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Ying Fu,1,2 Yufeng Zhu,1,3 Feng Zhao,1,2,4 Bingyan Yao,1,2 Yunsong Yu,5 Jun Zhang,1,2 Qiong Chen6 1Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 2Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang Province, People’s Republic of China; 3Department of Clinical Laboratory, Hangzhou Xixi Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 4Department of Clinical Laboratory, Zhejiang University Sir Run Run Shaw Alar Hospital, Alar, Xinjiang province, People’s Republic of China; 5Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang Province, People’s Republic of China; 6Department of Clinical Laboratory, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Qiong Chen; Jun Zhang, Email chenqiong2002@126.com; jameszhang2000@zju.edu.cnObjective: Our aim was to elucidate the resistance mechanisms and assess the combined synergistic and bactericidal activities of aztreonam in combination with ceftazidime/avibactam (CZA), meropenem/vaborbactam (MEV), and imipenem/relebactam (IMR) against Enterobacterales strains producing dual carbapenemases.Methods: Species identification, antimicrobial susceptibility testing and determination of carbapenemase type were performed for these strains. Plasmid sizes, plasmid conjugation abilities and the localization of carbapenemase genes were investigated. Whole-genome sequencing was performed for all strains and their molecular characteristics were analyzed. In vitro synergistic and bactericidal activities of the combination of aztreonam with CZA, MEV and IMR against these strains were determined using checkerboard assay and time-kill curve assay.Results: A total of 12 Enterobacterales strains producing dual-carbapenemases were collected, including nine K. pneumoniae, two P. rettgeri, and one E. hormaechei. The most common dual-carbapenemase gene pattern observed was bla(KPC-2+NDM-5) (n=4), followed by blaKPC-2+IMP-26 (n=3), bla(KPC-2+NDM-1) (n=2), bla(KPC-2+IMP-4) (n=1), bla(NDM-1+IMP-4) (n=1) and bla(KPC-2+KPC-2) (n=1). In each strain, the carbapenemase genes were found to be located on two distinct plasmids which were capable of conjugating from the original strain to the receipt strain E. coli J53. The results of the checkerboard synergy analysis consistently revealed good synergistic effects of the combination of ATM with CZA, MEV and IMR. Except for one strain, all strains exhibited significant synergistic activity and bactericidal activity between 2 and 8 hours.Conclusion: Dual-carbapenemase-producing Enterobacterales posed a significant threat to clinical anti-infection treatment. However, the combination of ATM with innovative β-lactam/β-lactamase inhibitor compounds had proven to be an effective treatment option.Keywords: dual-carbapenemase-producing enterobacterales, β‑lactam/β‑lactamase inhibitor combinations, aztreonam, checkerboard assay, time-kill curve

Liping Zou,1,* Wanli Kang,2,* Chunhui Guo,3,* Juan Du,4,* 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*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

Xuefeng Hou,1– 4,* Qi Chen,1,* Ying Fang,5 Li Zhang,1 Shuoheng Huang,1 Minjie Xu,1 Yaning Ren,1 Zhansen Shi,1 Yan Wei,1 Lihua Li1– 4 1School of Pharmacy, Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 2Anhui Provincial Engineering Laboratory for Screening and Re-Evaluation of Active Compounds of Herbal Medicines in Southern Anhui, Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 3Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 4Drug Research and Development Center, Wannan Medical College, Wuhu, Anhui Province, People’s Republic of China; 5School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Wei; Lihua Li, School of Pharmacy, Wannan Medical College, No. 22, West Wenchang Road, Wuhu, 241002, People’s Republic of China, Email yanwei@wnmc.edu.cn; llh05530226@126.comBackground: Breast cancer presents significant challenges due to the limited effectiveness of available treatments and the high likelihood of recurrence. iRGD possesses both RGD sequence and C-terminal sequence and has dual functions of targeting and membrane penetration. iRGD-modified nanocarriers can enhance drug targeting of tumor vascular endothelial cells and penetration of new microvessels, increasing drug concentration in tumor tissues.Methods: The amidation reaction was carried out between SiO2/AuNCs and iRGD/PTX, yielding a conjugated drug delivery system (SiO2/AuNCs-iRGD/PTX, SAIP@NPs). The assessment encompassed the characterization of the morphology, particle size distribution, physicochemical properties, in vitro release profile, cytotoxicity, and cellular uptake of SAIP@NPs. The tumor targeting and anti-tumor efficacy of SAIP@NPs were assessed using a small animal in vivo imaging system and a tumor-bearing nude mice model, respectively. The tumor targeting and anti-tumor efficacy of SAIP@NPs were assessed utilizing a small animal in vivo imaging system and an in situ nude mice breast cancer xenograft model, respectively.Results: The prepared SAIP@NPs exhibited decent stability and a certain slow-release effect in phosphate buffer (PBS, pH 7.4). In vitro studies had shown that, due to the dual functions of transmembrane and targeting of iRGD peptide, SAIP@NPs exhibited strong binding to integrin αvβ 3, which was highly expressed on the membrane of MDA-MB-231 cells, improving the uptake capacity of tumor cells, inhibiting the rapid growth of tumor cells, and promoting tumor cell apoptosis. The results of animal experiments further proved that SAIP@NPs had longer residence time in tumor sites, stronger anti-tumor effect, and no obvious toxicity to major organs of experimental animals.Conclusion: The engineered SAIP@NPs exhibited superior functionalities including efficient membrane permeability, precise tumor targeting, and imaging, thereby significantly augmenting the therapeutic efficacy against breast cancer with a favorable safety profile. Keywords: silicon dioxide nanoparticles, gold nanoclusters, iRGD penetrating peptide, integrin αvβ 3, tumor targeting, breast cancer

Zhengyi Han,1,2 Yangyang Zhang,1,2 Chenxi Xue,3 Shiyun Jin,1,2 Qi Chen,1,2 Ye Zhang1,2 1Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China; 2Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, 230601, People’s Republic of China; 3Department of Orthopedics, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of ChinaCorrespondence: Ye Zhang, Department of Anesthesiology, The Second Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, People’s Republic of China, Tel +86-055163869480, Email zhangye_hassan@sina.comPurpose: Total Knee Arthroplasty (TKA) is a highly invasive procedure causing severe postoperative pain, which hampers early mobility. Effective pain management is crucial for optimal recovery. This study aimed to evaluate how adductor canal block (ACB) and femoral nerve block (FNB) affect opioid use and inflammation factor levels in elderly TKA patients.Methods: This prospective observational study included 120 patients who received TKA, and divided them into three groups, based on the different nerve block technique: ACB, FNB, and no intervention before general anesthesia (CON). Postoperative opioid consumption, pain assessment, inflammation factor, knee function recovery and other clinical indicators were recorded.Results: The CON group had significantly higher cumulative sufentanil consumption compared to the ACB and FNB groups at both 12 h and 48h postoperative (P< 0.001). Compared with the CON group, the ACB and FNB groups persistently had lower pain scores until 12 h at rest and 24 h during motion after surgery. The ACB group showed significantly lower serum concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) compared to the CON group at 24 h postoperative (P=0.017, P=0.009), and IL-6 levels remained significantly lower at 72 h postoperative (P=0.005). Both ACB and FNB groups achieved earlier ambulation compared to the CON group (P=0.002). On the first day postoperative, both the ACB and FNB groups showed significantly better knee motion (P< 0.001), quadriceps strength (P< 0.001), and daily mobilization (P< 0.001) compared to the CON group. Additionally, the ACB group exhibited superior quadriceps strength (P< 0.001) and daily mobilization (P< 0.001) compared to the FNB group.Conclusion: The ACB and FNB groups exhibited comparable clinical efficacy outcomes in terms of pain scores and opioid consumption. However, the ACB group experienced reduced postoperative inflammation and improved knee recovery, especially in quadriceps strength.Keywords: adductor canal block, femoral nerve block, opioid, analgesia, inflammation, TKA

Qiu Chen,1 Ji-Lei Zhang,1 Jie-Shun Yang,2 Qing Jin,1 Jun Yang,3 Qiang Xue,1 Xue-feng Guang1 1Department of Cardiology, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, People’s Republic of China; 2Department of Pathology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Key Laboratory of Cardiovascular Disease of Yunnan Province, Yan’an Hospital Affiliated to Kunming Medical University, Kunming, People’s Republic of ChinaCorrespondence: Qiang Xue; Xue-feng Guang, Department of Cardiology, Yan’ an Hospital Affiliated to Kunming Medical University, No. 245 Renmin Dong Road, Kunming, Yunnan Province, 650051, People’s Republic of China, Email xueqiang3513@126.com; gxfyayy@163.comPurpose: Necroptosis, a monitored form of inflammatory cell death, contributes to coronary heart disease (CHD) progression. This study examined the potential of using necroptosis genes as diagnostic markers for CHD and sought to elucidate the underlying roles.Methods: Through bioinformatic analysis of GSE20680 and GSE20681, we first identified the differentially expressed genes (DEGs) related to necroptosis in CHD. Hub genes were identified using least absolute shrinkage and selection operator (LASSO) regression and random forest analysis after studying immune infiltration and transcription factor-miRNA interaction networks according to the DEGs. Quantitative polymerase chain reaction and immunohistochemistry were used to further investigate hub gene expression in vivo, for which a diagnostic model was constructed and the predictive efficacy was validated. Finally, the CHD group was categorized into high- and low-score groups in accordance with the single-sample gene set enrichment analysis (ssGSEA) score of the necroptosis genes. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, GSEA, and further immune infiltration analyses were performed on the two groups to explore the possible roles of hub genes.Results: Based on the results of the LASSO regression and random forest analyses, four genes were used to construct a diagnostic model to establish a nomogram. Additionally, an extensive analysis of all seventeen necroptosis genes revealed notable distinctions in expression between high-risk and low-risk groups. Evaluation of immune infiltration revealed that neutrophils, monocytes, B cells, and activated dendritic cells were highly distributed in the peripheral blood of patients with CHD. Specifically, the high CHD score group exhibited greater neutrophil and monocyte infiltration. Conversely, the high-score group showed lower infiltration of M0 and M2 macrophages, CD8+ T, plasma, and resting mast cells.Conclusion: TLR3, MLKL, HMGB1, and NDRG2 may be prospective biomarkers for CHD diagnosis. These findings offer plausible explanations for the role of necroptosis in CHD progression through immune infiltration and inflammatory response.Keywords: atherosclerosis, cell death, inflammations, diagnostic biomarkers, necroptosis, immune infiltration

