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Liu Liang,1 Xuemin Guo,1 Wei Ye,1 Yuxiang Liu2 1Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 2Department of Medical Oncology, Meizhou People’s Hospital, Meizhou, People’s Republic of ChinaCorrespondence: Liu Liang, Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou, People’s Republic of China, Email 19926117315@163.comBackground: The efficacy of targeted therapy for colorectal cancer (CRC) is affected by hub genes of epidermal growth factor receptor (EGFR) signaling pathways, such as KRAS. Immune cell infiltration may lead to gene mutation, but the relationship between KRAS status and peripheral immune-inflammatory indices has not been clarified in CRC.Methods: Clinical records of CRC patients were collected. The relationship between KRAS status and clinicopathological characteristics, peripheral immune-inflammatory indices (pan-immune inflammation value (PIV) (monocyte×neutrophil×platelet/lymphocyte), systemic immune inflammation index (SII) (platelet×neutrophil/lymphocyte), and system inflammation response index (SIRI) (monocyte×neutrophil/lymphocyte)) were analyzed.Results: 1033 CRC patients were collected, there were 514 (49.8%) patients with KRAS wild-type and 519 (50.2%) with KRAS mutation. Patients with KRAS mutation had higher proportions of female, III-IV stage, and lymph node metastasis and lower proportion of low grade of tumor budding (the presence of single tumor cells or small clusters of up to 5 cells in mesenchyma at the front of tumor invasion) than those with KRAS wild-type. The PIV, SII, and SIRI levels in KRAS mutation patients were significantly higher than those in KRAS wild-type patients. The proportion of aged ≥ 65 years old, dMMR, distant metastasis, and KRAS mutation were high in patients with high PIV, SII, and SIRI levels. Logistic regression analysis showed that non-low grade of tumor budding (odds ratio (OR): 1.970, 95% confidence interval (CI): 1.287– 3.016, p=0.002), and high SII level (≥ 807.81 vs < 807.81, OR: 1.915, 95% CI: 1.120– 3.272, p=0.018) were independently associated with KRAS mutation.Conclusion: Non-low grade of tumor budding, and high SII level were independently associated with KRAS mutation in CRC. It provides additional references for diagnosis and treatment options for patients with CRC.Keywords: colorectal cancer, KRAS, systemic immune inflammation index, tumor budding

Junyu Chen,1,&ast; Yupei Yuan,2,&ast; Ying Hu,1 Liang Liang1,3 1Department of Psychology, The Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Liang, Department of Psychology, The Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China, Tel +8609915848029, Email 79023556@qq.comBackground: The adjunctive therapeutic potential of simvastatin in schizophrenia treatment has generated interest due to its anti-inflammatory and neuroprotective properties. This meta-analysis aims to assess the efficacy of simvastatin as an adjunct treatment for schizophrenia, synthesizing results from various controlled trials.Methods: We performed a comprehensive search of databases including PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) evaluating the efficacy of simvastatin as an adjunct therapy in patients with schizophrenia. The primary outcome measures were improvements in the Positive and Negative Syndrome Scale (PANSS) scores. Secondary outcomes included changes in overall clinical condition and level of functioning. Data were pooled using random-effects models, and heterogeneity was assessed through I² statistics.Results: The four RCTs included in the analysis represented 425 participants. The combined results demonstrated no significant advantage of simvastatin over placebo in reducing PANSS total scores with a pooled effect size (Standard Mean Difference, SMD) of − 0.36 (95% Confidence Interval, CI: − 0.82 to 0.11) at 1 month, and − 1.80 (95% Confidence Interval, CI: − 4.82 to 1.21) at 3 months, indicating minimal to no effect. Similarly, analyses of secondary outcomes showed no significant improvements in overall clinical condition and level of functioning. The studies exhibited low heterogeneity (I² = 0%).Conclusion: This meta-analysis provides evidence that simvastatin, used as adjunctive therapy, does not significantly improve the symptomatic outcomes of schizophrenia compared to placebo. Although simvastatin is well-tolerated, its role in enhancing antipsychotic treatment efficacy in patients with schizophrenia appears limited. These findings suggest that simvastatin should not be recommended as an adjunctive treatment in the clinical management of schizophrenia. Further research may explore the potential subgroups that could benefit from such treatment or identify the biological reasons for the lack of efficacy.Keywords: schizophrenia, simvastatin, adjunctive therapy, meta-analysis, randomized controlled trials, efficacy

