keywords: Salmonella, invasiveness, HIV, serotype, antibiotic resistance

Hanzhi Chen,1,&ast; Leting Zhou,1,&ast; Meilin Yan,1,&ast; Cheng Li,1 Bin Liu,1 Xiaobin Liu,1 Weiwei Shan,1 Ya Guo,2 Zhijian Zhang,1 Liang Wang1 1Department of Nephrology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214000, People’s Republic of China; 2Key Laboratory of Advanced Process Control for Light Industry (Ministry of Education), Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Zhang, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214000, People’s Republic of China, Email zzjwxyy@163.com Liang Wang, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214000, People’s Republic of China, Email wangliang_wuxi@126.comBackground: End-stage kidney disease (ESKD) patients often face complications like anemia, malnutrition, and cardiovascular issues. Serological tests, which are uncomfortable and not frequently conducted, assist in medical assessments. A non-invasive, convenient method for determining these test results would be beneficial for monitoring patient health.Objective: This study develops machine learning models to estimate key serological test results using non-invasive cellular bioelectrical impedance measurements, a routine procedure for ESKD patients.Methods: The study employs two machine learning models, Support Vector Machine (SVM) and Random Forest (RF), to determine key serological tests by classifying cell bioelectrical indicators. Data from 688 patients, comprising 3,872 biochemical–bioelectrical records, were used for model validation.Results: Both SVM and RF models effectively categorized key serological results (albumin, phosphorus, parathyroid hormone) into low, normal, and high. RF generally outperformed SVM, except in classifying calcium levels in women.Conclusion: The machine learning models effectively classified serological test results for maintenance hemodialysis patients using cellular bioelectrical indicators, therefore can help in making judgments about physicochemical indicators using electrical signals, thereby reducing the frequency of serological tests.Keywords: serological test results, cellular bioelectrical indicators, machine learning, End-stage kidney disease

Caige Li,1,2 Yu Xue,1 Yiwei Liu,1 Kangning Zheng,1 Yuting Gao,1,3 Yi Gong,1 Junlan Lu,1 Yuman Zhang,1 Jingmin Ji,1 Zhiqin Zhang,1 Xinli Shi1 1Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3School of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, Shanxi, People’s Republic of ChinaCorrespondence: Xinli Shi, Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, 3 Xingyuan Road, Shijiazhuang, Hebei, 050200, People’s Republic of China, Tel +86-0311-89926237, Email sxlsunshine@sina.comIntroduction: Yes-associated protein 1 (YAP1) is a crucial molecule in the Hippo pathway. The impact of hepatocyte-specific Yap1 knockout (Yap1LKO) on hepatic lipid droplets (LD) and pePLIN2 in metabolic fatty liver has not been reported. This study aims to explore whether Yap1LKO could offer a protective effect in a liver injury model.Methods: Three-week-old Yap1LKO and Yap1Flox mice were given aristolochic acid I (AAI) combined carbon tetrachloride (CCL4) establish liver injury model. Eight-week-old Yap1LKO and Yap1Flox mice were fed with a high-fat diet for 18 weeks to establish obesity-related liver injury model. Further biochemical, histomorphological, immunohistochemical, and lipidomic analyses were performed on serum and liver tissues of these mice to elucidate the effects of hepatocyte-specific Yap1 knockout on hepatic lipid metabolism.Results: Yap1LKO reduced triglyceride (TG) content and PLIN2 expression level in the liver during the intervention of AAI combined CCl4. Moreover, Yap1LKO improved lipid metabolism homeostasis in the liver by increasing the beneficial lipid molecules and reducing the harmful lipid molecules through lipidomics. Finally, Yap1LKO reduced TG content in the serum and liver, hepatic vacuolar degeneration, and hepatic PLIN2 expression level in mice fed with a high-fat diet (HFD).Conclusion: Yap1LKO is protective in regulating liver and blood TG when induced with toxic substances AAI combined CCl4 and a high-fat diet.Keywords: yes-associated protein, hepatocyte-specific Yap1 knockout, perilipin-2, lipidomic, triglyceride

Lijuan Liang,1,&ast; Ming Jia,2,3,&ast; Min Zhao,4,&ast; Yiping Deng,5,&ast; Jun Tang,5 Xinghui He,2 Yilin Liu,2 Kexin Yan,2 Xin Yu,6 Hong Yang,7 Chunhong Li,2 Yao Li,2,8 Tao Li4 1Department of Pharmacy, Hejiang County People’s Hospital, Luzhou, Sichuan, People’s Republic of China; 2Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Nanchong Institute for Food and Drug Control, Nanchong, Sichuan, People’s Republic of China; 4Key Laboratory of Medical Electrophysiology of Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Analysis and Testing Center, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 6Chinese Pharmacy Laboratory, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 7Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 8Science and Technology department, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yao Li; Tao Li, Email lnetyao@163.com; leta49@swmu.edu.cnAbstract: As a pivotal transition metal oxide, manganese dioxide (MnO2) has garnered significant attention owing to its abundant reserves, diverse crystal structures and exceptional performance. Nanosizing MnO2 results in smaller particle sizes, larger specific surface areas, optimized material characteristics, and expanded application possibilities. With the burgeoning research efforts in this field, MnO2 has emerged as a promising nanomaterial for tumor diagnosis and therapy. The distinctive properties of MnO2 in regulating the tumor microenvironment (TME) have attracted considerable interest, leading to a rapid growth in research on MnO2-based nanomaterials for tumor diagnosis and treatment. Additionally, MnO2 nanomaterials are also gradually showing up in the regulation of chronic inflammatory diseases. In this review, we mainly summarized the recent advancements in various MnO2 nanomaterials for tumor diagnosis and therapy. Furthermore, we discuss the current challenges and future directions in the development of MnO2 nanomaterials, while also envisaging their potential for clinical translation.Keywords: manganese dioxide nanoparticles, tumors, inflammation, biomedicine, research progress

Junyi Li,1,2,&ast; Zugui Wu,3,&ast; Bin Lu,2,&ast; Congcong Li,1 Shuai Wang,1 Jiahao Zhang,1 Xingxing Shen,1 Ruian Xiang,1 Jiahao Chen,1 Tao Jiang,1 Chuanxi Zhao,1 Wengang Liu,1 Xuemeng Xu1 1Department of Orthopedics and Traumatology, The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Osteoarthropathy II, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang, People’s Republic of China; 3Department of Orthopedics and Traumatology, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming Municipal Hospital of Traditional Chinese Medicine, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemeng Xu; Wengang Liu, Department of Orthopedics and Traumatology, The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, No. 60 Hengfu Road, Guangzhou, 510030, People’s Republic of China, Email xuxuemeng@163.com; 914194079@qq.comPurpose: Our study aims to evaluate differences in muscle parameters of the quadriceps muscles in patients with knee osteoarthritis (KOA) in older adults.Methods: The study included 40 patients diagnosed with unilateral knee osteoarthritis in the KOA group (KG) and 40 asymptomatic elderly individuals in the control group (CG). Muscle ultrasonic mean echo intensity and shear modulus, as well as tone and stiffness of the rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) were analyzed. Additionally, clinical correlations were performed.Results: In the KG group, there were significant differences in echo intensity, shear modulus, and tone between the affected and unaffected sides for RF (p=0.003, 0.019, 0.014), while VM showed significant differences in shear modulus and tone (p=0.006, 0.002). Additionally, VL exhibited significant differences in echo intensity, shear modulus, and stiffness (p=0.007, 0.006, 0.010). Compared to the CG group, the KG group showed significant differences in echo intensity of the affected side RF (p=0.001). VM exhibited statistically significant differences in echo intensity and shear modulus (p < 0.001, p=0.008), while VL showed statistically significant differences in echo intensity, tone, and stiffness (p < 0.001, p=0.028, p < 0.001). The correlation results showed that patients with unilateral KOA, VM, and VL echo intensity were correlated with K-L grade (r = 0.443, p=0.004; r = 0.469, p=0.002). The tone of VL was correlated with VAS and WOMAC (r = 0.327, p=0.039; r = 0.344, p=0.030).Conclusion: The parameters of the quadriceps femoris muscle exhibit asymmetry between the affected and unaffected sides in patients with unilateral KOA, as well as a difference between the dominant side of healthy older individuals and the affected side of KOA.Keywords: knee osteoarthritis, quadriceps femoris, ultrasound, muscle tone, stiffness