Yue Lu,1– 3,&ast; Simin Pan,4,&ast; Wenzhen Li,5 Yao Qi,6,7 Li Li,1– 3 Yu-Hong Yan,1– 3 Jianan Wei,1– 3 Dan-Ni Yao,1– 3 Jingjing Wu,1– 3 Hao Deng,1– 3 Shuyan Ye,1– 3 Haiming Chen,1– 3 Qubo Chen,1– 3 Hengjun Gao,6,7 Ling Han,1– 3 Chuanjian Lu1– 3 1State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, People’s Republic of China; 3Guangdong-Hong Kong-Macau Joint Laboratory on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5The Clinical College of Acupuncture Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6Shanghai Molecular Medicine Engineering Technology Research Center, Shanghai, People’s Republic of China; 7Shanghai National Engineering Research Center of Biochip, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Han; Chuanjian Lu, Email linghan99@gzucm.edu.cn; lcj@gzucm.edu.cnBackground: Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored.Methods: The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression.Results: As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy.Conclusion: We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.Keywords: PSORI-CM01, Psoriasis vulgaris, MicroRNA expression profile, network pharmacology, autophagy

Jian Cui,1 Yunliang Sun,2 Haifeng Jing,3 Qiang Chen,1 Zhihao Huang,1 Xin Qi,1 Hao Cui1 1Department of Big Data and Fundamental Sciences, Shandong Institute of Petroleum and Chemical Technology, Dongying, Shandong, 257061, People’s Republic of China; 2Department of Respiratory and Sleep Medicine, Bin Zhou Medical University Hospital, Binzhou, Shandong, 256600, People’s Republic of China; 3College of Software and Microelectronics, Peking University, Beijing, 100000, People’s Republic of ChinaCorrespondence: Jian Cui, Department of Big Data and Fundamental Sciences, Shandong Institute of Petroleum and Chemical Technology, 271 Bei Er Lu, Dongying City, Shandong Province, 257061, People’s Republic of China, Tel +86-15066073763, Email jian.cui@sdipct.edu.cnPurpose: Sleep structure is crucial in sleep research, characterized by its dynamic nature and temporal progression. Traditional 30-second epochs falter in capturing the intricate subtleties of various micro-sleep states. This paper introduces an innovative artificial neural network model to generate continuous sleep depth value (SDV), utilizing a novel multi-feature fusion approach with EEG data, seamlessly integrating temporal consistency.Methods: The study involved 50 normal and 100 obstructive sleep apnea–hypopnea syndrome (OSAHS) participants. After segmenting the sleep data into 3-second intervals, a diverse array of 38 feature values were meticulously extracted, including power, spectrum entropy, frequency band duration and so on. The ensemble random forest model calculated the timing fitness value for all the features, from which the top 7 time-correlated features were selected to create detailed sleep sample values ranging from 0 to 1. Subsequently, an artificial neural network (ANN) model was trained to delineate sleep continuity details, unravel concealed patterns, and far surpassed the traditional 5-stage categorization (W, N1, N2, N3, and REM).Results: The SDV changes from wakeful stage (mean 0.7021, standard deviation 0.2702) to stage N3 (mean 0.0396, standard deviation 0.0969). During the arousal epochs, the SDV increases from the range (0.1 to 0.3) to the range around 0.7, and decreases below 0.3. When in the deep sleep (≤ 0.1), the probability of arousal of normal individuals is less than 10%, while the average arousal probability of OSA patients is close to 30%.Conclusion: A sleep continuity model is proposed based on multi-feature fusion, which generates SDV ranging from 0 to 1 (representing deep sleep to wakefulness). It can capture the nuances of the traditional five stages and subtle differences in microstates of sleep, considered as a complement or even an alternative to traditional sleep analysis.Keywords: sleep depth value, sleep continuity, EEG features, timing fitness, ANN model

Songtao Yang, Jie Cao, Ying Wang, Qi Chen, Fangyu Li, Yuanyuan Gao, Rui Li, Li Yuan Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Li Yuan, Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email yuanli18cn@126.comBackground: The “gut-islets axis” is an important endocrine signaling axis that regulates islets function by modulating the gut microbiota and endocrine metabolism within the gut. However, the specific mechanisms and roles of the intestine in islets regulation remain unclear. Recent studies investigated that exosomes derived from gut microbiota can transport signals to remotely regulate islets β-cell function, suggesting the possibility of novel signaling pathways mediated by gut exosomes in the regulation of the “gut-islet axis.”.Methods: The exosomes were isolated from the intestinal enteroendocrine cell-line STC-1cells culture supernatants treated with palmitate acid (PA) or BSA. Metabolic stress models were established by separately subjecting MIN6 cells to PA stimulation and feeding mice with a high-fat diet. Intervention with exosomes in vitro and in vivo to assess the biological effects of exosomes on islets β cells under metabolic stress. The Mas receptor antagonist A779 and ACE2ko mice were used to evaluate the role of exosomal ACE2.Results: We found ACE2, a molecule that plays a crucial role in the regulation of islets function, is abundantly expressed in exosomes derived from STC-1 under physiological normal condition (NCEO). These exosomes cannot only be taken up by β-cells in vitro but also selectively transported to the islets in vivo. Following intervention with NCEXO, both Min6 cells in a lipotoxic environment and mice on a high-fat diet exhibited significant improvements in islets β-cell function and β-cell mass. Further investigations demonstrated that these protective effects are attributed to exosomal ACE2, as ACE2 inhibits NLRP3 inflammasome activation and reduces β-cell pyroptosis.Conclusion: ACE2-enriched exosomes from the gut can selectively target islets, subsequently inhibiting NLRP3 inflammasome activation and β cell pyroptosis, thereby restoring islets β cell function under metabolic stress. This study provides novel insights into therapeutic strategies for the prevention and treatment of obesity and diabetes.Keywords: exosomes, ACE2, islets β cell, the NLRP3 inflammasome

Liuyang Hu,1 Qi Chen,2 Xingchun Chen1 1Department of Laboratory Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530016, People’s Republic of China; 2Department of Ophthalmology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530016, People’s Republic of ChinaCorrespondence: Xingchun Chen, Department of Laboratory Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530016, People’s Republic of China, Email 369609020@qq.comAbstract: Infection caused by the Humicola sp is extremely rare. We report the first case of fungal keratitis caused by Humicola pulvericola (H. pulvericola) in a 63-year-old man with a history of exposed to hot oil two weeks ago who developed keratitis. Direct examination of confocal microscopy and corneal scrapings showed fungal hyphae and isolates were identified by morphology and by sequencing the internal transcribed spacer region of ribosomal DNA. The in vitro antifungal susceptibilities of the case strain were tested for five antifungal agents. The results showed that the infectious agent was resistant towards fluconazole, caspofungin and amphotericin B; itraconazole and voriconazole were highly effective against H. pulvericola. He was diagnosed with H. pulvericola keratitis and treated with oral itraconazole and natamycin eyedrops. After one month of treatment, the lesion gradually improved, with the best-corrected visual acuity improving to 0.8.Keywords: Humicola pulvericola, keratitis, itraconazole, fungal infection, antifungal drugs

Qian Chen,1,2 Chengyin Yu,1,2 Qingqing Wu,1,2 Rong Song,1,2 Ye Liu,1,2 Sheng Feng,3 Chen Yu,1,2 Jingying Jia1,2 1Center Laboratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, People’s Republic of China; 3Jiangsu Hengrui Pharmaceuticals Co., Ltd, Lianyungang, Jiangsu, People’s Republic of ChinaCorrespondence: Jingying Jia, Center Laboratory, Shanghai Xuhui Central Hospital, No. 966, Huaihai Road (M), Shanghai, People’s Republic of China, Tel/Fax +86-21-54030254, Email jyjia@shxh-centerlab.comPurpose: Henagliflozin is an original, selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. Hydrochlorothiazide (HCTZ) is a common anti-hypertensive drug. This study aimed to evaluate the potential interaction between henagliflozin and HCTZ.Methods: This was a single-arm, open-label, multi-dose, three-period study that was conducted in healthy Chinese volunteers. Twelve subjects were treated in three periods, period 1: 25 mg HCTZ for four days, period 2: 10 mg henagliflozin for four days and period 3: 25 mg HCTZ + 10 mg henagliflozin for four days. Blood samples and urine samples were collected before and up to 24 hours after drug administrations on day 4, day 10 and day 14. The plasma concentrations of henagliflozin and HCTZ were analyzed using LC-MS/MS. The urine samples were collected for pharmacodynamic glucose and electrolyte analyses. Tolerability was also evaluated.Results: The 90% CI of the ratio of geometric means (combination: monotherapy) for AUCτ,ss of henagliflozin and HCTZ was within the bioequivalence interval of 0.80– 1.25. For henagliflozin, co-administration increased Css, max by 24.32% and the 90% CI of the GMR was (108.34%, 142.65%), and the 24-hour urine volume and glucose excretion decreased by 0.43% and 19.6%, respectively. For HCTZ, co-administration decreased Css, max by 19.41% and the 90% CI of the GMR was (71.60%, 90.72%), and the 24-hour urine volume and urinary calcium, potassium, phosphorus, chloride, and sodium excretion decreased by 11.7%, 20.8%, 11.8%, 11.9%, 22.0% and 15.5%, respectively. All subjects (12/12) reported adverse events (AEs), but the majority of theses AEs were mild and no serious AEs were reported.Conclusion: Although Css,max was affected by the combination of henagliflozin and HCTZ, there was no clinically meaningful safety interaction between them. Given these results, coadministration of HCTZ should not require any adaptation of henagliflozin dosing.Trial Registration: ClinicalTrials.gov NCT06083116.Keywords: henagliflozin, drug-drug interaction, hydrochlorothiazide, pharmacokinetics, tolerability, pharmacodynamics, selective sodium-glucose cotransporter 2