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

Liping Zou,1,&ast; Wanli Kang,2,&ast; Chunhui Guo,3,&ast; Juan Du,4,&ast; Qing Chen,1 Zhengyu Shi,1 Xianzhen Tang,1 Li Liang,1 Peijun Tang,5 Qing Pan,6 Qingdong Zhu,7 Song Yang,8 Zhanlin Chang,9 Zhouli Guo,1 Guihui Wu,1 Shenjie Tang2 1Department of Tuberculosis, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China; 2Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 3Department of Tuberculosis, Harbin Chest Hospital, Harbin, People’s Republic of China; 4Department of Tuberculosis, Wuhan Pulmonary Hotel, Wuhan, People’s Republic of China; 5Department of Tuberculosis, the Fifth People’s Hospital of Suzhou, Suzhou, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Anqing Municipal Hospital, Anqing, People’s Republic of China; 7Department of Tuberculosis, the Fourth People’s Hospital of Nanning, Nanning, People’s Republic of China; 8General Internal Medicine Department, Chongqing Public Health Medical Center, Chongqing, People’s Republic of China; 9Department of Surgery, the Third People’s Hospital of Tibet Autonomous Region, Lasa, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guihui Wu, Department of Tuberculosis, Public Health Clinical Center of Chengdu, Jingjusi 18 Street, Jingjiang District, Chengdu, Sichuan, People’s Republic of China, Tel +86-28-8455-0573, Email wghwgh2584@sina.com Shenjie Tang, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China, Tel +86-13621028338, Email tangsj1106@vip.sina.comObjective: Rifampin-resistant tuberculosis (RR-TB) remains a serious global public health concern. We assessed treatment outcomes and associated influencing factors among RR-TB patients in China.Methods: This research enrolled 1339 patients who started RR-TB treatment between May 2018 and April 2020 in China retrospectively. Data were collected from the electronic medical records. Multivariable logistic regression analysis was used to identify the influencing factors related to unfavorable outcomes.Results: Of the 1339 RR-TB patients, 78.8% (1055/1339) achieved treatment success (cured or treatment completed), 5.1% (68/1339) experienced treatment failure, 1.1% (15/1339) died during treatment, 10.1% (135/1339) were lost to follow-up, and 4.9% (66/1339) were not evaluated. About 67.7% (907/1339) of patients experienced at least one adverse event (AE). The most common AE was hypohepatia (507/1339, 37.9%), followed by hyperuricemia (429/1339, 32.0%), anemia (368/1339, 27.5%), electrolyte disturbance (318/1339, 23.7%), peripheral neuritis (245/1339, 18.3%), and gastrointestinal reactions (203/1339, 15.2%). Multivariate analysis showed that age ≥ 60 years [adjusted odds ratio (aOR): 1.96, 95% confidence interval (CI): 1.39– 2.77], national minority (aOR: 2.36, 95% CI: 1.42– 3.93), smoking (aOR: 1.50, 95% CI: 1.10– 2.04), cardiopathy (aOR: 2.90, 95% CI: 1.33– 6.31), tumors (aOR: 9.84, 95% CI: 2.27– 42.67), immunocompromise (aOR: 2.17, 95% CI: 1.21– 3.91), re-treated TB (aOR: 1.46, 95% CI: 1.08– 1.97), and experienced gastrointestinal reactions (aOR: 2.27, 95% CI: 1.52– 3.40) were associated with unfavorable outcomes. Body mass index (BMI) ≥ 18.5 kg/m2, regimens containing bedaquiline and experienced adverse events (AEs) such as hypohepatia, leukopenia, peripheral neuritis, and optic neuritis were associated with favorable outcomes.Conclusion: High rates of treatment success were achieved for RR-TB patients at tertiary tuberculosis hospitals in China. Age ≥ 60 years, national minority, smoking status, comorbidities, re-treated TB, and experienced gastrointestinal reactions were independent prognostic factors for unfavorable treatment outcomes.Keywords: RR-TB, treatment outcomes, influencing factors, China