Chengran Wang,1,&ast; Yihong Zhang,1,&ast; Weihui Kong,2 Xin’ao Rong,1 Ziming Zhong,1 Lei Jiang,3 Shuhan Chen,1 Chuang Li,1 Fuqiang Zhang,1 Jinlan Jiang1 1Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Department of Stomatology, the First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 3Department of Geriatric Medicine, Changchun Central Hospital, Changchun, Jilin Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fuqiang Zhang; Jinlan Jiang, Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China, Email zfqzhang@jlu.edu.cn; jiangjinlan@jlu.edu.cnAbstract: Osteosarcoma is the predominant primary malignant bone tumor that poses a significant global health challenge. MicroRNAs (miRNAs) that regulate gene expression are associated with osteosarcoma pathogenesis. Thus, miRNAs are potential therapeutic targets for osteosarcoma. Nanoparticles, widely used for targeted drug delivery, facilitate miRNA-based osteosarcoma treatment. Numerous studies have focused on miRNA delivery using nanoparticles to inhibit the progress of osteosarcoma. Polymer-based, lipid-based, inorganic-based nanoparticles and extracellular vesicles were used to deliver miRNAs for the treatment of osteosarcoma. They can be modified to enhance drug loading and delivery capabilities. Also, miRNA delivery was combined with traditional therapies, for example chemotherapy, to treat osteosarcoma. Consequently, miRNA delivery offers promising therapeutic avenues for osteosarcoma, providing renewed hope for patients. This review emphasizes the studies utilizing nanoparticles for miRNA delivery in osteosarcoma treatment, then introduced and summarized the nanoparticles in detail. And it also discusses the prospects for clinical applications. Keywords: osteosarcoma, MicroRNAs, nanoparticle delivery, molecular targeted therapy

Liu Yang,1 Kaijie Gao,1 Weihua Gong,1 Ci Li,1 Nan Chen,1 Tiewei Li,1 Shan Wang,1 Jiajia Ni,2,3 Junmei Yang1 1Department of Clinical Laboratory, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Zhengzhou, Henan, People’s Republic of China; 2Research and Development Center, Guangdong Meilikang Bio-Science Ltd, Foshan, Guangdong People’s Republic of China; 3Department of Detection and Diagnosis Technology Research, Guangzhou National Laboratory, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Junmei Yang, Email yangjunmei7683@163.comPurpose: Although allergic diseases in children are on the rise, there has been no comprehensive investigation of the allergens affecting children with allergic diseases in central China. Therefore, we aimed to analyze the distribution of serum allergen species among children with allergic conditions in central China to inform the prevention, diagnosis, and treatment of childhood allergies.Patients and Methods: A total of 9213 children (5543 males with 2.88 ± 0.04 years old and 3670 females with 2.91 ± 0.05 years old) underwent allergen screening, and serum allergen-specific IgE (sIgE) antibodies were detected using an automated fluorescent enzyme immunoassay system.Results: Our findings revealed a total sIgE-positive rate (sIgE-PR) of 57.83%, with mixed food (42.10%), egg whites (30.83%), milk (28.97%), mixed dust mites (24.57%), and mixed molds (23.20%) being the most prevalent source of allergens. The sIgE-PR for common sources of allergens exhibited significant sex-based differences, with males having greater susceptibility than females (p< 0.05). Dust mites were the primary source of inhaled allergens, whereas egg white was the predominant source of food allergens. Sources of food allergens were most dominant among infants (0– 3 years old); sIgE-PRs for most source of food allergens decreased with age, whereas those for most source of inhaled allergens increased. The autumn sIgE-PRs for mixed molds, weed pollen combinations, and tree pollen combinations were significantly higher than those found in other seasons (p< 0.05).Conclusion: Our findings suggest that sources of allergens profiles in children with allergies vary across age groups and seasons. Understanding these patterns can improve the effective prevention of childhood allergies.Keywords: allergen, childhood allergies, IgE antibodies, source of food allergens, allergy prevention

Zhiyuan Wu,1,&ast; Lili Hou,2,&ast; Cheng Li,1,&ast; Xiaohua Li,2 Ying Li1 1Department of Radio-Oncology, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, People’s Republic of China; 2Department of Breast Surgery, Suzhou Wuzhong People’s Hospital, Suzhou, People’s Republic of China&ast;These authors contributed equally to this worksCorrespondence: Ying Li; Xiaohua Li, Email lisalee198812@163.com; xq810@163.comPurpose: Breast cancer is the leading cause of cancer mortality among women. Radiotherapy can reduce recurrence and prolong survival of patients accepting breast-conserving surgery (BCS). This study aims to compare acute skin reactions in patients receiving hypofractionated versus conventional radiotherapy at a single institution and to summarize the relevant influencing factors.Methods: This study analyzed 152 patients who underwent either hypofractionated or conventional whole-breast irradiation (WBI) after BCS. Acute skin toxicity was assessed according to the Radiation Therapy Oncology Group (RTOG) criteria. Predictive factors for acute skin toxicity were identified using multivariate analysis and visualized using a forest spot.Results: Grade 0 reactions occurred in 75.34% vs 70.89%, grade 1 in 16.44% vs 15.19%, grade 2 in 8.22% vs 12.66%, and grade 3 in 0% vs 1.27% of patients receiving hypofractionated and conventional WBI, respectively. There was no statistically significant difference in acute skin reaction in patients treated with hypofractionated radiation compared with conventional radiation (P = 0.62). Multivariate analysis revealed that metastatic lymph nodes (P = 0.021), whole-breast planning target volume (PTV-WB) (P

Fang Xu,&ast; Peng Shu,&ast; Chenchen Li, Shanshan Huo, Zhuping Wen&ast; Nephrology Department, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Xu; Peng Shu, Nephrology Department, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No.26 Shengli Street, Jiang’ an District, Wuhan, Hubei Province, People’s Republic of China, Tel +8615802716692, Email 453328433@qq.com; 312855784@qq.comObjective: This study aimed to assess the effectiveness of an electronic cannulation atlas in preventing and treating complications of arteriovenous fistula.Methods: The observation group, consisting of 92 dialysis patients from July to December 2021, was managed with an electronic cannulation atlas. After 6 months, the incidence of complications such as stenosis, hematoma, thrombus, aneurysm, and cannulation failure was compared between the groups. Nurse satisfaction with the electronic cannulation atlas system was also assessed through a questionnaire.Results: The observation group had lower incidence rates of arteriovenous fistula stenosis, thrombus, aneurysm, and failure rate of cannulation compared to the control group, with statistically significant differences (p< 0.05). The incidence rates of hematoa were similar in both groups, showing no significant difference (p> 0.05). After 3 months of management, the incidence of arteriovenous fistula complications in the observation group was significantly lower than in the control group (p< 0.05). Additionally, utilizing the electronic cannulation atlas system was found to increase nurses’ job satisfaction.Conclusion: The use of electronic cannulation atlas for the treatment of patients’ arteriovenous fistula could effectively reduce the incidence of complications of patients’ arteriovenous fistula, reduce the failure rate of cannulation, reduce the workload of nurses, and improve the job satisfaction of nurses.Keywords: arteriovenous fistula, informatization, cannulation atlas, management of hemodialysis patients, complications

