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1. Introduction In early September 2022, tropical cyclone (TC) Hinnamnor struck South Korea, resulting in 12 fatalities and tremendous socioeconomic damages. (1) Hinnamnor was the first super typhoon (lifetime maximum [...]

Yanfang Luo,1,* Jianru Hao,2,* Zhenzhen Su,1,* Yujuan Huang,1 Fen Ye,1 Yanhui Qiu,2 Zhimin Liu,2 Yuping Chen,3 Renjuan Sun,1 Yuyu Qiu2 1Department of Neurology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, People’s Republic of China; 2Wuxi School of Medicine, Jiangnan University, Wuxi, 214126, People’s Republic of China; 3Department of Basic Medicine, Jiangsu Vocational College of Medicine, Yancheng, 224005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Renjuan Sun; Yuyu Qiu, Email 15061885987@163.com; yuyuqiu@jiangnan.edu.cnAim: This study aimed to investigate the prevalence and associated factors of hypokalemia in patients with acute ischemic stroke.Methods: A cohort of 996 patients was assessed using a general data questionnaire, laboratory indicators, the NIH Stroke Scale (NIHSS), the Barthel Index (BI), the Frail scale, Nutritional Risk Screening (NRS-2002), and the Kubota drinking water test.Results: Among the 996 patients, 205 (20.6%) were found to have hypokalemia. Logistic regression analysis identified several independent predictors of hypokalemia: age (OR 1.020, 95% CI 1.001– 1.039, P=0.041), hypertension (OR 2.691, 95% CI 1.190– 6.089, P=0.017), Frail score (OR 1.756, 95% CI 1.034– 2.981, P=0.037), Kubota drinking water test grade 3 (OR 2.124, 95% CI 1.055– 4.276, P=0.035), Kubota drinking water test grade 4 (OR 3.016, 95% CI 1.113– 8.174, P=0.037), NIHSS score (OR 1.135, 95% CI 1.018– 1.264, P=0.022), platelet count (OR 0.997, 95% CI 0.994– 0.999, P=0.021), and urea nitrogen levels (OR 0.833, 95% CI 0.750– 0.926, P=0.001).Conclusion: The prevalence of hypokalemia is high in patients with acute ischemic stroke. Independent risk factors included age, hypertension, frailty, neurological function, swallowing function, platelet count and blood urea level.Keywords: acute ischemic stroke, related factors, neurological function, function of deglutition, frail, laboratory indicators

Jiayun Liu, Rui Sun, Guomin Gao, Mogen Zhang, Huiping Fan, Xiaonan Ma, Yanhong Yu, Yanmei Yuan, Lulu Zhang, Changying Niu Department of Dermatology, Affiliated Hospital of Shandong Second Medical University, School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of ChinaCorrespondence: Changying Niu, Department of Dermatology, Affiliated Hospital of Shandong Second Medical University, School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China, Tel +86-536-3081272, Email niucy0125@126.comObjective: The relationship between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and psoriasis remains unclear. This study aims to analyze the association between ACE gene I/D polymorphism and the risk of psoriasis vulgaris in the Chinese Han population and to examine the correlation between ACE gene I/D polymorphism and psoriasis with comorbid hypertension and diabetes.Methods: A total of 358 patients with psoriasis vulgaris and 347 age- and sex-matched healthy volunteers from the Chinese Han population were selected. Clinical data, including blood pressure and fasting blood glucose, were collected from the patients. The ACE gene I/D polymorphism was analyzed using polymerase chain reaction (PCR). The association between ACE gene I/D polymorphism and psoriasis vulgaris, as well as comorbid hypertension and diabetes, was analyzed using the Pearson χ²-test.Results: The frequency of the ACE II genotype (OR = 1.84, 95% CI = 1.30, 2.61; P < 0.01) and the I allele (OR = 1.51, 95% CI = 1.22, 1.86; P < 0.01) was significantly higher in psoriasis patients compared to the control group. Conversely, the frequency of the ACE DD genotype (OR = 0.62, 95% CI = 0.44, 0.87; P < 0.01) and the D allele (OR = 0.66, 95% CI = 0.54, 0.82; P < 0.01) was significantly lower in psoriasis patients compared to the control group. No statistically significant differences were observed when stratified by blood pressure and blood glucose abnormalities (P > 0.05).Conclusion: The ACE II genotype and I allele are risk factors for psoriasis vulgaris in the Northern Chinese Han population.Keywords: psoriasis vulgaris, angiotensin-converting enzyme, insertion/deletion mutation, gene polymorphism, Chinese Han ethnic group

We assessed all 148 wetland nature reserves in China and the distribution of the four taxa of endemic and threatened terrestrial vertebrates, reptiles, amphibians, birds and mammals. Assessment of the wetland nature reserves was combined with the governmental list of the endemic and threatened vertebrates to identify the richness of the species. Species richness was scored as high, medium or low using a factor analysis method, and 31 wetland ecosystems were marked as high protection areas. The relationship between the threatened species and the endemic species in the reserves was also analyzed. We found that both richness patterns were similar. Based on the richness study, a nature reserve classification system with corresponding

Xiang Wen,1,&ast; Xiaohui Wu,1,&ast; Zhishan Deng,1,&ast; Fan Wu,1,2 Huajing Yang,1 Shan Xiao,1 Cuiqiong Dai,1 Changli Yang,3 Shuqing Yu,4 Ruiting Sun,1 Pixin Ran,1,2 Yumin Zhou1 1State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease & National Center for Respiratory Medicine & Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Guangzhou National Laboratory, Guangzhou, Guangdong, People’s Republic of China; 3Wengyuan County People’s Hospital, Shaoguan, People’s Republic of China; 4Lianping County People’s Hospital, Heyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumin Zhou; Pixin Ran, Email zhouyumin410@126.com; pxran@gzhmu.edu.cnBackground: The previous findings on the correlation between spirometry and high-density lipoprotein (HDL) cholesterol are intriguing yet conflicting. The aim of this research is to evaluate the relationship between HDL levels and spirometry as well as imaging parameters in patients with chronic obstructive pulmonary disease (COPD) in China.Methods: This study encompasses a total of 907 COPD patients. Participants with complete data from questionnaire interviews, lipid profile examinations, spirometry testing, and computed tomography (CT) scans were included in the analysis. A generalized additive model was employed to identify the non-linear relationship between HDL levels and both spirometry and imaging parameters. In the presence of non-linear correlations, segmented linear regression model was applied to ascertain threshold effects.Results: After adjusting for various factors, we found a non-linear correlation between HDL levels and spirometry/imaging parameters, with an inflection point at 4.2 (66 mg/dL). When Ln (HDL) was below 4.2, each unit increase correlated significantly with reduced post-bronchodilator FEV1 (0.32L, 95% CI: 0.09– 0.55), decreased predicted FEV1% (11.0%, 95% CI: 2.7– 19.3), and lowered FEV1/FVC (8.0%, 95% CI: 4.0– 12.0), along with notable increases in Ln (LAA− 950) by 1.20 (95% CI: 0.60– 1.79) and Ln (LAA− 856) by 0.77 (95% CI: 0.37– 1.17). However, no significant associations were observed when Ln (HDL) was greater than or equal to 4.2.Conclusion: A non-linear correlation existed between HDL levels with lung function and CT imaging in COPD patients. Prior to reaching 66 mg/dL, an elevation in HDL was significantly associated with impaired lung function, more severe gas trapping and emphysema.Keywords: COPD, high-density lipoprotein, lung function, computed tomography imaging