Xingtong Chen,1,&ast; Qian Chen,1– 3,&ast; Zhigang Qin,1,&ast; Azeem Alam,3 Hailin Zhao,3 Raha West,3 Xianzhe Liu,1 Jieyu Li,1 Xin Li,1 Bin Yi,1 Daqing Ma,2,3 Jianteng Gu1 1Department of Anesthesiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2Perioperative and Systems Medicine Laboratory, National Clinical Research Center for Child Health, Children’s Hospital, Zhejiang University School of Medicine, Zhejiang, People’s Republic of China; 3Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK&ast;These authors contributed equally to this workCorrespondence: Jianteng Gu, Department of Anesthesiology, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan Road, Chongqing, 400038, People’s Republic of China, Tel +86 23 68766122, Fax +86 23 65463270, Email jiantenggu@hotmail.com Daqing Ma, Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK, Email d.ma@imperial.ac.ukBackground: Dexmedetomidine (Dex) may have anti-inflammatory properties and potentially reduce the incidence of postoperative organ injury.Objective: To investigate whether Dex protects pulmonary and renal function via its anti-inflammatory effects in elderly patients undergoing prolonged major hepatobiliary and pancreatic surgery.Design and Setting: Between October 2019 and December 2020, this randomized controlled trial was carried out at a tertiary hospital in Chongqing, China.Patients: 86 patients aged 60– 75 who underwent long-duration (> 4 hrs) hepatobiliary and pancreatic surgery without significant comorbidities were enrolled and randomly assigned into two groups at a 1:1 ratio.Interventions: Patients were given either Dex or an equivalent volume of 0.9% saline (Placebo) with a loading dose of 1 μg kg− 1 for 10 min, followed by 0.5 μg kg− 1 hr− 1 for maintenance until the end of surgery.Main Outcome Measures: The changes in serum concentrations of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were primary outcomes.Results: At one hour postoperatively, serum IL-6 displayed a nine-fold increase (P< 0.05) in the Placebo group. Administration of Dex decreased IL-6 to 278.09 ± 45.43 pg/mL (95% CI: 187.75 to 368.43) compared to the Placebo group (P=0.019; 432.16 ± 45.43 pg/mL, 95% CI: 341.82 to 522.50). However, no significant differences in TNF-α were observed between the two groups. The incidence of postoperative acute kidney injury was twice as high in the Placebo group (9.30%) compared to the Dex group (4.65%), and the incidence of postoperative acute lung injury was 23.26% in the Dex group, lower than that in the Placebo group (30.23%), although there was no statistical significance between the two groups.Conclusion: Dex administration in elderly patients undergoing major hepatobiliary and pancreatic surgery reduces inflammation and potentially protects kidneys and lungs.Registration: Chinese Clinical Trials Registry, identifier: ChiCTR1900024162, on 28 June 2019.Keywords: dexmedetomidine, elderly patients, long-duration hepatobiliary and pancreatic laparotomy, perioperative renal function, perioperative pulmonary function

Qiong Chen,1,&ast; Xuejuan Wu,1,&ast; Yanjin Huang,2 Lingling Chen1 1Respiratory Medicine Department, Xiamen Haicang Hospital, Xiamen, Fujian, People’s Republic of China; 2Nursing Department, Xiamen Haicang Hospital, Xiamen, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuejuan Wu, Respiratory Medicine Department, Xiamen Haicang Hospital, No. 89 Haiyu Road, Haicang District, Xiamen, Fujian, 361026, People’s Republic of China, Tel +86 150 6070 2657, Email 15060702657@163.comPurpose: Whether Internet of Things (IoT)-based home respiratory muscle training (RMT) benefits patients with comorbid chronic obstructive pulmonary disease (COPD) remains unclear. Therefore, this study aims to evaluate the effectiveness of IoT-based home RMT for patients with COPD.Patients and Methods: Seventy-eight patients with stable COPD were randomly divided into two groups. The control group received routine health education, while the intervention group received IoT-based home RMT (30 inspiratory muscle training [IMT] and 30 expiratory muscle training [EMT] in different respiratory cycles twice daily for 12 consecutive weeks). Assessments took place pre-intervention and 12 weeks post-intervention, including lung function tests, respiratory muscle strength tests, the mMRC dyspnea scale, CAT questionnaires, the HAMA scale, and 6-month COPD-related readmission after intervention.Results: Seventy-four patients with COPD were analyzed (intervention group = 38, control group = 36), and the mean age and FEV1 of the patients were 68.65 ± 7.40 years, 1.21 ± 0.54 L. Compared to those of the control population, the intervention group exhibited higher FEV1/FVC (48.23 ± 10.97 vs 54.32 ± 10.31, p = 0.016), MIP (41.72 ± 7.70 vs 47.82 ± 10.99, p = 0.008), and MEP (42.94 ± 7.85 vs 50.29 ± 15.74, p = 0.013); lower mMRC (2.00 [2.00– 3.00] vs 1.50 [1.00– 2.00], p < 0.001), CAT (17.00 [12.00– 21.75] vs 11.00 [9.00– 13.25], p < 0.001), and HAMA (7.00 [5.00– 9.00] vs 2.00 [1.00– 3.00], p < 0.001) scores; and a lower incidence rate of 6-month readmission (22% vs 5%, p = 0.033).Conclusion: Compared with no intervention, IoT-based home RMT may be a more beneficial intervention for patients with COPD.Keywords: chronic obstructive pulmonary disease, internet of things, respiratory rehabilitation, respiratory muscle training

Si Liu, Dan Yang, Wen Li, Qiuping Chen, Danni Lu, Liang Xiong, Junjie Wu, Hui Ao, Lihua Huang State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of ChinaCorrespondence: Lihua Huang; Hui Ao, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China, Email huanglihua@cdutcm.edu.cn; aohui2005@126.comPurpose: Polygala tenuifolia Willd. (PT), a traditional Chinese medicinal plant extensively employed in managing Alzheimer’s disease, exhibits notable gastrointestinal side effects as highlighted by prior investigations. In contrast, Magnolia officinalis Rehd. et Wils (MO), a traditional remedy for gastrointestinal ailments, shows promising potential for ameliorating this adverse effect of PT. The objective of this study is to examine the underlying mechanism of MO in alleviating the side effects of PT.Methods: Hematoxylin-eosin (H&E) staining was used to observe the structural damage of zebrafish intestine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors and oxidative stress. The integrity of the intestinal tight junctions was examined using transmission electron microscope (TEM). Moreover, the expression of intestinal barrier genes and PI3K/AKT/NF-κB signaling pathway-related genes was determined through quantitative real-time PCR. The changes in intestinal microbial composition were analyzed using 16S rRNA and metagenomic techniques.Results: MO effectively ameliorated intestinal pathological damage and barrier gene expression, and significantly alleviated intestinal injury by reducing the expression of inflammatory cytokines IL-1β, IL-6, TNF-α, and inhibiting the activation of PI3K/AKT/NF-κB pathway. Furthermore, MO could significantly increase the relative abundance of beneficial microorganisms (Lactobacillus, Blautia and Saccharomyces cerevisiae), and reduce the relative abundance of pathogenic bacteria (Plesiomonas and Aeromonas).Conclusion: MO alleviated PT-induced intestinal injury, and its mechanism may be related to the inhibition of PI3K/AKT/NF-κB pathway activation and regulation of intestinal flora.Keywords: polygala tenuifolia, PI3K/AKT/NF-κB, gut microbiota, inflammation, intestinal injury

Ciming Wu,1,&ast; Ming Ling,2,&ast; Qiong Chen,3 Hui Chai,1 Huan Chen1,4 1Zhejiang Chinese Medical University, College of Life Science, Hangzhou, Zhejiang, 310012, People’s Republic of China; 2Jinhua Institute for Food and Drug Control, Jinhua, Zhejiang, People’s Republic of China; 3Hangzhou First People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China; 4Hangzhou Digital-Micro Biotech Co, Ltd, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huan Chen; Hui Chai, Email chenhuan7809@gmail.com; christychai@zcmu.edu.cnAbstract: Methicillin-resistant Staphylococcus aureus (MRSA) is a predominant nosocomial infection-causing bacteria. The aim of this study was to develop a novel single-bacteria multiplex digital PCR assays (SMD-PCR), which is capable of simultaneously detecting and discriminating Methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA. This protocol employed TaqMan probes to detect SAOUHSC_00106 and mecA genes, with the latter being linked to methicillin resistance. A total of 72 samples from various specimen types were evaluated. The accuracy rates for the sputum samples, pus samples, swab samples, ear secretion samples, and catheter samples were 94.44%, 100%, 92%, 100%, and 100%, respectively. Our results showed that the clinical practicability of SMD-PCR has applicability to the rapid detection of MRSA without DNA extraction or bacterial culture, and can be utilized for the rapid detection of Staphylococcus aureus and the timely identification of MRSA in clinical samples, thereby providing an advanced platform for the rapid diagnosis of clinical MRSA infection.Keywords: MSSA, MRSA, droplet digital PCR, SMD-PCR

Qinzheng Chen,1 Zhen He,1 Yaxin Wang,2 Xuanjin Yang,2 Nana Liu,2 Suhan Zhang,2 Liangkun Ma,2 Xuezhong Shi,1 Xiaocan Jia,1 Yongli Yang,1 Yin Sun,2 Yuan He3 1Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences (CAMS) and PUMC, Beijing, People’s Republic of China; 3National Human Genetic Resources Center, National Research Institute for Family Planning, Beijing, People’s Republic of ChinaCorrespondence: Yin Sun, Department of Obstetrics and Gynecology, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences (CAMS) and PUMC, Beijing, 100730, People’s Republic of China, Email yinsun_pumch@163.com Yongli Yang, Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China, Email ylyang377@zzu.edu.cnPurpose: To assess the impact of maternal pre-pregnancy body mass index (BMI) on longitudinal fetal growth, and the potential mediation effect of the maternal fasting plasma glucose in first trimester.Methods: In this retrospective cohort study, we collected pre-pregnancy BMI data and ultrasound measurements during pregnancy of 3879 singleton pregnant women who underwent antenatal examinations and delivered at Peking Union Medical College Hospital. Generalized estimation equations, linear regression, and logistic regression were used to examine the association between pre-pregnancy BMI with fetal growth and adverse neonatal outcomes. Mediation analyses were also used to examine the mediating role of maternal fasting plasma glucose (FPG) in first trimester.Results: A per 1 Kg/m² increase in pre-pregnancy BMI was associated with increase fetal body length Z-score (β 0.010, 95% CI 0.001, 0.019) and fetal body weight (β 0.017, 95% CI 0.008, 0.027). In mid pregnancy, pre-pregnancy BMI also correlated with an increase Z-score of fetal abdominal circumference, femur length (FL). Pre-pregnancy BMI was associated with an increased risk of large for gestational age and macrosomia. Mediation analysis indicated that the associations between pre-pregnancy BMI and fetal weight in mid and late pregnancy, and at birth were partially mediated by maternal FPG in first trimester (mediation proportion: 5.0%, 8.3%, 1.6%, respectively).Conclusion: Maternal pre-pregnancy BMI was associated with the longitudinal fetal growth, and the association was partly driven by maternal FPG in first trimester. The study emphasized the importance of identifying and managing mothers with higher pre-pregnancy BMI to prevent fetal overgrowth.Keywords: body mass index, fetal growth, adverse neonatal outcomes, fasting plasma glucose, mediation analysis, cohort study