Lixia Li,1,&ast; Xiaohui Huang,1,&ast; Jingxian Liu,2,&ast; Chao Li,1 Zhiyan Lin,1 Rongrong Ren,3 Yan Zhang,3 Haoshu Ding,3 Jihui Chen,1 Yanfei Mao3 1Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Clinical Laboratory, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Anesthesiology and SICU, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanfei Mao; Jihui Chen, Email maoyanfei@xinhuamed.com.cn; chenjihui@xinhuamed.com.cnBackground: Polymyxin B (PMB)-based combination therapies are used to treat severe carbapenem-resistant gram-negative bacterial (CR-GNB) infections. This observational study investigated the relationship between clinical factors, including PMB concentration, and clinical efficacy and safety.Patients and Methods: Polymyxin B regimens were optimized through therapeutic drug monitoring (TDM) and area under the concentration-time curve (AUC). In all, 382 samples were tested from 130 patients. Logistic regression was used to analyze the relationships between variables with clinical efficacy and 30-day mortality factors were analyzed by Cox regression. The sensitivity and specificity of Cmin and AUC for the occurrence of acute kidney injury (AKI) were determined by ROC curve analysis.Results: The clinical effectiveness of PMB was 65.4%. Multivariate logistic regression analysis revealed that lung infection, continuous renal replacement therapy, and C-reactive protein were independent factors significantly associated with efficacy. AKI occurred in 14.6% of the patients during treatment; age > 73 years (OR: 3.63; 95% CI: 1.035– 12.727; P = 0.044), Cmin greater than 2.3 μg/mL (OR: 7.37; 95% CI: 1.571– 34.580; P = 0.011), combined vancomycin (OR: 9.47; 95% CI: 1.732– 51.731; P = 0.009), and combined piperacillin-tazobactam (OR: 21.87; 95% CI: 3.139– 152.324; P = 0.002) were independent risk factors. The identified PMB cut-offs for predicting AKI were Cmin = 2.3 μg/mL and AUC = 82.0 mg h/L.Conclusion: Polymyxin B-based combination regimens are effective in treating CR-GNB infections, particularly bloodstream infections, but have shown unsatisfactory for lung infections. Cmin ≥ 2.3 μg /mL and AUC ≥ 82.0 mg h/L may increase PMB-associated AKI incidence. PMB dose should be adjusted based on TDM to ensure efficacy.Keywords: Polymyxin B, PMB therapeutic drug monitoring, TDM, carbapenem-resistant gram-negative bacteria, CR-GNB, clinical efficacy, acute kidney injury, AKI

Kaiyue Zhang, Chunnan Li, Peitong Wu, Xiaochen Gao, Xueqin Feng, Jiaming Shen, Nanxi Zhang, Xuesheng Hu, Shuo Wang, Hui Zhang, Jingwei Lv, Jiaming Sun Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Jiaming Sun; Jingwei Lv, Changchun University of Chinese Medicine, No. 1035, Boshuo Road, Nanguan District, Changchun, 130117, People’s Republic of China, Tel +0431-86763809, Fax + 8676 3968, Email Sun_jiaming2000@163.com; jingwei-lv@hotmail.comPurpose: Zhixiao Tang (ZXT), a traditional Chinese compound prescription, has been used clinically to treat pneumonia in China. However, the underlying mechanism of ZXT treatment in pneumonia is still unclear. The present study aimed to reveal the potential mechanism of ZXT in pneumonia using a strategy combining metabolomics and network pharmacology.Methods: Initially, the chemical compositions were identified by UPLC-QE-Orbitrap-MS, while the prediction of potential signal pathways was performed through network pharmacology. To assess the anti-inflammatory properties of ZXT in the context of pneumonia, models of 16HBE cells induced by LPS and zebrafish induced by CuSO4 were established to measure levels of inflammatory markers and apoptosis. Subsequently, the differential changes of endogenous metabolites in cells caused by ZXT were examined using metabolomics technology, and the molecular docking analysis of key targets was carried out using Autodock Vina software. Ultimately, the validation of the primary pathways and targets was conducted through quantitative RT-PCR and Western blot techniques.Results: A total of 75 compounds were identified through UPLC-QE-Orbitrap-MS analyses. Network pharmacological analysis shows that it plays an anti-inflammatory role in C-type lectin receptor signaling pathway. After ZXT intervention, the inflammatory factors and apoptosis in cells were significantly reduced. Metabonomics analysis showed that 18 metabolites changed significantly. Four key genes were identified, which exhibited partial compatibility with the findings of network pharmacology. Molecular docking analysis confirmed the substantial affinity of the primary targets for ZXT. Furthermore, ZXT exerted a suppressive effect on neutrophil migration, down-regulated the expression of pro-inflammatory cytokine genes, and inhibited the up-regulation of the Dectin-1/SYK/NF-κB signaling pathway. In vivo cell experiments also yielded consistent experimental outcomes.Conclusion: This study enhances comprehension of the pharmacological mechanism underlying ZXT’s efficacy in pneumonia treatment, thereby establishing a scholarly basis for future research and clinical utilization of ZXT in pneumonia management. Keywords: Zhixiao Tang, pneumonia, network pharmacology, integrated metabolomics, 16HBE, Zebrafish

Fan Zhao,1,2 Jitong Wang,1,2 Yu Zhang,1,2 Jinru Hu,1,2 Chenyang Li,3 Shuainan Liu,4,5 Ruixiang Li,2 Ruofei Du1,2 1Engineering Research Center of Modern Preparation Technology of TCM, Ministry of Education, Shanghai, 201203, People’s Republic of China; 2Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518055, People’s Republic of China; 4State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Key Laboratory of Polymorphic Drugs of Beijing, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, People’s Republic of China; 5Diabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Ruixiang Li, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Email ruixiangli@shutcm.edu.cn Ruofei Du, Engineering Research Center of Modern Preparation Technology of TCM, Ministry of Education, Shanghai, 201203, People’s Republic of China, Email drf790101@shutcm.edu.cnAbstract: This review aimed to systematically investigate the intracellular and subcellular fate of various types of targeting carriers. Upon entering the body via intravenous injection or other routes, a targeting carrier that can deliver therapeutic agents initiates their journey. If administered intravenously, the carrier initially faces challenges presented by the blood circulation before reaching specific tissues and interacting with cells within the tissue. At the subcellular level, the car2rier undergoes processes, such as drug release, degradation, and metabolism, through specific pathways. While studies on the fate of 13 types of carriers have been relatively conclusive, these studies are incomplete and lack a comprehensive analysis. Furthermore, there are still carriers whose fate remains unclear, underscoring the need for continuous research. This study highlights the importance of comprehending the in vivo and intracellular fate of targeting carriers and provides valuable insights into the operational mechanisms of different carriers within the body. By doing so, researchers can effectively select appropriate carriers and enhance the successful clinical translation of new formulations.Plain language summary: Nowadays, scientists are actively researching nanocarrier drugs. After administration via injection or other methods, these drugs experience in the body and reach the target treatment site to relieve or cure symptoms. As research progresses, scientists are gaining more insights into the behavior of nanocarrier drugs in the body, which is useful in developing safer and more effective drugs. Historically, research has focused primarily on the drug itself. However, it is important to understand that the carrier that delivers and protects the drug (often described as the drug sitting in a “car” or under an “umbrella”) plays an essential role in the drug’s therapeutic effect. This paper aims to highlight the importance of the carrier’s role, which is vital for developing new drugs and advancing basic research. Keywords: drug carriers, targeted delivery, in vivo fate, subcellular fate