Cuixiang Shao,1,2 Qi Chen,3 Siwen Tang,4 Chaowen Wang,1 Renjuan Sun5 1Department of Obstetrics, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214000, People’s Republic of China; 2Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China; 3Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214000, People’s Republic of China; 4Department of Intensive Care Unit, First People ‘s Hospital of Pinghu, Pinghu, Zhejiang, 314299, People’s Republic of China; 5Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214000, People’s Republic of ChinaCorrespondence: Renjuan Sun, Department of Nutrition, Affiliated Hospital of Jiangnan University, 1000 Hefeng Road, Wuxi, Jiangsu, 214000, People’s Republic of China, Tel +86 13813479833, Email sunrj2023rj@163.comPurpose: This study aimed to create, verify and assess the clinical utility of a prediction model for maternal and neonatal adverse outcomes in pregnant women with hypothyroidism.Methods: A prediction model was developed, and its accuracy was tested using data from a retrospective cohort. The study focused exclusively on female patients diagnosed with hypothyroidism who were admitted to a tertiary hospital. The development and validation cohort comprised individuals who gave birth between 1 October 2020 and 31 December 2022. The primary outcome was a combination of crucial maternal and newborn problems (eg premature births, abortions and neonatal asphyxia). The prediction model was developed using logistic regression. Evaluation of the model’s performance was conducted based on its ability to discriminate, calibrate and provide clinical value.Results: In total, nine variables were chosen to develop the predictive model for adverse maternal and neonatal outcomes during pregnancy with hypothyroidism. The area under the curve of the model for predicting maternal adverse outcomes was 0.845, and that for predicting neonatal adverse outcomes was 0.685. The calibration plots showed good agreement between the nomogram predictions and the actual observations in both the training and validation cohorts. Furthermore, decision curve analysis suggested that the nomograms were clinically useful and had good discriminative power to identify high-risk mother–infant cases.Conclusion: Two models to predict the risk probability of maternal and neonatal adverse outcomes in pregnant women with hypothyroidism were developed and verified to assist physicians in evaluating maternal and neonatal adverse outcomes throughout pregnancy with hypothyroidism and to facilitate decision-making regarding therapy.Keywords: pregnancy with hypothyroidism, maternal and neonatal adverse outcomes, nomogram, forecasting model

Rongxin Sun,1 Desheng Duan,2 Renzeng Li2 1Department of Orthopaedics, The Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Province, People’s Republic of China; 2Second Department of Orthopaedics, Third People’s Hospital of Anyang City, Anyang City, Henan Province, People’s Republic of ChinaCorrespondence: Renzeng Li, Second Department of Orthopaedics, Third People’s Hospital of Anyang City, 363 Dongfeng Road, Beiguan District, Anyang City, Henan Province, People’s Republic of China, Tel +86-13837247813, Email LRZ_doctor@163.comBackground: Recent studies have put forward the viewpoint of “bone immunology”, which holds that the immune system and immune factors play an important regulatory role in the occurrence and development of osteoporosis. This study was intended to identify genetic characteristics of differentially expressed immune-related mRNA and lncRNA in patients combined with osteoporosis and vertebral fracture.Methods: The peripheral blood samples were obtained from 3 groups of subjects: healthy control (HC), osteoporosis patients without vertebral fracture (OWF), and osteoporosis patients combined with vertebral fracture (OVF). The data were integrated to obtain differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs). Subsequently, the protein-protein interaction (PPI) networks were constructed. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were performed. Cytoscape-cytoHubba plug-in was used to identify key DEmRNAs. Furthermore, lncRNA-miRNA-mRNA, mRNA-lncRNA co-expression and transcription factors (TFs) networks were constructed. In addition, real-time PCR verification was performed.Results: Totally of 3378 lncRNA-mRNA pairs were obtained, and the lncRNA co-expressed mRNA was mainly enriched in immune-related pathways, especially in GO-biological process (GO-BP) analysis. A total of 8 hub immune-related DEmRNAs were obtained, including IL18R1, IL18RAP, SLC11A1, CSF2RA, CCR3, IL1R2, PGLYRP1, and IL1R1. The TFs network showed that 8 hub immune-related DEmRNAs had interacting TFs. The co-expression network showed that 7 hub immune-related DEmRNAs (IL18R1, IL18RAP, SLC11A1, CSF2RA, IL-1R2, PGLYRP1, and IL1R1) had lncRNA-mRNA co-expression relationship. In addition, the lncRNA-miRNA-mRNA network includes 32 miRNAs, 7 hub immune-related mRNAs (IL18R1, IL18RAP, CSF2RA, CCR3, IL1R2, PGLYRP1, and IL1R1), and 11 lncRNAs.Conclusion: Our study provides a novel and in-depth identification of co-expressed mRNAs and lncRNAs in patients combined with osteoporosis and vertebral fracture at a molecular level. This may provide new candidate biomarkers for the diagnosis of patients with high-risk fractures in the future.Keywords: osteoporosis, vertebral fracture, immune, mRNA, lncRNA, transcriptome

Ruonan Sun,1,&ast; Shuyuan Zhang,1,&ast; Jiarui Si,2 Liming Zhang,1 Haolun Yang,1 Zheng Ye,1 Xin Xiong2 1West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zheng Ye, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, People’s Republic of China, Email zheng_ye@scu.edu.cn Xin Xiong, West China Hospital of Stomatology, Sichuan University, No. 14 Section 3, Renmin South Road, Chengdu, 610041, People’s Republic of China, Tel/Fax +86-28-85503898, Email drxiongxin@scu.edu.cnBackground: Studies have reported correlations between various oral behaviors and painful temporomandibular disorders (TMD), yet comprehensive research on the independent effects of each oral behavior within the general population remains sparse.Objective: This cross-sectional study aimed to investigate the association between painful TMD (PT) and various oral behaviors in general population.Methods: A questionnaire survey was conducted with participants to collect data encompassing demographic characteristics, eight specific oral behaviors, and the 5 major TMD symptoms(5Ts) checklist. Participants were categorized into PT and non-PT (NPT) groups based on their responses to the 5Ts checklist. Those reporting TMJ/facial pain or headaches were assigned to the PT group, while all other participants constituted the NPT group. Both univariate and multivariate logistic regression analyses were employed to evaluate the association between individual oral behavior and the presence of PT, controlling for demographic confounders including age, sex, systemic diseases, and dental treatments history.Results: A total of 441 valid questionnaires were received, including 156 males and 285 females. The prevalence of PT was identified to be 33.33%, with 61.00% of participants engaging in one or more types of oral behaviors. Each oral behavior was more frequently reported in the PT group compared to the NPT group. The univariate logistic regression analysis identified positive correlations between all eight oral behaviors and PT. In the multivariate logistic regression analysis, these associations persisted after adjustment for demographic confounders including age, sex, history of systemic diseases and dental treatments (P< 0.01). The behaviors most strongly associated with PT were “Hold or jut jaw forward/to the side” (OR:4.478), “Hold, tighten or tense muscles without clench” (OR:3.343) and “Hold jaw in rigid or tense position” (OR:3.209).Conclusion: The presence of oral behaviors has significant association with PT. Individuals exhibiting multiple oral behaviors are more likely to experience PT. Additional studies are needed to clarify the effects of reducing oral behaviors on pain-related symptoms.Keywords: oral behaviors, painful temporomandibular disorders, Temporomandibular Joint, general population, cross-sectional study