Yanan Zhang,1 Qianqian Chen,1 Qingqing Sun,1 Mingyang Tang,1 Yi Yang,1,2 Zhen-Ni Guo,1,2 Zan Wang1,2 1Sleep Center, Department of Neurology, The First Hospital of Jilin University, Chang Chun, People’s Republic of China; 2Stroke Center, Department of Neurology, The First Hospital of Jilin University, Chang Chun, People’s Republic of ChinaCorrespondence: Zhen-Ni Guo, Stroke Center, Department of Neurology, The First Hospital of Jilin University, Xinmin Street 1&num;, Chang Chun, 130021, People’s Republic of China, Tel +86-431-88782378, Email zhen1ni2@jlu.edu.cn Zan Wang, Sleep Center, Department of Neurology, The First Hospital of Jilin University, Xinmin Street 1&num;, Chang Chun, 130021, People’s Republic of China, Tel +86-431-88782378, Email wangzan@jlu.edu.cnBackground: Restless legs syndrome (RLS) is a prevalent sensorimotor nervous system disorder in patients accompanied with insomnia, blood pressure fluctuation, and sympathetic dysfunction. These symptoms may disrupt cerebral hemodynamics. Dynamic cerebral autoregulation (dCA) describes the temporary response of cerebrovascular system to abrupt fluctuations in blood pressure, which keep cerebral blood flow stable and serve as a marker of cerebrovascular system ability.Objective: This research aimed to assess dCA in RLS patients.Methods: In this study, RLS patients were recruited and subsequently classified into four groups (mild, moderate, severe, and very severe) based on the International RLS Rating Scale (IRLS). Healthy controls matched for age and sex were enrolled. All participants were evaluated dCA by assessing phase difference (PD). A portion of patients with RLS was reassessed for dCA after one month of medication therapy (pramipexole [0.125 mg/day] and gabapentin [300 mg/day]).Results: There were altogether 120 patients with RLS and 30 controls completed the polysomnography and dCA assessment. PD was lower in the moderate, severe, and very severe RLS groups than that in the controls and mild RLS groups. Periodic limb movement index (PLMI), arousal index, and IRLS all showed a linear correlation with PD in RLS patients. Additionally, PD increased in RLS patients after therapy.Conclusion: The dCA was compromised in moderate, severe, and very severe RLS patients and was negatively correlated with the IRLS, arousal index, and PLMI. After 1 month of therapy, dCA improved in RLS patients.Keywords: restless legs syndrome, dynamic cerebral autoregulation, autonomic nerve dysfunction, dopaminergic

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

Jiewei Huang,1,2 Jiajing Zhuang,2,3 Huaxian Zheng,4 Ling Yao,5,6 Qingquan Chen,7,8 Jiaqi Wang,1,2 Chunmei Fan1 1The Clinical Laboratory Center of the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362018, People’s Republic of China; 2The Graduate School of Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 3Department of Ultrasound, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China; 4The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 5Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350000, People’s Republic of China; 6Department of Nephrology, Rheumatology and Immunology, Fujian Children’s Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350014, People’s Republic of China; 7The Sleep Disorder Medicine Center of the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362018, People’s Republic of China; 8The School of Public Health, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of ChinaCorrespondence: Chunmei Fan, The Clinical Laboratory Center of the Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362018, People’s Republic of China, Tel +86 15906069575, Email fanchunmei9575@163.comObjective: Obstructive sleep apnea (OSA) is a common and potentially fatal sleep disorder. The purpose of this study was to construct an objective and easy-to-promote model based on common clinical biochemical indicators and demographic data for OSA screening.Methods: The study collected the clinical data of patients who were referred to the Sleep Medicine Center of the Second Affiliated Hospital of Fujian Medical University from December 1, 2020, to July 31, 2023, including data for demographics, polysomnography (PSG), and 30 biochemical indicators. Univariate and multivariate analyses were performed to compare the differences between groups, and the Boruta method was used to analyze the importance of the predictors. We selected and compared 10 predictors using 4 machine learning algorithms which were “Gaussian Naive Bayes (GNB)”, “Support Vector Machine (SVM)”, “K Neighbors Classifier (KNN)”, and “Logistic Regression (LR)”. Finally, the optimal algorithm was selected to construct the final prediction model.Results: Among all the predictors of OSA, body mass index (BMI) showed the best predictive efficacy with an area under the receiver operating characteristic curve (AUC) = 0.699; among the predictors of biochemical indicators, triglyceride-glucose (TyG) index represented the best predictive performance (AUC = 0.656). The LR algorithm outperformed the 4 established machine learning (ML) algorithms, with an AUC (F1 score) of 0.794 (0.841), 0.777 (0.827), and 0.732 (0.788) in the training, validation, and testing cohorts, respectively.Conclusion: We have constructed an efficient OSA screening tool. The introduction of biochemical indicators in ML-based prediction models can provide a reference for clinicians in determining whether patients with suspected OSA need PSG. Keywords: biochemical indicators, obstructive sleep apnea, machine learning, prediction model, triglyceride-glucose index

Yang Li,&ast; Qiang Chen,&ast; Hong-Juan Sun, Jian-Hong Zhang, Xuan Liu Pharmaceutical Preparation Section, the Fourth Central Hospital of Tianjin, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Li, Pharmaceutical preparation section, the Fourth Central Hospital of Tianjin, No. 1, Zhongshan Road, Hebei District, Tianjin, 300142, People’s Republic of China, Tel +86-022-26249316, Email lyg_liyang@yeah.netBackground: Type 2 diabetes mellitus (T2DM) poses a huge threat to population health globally, and more drugs need to be explored for treatment. In this study, we investigated the mechanism of active ingredient catalpol in Rehmannia glutinosa on reduces blood glucose in diabetic.Methods: The T2DM model was constructed by intraperitoneal injection of streptozotocin into Sprague-Dawley (SD) rats, which were randomly grouped into diabetes model group, pioglitazone group, Rehmannia glutinosa group, catalpol high-dose group, catalpol low-dose group and normal control group.The intervention was continued for 28 d, and changes in body weight, fasting blood glucose, insulin and lipid levels were observed.Results: Of all the drugs, pioglitazone had the most pronounced hypoglycemic effect, which began to decline after 2 weeks of treatment in the low-dose catalpol group and had no hypoglycemic effect in the high-dose catalpol group. Among them, Rehmannia glutinosa was able to increase serum triglyceride level, and pioglitazone effectively reduced total cholesterol level in rats. The low dose of catalpol decreased the concentration of low-density lipoprotein cholesterol (LDL), while the high dose of catalpol increased the concentration of LDL.Conclusion: As an active ingredient in Rehmannia glutinosa, catalpol has the potential to lower blood glucose and improve blood lipids in diabetes treatment, and its action may be achieved by regulating the adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, which provides a new idea for the development of new diabetes therapeutic approaches.Keywords: catalpol, Rehmannia glutinosa, type 2 diabetes, traditional Chinese medicine

Lei Yuan,&ast; Lan Min Lai,&ast; Xinyu Zhu, Zhao Rui, Yang Liu, Qiang Chen Department of Clinical laboratory, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Chen, Email 674389899@qq.comBackground: The HACEK group comprises Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae, are Gram-negative bacteria that are slow-growing and fastidious. These organisms are common causes of culture-negative endocarditis. However, brain abscesses caused by Haemophilus aphrophilus and E. corrodens have been rarely reported. The case we describe, which was promptly identified and successfully treated, will be meaningful for the diagnosis and treatment of such infectious diseases.Case Presentation: Herein, we report a case of brain abscess in a young man who was infected with Haemophilus aphrophilus and E. corrodens. The patient was admitted to the hospital with sudden onset of vomiting, coma, and fever. Magnetic resonance imaging (MRI) of the brain and cerebrospinal fluid cell counts suggested cerebral abscess, he underwent drainage of the abscess and empirical antimicrobial therapy of meropenem (2 g every 8 hours) and linezolid (0.6 g every 12 hours) for more than 10 days without significant improvement. Metagenomic next-generation sequencing (mNGS) of drainage fluid and matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF MS) detection for isolated bacteria from samples suggested the presence of H. aphrophilus and E. corrodens. After 7 weeks of ceftriaxone (2 g every 12 hours) and meropenem (2 g every 8 hours) intravenously, the patient was discharged with a normal temperature and brain MRI showed improvement of the lesion.Conclusion: Similar cases reported in previous studies were always associated with bacterial blood dissemination after dental surgery or myocarditis; however, the patient in our case had no any associated risk factors. As far as we know, this is the only case of central nervous system infection caused by H. aphrophilus and E. corrodens that has utilized combined mNGS and MALDI-TOF MS in the diagnosis.Keywords: Haemophilus aphrophilus, Eikenella corrodens, HACEK, brain abscess