Lengnan Xu,1 Chen Yu,1 Aiqun Chen,1 Chuanbao Li,2 Yonghui Mao1 1Department of Nephrology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Laboratory Medicine, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Yonghui Mao; Chuanbao Li, Tel +86-10-85133880, Email maoyonghui0214@bjhmoh.cn; lichuanbao3662@bjhmoh.cnBackground: This study aims to investigate GFR decline in elderly subjects with varying physical conditions and analyze key risk factors impacting renal function changes.Methods: We obtained data from patients between 2017 and 2019, and matched healthy elderly subjects based on gender and age. Data collected for all subjects included annual measurements of fast blood glucose (GLU), glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-c), blood albumin (ALB), blood uric acid (UA), urine protein (UP), and systolic blood pressure (SBP). Additionally, information on coexisting diseases was gathered. The Full Age Spectrum (FAS) equation was used to calculate eGFR.Results: A total of 162 patients with complete 3-year renal dynamic imaging were included, including 84 patients in the kidney disease group (K group) and 78 patients in the non-kidney disease group (NK group). Ninety individuals were selected as the healthy group (H group). The annual decline rate in the K group was the fastest, which exceeded 5mL/min/1.73m2 (P < 0.05). Group (K group: β=− 40.31, P< 0.001; NK group: β=− 26.96, P< 0.001), ALB (β=− 0.38, P=0.038) and HbA1c (β=1.36, P=0.029) had a significant negative impact on the eGFR changes. For participants who had negative proteinuria: K group had the most significant annual eGFR decline.Conclusion: The presence of kidney disease, along with proteinuria nor not, can lead to a marked acceleration in kidney function decline in elderly. We categorize elderly individuals with an annual eGFR decline of more than 5 mL/min/1.73m2 as the “kidney accelerated aging” population.Keywords: elderly, GFR, kidney accelerated aging, risk factors

Chenxi Li,1,&ast; Xiaolei Chen,2,&ast; Xiaowen Zhu,1 Mengjiao Cao,3 Qunfeng Tang,3 Wenjun Wu1,4 1Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 2Department of Neurology, Jiangnan University Medical Center, Wuxi No. 2 People’s Hospital, Wuxi, People’s Republic of China; 3Department of Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 4Jinshan Branch of Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjun Wu, Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China, Tel +86-15358008856, Fax +86-510-85737592, Email wuwenjung@163.comPurpose: Arterial stiffness is often increased in overweight or obese individuals before the development of hypertension (HT). This study aimed to determine the connection between pancreatic fat and atherosclerosis in overweight and obese people without HT.Patients and methods: We included 128 patients who were non-hypertensive and overweight or obese in a study between December 2019 and November 2022. Medical history was collected, and all participants underwent a physical examination and blood tests. Pancreatic fat content was measured by magnetic resonance imaging (MRI) and was grouped into quartiles based on pancreatic fat fraction (PFF). The upper three quartiles (PFF≥ 10.33%) were defined as non-alcoholic fatty pancreas disease (NAFPD) and the first quartile (PFF< 10.33%) as non-NAFPD. High baPWV (H-baPWV) and low baPWV (L-baPWV) were classified according to the median baPWV (1159 cm/s). The effect of NAFPD on baPWV was examined using binary logistic regression. The study population consisted of 96 NAFPD and 32 non-NAFPD cases.Results: Participants with NAFPD had significantly higher levels of baPWV than people without. The rates of NAFPD and the PFF values varied significantly in the L-baPWV and H-baPWV groups. Logistic regression analysis suggested that the presence of NAFPD was independently correlated with increased baPWV after adjusting for age, smoking, body mass index, blood pressure, lipid profiles, and glycemic index.Conclusion: NAFPD is an independent risk factor for increased baPWV in individuals with overweight and obesity but no HT, suggesting that the presence of NAFPD may be a warning signal of early atherosclerosis.Keywords: obesity, non-alcoholic fatty pancreas disease, overweight, arterial stiffness, brachial-ankle pulse wave velocity

Hua Liu,1,2,&ast; Yang-Min Hao,1,2,&ast; Sheng Jiang,1,2,&ast; Maiheliya Baihetiyaer,1,2 Cheng Li,3 Guo-Yao Sang,4 Zhiming Li,5 Guo-Li Du1,2,6 1State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, People’s Republic of China; 2Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Data Statistics and Analysis Center of Operation Management Department, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 4Laboratory Medicine Diagnostic Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 5Department of Ultrasound, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 6Bazhou People’s Hospital, Korla, Xinjiang Uygur Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guo-Li Du, Email genemagic@126.comPurpose: This study aims to investigate the relationship between Sodium Glucose Co-transporter-2 inhibitors (SGLT2i) treatment and fibrosis in patients with Metabolic dysfunction-associated steatotic liver disease (MASLD) combined with Type 2 Diabetes Mellitus (T2DM) and Major Adverse Cardiovascular and Cerebrovascular Events (MACCEs).Methods: A case–control study was conducted, involving 280 patients with MASLD combined with T2DM treated at the First Affiliated Hospital of Xinjiang Medical University from January 2014 to October 2023. Among these patients, 135 received SGLT2i treatment. The association between the Fibrosis-4 (FIB-4) index and the occurrence of MACCEs, as well as the association between the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) scores and MACCEs, were evaluated.Results: The FIB-4 index and APRI scores were significantly lower in the SGLT2i treatment group compared to the non-SGLT2i group (1.59 vs 1.25, P< 0.001). SGLT2i treatment tended to reduce the occurrence of MACCEs compared to non-SGLT2i treatment (45.5% vs 38.5%, P=0.28). All patients who developed MACCEs in the non-SGLT2i treatment group had higher FIB-4 index (1.83 vs 1.35, P=0.003). Additionally, after SGLT2i treatment for a median duration of 22 months, patients showed significant reductions in blood glucose, APRI, and FIB-4 index.Conclusion: SGLT2i treatment significantly reduces the occurrence of MACCEs and liver fibrosis in patients with MASLD combined with T2DM. The FIB-4 index may serve as a potential surrogate marker for predicting the occurrence of MACCEs.Keywords: MASLD, type 2 diabetes mellitus, sodium-glucose co-transporter-2 inhibitors, MACCEs, FIB-4 index

Kongzhi Yang, Yaqin Song, Yingjie Su, Changluo Li, Ning Ding Department of Emergency Medicine, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Ning Ding, Department of Emergency Medicine, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, No. 161 Shaoshan South Road, Changsha, Hunan, 410004, People’s Republic of China, Tel + (86)731-8566-7935, Email doctordingning@sina.com; doctordingning@163.comObjective: The purpose of this study is to establishment and validation of an early predictive model for severe acute pancreatitis (SAP).Methods: From January 2015 to August 2022, 2986 AP patients admitted to Changsha Central Hospital were enrolled in this study. They were randomly divided into a modeling group (n = 2112) and a validation group (n = 874). In the modeling group, identify risk factors through logistic regression models and draw column charts. Use internal validation method to verify the accuracy of column chart prediction. Apply calibration curves to evaluate the consistency between nomograms and ideal observations. Draw a DCA curve to evaluate the net benefits of the prediction model.Results: Nine variables including respiratory rate, heart rate, WBC, PDW, PT, SCR, AMY, CK, and TG are the risk factors for SAP. The column chart risk prediction model which was constructed based on these 9 independent factors has high prediction accuracy (modeling group AUC = 0.788, validation group AUC = 7.789). The calibration curve analysis shows that the prediction probabilities of the modeling and validation groups are consistent with the observation probabilities. By drawing a DCA curve, it shows that the model has a wide threshold range (0.01– 0.88).Conclusion: The study developed an intuitive nomogram containing readily available laboratory parameters to predict the incidence rate of SAP.Keywords: acute pancreatitis, severe, risk factors, predictive model, nomogram