Abstract Given their conditions to reside in and intensify longer over warm oceans, tropical cyclones (TCs) in the western North Pacific (WNP) present a stronger lifetime maximum intensity during El Niño than during La Niña. By using observational data, we found that the anomalously cool sea surface temperature (SST)s in the basin act as effective barriers against intense TCs approaching East Asia during El Niño, weakening their destructiveness at landfall. Based on our high-resolution pseudo-global-warming simulations, the basin-wide 2K SST warming within the WNP basin can, however, shatter this cool SST barrier, exposing East Asia to more destructive TCs during El Niño, compared to those during La Niña. Considering that the 2K warmer WNP will likely occur in the mid-21st century under a high emission scenario and in the late 21st century under a moderate emission scenario, our findings support that more aggressive efforts of global warming mitigation are needed.

Yu Z, Chan S, Wang X, et al. Drug Des Devel Ther. 2023;17:993–1006. At the authors request, the Editor and Publisher of the journal Drug Design, Development and Therapy have retracted the published article. Following publication of the article, the authors raised concerns about the duplication of images from Figure 4. Specifically, The images for Figure 4G, HCT116, RUT and 5-FU, have been duplicated. The authors wished to apologize for this error and no longer have confidence in the data and corresponding findings. To maintain academic standards, the authors requested to retract the article and the Editor and Publisher agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Rui Sun,&ast; Lu Yuan,&ast; Yun Shen,&ast; Ziyang Shen, Bo Ding, Jianhua Ma Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Ding; Jianhua Ma, Email dingbonanjing@sina.com; majianhua196503@126.comAim: To compare the effect of metformin, a fixed combination of metformin and pioglitazone, or dapagliflozin on insulin resistance in patients with newly diagnosed type 2 diabetes.Methods: In this 6-week randomized open-label trial, 58 patients were randomly assigned to insulin with metformin, a fixed combination of metformin and pioglitazone, or dapagliflozin for 4 weeks. Hyperinsulinemic euglycemic clamp tests and FreeStyle Libre Pro Sensor were used to evaluate the insulin sensitivity represented by glucose-infusion rate (M value) and glycemic control, respectively. The main outcome was changes in insulin resistance compared with baseline.Results: The baseline characteristics were well matched among the three groups. When compared to baseline, insulin sensitivity after treatment was significantly improved. Further study revealed that the fixed combination of metformin and pioglitazone provided superior M-value improvement compared with metformin, but not different from dapagliflozin. Moreover, a greater reduction in insulin dose was observed in the fixed combination of metformin and pioglitazone group than the metformin or dapagliflozin group. However, there were no significant differences in the parameters of glycemic control within the groups.Conclusion: In patients with newly diagnosed type 2 diabetes, a fixed combination of metformin and pioglitazone provided greater improvement in insulin resistance than metformin alone and similar changes in insulin resistance to dapagliflozin.Keywords: insulin resistance, metformin, pioglitazone, dapagliflozin, type 2 diabetes

Wenwen Sun,1,&ast; Jun Shen,1,&ast; Ru Sun,1 Dan Zhou,1 Haihong Li2 1Department of Breast Surgery, the First People’s Hospital of Lianyungang, the Affiliated Hospital of XuZhou Medical University, LianYunGang, Jiangsu, 222002, People’s Republic of China; 2Department of Nursing, the First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, LianYunGang, Jiangsu, 222002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haihong Li, Department of Nursing, the First People’s Hospital of Lianyungang, the affiliated hospital of XuZhou medical university, No. 6 Zhenhua East Road, High-Tech Square, LianYunGang, Jiangsu Province, 222002, People’s Republic of China, Tel +86 18961322059, Email haihonglired@126.comObjective: In this study, we aim to establish and evaluate a predictive model for post-treatment anxiety state based on basic patient attributes and pre-treatment SAS scores, with the expectation that this model will guide clinical precision intervention.Methods: Data were collected from 606 patients with breast cancer who underwent surgery at our hospital between January 1, 2015 and December 30, 2018 and 144 newly diagnosed patients with breast cancer who were admitted between June 1, 2019 and December 30, 2019, for a total of 750 patients with breast cancer. The relationship between SAS_A scores and prognosis was verified by analyzing patient baseline characteristics, follow-up data, pre-treatment self-rating anxiety scale (SAS) scores, and SAS_A scores in follow-up period after the end of treatment. A risk prediction model was developed in view of the SAS_A scores, which was then screened, validated, and simplified by scoring, with a nomogram plotted.Results: The SAS_A score can be utilized to differentiate prognosis. In K-M analysis, the high SAS_A score group had a significantly poorer progression-free survival rate than the low score group, p-value < 0.0001. Through model feature selection and clinical analysis, all variables were finally incorporated to establish a predictive model with a ROC AUC of 0.721 (0.637– 0.805) for the validation set and external data, and an AUC of 0.810 (0.719– 0.902) for external data, demonstrating good predictive performance. Calibration curves and probability distribution maps were constructed. DCA and CIC analyses demonstrated that model intervention could boost clinical benefits more effectively than intervention for all patients.Conclusion: Using a predictive model to guide clinical management for anxiety in breast cancer patients is feasible, but additional research is required.Keywords: breast cancer, negative emotions, nomogram, predictive model

Meng Zhou,&ast; Fang Lu,&ast; Ling Jiang, Chen Chen, Si Chen, Luhan Geng, Rui Sun, Qing Li, Suyan Duan, Bo Zhang, Huijuan Mao, Changying Xing, Yanggang Yuan Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanggang Yuan; Changying Xing, Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, Tel/Fax +86-25-6830-6462, Email ygyuan@njmu.edu.cn; cyxing62@126.comAim: Diabetic kidney disease (DKD) continues to be devastating complication of diabetes mellitus. Immune response and inflammatory reaction play essential roles in the progression of DKD. But the specific mechanism of immune cells, and their act on renal innate cells remains unclear. This article focused on immune cells and their communication with renal innate cells to provide bioinformatic evidence for further understanding the immune mechanism in DKD.Methods: Data were analyzed to evaluate the differentially expressed genes (DEGs) and their pathways in DKD patients and mice. Gene set enrichment analysis (GSEA) was used to explore the immune inflammation-related pathways. CIBERSORT was applied to evaluate the distribution of inflammatory cells in different states. Cell-type DEGs and their enrichment pathways were further explored in podocytes, proximal tubule cells and injured tubule cells. Cellchat was used to reveal the cellular communication between immune cells and renal innate cells in DKD.Results: GO and KEGG analysis showed that DEGs were mainly enriched in immune inflammation-related pathways. Monocytes, M2 macrophages and T cells were significantly increased in DKD samples, especially in renal tubule. ScRNA datasets showed that the immune cells number in DKD were significantly increased. Cell-type DEGs were involved in kidney growth and development. In DKD, the interaction numbers and strength between immune cells and innate cells were significantly increased. VISTANT, SPP1 and IGF signal flow were increased in DKD. SPP1-CD44, NRG1-ERBB4, NAMPT-INSR, and Igf1-Igf1r receptor ligand pairs were enhanced in DKD, which mediated the communication between immune-inflammatory cells and innate cells.Conclusion: Our study explored the pathogenesis of renal injury promoted by immunoinflammatory in DKD. VISTANT, SPP1, and IGF signaling pathways and SPP1-CD44, NRG1-ERBB4, NAMPT-INSR, and Igf1- Igf1r receptor ligand pairs might occupy essential place in the occurrence and progress of DKD.Keywords: diabetic kidney disease, immune cells, renal innate cells, bioinformatics