Ailin Zou,1,&ast; Tingting Xiao,1,&ast; Boyu Chi,1,2 Yu Wang,1 Lipeng Mao,1,2 Dabei Cai,1,2 Qingqing Gu,1 Qianwen Chen,1 Qingjie Wang,1 Yuan Ji,1 Ling Sun1,2 1Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 2Changzhou Clinical Medical College, Dalian Medical University, Dalian, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Sun; Qingjie Wang, Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213003, People’s Republic of China, Email sunling85125@hotmail.com; wang-qingjie@hotmail.comBackground: Cardiac repair remains a thorny issue for survivors of acute myocardial infarction (AMI), due to the regenerative inertia of myocardial cells. Cell-free therapies, such as exosome transplantation, have become a potential strategy for myocardial injury. The aim of this study was to investigate the role of engineered exosomes in overexpressing Growth Differentiation Factor-15 (GDF-15) (GDF15-EVs) after myocardial injury, and their molecular mechanisms in cardiac repair.Methods: H9C2 cells were transfected with GDF-15 lentivirus or negative control. The exosomes secreted from H9C2 cells were collected and identified. The cellular apoptosis and autophagy of H2O2-injured H9C2 cells were assessed by Western blotting, TUNEL assay, electron microscopy, CCK-8 and caspase 3/7 assay. A rat model of AMI was constructed by ligating the left anterior descending artery. The anti-apoptotic, pro-angiogenic effects of GDF15-EVs treatment, as well as ensuing functional and histological recovery were evaluated. Then, mRNA sequencing was performed to identify the differentially expressed mRNAs after GDF15-EVs treatment.Results: GDF15-EVs inhibited apoptosis and promoted autophagy in H2O2 injured H9C2 cells. GDF15-EVs effectively decreased the infarct area and enhanced the cardiac function in rats with AMI. Moreover, GDF15-EVs hindered inflammatory cell infiltration, inhibited cell apoptosis, and promoted cardiac angiogenesis in rats with AMI. RNA sequence showed that telomerase reverse transcriptase (TERT) mRNA was upregulated in GDF15-EVs-treated H9C2 cells. AMPK signaling was activated after GDF15-EVs. Silencing TERT impaired the protective effects of GDF15-EVs on H2O2-injured H9C2 cells.Conclusion: GDF15-EVs could fulfil their protective effects against myocardial injury by upregulating the expression of TERT and activating the AMPK signaling pathway. GDF15-EVs might be exploited to design new therapies for AMI.Keywords: exosomes, growth differentiation factor-15, telomerase reverse transcriptase, acute myocardial infarction

Yingfan Chen,1,2,&ast; Zhenhui Wu,3,&ast; Shaodan Li,2 Qi Chen,2 Liang Wang,2 Xiaorong Qi,1 Chujiao Tian,1 Minghui Yang2 1Medical School of Chinese People’s Liberation Army, Beijing, People’s Republic of China; 2Department of Traditional Chinese Medicine, the Six Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 3College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minghui Yang, Department of Traditional Chinese Medicine, the Six Medical Center, Chinese People’s Liberation Army General Hospital, 6 Fucheng Road, Beijing, 100048, People’s Republic of China, Tel +86-10-66939651, Email ymh9651@sina.comMethods: Related studies on PD and ferroptosis were searched in Web of Science Core Collection (WOSCC) from inception to 2023. VOSviewer, CiteSpace, RStudio, and Scimago Graphica were employed as bibliometric analysis tools to generate network maps about the collaborations between authors, countries, and institutions and to visualize the co-occurrence and trends of co-cited references and keywords.Results: A total of 160 original articles and reviews related to PD and ferroptosis were retrieved, produced by from 958 authors from 162 institutions. Devos David was the most prolific author, with 9 articles. China and the University of Melbourne had leading positions in publication volume with 84 and 12 publications, respectively. Current hot topics focus on excavating potential new targets for treating PD based on ferroptosis by gaining insight into specific molecular mechanisms, including iron metabolism disorders, lipid peroxidation, and imbalanced antioxidant regulation. Clinical studies aimed at treating PD by targeting ferroptosis remain in their preliminary stages.Conclusion: A continued increase was shown in the literature within the related field over the past decade. The current study suggested active collaborations among authors, countries, and institutions. Research into the pathogenesis and treatment of PD based on ferroptosis has remained a prominent topic in the field in recent years, indicating that ferroptosis-targeted therapy is a potential approach to halting the progression of PD.Keywords: Parkinson’s disease, ferroptosis, bibliometric analysis, iron accumulation, alpha-synuclein, mitochondrial dysfunction, oxidative stress, lipid peroxidation

Diguo Zhai,1,2 Qingwei Chen,1,2 Ying Yao,3 Taotao Ru,1,2 Guofu Zhou1,2 1Guangdong Provincial Key Laboratory of Optical Information Materials and Technology, Institute of Electronic Paper Displays, South China Academy of Advanced Optoelectronics, South China Normal University, Guangzhou, 510006, People’s Republic of China; 2National Center for International Research on Green Optoelectronics, South China Normal University, Guangzhou, 510006, People’s Republic of China; 3Anhui Provincial Library, Hefei, 230000, People’s Republic of ChinaCorrespondence: Taotao Ru; Qingwei Chen, Lab of Light and Physio-Psychological Health-National Center for International Research on Green Optoelectronics-South China Academy of Advanced Optoelectronics-South China Normal University, No. 55, West Zhongshan Road, Tianhe District, Guangzhou, 510631, People’s Republic of China, Tel +86 15603063417 ; +86 15521094813, Email taotao.ru@m.scnu.edu.cn; qingwei.chen@m.scnu.edu.cnPurpose: To explore whether sleep electroencephalogram (EEG) microarousals of different standard durations predict daytime mood and attention performance in healthy individuals after mild sleep restriction.Participants and Methods: Sixteen (nine female) healthy college students were recruited to examine the correlations between nocturnal EEG microarousals of different standard durations (≥ 3 s, ≥ 5 s, ≥ 7 s, ≥ 9 s) under mild sleep restriction (1.5 h) and the following morning’s subjective alertness, mood, sustained attention, and selective attention task performance.Results: Results revealed that mild sleep restriction significantly reduced subjective alertness and positive mood, while having no significant effect on negative mood, sustained attention and selective attention performance. The number of microarousals (≥ 5 s) was negatively associated with positive mood at 6:30. The number of microarousals was significantly and positively correlated with the response time difference value of disengagement component of the selective attention task at around 7:30 (≥ 5 s and ≥ 7 s) and 9:00 (≥ 5 s). The number of microarousals (≥ 7 s) was significantly and positively correlated with the inaccuracy difference value of orientation component of the selective attention task at around 9:00.Conclusion: The number of EEG microarousals during sleep in healthy adults with mild sleep restriction was significantly and negatively related to their daytime positive affect while positively associated with the deterioration of disengagement and orientation of selective attention performance, but this link is dependent on the standard duration of microarousals, test time and the type of task.Keywords: microarousal, alertness, sustained attention, selective attention, sleep restriction

Qiumiao Chen,1 Bin Qin,2 Manqing Zhang,2 Yumei Zhou,2 Xiaotong Shi,2 Yubo Xie1,3 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Anesthesiology, College of Stomatology, Hospital of Stomatology, Guangxi Medical University, Nanning, People’s Republic of China; 3Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Yubo Xie; Xiaotong Shi, Email xybdoctor@163.com; Hbb38@163.comBackground: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that has the potential to be an alternative for procedural sedation due to its rapid sedation and recovery, no accumulation effect, stable hemodynamics, minimal respiratory depression, anterograde amnesia effect, and specific antagonist. Here, we aimed to compare the safety and efficacy of remimazolam with dexmedetomidine for awake tracheal intubation by flexible bronchoscopy (ATI-FB).Methods: Ninety patients scheduled for ATI-FB were randomly divided into three groups, each consisting of 30 cases: dexmedetomidine 0.6 μg/kg + sufentanil (group DS), remimazolam 0.073 mg/kg + sufentanil (group R1S), or remimazolam 0.093 mg/kg + sufentanil (group R2S). The primary outcome was the success rate of sedation. Secondary outcomes were MOAA/S scores, hemodynamic and respiratory parameters, intubation conditions, intubation time, tracheal intubation amnesia, and adverse events.Results: The success rates of sedation in groups R2S and DS were higher than that in group R1S (93.3%, 86.7%, respectively, vs 58.6%; P = 0.002), and intubation conditions were better than those in group R1S (P < 0.05). Group R2S had shorter intubation times than groups R1S and DS (P = 0.003), and a higher incidence of tracheal intubation amnesia than group DS (P = 0.006). No patient in the three groups developed hypoxemia or hypotension, and there were no significant differences in oligopnea, PetCO2, or bradycardia (P > 0.05).Conclusion: In conclusion, both DS and R2S had higher success rates of sedation, better intubation conditions, and minor respiratory depression, but R2S, with its shorter intubation time, higher incidence of anterograde amnesia, and ability to be antagonized by specific antagonists, may be a good alternative sedation regimen for patients undergoing ATI-FB.Keywords: remimazolam, dexmedetomidine, difficult airways, awake tracheal intubation

Jinling Ma,&ast; Suyan Bian, Ang Li, Qian Chen&ast; Department of Geriatric Cardiology, the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinling Ma, Department of Geriatric Cardiology, the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of China, Email majinling1@163.comBackground: Type 2 myocardial infarction (MI) is becoming more recognized. This study aimed to assess the factors linked to type 2 MI in older adults with pneumonia and further determine the predictive factors of 90-day adverse events (refractory heart failure, cardiogenic shock, and all-cause mortality).Methods: A single-center retrospective analysis was conducted among older adults with pneumonia. The primary outcome was the prevalence of type 2 MI. The secondary objective was to assess the adverse events in these patients with type 2 MI within 90 days.Results: A total of 2618 patients were included. Of these, 361 patients (13.8%) suffered from type 2 MI. Multivariable predictors of type 2 MI were chronic kidney disease (CKD), age-adjusted Charlson comorbidity index (ACCI) score, and NT-proBNP > 4165pg/mL. Moreover, the independent predictive factors of 90-day adverse events included NT-proBNP > 4165pg/mL, age, ACCI score, and CKD. The Kaplan–Meier adverse events curves revealed that the type 2 MI patients with CKD and NT-proBNP > 4165pg/mL had a higher risk than CKD or NT-proBNP > 4165pg/mL alone.Conclusion: Type 2 MI in older pneumonia hospitalization represents a heterogeneous population. Elevated NT-proBNP level and prevalence of CKD are important predictors of type 2 MI and 90-day adverse events in type 2 MI patients.Keywords: type 2 myocardial infarction, pneumonia, older, mortality