Changzhen Li,1,&ast; Xiaomei Wang,1,&ast; Jingjing Rao,1,&ast; Ye Zeng,1 Jianjun Liu,2 Feng Tang1 1Department of Laboratory Medicine, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430015, People’s Republic of China; 2Office of the Dean, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430015, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Tang; Jianjun Liu, Email tang33feng66@163.com; liujianjun5221@163.comObjective: To analyze bacterial distribution and antibiotic resistance in clinical specimens from a Chinese hospital for evaluating environmental factors’ impact on pathogen prevalence.Methods: From January 2017 to December 2021, we collected 42,854 clinical specimens from hospitalized children and women. The specimens were cultured on various agar plates and incubated at 35°C for 18– 48 h. Their identification was performed using standard biochemical methods and Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF), whereas antibiotic susceptibilities were determined using the VITEK 2 system. Concurrent environmental data from Wuhan were analyzed for correlations with pathogen prevalence using multiple linear stepwise regression.Results: Of the 24,555 bacterial strains isolated, the majority were gram-positive, and sputum was the most common specimen type. Haemophilus influenzae and Escherichia coli were the most prevalent pathogens in sputum and urine samples, respectively. Notably, H. influenzae and Streptococcus pneumoniae affected children under 6 years of age the most. Furthermore, H. influenzae showed high ampicillin resistance but low cefotaxime resistance; S. pneumoniae was sensitive to penicillin G, and E. coli was resistant to ampicillin but sensitive to cefotetan. The prevalence of multidrug-resistant organisms was below national averages. In terms of seasonality, H. influenzae peaked during late winter and early spring, and environmental analysis indicated positive correlations between PM2.5 and PM10, and H. influenzae and S. pneumoniae prevalence. In addition, NO2 levels were positively correlated with increased S. aureus and M. catarrhalis prevalence; E coli prevalence was negatively correlated with ozone levels.Conclusion: This study provides valuable insights into the distribution and antibiotic resistance patterns of bacterial pathogens in maternal and child healthcare facilities in Wuhan, China. Environmental factors significantly influence the epidemiology of certain bacterial pathogens. Implementing integrated health strategies that combine microbial surveillance with environmental monitoring is needed to effectively manage and prevent bacterial infections.Keywords: epidemiology, multidrug-resistant pathogens, seasonality, particulate matter

Jia-Jun Qin,&ast; Chao Li,&ast; Jin Fu, Xian-Zhen Chen Department of Neurosurgery, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian-Zhen Chen; Jin Fu, Department of Neurosurgery, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, No. 301, Yanchang Middle Road, Jing’an District, Shanghai, 200072, People’s Republic of China, Tel +8613901793331 ; +86 13262727292, Email fujinfu0226@126.com; chenxianzhencxzk@126.comObjective: The aim of this study is to evaluate the impact of different surgical and postoperative treatment options on the long-term overall survival (OS) in patients with primary single intracranial atypical meningioma.Methods: In this retrospective study, participants were drawn from the Surveillance, Epidemiology, and End Results (SEER) database. Inclusion criteria comprised patients who underwent either gross total resection (GTR) or subtotal resection (STR). The inverse probability weighting (IPW) method using generalized boosted models was used to achieve balance in variables across various treatment groups. Subsequent to IPW, multivariate Cox analysis and Kaplan–Meier analysis were conducted, with OS as the endpoint.Results: GTR was conducted on 1650 patients, while STR was conducted on 1109 patients. Among these, 432 patients who underwent GTR and 401 patients who underwent STR received postoperative radiotherapy (PORT). In the case of patients who were under 60 years old, PORT emerged as a significant protective factor for OS in those who underwent STR (HR 0.44; 95% CI 0.23– 0.84; p = 0.013). Survival curves demonstrated that patients who underwent STR with PORT exhibited comparable OS to those who underwent GTR without PORT (p = 0.546). Conversely, for patients aged 60 years or older, PORT emerged as an independent risk factor for both GTR (HR 1.42; 95% CI 1.00– 2.00; p = 0.048) and STR (HR 1.81; 95% CI 1.26– 2.60; p = 0.001).Conclusion: PORT may contribute to improving OS in primary single atypical meningioma patients under 60 years old who receive STR. However, in older patients who underwent either GTR or STR, the administration of PORT may be associated with a potential risk of OS. Therefore, age should be taken into account in applying PORT therapy, and the optimal treatment strategy for PORT in patients with atypical meningiomas needs to be further explored and validated.Keywords: age, atypical meningioma, gross total resection, postoperative radiotherapy, subtotal resection

Jiangping Ye,1– 3 Dongxia Xu,1– 3 Rikang Yuan,1– 3 Shaoqing Cao,1– 3 Zhangyu Wang,1– 3 Yuqin Wang,1– 3 Chengsi Li,1– 3 Gangjun Zong1– 3 1Wuxi Clinical College of Anhui Medical University, Wuxi, Jiangsu, People’s Republic of China; 2Anhui Medical University Fifth Clinical Medical College, Wuxi, Jiangsu, People’s Republic of China; 3Department of Cardiology, The 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, Jiangsu, People’s Republic of ChinaCorrespondence: Gangjun Zong, Email zonggj@163.comAim: The high morbidity and mortality associated with ST-segment elevation myocardial infarction (STEMI) are an urgent concern. This study aimed to investigate the ratio of lymphocyte count to C-reactive protein ratio (LCR) in multiple measurements in the perioperative period, exploring dynamic changes as the best predictor of major adverse cardiovascular events (MACE) in STEMI patients.Methods: We enrolled 205 STEMI patients, conducting blood counts at admission, 24 hours post-percutaneous coronary intervention (PCI), and at discharge. Cox proportional risk models evaluated factors independently associated with STEMI prognosis. The receiver operating characteristic (ROC) curve and the De-Long test determined the best predictor. Kaplan–Meier analysis assessed the prognostic value of LCR for STEMI patients. Statistical differences and correlations between LCR at 24 hours post-PCI and cardiovascular disease risk factors were also analyzed.Results: Gensini score (HR, 1.015; 95% CI, 1.007– 1.022; P < 0.001), total stent length (HR, 1.015; 95% CI, 1.002– 1.029; P=0.025), lipoprotein (a) (HR, 1.001; 95% CI, 1.000– 1.002; P=0.043), LCR at admission (HR, 0.995; 95% CI, 0.989– 1.000; P=0.002), and LCR at 24 hours post-PCI (HR, 0.587; 95% CI, 0.486– 0.708; P < 0.001) were independent risk factors for long-term STEMI prognosis after PCI. LCR at admission (cut-off value, 2.252; 95% CI, 0.040– 0.768; P < 0.001) and LCR at 24 hours post-PCI (cut-off value, 2.252; 95% CI, 0.831– 0.924; P < 0.001) effectively predicted MACEs occurrence, with the latter exhibiting a superior predictive effect (P< 0.001). Kaplan-Meier analysis revealed that patients with LCR at admission ≤ 50.29 and LCR at 24 hours post-PCI ≤ 2.25 had significantly higher risks of developing MACEs (Log-rank P < 0.0001).Conclusion: LCR at 24 hours post-PCI may be a superior marker for long-term MACE prediction in STEMI patients, serving as the best predictor for distant MACE occurrence.Keywords: lymphocyte, C-reactive protein, major cardiovascular adverse events, percutaneous coronary intervention, ST-segment elevation myocardial infarction