Hongxiang Ji,1 Ziyi Zhao,2 Zeyu Liu,3 Ruitao Sun,3 Yuquan Li,1 Xiaoheng Ding,2 Tongshang Ni4 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Department of Hand and Foot, Microsurgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 3School of Clinical Medicine, Department of Medicine, Qingdao University, Qingdao, People’s Republic of China; 4Center of Integrated Traditional Chinese and Western Medicine, School of Basic Medicine, Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Tongshang Ni, Center of Integrated Traditional Chinese and Western Medicine, School of Basic Medicine, Qingdao University, No. 308, Ningxia Road, Qingdao, Shandong, People’s Republic of China, Email neetongshang@126.com Xiaoheng Ding, Department of Hand and Foot, Microsurgery, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Qingdao, Shandong, People’s Republic of China, Email dxhqd@126.comAim: To evaluate the real-life effectiveness and safety of Chinese patients with type 2 diabetes mellitus (T2DM) receiving hydrogen inhalation (HI) treatment as a supplementary treatment.Methods: This retrospective, multicenter, observational 6-months clinical study included T2DM patients maintaining HI, visited at 4 time points. The primary outcome is the mean change in glycated hemoglobin (HbA1c) at the end of the study compared to baseline. The secondary outcome is analyzing the mean change of fasting plasma glucose (FPG), weight, lipid profile, insulin dose and homeostasis model assessment. Linear regression and logistics regression are applied to evaluate the effect of HI after the treatment.Results: Of the 431 patients comprised, it is observed a significant decrease in HbA1c level (9.04± 0.82% at baseline to 8.30± 0.99% and 8.00± 0.80% at the end, p< 0.001), FPG (165.6± 40.2 mg/dL at baseline to 157.1± 36.3mg/dL and 143.6± 32.3mg/dL at the end, p< 0.001), weight (74.7± 7.1kg at baseline to 74.8± 10.0kg and 73.6± 8.1kg at the end, p< 0.001), insulin dose (49.3± 10.8U/d at baseline to 46.7± 8.0U/d and 45.2± 8.7U/d, p< 0.001). The individuals in subgroup with higher baseline HbA1c and longer daily HI time duration gain greater HbA1c decrease after 6 months. Linear regression shows that higher baseline HbA1c level and shorter diabetes duration are significantly in relation to greater HbA1c reduction. Logistics regression reveals that lower weight is associated with a higher possibility of reaching HbA1c< 7%. The most common adverse event is hypoglycemia.Conclusion: HI therapy significantly improves glycemic control, weight, insulin dose, lipid metabolism, β-cell function and insulin resistance of patients with type 2 diabetes after 6 months. Higher baseline HbA1c level and shorter diabetes duration is related to greater clinical response to HI.Keywords: type 2 diabetes, observational study, hydrogen inhalation, glycemic control, real-world study

Zhen Yu,1,&ast; Shixin Chan,2,&ast; Xu Wang,2 Rui Sun,2 Ming Wang,1 Zhenglin Wang,2 Xiaomin Zuo,2 Jiajie Chen,3 Huabing Zhang,4 Wei Chen1,2,5 1Department of General Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 3Department of Dermatology, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 4Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, Hefei, 230032, People’s Republic of China; 5Anhui Provincial Institute of Translational Medicine, Hefei, 230022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huabing Zhang, Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, Hefei, 230032, People’s Republic of China, Email slzhang1977@163.com; huabingzhang@ahmu.edu.cn Wei Chen, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Tel +86 13966711566, Fax +86 0551-63633742, Email chenwei366@126.com; chenwei366@ahmu.edu.cnPurpose: To evaluate the effect of 5-fluorouracil (5-FU) combined with rutaecarpine (RUT) on the antiproliferative, anti-migratory, and apoptosis-promoting ability of colorectal cancer (CRC) cells and explore the underlying mechanism.Methods: The antiproliferative effects of RUT and 5-FU on CRC cells were evaluated using MTT and colony formation assays. Anti-migration was assessed by cell scratch and transwell tests. The synergistic effect of RUT and 5-FU was assessed by isobologram and combination index analysis using CompuSyn software. The effects of RUT and 5-FU on cell apoptosis were detected by flow cytometry. Differences in protein expression levels with or without RUT and/or 5-FU treatment were assessed by Western blot. Moreover, a mouse xenograft model of CRC was established to investigate the antitumor effect of RUT and 5-FU in vivo, and Ki67 and cleaved caspase-3 expression was detected by immunofluorescence.Results: In this study, we found that 5-FU combined with RUT can inhibit the proliferative, migratory, and antiapoptotic abilities of CRC cells to a significantly greater extent than either RUT or 5-FU alone both in vivo and in vitro. Western blot analysis showed that the level of signal transducer and activator of transcription 3 (STAT3) phosphorylation in CRC cells was significantly reduced after combination therapy compared with that seen with the respective monotherapies. In addition, combination therapy influenced the STAT3 signaling pathway, namely, it inhibited the expression of c-Myc, CDK4, and Bcl-2 while enhancing that of the proapoptotic protein cleaved caspase-3. Immunofluorescence staining further showed that the expression of Ki67 and cleaved caspase-3 was significantly downregulated and upregulated, respectively, in tumor tissues of mice treated with combination therapy compared with that observed with 5-FU treatment alone.Conclusion: Combined therapy with 5-FU and RUT exerted a superior curative effect in CRC than treatment with either single drug alone and has potential as a novel therapeutic modality for the treatment of CRC.Keywords: 5-fluorouracil, colorectal cancer, rutaecarpine, signal transducer and activator of transcription 3, synergistic therapy