Yan Wang,1 Lihua Liang,2,&ast; Ran Li,2,&ast; Yihua Wang,3 Changfu Hao1 1Department of Child and Adolescent Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Primary and Secondary School Health Center, Zhengzhou Education Science Planning and Evaluation Center, Zhengzhou Municipal Education Bureau, Zhengzhou, Henan, People’s Republic of China; 3Institute of Science and Technology Information, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yihua Wang, Institute of Science and Technology Information, Zhengzhou University, Science Avenue, Zhengzhou, Henan Province, 450001, People’s Republic of China, Email wangyh2015@icloud.com Changfu Hao, Department of Child and Adolescent Health, School of Public Health, Zhengzhou University, Science Avenue, Zhengzhou, Henan Province, 450001, People’s Republic of China, Email haochangfu@126.comPurpose: Chatbots, which are based on large language models, are increasingly being used in public health. However, the effectiveness of chatbot responses has been debated, and their performance in myopia prevention and control has not been fully explored. This study aimed to evaluate the effectiveness of three well-known chatbots—ChatGPT, Claude, and Bard—in responding to public health questions about myopia.Methods: Nineteen public health questions about myopia (including three topics of policy, basics and measures) were responded individually by three chatbots. After shuffling the order, each chatbot response was independently rated by 4 raters for comprehensiveness, accuracy and relevance.Results: The study’s questions have undergone reliable testing. There was a significant difference among the word count responses of all 3 chatbots. From most to least, the order was ChatGPT, Bard, and Claude. All 3 chatbots had a composite score above 4 out of 5. ChatGPT scored the highest in all aspects of the assessment. However, all chatbots exhibit shortcomings, such as giving fabricated responses.Conclusion: Chatbots have shown great potential in public health, with ChatGPT being the best. The future use of chatbots as a public health tool will require rapid development of standards for their use and monitoring, as well as continued research, evaluation and improvement of chatbots.Keywords: chatbot, large language model, public health, myopia

Haisong Hou,1,2 Liu Liang,3 Lihong Deng,4 Wanping Ye,5 Yuanzhang Wen,6 Jun Liu1 1Laboratory of Pathogenic Biology, Guangdong Medical University, Zhanjiang, People’s Republic of China; 2Department of Blood Transfusion, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 4Department of Hepatology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 5Department of Gastroenterology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 6Department of Hepatobiliary Surgery, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Jun Liu, Laboratory of Pathogenic Biology, Guangdong Medical University, Zhanjiang, People’s Republic of China, Email liujungd6@163.comBackground: The aim of this study was to describe the demographic and clinical characteristics of hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC), analyse the risk factors associated with HBV-associated HCC, and to provide some references to the diagnosis and treatment of HCC.Methods: This study retrospectively enrolled 730 patients, including 390 patients with chronic hepatitis B (CHB) as controls, and 340 patients with CHB complicated with HCC as patients. Relevant information and medical records of these participants were collected, including age, sex, cigarette smoking, alcoholism, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), cirrhosis, occupation, ascites, HBV-DNA load, the qualitative analysis of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb serological markers, and levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), gamma-glutamyltransferase (GGT), TNM stage, tumor size and tumor number. The T test, Chi-square test, non-parametric rank-sum test, logistic regression analyses were used to explore the influencing factors and their degree of association with HCC in patients with HBV.Results: The proportion of smoking, alcoholism, married status, DM, hypertension, and the rate of HBV-DNA with a viral load of ≥ 500 copies/mL were significantly higher in the HCC group than in the controls (all p< 0.05). Cirrhosis was more common among patients with CHB+HCC than in controls (p=0.013). The proportion of patients with HBsAg, HBeAb, and HBcAb positive was greater in CHB+HCC group than that in CHB group. Logistic regression analysis indicated that age ≥ 60 years (OR: 1.835, 95% CI: 1.020– 3.302, p=0.043), HBeAb positive (OR: 9.105, 95% CI: 4.796– 17.288, p< 0.001), antiviral treatment with entecavir (OR: 2.209, 95% CI: 1.106– 4.409, p=0.025), and GGT (OR: 1.004, 95% CI: 1.001– 1.007, p=0.002) were risk factors for HCC in patients with CHB.Conclusion: Advanced age, HBeAb positive, antiviral treatment with entecavir, and GGT were independent risk factors for HCC in HBV patients.Keywords: chronic hepatitis B, hepatocellular carcinoma, cirrhosis, hepatitis B virus