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

Cunzi Li,1 Lan Zhou,2,3 Hongyan Sun,2 Ming Ming Yang2 1The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), Shenzhen, 518020, People’s Republic of China; 2Department of Ophthalmology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, People’s Republic of China; 3Post-Doctoral Scientific Research Station of Basic Medicine, Jinan University, Guangzhou, 510632, People’s Republic of ChinaCorrespondence: Ming Ming Yang, Department of Ophthalmology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), No. 1017 Dongmen North Road, Luohu District, Shenzhen, 518020, People’s Republic of China, Tel +86 22944163, Email ming4622@163.comAbstract: Age-related macular degeneration (AMD) is a degenerative ocular disease primarily affecting central vision in the elderly. Its pathogenesis is complex, involving cellular senescence and immune homeostasis dysregulation. This review investigates the interaction between these two critical biological processes in AMD pathogenesis and their impact on disease progression. Initially, cellular senescence is analyzed, with particular emphasis on retinal damage induced by senescent retinal pigment epithelial cells. Subsequently, the occurrence of immune homeostasis dysregulation within the retina and its mechanistic role in AMD areis explored. Furthermore, the paper also discusses in detail the interplay between cellular senescence and immune responses, forming a vicious cycle that exacerbates retinal damage and may influence treatment outcomes. In summary, a deeper understanding of the interrelation between cellular senescence and immune dysregulation is vital for the developing innovative therapeutic strategies for AMD.Keywords: age-related macular degeneration, cellular senescence, immune homeostasis dysregulation

Hua Zheng,1 Changqing Li,1 Lirong Zhang,2 Tailin Wang,3 Zengliang Cai,4 Mingxing Lei5,6 1College of Physical Education and Health Science, Chongqing Normal University, Chongqing, 401331, People’s Republic of China; 2Department of Physical Education, Xiamen University of Technology, Xiamen, Fujian, 361024, People’s Republic of China; 3School of Physical Education, North University of China, Taiyuan, Shanxi, 030051, People’s Republic of China; 4Department of Physical Education, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 5Chinese PLA General School, Beijing, 100853, People’s Republic of China; 6Chinese PLA General Hospital, Beijing, 100853, People’s Republic of ChinaCorrespondence: Mingxing Lei, Department of Orthopedic Surgery, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100039, People’s Republic of China, Tel +8618811772189, Email leimingxing@301hospital.com.cn Zengliang Cai, Department of Physical Education, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai, 201203, People’s Republic of China, Email caizengliang@shutcm.edu.cnBackground: University students are a vulnerable population prone to mental health challenges. This study aimed to investigate depression and its associated factors among university students in terms of demographics, eating habits, and exercises.Methods: A total of 2891 university students from three universities participated in this study between January 2024 and February 2024. An online survey questionnaire was distributed using a snow-ball strategy. The survey collected demographic, lifestyle, and psychological data, including depression and anxiety scores using the PHQ-9 and GAD-7 screening tools. Subgroup analysis was conducted according to sport frequency and sport type using Chi-square test for qualitative data and t-test for quantitative data. Multiple linear regression analysis was performed to identify risk factors for depression.Results: A total of 44.2% and 39.5% of the participants reported symptoms of depression and anxiety, respectively. Significant differences were observed in various characteristics across different sport frequency groups, with participants with higher sport frequency tending to have less depression (P< 0.001) and anxiety (P< 0.001) symptoms. As the frequency of weekly exercise increased, anxiety and depression scores gradually decreased. The mean PHQ-9 and GAD-7 scores were highest in the group with no sports and lowest in the group with a sport frequency of 3– 4 times per week (P< 0.001). Additionally, once exercise frequency reached 5 times per week or more, anxiety and depression scores no longer decreased. Subgroup analysis based on sport type revealed that participants engaging in specific sports, such as basketball, tennis, dance, and running, had lower depression (P< 0.001) and anxiety (P< 0.001) scores compared to the overall average. Based on multiple linear regression analysis, married status (P=0.036), enjoying barbecue food (P< 0.001), prolonged sedentary time (P=0.001), experiencing stress events (P< 0.001), and electronic device usage time (P< 0.001) were positively associated with depression scores, while loving eating vegetables (P=0.007), a relatively longer sport time (P=0.005), a higher exercise frequency (P=0.064), and no chronic disease (P< 0.001) were negatively associated with depression scores.Conclusion: This study highlights the importance of a healthy lifestyle, including regular exercise, limited exposure to electronic screens, and a balanced diet, in preventing and mitigating depression among university students. This study also suggests that exercising 3– 4 times a week is associated with the lowest levels of anxiety and depression. Activities such as basketball, tennis, dance, and running are effective in alleviating these mental health issues through regular exercise.Keywords: depression, eating habits, sports, university students, cross-sectional study

Cheng Su,1,&ast; Cai Li,2,&ast; Xinyi Hu,3,&ast; Jing Wang,1,&ast; Linlin Liu,4,&ast; Xianfeng Zhang,4 Yeqing Tong4 1School of Public Health, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Infectious Disease Prevention and Control Center, Wuhan Center for Disease Control and Prevention, Wuhan, Hubei, People’s Republic of China; 3Global Study Institute, University of Geneva, Geneva, 1205, Switzerland; 4Infectious Disease Prevention and Control Center, Hubei Center for Disease Control and Prevention, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yeqing Tong; Xianfeng Zhang, Email t_yeqing@163.com; 63382251@qq.comAbstract: Angiotensin-converting enzyme 2 (ACE2) is an important regulator of the Renin-Angiotensin System (RAS). Additionally, it has been identified as a functional receptor for the Coronavirus. Research indicates that ACE2 plays a role in the regulation of cardiovascular systems by modulating blood pressure and electrolyte balance. Its role in pulmonary diseases has also garnered significant attention due to the widespread prevalence of Coronavirus. There is solid evidence linking ACE2 to other pulmonary diseases, including chronic obstructive pulmonary disease, acute respiratory distress syndrome, allergic asthma, among others. However, the exact pathological and physiological mechanisms of ACE2 in these diseases remain elusive. Our research aims to review and explore the latest advancements in ACE2-related studies in pulmonary diseases. These findings have the potential to open new avenues for utilizing ACE2 as a potential biomarker for early diagnosis and monitoring of pulmonary diseases.Keywords: ACE2, lung diseases, ARDS, Lung Cancer, COPD