Yuan Ze,1 Huiming Tu,2 Lin Zhang,3,4 Yu Bai,5 Yilin Ren,2 Xin Chen,1 Yuzheng Xue,2 Renjuan Sun,6 Yuling Yang,7 Jie Yang,2 Xuan Zhou,2 Li Liu8 1Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 3Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, People’s Republic of China; 4School of Population Medicine and Public Health, Peking Union Medical College/Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Department of Gastroenterology, Changhai Hospital of Shanghai, Shanghai, People’s Republic of China; 6Outpatient Nursing department, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 7Nursing department of Geriatrics Ward, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 8Data Center, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of ChinaCorrespondence: Huiming Tu, Department of Gastroenterology, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Binhu District, Wuxi, 214122, People’s Republic of China, Tel +86-13861753621, Email tuhuiming1891@163.comObjective: To compare the screening efficacy of colonoscopy and pathologically confirmed single and combined Asia-Pacific colorectal screening (APCS), faecal immunochemical testing (FIT) and stool deoxyribonucleic acid (sDNA) testing protocols.Methods: From April 2021 to April 2022, 842 volunteers participated in primary colorectal cancer (CRC) screenings using APCS scoring, FIT and sDNA testing and 115 underwent a colonoscopy. One hundred high-risk participants were then identified from the results of both processes. The differences in the three CRC screening tests in combination with the colonoscopy pathology diagnostics were evaluated using Cochran’s Q test, the Dunn–Bonferroni test and area under the receiver operating characteristic curve (AUC) value analysis.Results: Both FIT and sDNA testing demonstrated a 100% performance in detecting CRC. For advanced adenoma, the sensitivity of the FIT + sDNA test scheme (double positive) was 29.2%, and the sensitivities of the combined FIT + sDNA test and APCS scoring + sDNA test schemes were 62.5% and 95.8%, respectively. The FIT + sDNA testing kappa value of advanced colorectal neoplasia was 0.344 (p = 0.011). The sensitivity for nonadvanced adenoma of the APCS score + sDNA test scheme was 91.1%. In terms of positive results, the sensitivity of the APCS score + FIT + sDNA detection protocol was significantly higher than that of the APCS score, FIT, sDNA detection, and FIT + sDNA detection methods (adjusted p < 0.001, respectively). For the FIT + sDNA test, the kappa value was 0.220 (p = 0.015) and the AUC was 0.634 (p = 0.037). The specificity of the FIT + sDNA test scheme was 69.0%.Conclusion: The FIT + sDNA test scheme demonstrated superior diagnostic efficacy, and the combined APCS score + FIT + sDNA test scheme demonstrated remarkable improvements in CRC screening efficiency and sensitivity for detecting positive lesions.Keywords: faecal immunochemical testing, stool DNA test, colonoscopy, primary screening, colorectal cancer

Miao Li,1,2 Jiazhao Zhang,3 Chenguang Jiang,2,4 Jun Wang,2 Ruhong Sun,5 Shayu Jin,5 Ning Zhang,1,&ast; Zhenhe Zhou2,&ast; 1Department of Psychology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, People’s Republic of China; 3Grade 2019 Class 6, Basic Medicine College of Jinzhou Medical University, Jinzhou, People’s Republic of China; 4Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 5Department of Psychiatry, Nanjing Medical University Graduate School, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Zhang, Department of Psychology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China, Tel +86-13601588630, Email zn6360@126.com Zhenhe Zhou, Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, People’s Republic of China, Tel +86-13358118986, Email zhouzh@njmu.edu.cnPurpose: Deficits in facial emotional intensity recognition have been associated with social cognition in patients with major depression. The study examined multiple event-related potential (ERP) components in patients with major depression and investigated the relationships between ERPs, social cognition, and clinical features.Participants and Methods: Thirty-one patients met DSM-IV diagnosis of depression and 31 healthy participants completed the emotion intensity recognition task (EIRT), while ERPs were recorded. Data on ERP components (P100, N170, P200, and P300) were analyzed.Results: The behavioral results showed that patients with major depression performed worse on EIRT, including all six categories of emotions (sadness, disgust, happiness, surprise, anger, and fear), compared to healthy participants. The ERP results showed that patients with major depression exhibited higher P100 amplitudes for sad and happy faces than healthy participants; P300 amplitudes induced by sad and surprise faces were also higher than in healthy participants, mainly in the central and temporal lobes. A positive correlation was found between sadness intensity scores and P100 amplitudes in patients with major depression.Conclusion: Patients with major depression are biased in their identification of facial expressions indicating emotional intensity. Specifically, they have emotional biases in the early and late stages of cognitive processing, mainly in the form of sensitivity to sad stimuli. It may lead to a persistent rumination of sadness that is detrimental to the remission of depression. Additionally, patients with major depression devote different amounts of cognitive resources for different intensities of sad faces during the preconscious stage of cognitive processing. The more intense their perception of sadness, the more cognitive resources they devote. Therefore, the assessment of the intensity of facial expressions is an important research topic, with clinical implications on social cognitive function in patients with major depression.Keywords: major depression, event-related potentials, emotional intensity recognition, social cognition, emotional tasks

Yan Zhang,1 Wenjie Li,1 Xiaomin Tian,1 Ruanyang Sun,1 Shidan Zhou,2 Ling Jia,1 Jian Sun,1,3,4 Xiao-Ping Liao,1,3,4 Ya-Hong Liu,1,3,4 Yang Yu1,3,4 1Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, People’s Republic of China; 2Intensive Care Unit, Huizhou Municipal Central Hospital, Huizhou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Microbial Safety and Health, Guangdong Institute of Microbiology, Guangdong Academy of Science, Guangzhou, People’s Republic of China; 4Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, People’s Republic of ChinaCorrespondence: Yang Yu, Email graceyyu@scau.edu.cnObjective: Carbapenem-resistant Enterobacteriaceae (CRE) have become an increasingly common cause of healthcare-related infections and present a serious challenge to clinical treatment. This study examined the phenotypic, genotypic characterization, clinical, and microbiological data of CRE in the Huizhou Municipal Central Hospital.Methods: We conducted a phenotypic susceptibility evaluation and whole genome sequence analysis for 52 CRE strains isolated from 37 patients and 2 medical device-related samples during 2013– 2017 to characterize risk factors, antimicrobial resistance profiles, dominant clones and hospital transmission.Results: Long-term hospitalization, treatment time with antibiotics and use of invasive devices were linked to the risk of CRE infection. The carbapenem resistance genes (CRGs) we found included blaNDM (82.7%), blaIMP (19.2%) and blaKPC (3.8%), Escherichia coli (44.2%) and Klebsiella pneumoniae (44.2%) were the dominant species we identified, and the type of CRG carried by isolates was highly correlated with species. The coexistence of CRGs with a variety of other antibiotic resistance genes leads to an increased prevalence of high resistance levels for CRE to β-lactams and other antibiotic classes such as aminoglycosides and fluoroquinolones. These isolates were sensitive only to colistin and tigecycline. In addition to this, we observed significantly genomic diversity of CRE isolates in this hospital. Importantly, we found that long-term transmission of multiple CRE clones had occurred at this hospital between various wards.Conclusion: Evaluating and improving the current infection control strategies may be necessary, and reducing nosocomial transmission remains the primary control element for CRE infections in China.Keywords: carbapenem-resistant Enterobacteriaceae, bacteremia, carbapenem resistance genes, nosocomial transmission

Abstract The parametric hurricane rainfall model (PHRaM), firstly introduced in 2007, has been widely used to forecast and quantify tropical-cyclone-induced rainfall (TC rainfall). The PHRaM is much more computationally efficient than global climate models, but PHRaM cannot be effectively utilized in the context of climate change because it does not have any parameters to capture the increase of tropospheric water vapor under the warming world. This study develops a new model that incorporates tropospheric water vapor to the PHRaM framework, named as the PHRaM with moisture (PHRaMM). The PHRaMM is trained to best fit the TC rainfall over the western North Pacific (WNP) unlike the PHRaM trained with the TCs over the continental US. The PHRaMM reliably simulates radial profile of TC rainfall and spatial distribution of accumulated rainfall during landfall in the present climate with the better prediction skills than existing statistical and operational numerical models. Using the PHRaMM, we evaluated the impacts of TC intensity and environmental moisture increase on TC rainfall change in a future climate. An increased TC intensity causes TC rainfall to increase in the inner-core region but to decrease in the outer region, whereas an increased environmental moisture causes the TC rainfall to increase over the entire TC area. According to the both effects of increased TC intensity and environmental moisture, the PHRaMM projected that the WNP TC rainfall could increase by 4.61–8.51% in the inner-core region and by 17.96–20.91% over the entire TC area under the 2-K warming scenario.