Yanzhi Feng,1– 4,&ast; Litao Liang,1– 4,&ast; Wenbo Jia,1– 4 Jinyi Wang,1– 4 Chao Xu,1– 4 Deming Zhu,1– 4 Bin Xu,1– 4 Wenhu Zhao,1– 4 Xiangyu Ling,1– 4 Yongping Zhou,5 Lianbao Kong,1– 4,&ast; Wenzhou Ding1– 4,&ast; 1Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, National Health Commission Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, Jiangsu, People’s Republic of China; 3Jiangsu Provincial Medical Innovation Center, Nanjing, Jiangsu, People’s Republic of China; 4Jiangsu Provincial Medical Key Laboratory, Nanjing, Jiangsu, People’s Republic of China; 5Jiangnan University Medical Center, JUMC, Department of Hepatobiliary, Wuxi, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenzhou Ding; Lianbao Kong, Hepatobiliary Centre, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email dingwenzhou@njmu.edu.cn; lbkong@njmu.edu.cnBackground: Circular RNAs (circRNAs) have been shown to play a crucial role in the initiation and development of Hepatocellular carcinoma (HCC). However, the mechanism and function of circ_0007386 in HCC are still unknown.Methods: Circ_0007386 expression level in HCC tissues, and HCC cell lines was further analyzed by qRT-PCR. Agarose gel electrophoresis and Sanger sequencing were used to figure out the structure of circ_0007386. The involvement of circ_0007386 in HCC development was evaluated by experimental investigations conducted in both laboratory settings (in vitro) and living organisms (in vivo). RNA immunoprecipitation, Western blotting, luciferase reporter assay and fluorescence in situ hybridization (FISH) were applied for finding out the interaction among circ_0007386, miR-507 and CCNT2. To assess the connection between circ_0007386 and lenvatinib resistance, lenvatinib-resistant HCC cell lines were employed.Results: The expression of circ_0007386 was found to increase in HCC tissues, and it was observed to be associated with a worse prognosis. Overexpression of circ_0007386 stimulated HCC cells proliferation, invasion, migration and the epithelial–mesenchymal transition (EMT) while silencing of circ_0007386 resulted in the opposite effect. Mechanistic investigations revealed that circ_0007386 acted as a competing endogenous RNA of miR-507 to prevent CCNT2 downregulation. Downregulating miR-507 or overexpressing CCNT2 could reverse phenotypic alterations that originated from inhibiting of circ_0007386. Importantly, circ_0007386 determines the resistance of hepatoma cells to lenvatinib treatment.Conclusion: Circ_0007386 advanced HCC progression and lenvatinib resistance through the miR-507/ CCNT2 axis. Meanwhile, circ_0007386 served as a potential biomarker and therapeutic target in HCC patients. Keywords: hepatocellular carcinoma, circ_0007386, miR-507, CCNT2, Lenvatinib

Jingzhan Huang,1,&ast; Jialong Liu,1,&ast; Jin Lan,1,&ast; Jingbo Sun,1 Kun Zhou,1 Yunyao Deng,1 Li Liang,2 Lixin Liu,1,&ast; Xiaolong Liu1 1Department of General Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixin Liu; Xiaolong Liu, Department of General Surgery, The Third Affiliated Hospital, Southern Medical University, 183 West Zhongshan Avenue, Guangzhou, Guangdong, 510630, People’s Republic of China, Email llx0129@i.smu.edu.cn; lxl1979@i.smu.edu.cnBackground: Guanine-rich RNA sequence binding factor 1 (GRSF1), part of the RNA-binding protein family, is now attracting interest due to its potential association with the progression of a variety of human cancers. The precise contribution and molecular mechanism of GRSF1 to colorectal cancer (CRC) progression, however, have yet to be clarified.Methods: Immunohistochemistry and Western Blot analysis was carried out to detect the expression of GRSF1 in CRC at both mRNA and protein levels and its subsequent effects on prognosis. A series of functional tests were performed to understand its influence on proliferation, migration, and invasion of CRC cells.Results: The universal downregulation of GRSF1 in CRC was identified, indicating a correlation with poor prognosis. Our functional studies unveiled that the elimination of GRSF1 enhances tumour activities such as proliferation, migration, and invasion of CRC cells, while GRSF1 overexpression curtailed these abilities.Conclusion: Notably, we uncovered that GRSF1 insufficiency modulates the PI3K/Akt signaling pathway and Ras activation in CRC. Therefore, our data suggest GRSF1 operates as a tumor suppressor gene in CRC and may offer promise as a potential biomarker and novel therapeutic target in CRC management. Keywords: GRSF1, CRC, proliferation, metastasis, Ras/PI3K/Akt