Wenyan Sun,1,&ast; Xuetong Zhao,2– 4,&ast; Nicola Dalbeth,5,&ast; Robert Terkeltaub,6 Lingling Cui,1 Zhen Liu,1 Lin Han,1 Can Wang,1 Hui Zhang,1,7 Yiming Bao,2– 4 Changgui Li,1,7 Jie Lu1,7 1Shandong Provincial Key Laboratory of Metabolic Diseases, Shandong Provincial Clinical Research Center for Immune Diseases, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2National Genomics Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, 100101, People’s Republic of China; 3CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Science and China National Center for Bioinformation, Beijing, People’s Republic of China; 4University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China; 5Department of Medicine, University of Auckland, Auckland, New Zealand; 6VA San Diego VA Healthcare Center, University of California San Diego, San Diego, CA, USA; 7Institute of Metabolic Diseases, Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Lu, Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, Shandong Provincial Clinical Research Center for Immune Diseases, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China, Email 13127006046@163.com Changgui Li, Shandong Provincial Key Laboratory of Metabolic Diseases, Shandong Provincial Clinical Research Center for Immune Diseases, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China, Email changguili@vip.163.comObjective: This study aimed to understand predictors of inadequate response (IR) to low-dose febuxostat treatment based on clinical variables.Methods: We pooled data from 340 patients of an observational cohort and two clinical trials who received febuxostat 20 mg/day for at least 3 months. IR was defined as failure to reach the target serum urate level (sUA< 6 mg/dL) at any time point during 3 months treatment. The potential predictors associated with short- or mid-term febuxostat IR after pooling the three cohorts were explored using mixed-effect logistic analysis. Machine learning models were performed to evaluate the predictors for IR using the pooled data as the discovery set and validated in an external test set.Results: Of the 340 patients, 68.9% and 51.8% were non-responders to low-dose febuxostat during short- and mid-term follow-up, respectively. Serum urate and triglyceride (TG) levels were significantly associated with febuxostat IR, but were also selected as significant features by LASSO analysis combined with age, BMI, and C-reactive protein (CRP). These five features in combination, using the best-performing stochastic gradient descent classifier, achieved an area under the receiver operating characteristic curve of 0.873 (95% CI [0.763, 0.942]) and 0.706 (95% CI [0.636, 0.727]) in the internal and external test sets, respectively, to predict febuxostat IR.Conclusion: Response to low-dose febuxostat is associated with early sUA improvement in individual patients, as well as patient age, BMI, and levels of TG and CRP.Keywords: gout, febuxostat, urate-lowering therapy, machine learning model

Dingbin Yang,1,2 Yu Mao,3 Lu Peng,2 Shuqiong Huang,2 Lijun Zhou,2 Changqiang Li1 1Department of Dermatology, the Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Dermatology, People’s Hospital of Leshan, Leshan, 614000, People’s Republic of China; 3Department of Pathology, People’s Hospital of Leshan, Leshan, 614000, People’s Republic of ChinaCorrespondence: Changqiang Li, Department of Dermatology, the Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Email lcq-1973@163.comAbstract: Keratoacanthoma (KA) is a papule, plaque, or nodule in an exposed area, with a crater-like horn plug in the center. Multiple KAs are rare disorders, especially when the lesions are agglomerated together. Herein, we report a case of 65-year-old man who presented with four red nodules of different sizes on the right side of the chest. The lesions were clustered, with central keratotic cores, similar in appearance to a four-leaf clover. The nodules were completely removed by excisional surgery and the diagnosis of Agglomerate KAs was made based on clinical and pathological results. A 6-year follow-up found no recurrence.Keywords: agglomerate keratoacanthomas, four-leaf clover

Shina Song,1,2 Xiaofeng Li,1 Xuting Xue,3 Wenping Dong,2 Changxin Li1 1Department of Neurology, The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Geriatrics, General Hospital of TISCO, Taiyuan, People’s Republic of China; 3Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Wenping Dong, Department of Geriatrics, General Hospital of TISCO, North Street, Xinhualing District, Taiyuan, Shanxi Province, 030009, People’s Republic of China, Tel +86 13703581782, Email tgzyydwp@163.com Changxin Li, Department of Neurology, The First Hospital of Shanxi Medical University, Jiefangnan Road 85, Taiyuan, Shanxi Province, 030001, People’s Republic of China, Tel +86 13834635428, Email dslcxyx@126.comAbstract: High temperature requirement A1 (HTRA1) is a member of the serine protease family, comprising four structural domains: IGFBP domain, Kazal domain, protease domain and PDZ domain. HTRA1 encodes a serine protease, a secreted protein that is widely expressed in the vasculature. HTRA1 regulates a wide range of physiological processes through its proteolytic activity, and is also involved in a variety of vascular abnormalities-related diseases. This article reviews the role of HTRA1 in the development of vascular abnormalities-related hereditary cerebral small vessel disease (CSVD), age-related macular degeneration (AMD), tumors and other diseases. Through relevant research advances to understand the role of HTRA1 in regulating signaling pathways or refolding, translocation, degradation of extracellular matrix (ECM) proteins, thus directly or indirectly regulating angiogenesis, vascular remodeling, and playing an important role in vascular homeostasis, further understanding the mechanism of HTRA1’s role in vascular abnormality-related diseases is important for HTRA1 to be used as a therapeutic target in related diseases.Keywords: HTRA1, vascular anomalies, cerebral small vessel disease, AMD, tumor

Yan Wang,1,2,&ast; Cong Li,1,2,&ast; Lei Liu,1,&ast; Yuan Yang,3,&ast; Xue He,1,2 Gang Li,3 Xianzhen Zheng,3 Yun Ren,1,4 Hanpeng Zhao,1,5 Zhenchao Du,1,4 Jianrong Jiang,1,5 Yu Kuang,1 Fujun Jia,3 Honghua Yu,1 Xiaohong Yang1,2 1Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 2School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 3Guangdong Mental Health Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 4Shantou University Medical College, Shantou, People’s Republic of China; 5The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohong Yang; Honghua Yu, Email syyangxh@scut.edu.cn; yuhonghua@gdph.org.cnBackground: Identifying the fundus objective biomarkers for the major depressive disorders (MDD) may help promote mental health. The aim of this study was to evaluate retinal neurovascular changes and further investigate their association with disease severity in MDD.Methods: This cross-sectional study conducted in the hospital enrolled patients with MDD and healthy controls.The retinal neurovascular parameters for all subjects, including vessel density (VD), thickness of ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL), and optic nerve head (ONH) eg are automatically calculated by the software in optical coherence tomography angiography (OCTA). The severity of MDD including depressive symptoms, anxiety, cognition, and insomnia was assessed by Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale (HAMA), Montreal Cognitive Assessment (MoCA), and Insomnia Severity Index (ISI) respectively.Results: This study included 74 MDD patients (n=74 eyes) and 60 healthy controls (HCs) (n=60 eyes). MDD patients showed significantly decreased VD of superficial and deep capillary plexus, thickness of GCC and RNFL, and volume of ONH (all p< 0.05) and increased vertical cup-to-disc ratio and global loss volume (GLV) (all p< 0.05) compared to HCs. Positive associations were found between HAMD scores and cup area (r=0.30, p=0.035), cup volume (r=0.31, p=0.029), and disc area (r=0.33, p=0.020) as well as ISI scores and RNFL thickness (r=0.34, p=0.047).Conclusion: We found the retinal neurovascular impairment and its association with disease severity in MDD patients. OCTA showed promise as a potential complementary assessment tool for MDD.Keywords: major depressive disorder, retinal neurovasculature, optical coherence tomography angiography, disease severity