Chaoping Yang,1,&ast; Jing Xie,2,&ast; Qianjun Chen,2 Qiongyin Yuan,3 Jianping Shang,4 Haibo Wu,5 Youhua Yang,6 Mingfang Wang,7 Xiaolan Shu,8 Jing Yue,9 Danna Tu,10 Ying Lin,1,&ast; Ronghao Zheng,4,&ast; Xiaolin Wu4 1Nursing Department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 3Obstetrical department, Huanggang Maternal and Child Health Hospital, Hubei, People’s Republic of China; 4Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5School of Health and Nursing, Wuchang University of Technology, Wuhan, People’s Republic of China; 6Department of Basic Medical Sciences, School of Medicine, Jianghan University, Wuhan, People’s Republic of China; 7Department of Pediatric Gastroenterology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 8Department of Pediatric Intensive Care Unit (PICU), Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 9Emergency Department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 10Department of Pediatric Cardiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghao Zheng, Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 745 Wu Luo Road, Hongshan District, Wuhan, Hubei Province, 430070, People’s Republic of China, Email hytwo2001@126.com Ying Lin, Nursing department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email 523933025@qq.comPurpose: The knowledge, attitude, and practices (KAP) concerning antibiotics by healthcare students have the potential impact on controlling antibiotic abuse and antimicrobial resistance (AMR) growth. This study aims to evaluate the levels and explore the associated factors with KAP on antibiotic use and AMR in Chinese nursing students.Methods: A cross-sectional survey using a self-administered questionnaire consisting of demographics and selected features and KAP on antibiotic use and AMR was conducted to measure KAP levels among nursing students at various universities in Hubei Province, China. The logistic regression analyses were performed to analyze the potential factors associated with the KAP.Results: The survey eventually included a total of 1959 nursing students. The mean scores for KAP were 57.89 ± 26.32, 55.00 ± 12.50, and 71.88 ± 15.63, respectively. Regarding knowledge, 54.3% of participants were unaware that antibiotic was ineffective against viral infections. Regarding attitude, 36% of participants agreed that current antibiotic abuse existed; 96.2% of participants thought it necessary to set up a special course on antibiotics. Regarding practice, only 48.4% of participants usually purchased antibiotics with a prescription. Multivariable analyses indicated that lack of discussion on AMR in school courses was an independent risk factor against KAP, respectively. The main knowledge sources of antibiotic being outside the classroom was an independent risk factor related to knowledge and practice. The average score > 80 points was an independent protective factor related to knowledge and practice.Conclusion: The KAP level on antibiotic use and AMR among Hubei nursing students was general and required further strengthening. Nursing students with risk factors should be prioritized in educational interventions. The findings of our study pointed out some directions for tailored interventions to improve the training on antibiotics.Keywords: antibiotic use, antimicrobial resistance, knowledge, attitude, practice, nursing students

Qianwen Chen,1,&ast; Qingqing Gu,1,&ast; Anwen Yin,2,&ast; Dabei Cai,1 Tingting Xiao,1 Yu Wang,1 Yuan Ji,1 Qingjie Wang,1 Jun Wei,3 Ling Sun1 1Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213000, People’s Republic of China; 2Department of Cardiology, the Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu, 214023, People’s Republic of China; 3Department of Cardiovascular Surgery, the First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingjie Wang; Ling Sun, Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou, Jiangsu, 213003, People’s Republic of China, Email wang-qingjie@hotmail.com; sunling85125@hotmail.comObjective: This study aimed to explore the association of preoperative neutrophil percentage (NEUT%) with the risk of acute kidney injury (AKI) in patients with acute myocardial infarction (AMI) having undergone coronary interventional therapy.Methods: A single-center, retrospective and observational study was conducted. From December 2012 to June 2021, patients with AMI were enrolled and divided into AKI group and non-AKI group. The NEUT% in the two groups was compared. The association between NEUT% with the risk of post-AMI AKI was analyzed by univariate and multivariable logistic regression. Kaplan-Meier survival curve was drawn to evaluate the prognostic ability of NEUT% for short-term all-cause death following AMI.Results: A total of 3001 consecutive patients were enrolled with an average age of 64.38 years. AKI occurred in 327 (10.9%) patients. The NEUT% was higher in the AKI group than in the non-AKI group ([76.65± 11.43]% versus [73.22± 11.83]%, P< 0.001). NEUT% was also identified as an independent risk factor for AKI in AMI patients after adjustment (OR=1.021, 95% CI: 1.010– 1.033, P < 0.001). Compared with those at the lowest quartile of NEUT%, the patients at quartiles 2– 4 had a higher risk of AKI (P for trend = 0.003). The odds of AKI increased by 29.0% as NEUT% increased by 1 standard deviation (OR=1.290, 95% CI: 1.087– 1.531, P = 0.004). After a median of 35 days follow-up, 93 patients died. Patients with a higher NEUT% presented a higher risk of all-cause death after AMI (Log rank: χ2 =24.753, P< 0.001).Conclusion: In AMI patients, the peripheral blood NEUT% was positively associated with the odds of AKI and short-term all-cause mortality. NEUT% may provide physicians with more information about disease development and prognosis.Keywords: neutrophil percentage, acute kidney injury, acute myocardial infarction

Mi Qi, Yajuan Cheng, Ke Liu, Jingxing Cai, Tianyu Liu, Xiaoying Wu, Huili Tang, He Huang, Qinbiao Chen, Xiaoguang Zhou The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Mi Qi; Xiaoguang Zhou, Tel +86-13510794978 ; +86-18818780760, Email qimi@mail.sysu.edu.cn; gzzhouxg@163.comPurpose: Ischemic stroke is a high-incidence disease that threatens human well-being. The potent neuroprotective effects render reactive oxygen species (ROS) scavengers potential agents for acute ischemic stroke therapy. Challenges such as inadequate permeability across the blood-brain barrier (BBB), limited half-life, and adverse effects hinder the widespread utilization of small molecule and inorganic ROS scavengers. Thus, there is an urgent demand for efficacious neuroprotective agents targeting ischemic stroke. Our study discovered the superoxide dismutase (SOD)-mimetic activity of recombinant human heavy chain ferritin (rHF) nanoparticles expressed from Escherichia coli (E. coli). Subsequent investigations delved into the ROS-scavenging proficiency of rHF within neural cells, its therapeutic efficacy against ischemic stroke, and the elucidation of its neuroprotective mechanisms.Methods: rHF protein nanoparticles were expressed in E. coli and purified via size-exclusion chromatography. The superoxide anion (•O2−) scavenging SOD-mimetic activity of rHF nanoparticles was measured using a SOD detection kit. The ROS scavenging ability and protection effects against oxidative damage of rHF nanoparticles were studied in H2O2-induced PC12 cells. Therapeutic effects and neuroprotective mechanisms of rHF against ischemic stroke were investigated with transient middle cerebral artery occlusion (MCAO) reperfusion mice model.Results: rHF nanoparticles can eliminate excessive ROS in nerve cells and alleviate oxidative damage. The results of animal experiments demonstrated that rHF nanoparticles passed across BBB, reduced infarct areas in brain tissue, and lowered the neurological deficit score of ischemia-reperfusion model mice. Additionally, rHF nanoparticles mitigated neuronal apoptosis and ferroptosis, suppressed microglial activation, maintained oxygen homeostasis, and exhibited negligible organ toxicity.Conclusion: rHF nanoparticle could be developed as a new ROS scavenger for nerve cells and has therapeutic potential as a drug for cerebral ischemia-reperfusion injury. Keywords: human heavy chain ferritin, ROS scavenger, ischemic stroke, SOD-mimetic, neuroprotection

Hao Zhan,1,2 Qichun Chen,1,2 Tiantian Liu,1,2 Yuting Shi,1,2 Jinxia Pei,1,2 Liwei Zou,1,2 Longsheng Wang1,2 1Department of Radiology, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China; 2Medical Imaging Research Center of Anhui Medical University, Hefei, 230601, People’s Republic of ChinaCorrespondence: Liwei Zou; Longsheng Wang, Email zouliwei@ahmu.edu.cn; wangls1125@sina.comPurpose: The main aim of this study is to analyze the relationship between body composition indices and metabolic unhealthy phenotypes in young and middle-aged obese patients and to assess their joint predictive ability.Patients and Methods: A cross-sectional study method was used to select 207 patients who were proposed to undergo weight loss surgery for morbid obesity from March to November 2022. Total adipose tissue (TAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), liver fat content (LFC), cross-sectional area (CSAmuscle), and intermuscular adipose tissue (CSAIMAT) of paraspinal muscles were measured using quantitative computed tomography. Participants were categorized into two groups: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). The receiver operating characteristic curve comprised body composition variables that correlated with MUO, and the area under the curve (AUC) was calculated to compare their prediction capacity for MUO.Results: There were 71 patients with MHO (34.3%) and 136 patients with MUO (65.7%). The VAT, VAT/TAT ratio, LFC, and CSAmuscle was higher in MUO patients than in MHO (all P < 0.001), and SAT was lower than in MHO (P = 0.008). And all of these metrics were correlated with MUO (all P < 0.05). Inclusion of these body composition metrics in the ROC analysis showed that the AUC values for SAT, VAT, VAT/TAT ratio, LFC and CSAmuscle were 0.615, 0.663, 0.727, 0.694, 0.671, respectively, and the combination of the VAT/TAT ratio and the LFC had the ability to predict MUO best (AUC=0.746, P = 0.025).Conclusion: The combined use of VAT/TAT ratio and LFC is superior to the use of these two metrics alone in terms of their ability to predict the MUO, providing a more accurate approach to the management and prevention of obesity-related metabolic risk.Keywords: metabolically unhealthy, obesity, body composition, quantitative computed tomography