Climate change due to greenhouse gases has fueled more intense tropical cyclones (TCs) globally. However, the characteristics rainfall strength (RS) and rainfall area (RA) of TCs and their future changes in regional scales are not yet fully understood. Here, using ultra-high-resolution coupled model simulations, we investigate the dominant factors which control rainfall characteristics of landfalling TCs in the North Indian Ocean (NIO) and western-North Pacific (WNP) and their future change in responses to doubling and quadrupling of atmospheric CO2 concentrations. In the NIO, RS increases more than RA when CO2 rises, but the WNP shows the opposite behavior. We demonstrate that RS is highly related to the lifetime maximum intensity, landfall intensity, and latent heat flux (LHFLX), while RA depends mainly on LHFLX, relative humidity at 600 hPa, and vertical wind shear over the WNP. Our results suggest the need to establish regional-scale adaptation strategies for future changes in landfalling TCs rainfall.

Lanyao Yang1,2 &ast;, Lanlan Wu3 &ast;, Yao Liu,3 Hengying Chen,4 Yuanhuan Wei,3 Ruifang Sun,3 Siwen Shen,3 Bowen Zhan,1,2 Jianjun Yang,1,2 Guifang Deng3 1Department of Nutrition and Food Hygiene, School of Public Health and Management, Ningxia Medical University, Yinchuan, People’s Republic of China; 2Key Laboratory of Environmental Factors and Chronic Disease Control, School of Public Health and Management, Ningxia Medical University, Yinchuan, People’s Republic of China; 3Department of Clinical Nutrition, Union Shenzhen Hospital of Huazhong University of Science and Technology, Shenzhen, People’s Republic of China; 4Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guifang Deng, Department of Clinical Nutrition, Union Shenzhen Hospital of Huazhong University of Science and Technology, No. 89 Taoyuan Road, Shenzhen, Guangdong, 518052, People’s Republic of China, Email misyfly@163.com Jianjun Yang, Department of Nutrition and Food Hygiene, School of Public Health and Management, Ningxia Medical University, No. 1160 Shengli Road, Yinchuan, Ningxia, 750004, People’s Republic of China, Email yangjj@nxmu.edu.cnObjective: This study evaluated the associations of serum ferritin (SF) concentration during pregnancy with the risk of adverse maternal and fetal pregnancy outcomes.Methods: We conducted a retrospective study of 2327 pregnant women from 2015 to 2020 in Guangdong, China. SF concentrations were measured at 16– 18th and 28– 32th week of gestation. Logistic regression models were applied to estimate the association between SF concentration and the risk of adverse pregnancy outcomes.Results: After multivariable adjustment, the odds ratio (OR) of the highest quartile of SF concentration at 16– 18th week of gestation was 1.43 (95% confidence interval [CI]: 1.09, 1.89) for gestational diabetes mellitus (GDM) and 1.79 (95% CI: 1.15, 2.79) for small for gestational age (SGA) when compared with the lowest quartile. At 28– 32th week of gestation compared with the lowest quartile, women with SF in the highest quartile had an increased risk of SGA (OR: 1.62; 95% CI: 1.01, 2.62). Moreover, the lowest quartile of SF concentration decreased risk of SGA by 90% (95% CI: 0.01, 0.80) when compared with the highest quartile among pregnancy women with GDM.Conclusion: Elevated SF concentrations increased the risk of GDM and SGA during pregnancy. Maintaining an appropriately low level of maternal SF at 28– 32th week of gestation in women with GDM could reduce the risk of SGA.Keywords: ferritin, adverse pregnancy outcomes, gestational diabetes mellitus, small for gestational age

Hanrui Liu,1 Chengyong Ma,2 Huayan Xu,1 Huan Zhang,3 Rong Xu,1 Kun Zhang,1 Ran Sun,1 Kuan Li,1 Qihong Wu,1 Lingyi Wen,1 Lizhi Zhang,2 Yingkun Guo1 1West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3College of Chemistry and Materials Science, Northwest University, Xi’an, People’s Republic of ChinaCorrespondence: Yingkun Guo, Development and Related Diseases of Women and Children Key Laboratory, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin South Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86+18180609256, Email gykpanda@163.com Lizhi Zhang, Department of Radiology, West China Hospital of Sichuan University, No. 37, Guoxue Road, Chengdu, Sichuan, 610041, People’s Republic of China, Email littche_2000@163.comIntroduction: Free radicals in oxidative stress are known to play a pathogenic role in sepsis. A major clinical challenge associated with sepsis is sepsis-associated encephalopathy (SAE). The rapid increase of free radicals in the brain promotes SAE progression. Here, macromolecule free radicals in the mouse brain were uniquely detected by immunospin trapping (IST) and magnetic resonance imaging (MRI).Methods: The new strategy uses spin trapping agent DEPMPO-biotin to capture macromolecule free radicals in lesions and form biotin-DEPMPO-radical adducts. Then, a targeting MRI probe, avidin-BSA@Gd-ESIO, was used to detect the radical adducts through the highly specific binding of avidin and biotin. The avidin-BSA@Gd-ESIO probe was synthesized and systematically characterized. The detection capability of the new strategy was evaluated in vitro and in vivo using a confocal microscope and a 7T MRI, respectively.Results: In reactive oxygen species (ROS)–induced microglial cells, the accumulation of the avidin-BSA@Gd-ESIO probe in the DEPMPO-biotin-treated group was significantly higher than that of control groups. In vivo MRI T1 signal intensities were significantly higher within the hippocampus, striatum, and medial cortex of the brain in mice with a mild or severe degree of sepsis compared with the sham control group. Histological analysis validated that the distribution of the avidin-BSA@Gd-ESIO probe in brain tissue slices was consistent with the MRI images. The fluorescence signals of ROS and avidin-BSA@Gd-ESIO probe were overlapped and visualized using immunofluorescent staining. By evaluating the T1 signal changes over time in different areas of the brain, we estimated the optimal MRI detection time to be 30 minutes after the probe administration.Discussion: This method can be applied specifically to assess the level of macromolecular free radicals in vivo in a simple and stable manner, providing a pathway for a more comprehensive understanding of the role of free radicals in SAE.Graphical-Abstract: Keywords: macromolecule radical, ESIO, spin trapping, sepsis-associated encephalopathy