Hui Rao,1 Xianfang Wang,2 Yu Luo,3 Liu Liang,1 Wei Ye,1 Xuemin Guo1 1Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Gynaecology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Xuemin Guo, Department of Laboratory Medicine, Meizhou People’s Hospital, No. 63 Huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email Guoxm12@126.comBackground: The role of aldehyde dehydrogenase 2 (ALDH2) in cardiovascular diseases has been gradually studied. However, it is unclear whether ALDH2 polymorphism is associated with the risk of early onset (onset age ≤ 55 years old in men and ≤ 65 years old in women) coronary artery stenosis (CAS). The association between ALDH2 single nucleotide polymorphism (SNP) rs671 and risk in patients with early onset CAS was investigated in this study.Methods: The study included 213 early onset CAS patients and 352 individuals without CAS were set as controls. The ALDH2 rs671 polymorphism was genotyped by polymerase chain reaction (PCR) - microarray. Differences in ALDH2 rs671 genotypes and alleles between patients and controls were compared. Multiple logistic regression analysis was performed after adjusting for gender, body mass index (BMI), smoking history, drinking history, and diabetes mellitus to assess the relationship between ALDH2 rs671 genotypes and early onset CAS risk.Results: The frequency of the ALDH2 rs671 G/G genotype was lower in the early onset CAS patients (43.7% vs 55.3%, p=0.007) than that in the controls. The frequency of the ALDH2 rs671 A allele was higher (32.9% vs 25.0%) than that in the controls (p=0.005). After adjusting for other confounding factors, multivariate logistic regression showed that ALDH2 rs671 A/A genotype (A/A vs G/G: odds ratio (OR) 2.508, 95% confidence interval (CI): 1.130– 5.569, p=0.024), overweight (BMI≥ 24.0 vs 18.5– 23.9: OR 5.047, 95% CI: 3.275– 7.777, p< 0.001), history of smoking (yes vs no: OR 2.813, 95% CI: 1.595– 4.961, p< 0.001), and diabetes mellitus (yes vs no: OR 2.191, 95% CI: 1.397– 3.437, p=0.001) were the independent risk factors of early onset CAS.Conclusion: In men ≤ 55 years old and women ≤ 65 years old, individuals with ALDH2 rs671 A/A genotype, overweight (BMI ≥ 24.0 kg/m2), smoking history, and diabetes mellitus increased risk of developing CAS.Keywords: aldehyde dehydrogenase 2, gene polymorphism, coronary artery stenosis, early onset

Mu-Gen Dai,1,2 Si-Yu Liu,2 Lin Zhu,3 Wen-Feng Lu,4 Gui-Lin Xie,5 Lei Liang,6 Jun-Wei Liu,6 Bin Ye1 1Department of Gastroenterology, The Fifth Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2Department of Laboratory Medicine, The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Zhejiang University Lishui Hospital, Lishui, Zhejiang, People’s Republic of China; 3Department of Gastroenterology, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 4Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, People’s Republic of China; 5Department of Hepatobiliary Surgery, Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang Province, 312000, People’s Republic of China; 6General Surgery, Cancer Center, Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Jun-Wei Liu, General Surgery, Cancer Center, Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Email liujunwei@hmc.edu.cn Bin Ye, Department of Gastroenterology, The Fifth Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China, Email 408252097@qq.comBackground & Aims: To examine the association of the history of preoperative antiviral therapy (AVT) with the tumor recurrence and overall survival in HBV-related HCC patients undergoing curative-intent hepatectomy.Methods: Patients who underwent curative-intent hepatectomy for HBV-related HCC between 2014 and 2019 at 4 Chinese hospitals were analyzed. Patients were categorized as having undergone preoperative antiviral therapy (AVT) > 1 year or without antiviral therapy (non-AVT). Patient clinical features, short-term outcomes, overall survival (OS), and time-to-recurrence (TTR) were also compared. Multivariate Cox regression analysis was performed to identify the impact of preoperative AVT on the OS and TTR.Results: Among the 565 patients, 190 (33.6%) underwent continuous AVT > 1 year before surgery. Patients in the non-AVT group were more likely to have worse liver function and more advanced tumor pathological characteristics than those in the AVT group. Postoperative morbidity and mortality rates were comparable between the two groups. Multivariate analyses revealed that a preoperative HBV viral level ≥ 2000 IU/mL was independently associated with poorer TTR (hazard ratio, 1.328; 95% CI, 1.049– 1.682) and preoperative AVT was a protective factor for OS (hazard ratio, 0.691; 95% CI, 0.484– 0.986).Conclusion: A high preoperative HBV DNA level was an independent risk factor for tumor recurrence. Preoperative AVT > 1 year was associated with better OS and a reduced incidence of tumor recurrence by inhibiting the preoperative level of HBV DNA. Keywords: hepatectomy, hepatitis B virus, antiviral therapy, survival, recurrence