Yirui Song, Qianqian Chen, Lei Wang Department of Psychology, Wuhan Sports University, Wuhan, People’s Republic of ChinaCorrespondence: Lei Wang, Department of Psychology, Wuhan Sports University, No. 461 Luoyu Road, Hongshan District, Wuhan, 430079, People’s Republic of China, Email 378299706@qq.comPurpose: Post-traumatic growth is a significant social issue in the management of active aging in elderly people. This study investigates the influence of familism emotions on post-traumatic growth (PTG) of the elderly, and the mediating role of Taoist personality and sense of community (SOC) therein, to provide a scientific basis for the development of positive aging in the elderly.Methods: A cross-sectional study was conducted in several communities of Hubei Province in China. A total of 338 elderly people were investigated with the Familism Emotion Scale, PTG Scale, Taoist Personality Scale and SOC Scale. SPSS 23.0 was used to derive descriptive statistics and conduct a common method bias test, Pearson correlation analysis, and multiple stepwise regression analysis. Mplus 7.3 was used for structural equation modeling to test the significance of parallel mediation effects on the data.Results: The results show that: (1) Familism emotions, Taoist personality and SOC are positively correlated with PTG; (2) Familism emotions, Taoist personality and SOC can all positively predict PTG in the elderly; (3) Both Taoist personality and SOC partially mediated the link between familism emotions and PTG in the elderly.Conclusion: In the context of particularly constraining societal events such as COVID-19, it is necessary to pay careful attention to the impact of external environmental influences upon the elderly, such as family and community, and to encourage elderly people to cultivate a more Taoist personality. The formation of a Taoist personality offers a promising new focus for research in elderly healthcare.Keywords: familism emotions, post-traumatic growth, Taoist personality, sense of community, elderly

Xiaolan Zhou,1 Rumeng Chen,2 Yichen Cai,1 Qiu Chen1 1Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Qiu Chen, Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39, Shierqiao Road, Chengdu, Sichuan, People’s Republic of China, Tel +86 18981885702, Fax +86 28-87765517, Email chenqiu1005@cdutcm.edu.cnPurpose of Review: The aim of this review is to summarize the role of gastrointestinal microbiome (GM) in the development of type 2 diabetes mellitus (T2DM). Besides, we discuss the feasibility of applying FMT in the treatment of T2DM and propose a series of processes to refine the use of FMT in the treatment of T2DM.Recent Findings: T2DM is a metabolic disease which is connected with the GM. According to many researches, GM can produce a variety of metabolites such as bile acid, short chain fatty acids, lipopolysaccharides and trimethylamine oxide which play an important role in metabolism. FMT is a method to regulate GM and has been observed to be effective in the treatment of metabolic diseases such as T2DM in some mouse models and people. However, there is still a lack of direct evidence for the use of FMT in the treatment of T2DM, and the process of FMT is not standardized.Summary: Dysregulation of GM is closely related to the development of T2DM. Promoting the conversion of GM in T2DM patients to normal population through FMT can reduce insulin resistance and lower their blood glucose level, which is an optional treatment for T2DM patients in the future. At present, the feasibility and limitations of applying FMT to the treatment of T2DM need to be further studied.Keywords: fecal microbiota transplantation, type 2 diabetes mellitus, gastrointestinal microbiome, treatment

Zhanlin Liao,1,&ast; Liangzhi Huang,1,&ast; Jun Chen,2 Ting Chen,1 Dezhi Kong,1 Qifeng Wei,1 Qiao Chen,1 Bin Deng,1 Yanyan Li,1 Shuai Zhong,1 Zugui Huang1 1Department of Endocrine, Affiliated Nanping First Hospital of Fujian Medical University, Nanping, Fujian, 353006, People’s Republic of China; 2Department of Ophthalmology, Affiliated Nanping First Hospital of Fujian Medical University, Nanping, Fujian, 353006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zugui Huang, Department of Endocrine, Affiliated Nanping First Hospital of Fujian Medical University, No. 317 Zhongshan Road, Nanping, Fujian, 353006, People’s Republic of China, Email 15159969783@163.comBackground: Type 2 diabetes (T2DM) combined nonalcoholic fatty liver disease (NAFLD) are characterized by metabolic disruptions. Liraglutide has been proved to be effective in T2DM. If LRG could regulate NAFLD combined T2DM has not been reported.Methods: Intraperitoneal injection of 1% streptozotocin (STZ) plus high-sugar and high-fat diet was used to induce NAFLD combined T2DM animal model. Palmitic acid (200 μmol/L) and glucose (25 mmol/L) incubation were used to induce cell model. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and Western blotting, respectively.Results: Liraglutide significantly improved the liver injury of NAFLD combined T2DM rats, but Com-C reversed the effect of liraglutide. The decreased AMPK/mTOR signaling pathway in the NAFLD combined T2DM animals was greatly activated by liraglutide. Com-C reversed the protection effects of liraglutide on palmitic acid+glucose induced cell damage.Conclusion: Liraglutide could greatly alleviate the damage caused by NAFLD+T2DM and palmitic acid+glucose. The protection effects of liraglutide were greatly inhibited by suppressing AMPK/mTOR signaling pathway. This research might provide a novel therapeutic strategy for the prevention and treatment of NAFLD combined T2DM disease.Keywords: type 2 diabetes, nonalcoholic fatty liver disease, liraglutide, AMPK/mTOR, autophagy

Yang Xu,1 Qinglin Chen,1,2 Yu Tian1 1Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu, 610066, People’s Republic of China; 2Sichuan Key Laboratory of Psychology and Behavior of Discipline lnspection and Supervision (Sichuan Normal University), Chengdu, 610066, People’s Republic of ChinaCorrespondence: Yu Tian, Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu, 610066, People’s Republic of China, Tel +86 13888583767, Email tianyu@sicnu.edu.cnIntroduction: The general deficit in inhibitory control of problematic social media users has received widespread attention. However, the neural correlates of problematic social media use (PSMU) and inhibitory control remain unclear. Additionally, the co-occurrence of the fear of missing out (FoMO) with social media use is common, yet its role in the relationship between PSMU and inhibitory control has not been investigated.Methods: This study aimed to examine the electrophysiological correlates of PSMU and inhibitory control using a modified two-choice oddball task combined with event-related potentials (ERPs), and to explore the role of FoMO in this relationship. A total of 66 participants with varying degrees of PSMU were included in the analysis based on the Problematic Mobile Social Media Usage Questionnaire.Results: The study found that PSMU could impact inhibitory control. Specifically, as the PSMU score increases, the N2 amplitude is greater for social media-related pictures, and the P3 amplitude is smaller, while no significant differences are observed for neutral pictures. This suggests that PSMU affects inhibitory control by consuming more cognitive resources in the early conflict detection stage and leading to insufficient cognitive resources in the later stages of the inhibitory process. Furthermore, FoMO played a mediating role between PSMU and inhibitory control. PSMU could further impact inhibitory control through FoMO.Conclusion: This study provides electrophysiological evidence for deficits in inhibitory control in PSMU and suggests that FoMO may further reduce inhibitory control in PSMU individuals.Keywords: problematic social media use, inhibitory control, fear of missing out, event-related potentials

Zhenhua Liu,1,&ast; Mingxi Cai,2,&ast; Haoteng Ke,2,&ast; Huazong Deng,2 Weijia Ye,2 Tao Wang,1 Qifan Chen,1 Shuizhong Cen1 1Department of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 2The Second Clinical School, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuizhong Cen, Department of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China, Tel +86 13480297160, Email censhzh3@mail2.sysu.edu.cnPurpose of the Review: Emerging evidence has shown that ankylosing spondylitis fibroblasts (ASFs) act as crucial participants in inflammation and abnormal ossification in ankylosing spondylitis (AS). This review examines the investigations into ASFs and their pathological behavior, which contributes to inflammatory microenvironments and abnormal bone formation. The review spans the period from 2000 to 2023, with a primary focus on the most recent decade. Additionally, the review provides an in-depth discussion on studies on ASF ossification at the cellular level.Recent Findings: ASFs organize immune functions by recruiting immune cells and influencing their differentiation and activation, thus mediate the inflammatory response in the early phase of disease. ASFs promote joint destruction at sites of cartilage and actively promote abnormal ossification by recruiting osteoblasts, differentiation into myofibroblasts or ossification directly. Many signaling pathways and cytokines such as Wnt signaling and BMP/TGF-β signaling are involved in ASF ossification.Summary: ASFs play a key role in AS inflammation and osteogenesis. Further studies are required to elucidate molecular mechanisms behind that and provide new targets and directions for AS diagnosis and treatment from a new perspective of fibroblasts.Keywords: ankylosing spondylitis, fibroblast, inflammation, ossification

Qiping Liu,1,&ast; Huiling Gong,1,&ast; Qiqi Chen,1 Chunyan Yuan,2 Bin Hu1 1Department of Ultrasound, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of China; 2Department of Pathology, Minhang Hospital, Fudan University, Shanghai, 201199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Hu; Chunyan Yuan, Email Niuniuhu1213@qq.com; masterychy@126.comObjective: To study the clinical application value of contrast-enhanced ultrasound (CEUS) in diagnosing renal space-occupying lesions.Methods: Sixty-seven patients with renal space-occupying lesions detected by routine ultrasound examination received the contrast-enhanced ultrasound examination. When observing the perfusion mode of the mass, we analyzed the perfusion characteristics of contrast-enhanced ultrasound and compared them with the surgical pathological results.Results: Sixty-seven lesions, which were identified in 67 patients with renal space-occupying lesions, included 55 renal malignant tumors and 12 benign ones. The sensitivity of qualitative diagnosis by CEUS imaging was 96.4%, the specificity was 66.7%, and the accuracy was 91.0%.Conclusion: The real-time blood supply of renal space-occupying lesions helps judge their nature according to the enhancement mode. It has high clinical application value in diagnosing benign and malignant lesions.Keywords: ultrasound examination, renal lesions, contrast-enhanced ultrasound