Li Li,1 Rongjin Sun,1 Joseph Zenga,2 Heather Himburg,3 Lu Wang,1 Shengnan Duan,1 Jingwen Liu,1 Dinh Bui,1 Zuoxu Xie,1 Ting Du,4 Lijun Xie,1 Taijun Yin,1 Stu Wong,2 Song Gao,4 Ming Hu1 1Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA; 2Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA; 3Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA; 4Department of Pharmaceutical Science, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USACorrespondence: Ming Hu, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA, Email mhu@uh.edu Song Gao, Department of Pharmaceutical Science, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA, Email Song.Gao@tsu.eduObjective: We aim to quantify the absolute protein expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in various cells and tissues to determine the relative contribution of COX-1 and COX-2 to PGE2 production.Methods: An LC-MS method was developed and validated, then used for quantifying the absolute amounts of COX-1 and COX-2 in recombinant human COX-1 and COX-2, lysates from different cells, tissue microsomes of rodents and humans, Pirc rat colonic polyps, and biopsy specimens from squamous cell carcinoma (SCC) patients. The COX-1 and COX-2 turnover numbers were subsequently calculated based on apparent formation rates of PGE2.Results: A robust LC-MS method for quantification of COX-1 and COX-2 was developed and validated and then used to calculate their apparent turnover numbers. The results showed that COX-1 expression levels were much higher than that of COX-2 in all the tested tissues including the colonic epithelium of F344 (28-fold) and Pirc rats (20-fold), colonic polyps of Pirc rats (8-fold), and biopsy specimens of SCC patients (11– 17-fold). In addition, both COX-1 and COX-2 were higher in polyps when compared to adjacent mucosa of Pirc rats. The turnover number of recombinant human COX-2 was 14-fold higher than that of recombinant human COX-1. LPS stimulation increased COX-2 protein expression in three cell lines (Raw 264.7, SCC9 and EOMA) as expected but unexpectedly increased COX-1 protein expression (13.8-fold) in EOMA cells.Conclusion: In human oral cancer tissues and cells as well as Pirc rat colon, COX-1 plays an unexpectedly but more important role than COX-2 in abnormal PGE2 production since COX-1 expression is much higher than COX-2. In addition, COX-1 expression levels are inducible in cells, and higher in polyps than surrounding mucosa in Pirc rat colon. These results indicate that targeted suppression of local COX-1 should be considered to reduce colon-specific PGE2-mediated inflammation.Graphical Abstract: Keywords: cyclooxygenase-1, cyclooxygenase-2, turnover number, inflammation, absolute quantification, liquid chromatography with tandem mass spectrometry

Yunfan Xia,1 Ruohan Sun,1 Rongrong Li,1 Leilei Ren,1 Yiyi Wang,1 Jianqiao Fang2 1The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou City, People’s Republic of China; 2The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou City, People’s Republic of ChinaCorrespondence: Jianqiao Fang, 23 Qingchun Road, Hangzhou City, People’s Republic of China, Tel +86(0)571-87238254, Fax +86(0)571-87238005, Email fangjianqiao7532@163.comBackground: Accumulate evidence indicated that moxibustion has a positive effect on pain treatment. However, the bibliometric analysis of moxibustion on pain remains uncertain. Herein, this study aimed to explore the current hotspots and the research trends over the past decade to bring a great panorama in this field.Methods: Publications were retrieved from the database Web of Science Core Collection (WoSCC) related to moxibustion therapy for pain treatment from January 1, 2012, to December 31, 2021. CiteSpace and Excel were applied to analyze the volume of publications, journals, cited journals, dual-map analysis, countries, institutes, authors, references, and keywords with citation bursts.Results: A total of 360 publications were retrieved from 2012 to 2021. The annual number of publications increased steadily with some fluctuations over the past 10 years. “The Evid Based Complement Alternat Med” and “the Gut” were the top-cited journals in frequency and centrality. China and Shanghai University of Traditional Chinese Medicine were the most prolific country and institutions, respectively. Among authors, Huangan Wu was the most active author with the highest cited frequency. Jun Xiong, Fanrong Liang and Guixing Xu held the articles with higher centrality. In the ranking of frequency and centrality in cited references, the top one was the article published by Shamseer L and Deng HY, respectively. “Acupuncture” was the keyword with the highest frequency. Pain disease (including rheumatoid arthritis, knee osteoarthritis, herpes zoster), research method (including randomized controlled trial), and risk (including quality of life, economic burden, physical and psychological problems) were the hotspots and frontier trends in this field.Conclusion: This bibliometric study reveals the current status and research trend in the treatment of pain with moxibustion. The formulation with bibliometric analysis further elicits hot spots and frontier issues in this field.Keywords: moxibustion, pain, CiteSpace, bibliometric analysis

Rongrong Sun,1 Zhixin Yan,2 Wenxia Yi,2 Wenqiu Tian,2 Mei Sun,2 Jing Zhang1 1Children’s Ward, Cangzhou Central Hospital, Cangzhou, Hebei Province, People’s Republic of China; 2Cangzhou Central Hospital, Cangzhou, Hebei Province, People’s Republic of ChinaCorrespondence: Jing Zhang, Children’s Ward, Cangzhou Central Hospital, Cangzhou City, Hebei Province, 061001, People’s Republic of China, Tel +86 15031730097, Email wuwo681230754@163.comObjective: To study serum levels of vitamins A, D and E in children with recurrent respiratory tract infections of different ages and the correlation.Methods: The clinical data of two groups of children of different ages were collected. The serum levels and deficiencies of vitamins A, D and E in children were statistically analyzed.Results: The proportions of premature infants, low body weight infants, special physique, hospitalization history, hypocalcemia, living in a bungalow, and daily outdoor activities in less than 30 minutes in the case group were higher than those in the control group (χ2=4.507, 5.165, 7.040, 14.907, 4.267, 33.800, 4.507, 8.571, P < 0.05). The serum levels of vitamins A, D and E of children aged 0– 1, 2– 5, and 6– 12 in the case group were lower than those in the control group (P < 0.05). Compared with the control group, the serum vitamin A level of children in the case group was lower (t = 2.631, P < 0.05), and the deficiency rate was higher (χ2=24.200, P < 0.05).Conclusion: Serum levels of vitamins A, D and E, which are related to birth mode, physical fitness, hospitalization history, hypocalcemia, vitamin deficiency, living environment, and daily outdoor activity time, vary in children with recurrent respiratory tract infections of different ages, and are lower in children with recurrent respiratory tract infections than in healthy children.Keywords: different age groups, recurrent respiratory tract infections, children, serum vitamins A, D and E levels, correlation

Runjie Sun,1 Jiang Liu,2 Manya Yu,1 Mengting Xia,3 Yanyu Zhang,1 Xiaoqi Sun,1 Yunsheng Xu,4 Xing Cui4 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 2Department of Foreign Affairs Office, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 3First School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 4Second School of Clinical Medicine, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250001, People’s Republic of ChinaCorrespondence: Yunsheng Xu; Xing Cui, Second School of Clinical Medicine, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 1 Jingba Road, Jinan, 250001, People’s Republic of China, Email xys65@126.com; cdz45@foxmail.comBackground: Bortezomib-induced peripheral neuropathy (BiPN) is a common complication of multiple myeloma (MM) treatment that seriously affects the quality of life of patients. The purpose of the present study was to explore the therapeutic effect of paeoniflorin on BiPN and its possible mechanism.Methods: ELISA was used to measure the level of interleukin-6 (IL6) in the plasma of MM patients, and bioinformatics analysis was used to predict the mechanism underlying the effect of paeoniflorin on peripheral neuropathy. Cell and animal models of BiPN were constructed to evaluate mitochondrial function by measuring cell viability and mitochondrial quality and labeling mitochondria with MitoTracker Green. Nerve injury in mice with BiPN was assessed by behavioral tests, evaluation of motor nerve conduction velocity, hematoxylin-eosin (HE) staining, electron microscopy and analysis of the levels of reactive oxygen species (ROS). Western blotting and immunohistochemistry (IHC) were used to assess the expression of autophagy-related proteins.Results: In MM patients, IL6 levels were positively correlated with the degree of PN. The results of bioinformatics analysis suggested that paeoniflorin ameliorated PN by altering inflammation levels and mitochondrial autophagy. Paeoniflorin increased PC12 cell viability and mitochondrial autophagy levels, alleviated mitochondrial damage, and reduced IL6 levels. In addition, paeoniflorin effectively improved the behavior of mice with BiPN, relieved sciatic nerve injury in mice, increased the expression of LC3II/I, beclin-1, and Parkin in sciatic nerve cells, and increased the expression of LC3B and Parkin in the nerve tissue.Conclusion: The present study confirmed that paeoniflorin significantly ameliorated peripheral neuropathy (PN) caused by bortezomib, possibly by reducing IL6 levels to regulate PARKIN-mediated mitochondrial autophagy and mitochondrial damage.Keywords: multiple myeloma, paeoniflorin, peripheral neuropathy, mitochondria, autophagy