Shitong Su,1,2 Lianjing Liang,1 Lin Lü,1 Mingfeng Li,3 Xiaoling Zhang,4 Yongmei Jin,5 Wei Wei,1 Zhi Wan6 1Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Division of Head & Neck Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 3Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 4Department of Cardiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 5Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 6Rare Diseases Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Wei Wei, Chest Pain center, Department of Emergency Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu, 610041, People’s Republic of China, Email ww8075@126.com Zhi Wan, Rare Diseases Center, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu, 610041, People’s Republic of China, Email 456wz@163.comAbstract: Loeffler endocarditis, eosinophilic endocarditis or eosinophilic endomyocardial disease are conditions associated with hypereosinophilia and they affect the heart function. Loeffler endocarditis is a rare endomyocardial disorder thought to be caused by eosinophilic damage. The disorder is characterized by inflammatory infiltration, formation of thrombus within cardiovascular system, and ultimately fibrosis of the afflicted area. It can lead to multiple severe complications, including thromboembolic disease, thickening of fibrous tissue in the endocardium of ventricles, valve involvement, apical obliteration, and various heart disorders. Although early clinical intervention can lead to remission, the underlying mechanisms of the disorder remain unresolved. In the present article, we summarise the existing literature concerning Loeffler endocarditis based on PubMed, Web of Science, and other medical databases to conduct an in-depth review of the epidemiology, etiology, pathophysiological mechanisms, staging, diagnosis, treatment and prognosis of Loeffler endocarditis. Meanwhile, we provide novel patients data and clinical figures of Loeffler endocarditis to supplement the understanding of this cardiac disorder. The findings presented in this article provide a basis for further studies and can be used to improve management of the disorder.Keywords: Loeffler endocarditis, hypereosinophilia, eosinophils damage

Lina Yu,1,&ast; Zidan Xu,1,&ast; Guanxiong Zhu,1,&ast; Liting Zeng,1 Zeyu Zhang,1 Yang Yu,2 Siran Wang,1 Xin Zhang,3 Na Zhou,3 Lu Liang1,4 1Department of Preventive Dentistry, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Sports and Health, Guangzhou Sport University, Guangzhou, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wailong, Taipa, Macau, People’s Republic of China; 4Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lina Yu; Lu Liang, Email yulina@gzhmu.edu.cn; lliangaa@gzhmu.edu.cnBackground: The photodynamic therapy (PDT) showed promising potential in treating tongue squamous cell carcinoma (TSCC). The Food and Drug Administration approved Verteporfin (Ver) is a powerful alternative in this field for its penetrating power and high production of reactive oxygen species (ROS). However, its applications in the treatment of TSCC are still rare.Methods: Ver was loaded onto Poly (lactic-co-glycolic acid) (PLGA) nanoparticles, followed by the modification with RGD peptide as the ligand. The nanostructured was named as RPV. In vitro assessments were conducted to evaluate the cytotoxicity of RPV through the Live/Dead assay analysis and Cell Counting Kit-8 (CCK-8) assay. Using the reactive oxygen species assay kit, the potential for inducing targeted tumor cell death upon laser irradiation by promoting ROS production was investigated. In vivo experiments involved with the biological distribution of RPV, the administration with RPV followed by laser irradiation, and the measurement of the tumor volumes. Immunohistochemical analysis was used to detect the Ki-67 expression, and apoptosis induced by RPV-treated group. Systemic toxicity was evaluated through hematoxylin-eosin staining and blood routine analysis. Real-time monitoring was employed to track RPV accumulation at tumor sites.Results: The in vitro assessments demonstrated the low cytotoxicity of RPV and indicated its potential for targeted killing TSCC cells under laser irradiation. In vivo experiments revealed significant tumor growth inhibition with RPV treatment and laser irradiation. Immunohistochemical analysis showed a notable decrease in Ki-67 expression, suggesting the effective suppression of cell proliferation, and TUNEL assay indicated the increased apoptosis in the RPV-treated group. Pathological examination and blood routine analysis revealed no significant systemic toxicity. Real-time monitoring exhibited selective accumulation of RPV at tumor sites.Conclusion: The findings collectively suggest that RPV holds promise as a safe and effective therapeutic strategy for TSCC, offering a combination of targeted drug delivery with photodynamic therapy.Keywords: photodynamic therapy, verteporfin, RGD sequence, tumor-specific drug delivery