Shi Zhang,1 Yanju Zhang,2 Jing Li,1 Xincheng Wang,1 Minying Zhang,3 Meiyang Du,1 Weiran Jiang,4 Chunjun Li1 1Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, People’s Republic of China; 2Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3School of Medicine, Nankai University, Tianjin, People’s Republic of China; 4Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USACorrespondence: Chunjun Li, Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, People’s Republic of China, Email li_chunjun@126.comBackground: Growing evidence has demonstrated the important roles of gut microbiota and short chain fatty acids, especially acetate, propionate and butyrate, in the development of obesity and metabolic diseases. To date, the effects of acetate, propionate and butyrate on human adiposity and glucose metabolism remain controversial. This study aimed to explore the associations of systemically acetate, propionate and butyrate with obesity and glucose homeostasis in patients with type 2 diabetes (T2D) and obesity.Methods: A total of 12 patients with T2D and obesity and 8 age- and sex-matched healthy individuals with BMI < 24 kg/m2 were enrolled in this study. Height, weight, body composition, blood pressure, biochemical indices, a 75-g oral glucose tolerance test, and plasma acetate, propionate and butyrate were measured at baseline. Then, participants in T2D group were given a weight control therapy, in addition to conventional medication, and all the measurements were repeated 12 months from baseline. The direct segmental multi-frequency bioelectrical impedance analysis was used to assess body composition. Acetate, propionate and butyrate levels were determined by liquid chromatography coupled to tandem mass spectrometry.Results: Butyrate concentration significantly increased from baseline after obvious weight loss (P< 0.05). Correlation analysis showed that propionate was negatively correlated with percent of body fat (PBF) and 2-h plasma glucose (2-h PG) (P< 0.05), and butyrate was negatively associated with body mass index, visceral fat area, PBF and 2-h PG (P< 0.05). No association was found between acetate and obesity.Conclusion: Butyrate and propionate are negatively correlated with obesity and glucose levels in patients with T2D and obesity.Keywords: obesity, type 2 diabetes, gut microbiota, short chain fatty acids

Yuhang Wang,1,&ast; Chunsun Li,2,&ast; Huan Zhang,1 Yulong Chi,1 Yun Cai1 1Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, People’s Republic of China; 2Laboratory of Department of Pulmonary and Critical Care Medicine, PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Cai, Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies center of PLA General Hospital, Postal Address: 28 Fu Xing Road, Beijing, 100853, People’s Republic of China, Tel +86-10-6693-7166, Fax +86-10-8821-4425, Email caicai_hh@126.comObjective: Pseudomonas aeruginosa (PA) often displays drug resistance and biofilm-mediated adaptability. Here, we aimed to evaluate the antibiofilm efficacy of azithromycin-based combination regimens.Methods: Minimum inhibitory concentrations (MICs), minimal biofilm eradication concentrations (MBECs), and MBEC-combination of azithromycin, colistin, amikacin, and levofloxacin to bioluminescent strain PAO1 and carbapenem-resistant PAO1 (CRPAO1) were assessed. An animal biofilm infection model was established and detected using a live animal bio-photonic imaging system.Results: In vitro, PAO1 and CRPAO1 were susceptible to colistin, amikacin, and levofloxacin, while they were unsusceptible to azithromycin. The combinations based on azithromycin have no synergistic effect on biofilm in vitro. In vivo, azithromycin plus colistin or levofloxacin could shorten the PAO1 biofilm eradication time, which totally eradicates the biofilm in all mice on the 8th or 6th day, while monotherapy only eradicate biofilm in 70% or 80% mice on the 8th day. For CRPAO1 biofilm, only azithromycin–colistin combination and colistin monotherapy eradicated the bacteria in 60% and 40% of mice at the 6th day.Conclusion: Azithromycin-based combinations containing levofloxacin or colistin had no synergistic effect in vitro, and they are promising for clinical applications due to the good synergistic activity against PAO1 biofilms in vivo.Keywords: Pseudomonas aeruginosa, biofilm, azithromycin, combinations

Xiaochen Ma, Xiangyang Sun, Fubo Xie, Wencheng Jian, Qingliang Wang, Yang Xie, Caixia Li, Kai Zhang Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Kai Zhang, Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China, Email zhangkai@qiluhospital.comAim: This study aims to explore the role of soluble programmed cell death protein 1 (sPD-1) in individuals with hepatocellular carcinoma (HCC) undergoing treatment with drug-eluting beads transarterial chemoembolization (D-TACE). Additionally, we aim to assess the potential utility of sPD-1 for determining the optimal timing for combining D-TACE with immune checkpoint inhibitors (ICIs).Materials and Methods: A total of 44 HCC patients eligible for D-TACE and 55 healthy volunteers were enrolled in this study. Three milliliters of peripheral venous blood from the patients were collected on the day before D-TACE and 3, 7, and 30 days after D-TACE, respectively, for the assay of sPD-1. The relationships between sPD-1 levels, clinical features, outcomes, and the fluctuation of sPD-1 during treatment were analyzed.Results: The initial sPD-1 levels in patients were found to be significantly higher than those in the control group. Although the initial sPD-1 levels displayed a decreasing trend with an increase in BCLC stage, no significant differences were observed among patients at different BCLC stages. The sPD-1 level on day 3 after D-TACE was similar to that on day 7 after D-TACE and significantly lower than the initial level. The sPD-1 level on day 30 after D-TACE was significantly higher than that on day 3 and day 7 after D-TACE and nearly returned to the initial level before D-TACE.Conclusion: The level of sPD-1 was found to be significantly elevated in patients with HCC. However, further research is deemed necessary to fully understand the role of sPD-1 as a potential biomarker in the initiation, progression, and prognosis of HCC. The decrease in sPD-1 following D-TACE suggests that immune effector cells might potentially be reduced, as well as immune function weakened, highlighting the need to avoid the prompt administration of ICIs after D-TACE.Keywords: hepatocellular carcinoma, immunotherapy, soluble programmed cell death protein 1, drug-eluting beads transarterial chemoembolization

Cantao Li,&ast; Chenxi Wu,&ast; Fenfen Li, Wenjing Xu, Xiaoxi Zhang, Yan Huang, Daozong Xia School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daozong Xia, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Baichuan Street, Fuyang District, Hangzhou, Zhejiang Province, People’s Republic of China, Email xdz_zjtcm@hotmail.comAbstract: Gouty arthritis (GA) is an immune-mediated disorder characterized by severe inflammation due to the deposition of monosodium urate (MSU) crystals in the joints. The pathophysiological mechanisms of GA are not yet fully understood, and therefore, the identification of effective therapeutic targets is of paramount importance. Neutrophil extracellular traps (NETs), an intricate structure of DNA scaffold, encompassing myeloperoxidase, histones, and elastases - have gained significant attention as a prospective therapeutic target for gouty arthritis, due to their innate antimicrobial and immunomodulatory properties. Hence, exploring the therapeutic potential of NETs in gouty arthritis remains an enticing avenue for further investigation. During the process of gouty arthritis, the formation of NETs triggers the release of inflammatory cytokines, thereby contributing to the inflammatory response, while MSU crystals and cytokines are sequestered and degraded by the aggregation of NETs. Here, we provide a concise summary of the inflammatory processes underlying the initiation and resolution of gouty arthritis mediated by NETs. Furthermore, this review presents an overview of the current pharmacological approaches for treating gouty arthritis and summarizes the potential of natural and synthetic product-based inhibitors that target NET formation as novel therapeutic options, alongside elucidating the intrinsic challenges of these inhibitors in NETs research. Lastly, the limitations of HL-60 cell as a suitable substitute of neutrophils in NETs research are summarized and discussed. Series of recommendations are provided, strategically oriented towards guiding future investigations to effectively address these concerns. These findings will contribute to an enhanced comprehension of the interplay between NETs and GA, facilitating the proposition of innovative therapeutic strategies and novel approaches for the management of GA. Keywords: neutrophils, neutrophil extracellular traps, gouty arthritis, inflammation, NETs inhibitor