Ruohan Sun,1,2,&ast; Shimin Li,1,&ast; Leilei Ren,2 Yunfan Xia,2 Yiyi Wang,2 Zhiyuan Bian,2 Jianqiao Fang,2 Zuyong Zhang1 1Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Acupuncture, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuyong Zhang, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, No. 38 West Lake Road, Hangzhou, Zhejiang, People’s Republic of China, Email zzynwk@126.com Jianqiao Fang, The Third Affiliated Hospital of Zhejiang Chinese Medical University, No. 23 Qinchun Road, Hangzhou, Zhejiang, People’s Republic of China, Email fangjianqiao7532@163.comIntroduction: Postherpetic neuralgia (PHN) is a severe complication of herpes zoster (HZ), representing an important burden of disease in the elderly. Electroacupuncture (EA) has become growingly appreciated as a therapy of PHN with the situation that effectiveness of conventional therapy of PHN is less than ideal. Owing to its low price, no side effects, high safety and high patients acceptance, EA has been used in treating PHN more frequently. Therefore, the randomized controlled trial which is to evaluate the effectiveness and safety of EA in patients with PHN and whether EA could be an alternative therapy of medication is needed.Patients and Methods: A total of 88 patients with PHN will be recruited from 2 hospitals and randomized assigned to EA group or Medication group in a 1:1 ratio, utilizing a central randomization system. The trial will involve a 4-week treatment period, and a 4-week follow-up period. All variables will be evaluated at week 0 (baseline), week 2 (treatment), week 4 (treatment), week 8 (follow-up) and week 16 (follow-up). Primary outcomes will be pain intensity. Secondary outcomes will contain quality of life, mood state and sleep quality. All adverse effects will be assessed during the trial.Conclusion: This study will provide significant evidence that whether EA therapy is effective and safe for patients with PHN and whether EA could be an alternative therapy of medication.Ethics and Dissemination: Ethics approval has been obtained from the Ethics Committee of the Hangzhou Third People’s Hospital (No. 2021KAO43). Informed consent will be signed before enrolment. Results of this trial will be presented to international journals for publication and be reported in relevant international conferences.Trial Registration Number: This protocol has been registered in the Chinese Clinical Trial registry with the identification code ChiCTR2100054592.Keywords: postherpetic neuralgia, electroacupuncture, pain, randomized controlled trial, protocol

Xue C, He Y, Hu Q, et al. Cancer Manag Res. 2018;10:5101–5112. We, the Editors and Publisher of Cancer Management and Research, have retracted the published article. Concerns were raised about the integrity of the data in the article following the author’s request to correct images in Figures 2 and 3. It was found images from these figures had been duplicated within the article and with those from another article. Specifically, The images for Figure 2D, GBC-SD, NC and PIM1-siRNA, have been duplicated with the images for Figure 3C, GBC-SD, NC and NOZ, PIM1-siRNA, respectively. The images for Figure 2D, NOZ, NC, have been duplicated with the images from Figure 5d, Hep3B, PLK-4 from Bao J, Yu Y, Chen J, et al. MiR-126 negatively regulates PLK-4 to impact the development of hepatocellular carcinoma via ATR/CHEK1 pathway. Cell Death Dis. 2018;9:1045. https://doi.org/10.1038/s41419-018-1020-0. When approached for an explanation, the authors were cooperative and provided some original data for their study, however, the provided data was not satisfactory, and the results could not be adequately verified. As verifying the validity of the published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors do not agree with this decision. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Liang Zhang,1,&ast; Zhentao Yang,1,&ast; Shiyu Zhang,1 Ke Zhou,1 Wu Zhang,2 Sunbin Ling,1 Ruiqi Sun,1 Hong Tang,1 Xue Wen,3 Xiaowen Feng,1 Penghong Song,1 Xiao Xu,1 Haiyang Xie,1 Shusen Zheng1,2 1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), Hangzhou, Zhejiang, 310003, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, Zhejiang, 310004, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiyang Xie; Shusen ZhengSchool of Medicine, Zhejiang University, 79# Qingchun Road, Hangzhou, Zhejiang, 310000, People’s Republic of ChinaTel/Fax +86 571 87236570; +86 571 87236466Email xiehy@zju.edu.cn; shusenzheng@zju.edu.cnPurpose: Patients receiving liver transplantation (LT) for hepatocellular carcinoma (HCC) are at high risk of tumor recurrence. Polyploidy is a fascinating characteristic of the liver and correlates with HCC development and progression. This study aims to investigate the association between hepatocyte polyploidy spectrum and HCC recurrence after LT.Patients and Methods: Thirty-two paired HCC, peritumoral, cirrhotic, and normal liver specimens were employed to examine the hepatocyte polyploidization pattern during liver tumorigenesis. Clinicopathological implications of polyploidy spectrum for LT recipients with HCC were investigated in 205 patients from two transplant centers. Immunofluorescence staining was performed on paraffin-embedded tissue sections to determine the ploidy profiles in situ. Expression levels of CD4, CD8, forkhead box protein 3 (Foxp3) and programmed death-ligand 1 (PD-L1) were measured using immunohistochemistry. An array-based multiplex ELISA system was used for the quantitative measurement of 40 unique inflammatory cytokines.Results: The fraction of mononuclear polyploidy increased, whereas that of binuclear polyploidy reduced during hepatocarcinogenesis. Recipients with highly mononuclear polyploid HCC (HMP–HCC) had inferior recurrence-free survival and HCC-specific survival than poorly mononuclear polyploid HCC recipients. These two groups differed in abundance of infiltrative CD8+ cytotoxic T cells and FoxP3+ Treg cells, and PD-L1 expression, as well as circulating granulocyte–macrophage colony-stimulating factor, interferon-γ and interleukin-10 levels. HMP–HCC constituted an independent recurrence predictor and could improve the discriminative efficacy of clinical prediction models (Milan criteria, AFP model, and Metroticket 2.0 criteria). A scoring system incorporating the ploidy signature was developed and validated, allowing for an improved risk prediction relative to the RETREAT score and post-MORAL score.Conclusion: Polyploid spectra are associated with tumor immunophenotype and provide supplementary prognostic information in LT for HCC.Keywords: polyploidy, immunosurveillance, tumor-infiltrating lymphocytes, cytokines, tumor recurrence