Lin Feng,1 Jiachen Li,1 Zhenbei Qian,2 Chenglong Li,3,4 Darui Gao,3,4 Yongqian Wang,3,4 Wuxiang Xie,3,4 Yutong Cai,5 Zhaohui Tong,2 Lirong Liang1 1Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Heart and Vascular Health Research Center, Peking University Clinical Research Institute, Peking University First Hospital, Beijing, People’s Republic of China; 4Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, People’s Republic of China; 5Centre for Environmental Health and Sustainability, Department of Health Sciences, University of Leicester, Leicester, UKCorrespondence: Lirong Liang, Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email llrcruie@163.comPurpose: Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) exhibit heterogeneous responses to corticosteroid treatment. We aimed to determine whether combining eosinophil levels with other routine clinical indicators can enhance the predictability of corticosteroid treatment outcomes and to come up with a scoring system.Patients and Methods: Consecutive patients admitted with AECOPD receiving corticosteroid treatment between July 2013 and March 2022 at Beijing Chao-Yang Hospital were retrospectively analyzed. Data on patients’ demographics, smoking status, hospitalization for AECOPD in the previous year, comorbidities, blood laboratory tests, in-hospital treatment and clinical outcomes were collected. Least absolute shrinkage and selection operator (LASSO) regression and backward logistic regression were used for predictor selection, and predictive nomograms were developed. The discrimination and calibration of the nomograms were assessed using the area under the receiver operating curve (AUC) and calibration plots. Internal validation was performed using the 500-bootstrap method, and clinical utility was evaluated using decision curve analysis (DCA).Results: Among the 3254 patients included, 804 (24.7%) had treatment failure. A nomogram of eosinophils, platelets, C-reactive protein (CRP), low density lipoprotein cholesterol, prognostic nutritional index (PNI), hospitalization for AECOPD in the previous year, ischemic heart diseases and chronic hepatic disease was developed to predict treatment failure for patients with a smoking history. For patients without a smoking history, a nomogram of CRP, PNI, ischemic heart diseases and chronic hepatic disease was developed. Although the AUCs of these two nomograms were only 0.644 and 0.647 respectively, they were significantly superior to predictions based solely on blood eosinophil levels.Conclusion: We developed easy-to-use comprehensive nomograms utilizing readily available clinical biomarkers related to inflammation, nutrition and immunity, offering modestly enhanced predictive value for treatment outcomes in corticosteroid-treated patients with AECOPD. Further investigations into novel biomarkers and additional patient data are imperative to optimize the predictive performance.Keywords: chronic obstructive pulmonary disease, glucocorticoids, prediction model, least absolute shrinkage and selection operator

The liquefaction of crop residues in the presence of ethylene glycol, ethylene carbonate, or polyethylene glycol using sulfuric acid as a catalyst was studied. For all experiments, the liquefaction was conducted at 160C and atmospheric pressure. The mass ratio of feedstock to liquefaction solvents used in all the experiments was 30:100. The results show that the acid catalyzed liquefaction process fit a pseudo-first-order kinetics model. Liquefaction yields of 80, 74, and 60% were obtained in 60 minutes of reaction when corn stover was liquefied with ethylene glycol, a mixture of polyethylene glycol and glycerol (9:1, w/w), and ethylene carbonate, respectively. When ethylene carbonate was used as solvent, the liquefaction yields of rice straw and wheat straw were 67% and 73%, respectively, which is lower than that of corn stover (80%). When a mixture of ethylene carbonate and ethylene glycol (8:2, w/w) was used as solvent, the liquefaction yields for corn stover, rice straw and wheat straw were 78, 68, and 70%, respectively.

Liping Lei,1,2,&ast; Jingjing Yang,1,&ast; Hao Peng,1 Ruiyan Huang,1 Lichun Liang,1 Ruifang Liu,1 Jiangfa Li1 1Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China; 2Department of Geriatric Medicine, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiangfa Li, Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China, Tel +86-7732824373, Email 247546160@qq.comBackground: Abnormal expression of genes causes tumorigenesis, tumor progression, and poor prognosis in hepatocellular carcinoma (HCC). Therefore, the aims of this study were to explore the transcription enhancer domain factor 4 (TEAD4) in patients with liver cancer and its relationship with prognosis.Methods: HTSeq-FPKM data and corresponding clinical data of HCC patients were obtained from The Cancer Genome Atlas (TCGA). Difference in TEAD4 expression between normal and tumor and the correlation with clinical characteristics were analyzed by the chi-squared test based on UALCAN. HepG2 cell lines were used to study the effect of TEAD4 on HCC cell lines. The expression and clinical significance of TEAD4 in HCC were detected in clinical cases.Results: The transcription and post-transcription levels of TEAD4 were higher in HCC tumors than normal illustrated different expressed transcription of TEAD4 in gender, nodal metastasis status, tumor grades, and individual cancer stages. The high TEAD4 expression was significantly associated with tumor grades. The high expression of TEAD4 was significantly correlated to shorter 2– 5 years overall survival. Inhibition of TEAD4 expression in HepG2 cells resulted in significantly decreased cell proliferation and invasion.Conclusion: TEAD4 was identified as an independent prognostic factor, and inhibition of TEAD4 expression in HepG2 cells resulted in significantly decreased cell proliferation and invasion.Keywords: TCGA, TEAD4, hepatocellular carcinoma

This scale-up study demonstrated the feasibility of an ionic liquid (IL) pretreatment process at 40 kg scale, using the IL 1-ethyl-3-methylimidazolium acetate ([C2C1Im][OAc]) as the solvent. The pretreatment was followed by enzymatic hydrolysis through which the process efficiency for biomass conversion to monomeric sugars was determined. The results show that 43 wt% of switchgrass was dissolved in IL after 2 h of pretreatment at 160 °C with 15 wt% solid loading. A 120 h enzymatic hydrolysis of the pretreated switchgrass results in 96% glucan and 98% xylan conversion. [C2C1Im][OAc] pretreatment has been successfully scaled up to 40 kg with improved sugar titers and yields relative to bench scale (6 kg). The mass flow of the overall process was established and the major scale-up challenges of the process were identified.

Introduction Methods Results Conclusions In this study, we aimed to assess the effect of prophylactic central compartment neck dissection (pCCND) in conjunction with hemithyroidectomy (HT) for clinically low‐risk node‐negative (cN0) papillary thyroid carcinoma (PTC).A thorough literature search was performed utilizing PubMed and EMBASE for articles published until October 2023. Subsequently, a meta‐analysis was performed on studies involving patients with cN0 PTC, with postoperative locoregional recurrence (LRR) and survival data, treated with HT + pCCND or HT. The study was registered with PROSPERO (CRD42024560962).We included seven studies in this meta‐analysis, including 2132 patients who met the inclusion criteria: six retrospective cohort studies and one randomized controlled trial. The HT + pCCND group consisted of 1090 cases, and the HT group had 1042 cases. The LRR rates after HT with or without pCCND were similar (3.58% vs. 4.51%; odds ratio (OR) = 0.65; 95% confidence interval (CI) = 0.41–1.03). Five of the seven studies provided prognostic and survival data, particularly the log hazard ratio (log HR) of disease‐free survival (DFS) between the two groups. There was also no significant difference in terms of DFS between the HT + pCCND and HT groups (OR = 0.67; 95% CI = 0.42–1.07).There was no significant difference in LRR and DFS between the HT + pCCND and HT groups. pCCND did not demonstrate significant efficacy in improving oncological outcomes for low‐risk patients with cN0 PTC. Therefore, for patients with low‐risk cN0 PTC, thyroid surgeons should make reasonable and individualized decisions regarding the extent of surgical removal. [ABSTRACT FROM AUTHOR]

Van der Waals (vdW) heterojunctions composed of GaN/graphene have high transmittance and excellent carrier transport properties. The combination of multidimensional hybrid heterojunctions with metasurfaces can open up many fascinating prospects for novel optical components over a broad range of the electromagnetic spectrum. This work experimentally demonstrates a multifunctional temperature‐sensitive meta‐device based on GaN/graphene vdW heterojunctions integrated with a metasurface. Notably, it is discovered that the conductivity of the vdW heterojunctions increases rapidly when it is excited by a thermal signal, resulting in a significant change in the relative phase retardation as well as amplitude modulation of an incident THz wave. Then a continuous wavelet transform is used instead of the traditional Fourier transform, and the two‐dimensional wavelet coefficient card is built to achieve fast detection over a wider range of temperature. Simultaneously, the variation of temperature dynamically controls the contributions of the multipoles, eventually determining the active switching of exotic anapoles with extreme non‐radiative confinement to highly radiative electric dipoles. This work offers the possibility of designing novel chip‐scale multifunctional thermal tuning devices and promotes the potential application of active micro‐nanophotonic devices in temperature sensors, terahertz modulators, and dynamic near‐field imaging. [ABSTRACT FROM AUTHOR]