Hanbing Song,&ast; Hongpeng Liu,&ast; XiaoDong Li, Bing Lv, Zonghan Tang, Qipeng Chen, Danqi Zhang, Fei Wang Department of Orthopedics, Heilongjiang University of Traditional Chinese Medicine, Harbin, 150000, Heilongjiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Danqi Zhang; Fei Wang, Surgery Building, Department of Orthopedics, Heilongjiang University of Traditional Chinese Medicine, No. 26 Heping Road, Xiangfang District, Harbin, Heilongjiang Province, People’s Republic of China, Email hljzymzdq@163.com; wangfei631@126.comBackground: This study aims to identify new therapeutic targets and explore the molecular mechanism of ankylosing spondylitis (AS), a rheumatic immune disease that mainly affects the sacroiliac and spinal joints. Despite extensive research, the exact cause of AS is still unknown. The research team utilized a bioinformatics approach to achieve their objectives.Methods: The GSE73754 dataset was downloaded from GEO database. Autophagy-related genes (ARGs) were collected from the Human Autophagy-dedicated Database. The limma package was used to screen for differentially expressed genes (DEGs), which were then intersected with the autophagy-related genes (ARGs) to identify differentially expressed autophagy-related genes (DEARGs). Subsequently, the DEARGs associated with AS were subjected to GO-BP and KEGG enrichment analyses using the clusterProfiler package. Core genes were identified using the cytoHubba plug-in of Cytoscape and were validated by clinical blood samples. Additionally, the Cell algorithm was utilized to evaluate the proportion of immune cell infiltration.Results: A total of 29 DEARGs were identified, which were found to be mainly enriched in autophagy, apoptosis, and necroptosis through functional enrichment analysis. Two core genes, HSPA5 and SQSTM1, were confirmed to have diagnostic value in AS. Immune cell infiltration analysis revealed CD8+ T cells, CD8+ T effector memory (Tem), natural killer (NK) cells, T gamma delta (Tgd) cells, and T-helper 1 (Th1) cells as major participants in AS development. Furthermore, HSPA5 expression was significantly correlated with Th1 cells, CD8+ T cells, CD4+ memory cells, and macrophages.Conclusion: This study suggested that HSPA5 and SQSTM1 can serve as useful diagnostic biomarkers for AS. These findings lay the foundation for identifying crucial mRNAs in the whole blood of AS patients, which may aid in the development of novel markers for AS.Keywords: diagnostic biomarkers, autophagy, immune cell, ankylosing spondylitis

Xiaojuan Qian,1,2,&ast; Weiwei Bao,1,2,&ast; Shenghai Wu,2 Jiawei Zhou,3 Yunxing Yang,2 Xianjun Wang,2 Daojun Yu,2 Qiong Chen2 1Department of Laboratory Medicine, Affiliated Hangzhou First People’s Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Laboratory Medicine, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3State Key Laboratory of Diagnosis and Treatment for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiong Chen, Department of Laboratory Medicine, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, People’s Republic of China, Email chenqiong2002@126.comPurpose: This study aims to investigate the clinical and molecular characteristics of carbapenemase-producing E. coli strains (CPECO).Patients and Methods: We collected 38 non-repetitive CPECO strains, identified them using MALDI-TOF, and assessed their antimicrobial susceptibility via the VITEK-Compact II system. We gathered demographic and clinical patient data. Phenotypic assays were employed to detect carbapenemase types. Polymerase chain reaction (PCR) was utilized to identify the carbapenemase genes. Seven housekeeping genes were amplified and sequenced to determine the multilocus sequence typings (MLSTs).Results: These CPECO strains, primarily isolated from aseptic site and stool screening specimens, exhibited significant resistance to most clinical antibiotics, except for tigecycline and amikacin. Most patients had underlying medical conditions and underwent invasive procedures. There were significant differences among patients concerning the presence of malignancies, digestive system disorders, endoscopic retrograde cholangiopancreatography (ERCP) surgeries and abdominal drainage tubes. However, no significant differences were observed among patients regarding conditions, including hypertension, diabetes, respiratory diseases, urinary diseases and cardiovascular diseases, as well as invasive procedures such as deep venous catheterization, endotracheal intubation and gastrointestinal catheterization. Metallo-β-lactamase was primarily responsible for carbapenem resistance, including blaNDM-5(24/38), blaNDM-1(5/38), blaNDM-9(1/38) and blaIMP-4(1/38). Additionally, 7 CPECO strains carried blaKPC-2. The distribution of CPECO sequence types (STs) was diverse, with seven strains being ST131, six strains being ST410, three strains each of ST1196 and ST10, although most STs were represented by only one strain.Conclusion: CPECO infections in patients with biliary system diseases may result from intestinal CPECO translocation, with ERCP surgery potentially facilitating this. Meanwhile, malignant tumor was found to be a significant factor affecting CPECO infections in patients with hematological diseases. blaNDM-5, blaNDM-1 and blaNDM-9 were primarily responsible for carbapenem resistance in CPECO strains. The emergence of carbapenem-resistant ST131 and ST410 strains should be alert to prevent the spread of carbapenem-resistant genes within high-risk epidemic clones.Keywords: carbapenemase-producing E. coli, underlying diseases, endoscopic retrograde cholangiopancreatography, ERCP, NDM

Chen Jiang,1,2,&ast; Meijuan Peng,1,2,&ast; Ziyu Dai,1,2 Qiong Chen1,2 1Department of Geriatrics, Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China&ast;These authors contributed equally to this workCorrespondence: Qiong Chen, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Kaifu District, Changsha, Hunan, 410008, China, Email qiongch@163.comObjective: It has been observed that local and systemic disorders of lipid metabolism occur during the development of chronic obstructive pulmonary disease (COPD), but no specific mechanism has yet been identified.Methods: The mRNA microarray dataset GSE76925 of COPD patients was downloaded from the Gene Expression Omnibus database and screened for differentially expressed genes (DEGs). Lipid metabolism-related genes (LMRGs) were extracted from the Kyoto Encyclopedia of Genes and Genomes database and Molecular Signature Database. The DEGs were intersected with LMRGs to obtain differentially expressed lipid metabolism-related genes (DeLMRGs). GO enrichment analysis and KEGG pathway analysis were performed on DeLMRGs, and protein-protein interaction networks were constructed and screened to identify hub genes. The GSE8581 validation set and further ELISA experiments were used to validate key DeLMRG expression.Results: Differential analysis of dataset GSE76925 identified 587 DEGs, of which 62 genes were up-regulated and 525 were down-regulated. Taking the intersection of 587 DEGs with 1102 LMRGs, 20 DeLMRGs were obtained, including 1 up-regulated gene and 19 down-regulated genes. 10 hub genes were screened by cytohubba plugin, including 9 down-regulated genes PLA2G4A, HPGDS, LEP, PTGES3, LEPR, PLA2G2D, MED21, SPTLC1 and BCHE, as well as the only up-regulated gene PLA2G7. Validation of the identified 10 DeLMRGs using the validation set GSE8581 revealed that BCHE and PLA2G7 expression levels differed between the two groups. We further constructed the ceRNA network of BCHE and PLA2G7. Cell experiments also showed that PLA2G7 expression was up-regulated and BCHE expression was down-regulated in CSE-treated RAW264.7 and THP-1 cells.Conclusion: Based on a comprehensive bioinformatic analysis of lipid metabolism genes, we identified BCHE and PLA2G7 as potentially significant biomarkers of COPD. These biomarkers may represent promising targets for COPD diagnosis and treatment.Keywords: COPD, lipid metabolism, bioinformatics, BHCE, PLA2G7

Xiaobo Xu,1 Mengya Xia,2 Qinghua Chen,3 Weiguo Pang4 1School of Psychology, Shanghai Normal University, Shanghai, People’s Republic of China; 2T. Denny Sanford School of Social and Family Dynamics, Arizona State University, Tempe, AZ, USA; 3Department of Psychology, Hefei Normal University, Hefei, People’s Republic of China; 4School of Psychology and Cognitive Science, East China Normal University, Shanghai, People’s Republic of ChinaCorrespondence: Xiaobo Xu, School of Psychology, Shanghai Normal University, 100&num; Guilin Road, Shanghai, 200234, People’s Republic of China, Email xbxu@shnu.edu.cn Weiguo Pang, School of Psychology and Cognitive Science, East China Normal University, 3663&num; North Zhongshan Road, Shanghai, 200062, People’s Republic of China, Email wgpang@psy.ecnu.edu.cnPurpose: Prior studies revealed several beneficial aspects of being authentic, such as higher subjective well-being, more harmonious interpersonal relationships, and better workplace performance. However, how authenticity relates to unethical cheating behaviors in the academic context remains to be seen. Based on the literature review, the present study hypothesized that authenticity may be negatively linked to academic cheating through the mediating path of mastery approach goals.Methods: In Study 1, 250 college students self-reported their demographics and academic performance, and completed the scales of authenticity, academic cheating, mastery approach goals, and social desirability. In Study 2, 111 college students completed the same measures as in Study 1 at two different time points (5 months in between).Results: In Study 1, the results indicated that authenticity was positively associated with mastery approach goals, and both were negatively associated with academic cheating. After controlling for the confounding effect of gender, age, academic performance, and social desirability, mastery approach goals were identified as a mediator in the authenticity–academic cheating relationship. In Study 2, the correlation result confirmed the association patterns found in Study 1. Moreover, cross-lagged analysis supported the directionality proposed in the mediation model.Conclusion: The findings identified the mediating role of mastery approach goals in the link between authenticity and academic cheating, supporting the motivated cognition perspective of personality, the motivational model of academic cheating, and the self-determination theory. Implications, limitations, and directions for future research were provided.Keywords: authenticity, mastery approach goals, academic cheating, mediation

Haibang Pan,1,&ast; Tianming Wang,1,2,&ast; Ying Che,3,4 Xiaoli Li,1,5 Yan Cui,1 Quanxin Chen,1 Zhihang Wu,1 Jianfeng Yi,1 Bo Wang3 1First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 2Gansu Provincial Key Laboratory of Traditional Chinese Medicine Recipe Mining and Innovation Transformation, Gansu Province New Production of Traditional Chinese Medicine Product Creation Engineering Laboratory, Lanzhou, People’s Republic of China; 3School of Nursing, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 4Research Ward, Gansu Provincial People’s Hospital, Lanzhou, People’s Republic of China; 5Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Wang; Jianfeng Yi, Email wbbphb@gszy.edu.cn; yijf02@163.comIntroduction: Skin and soft tissue infection (SSTI) is a frequently encountered clinical disease, and Sanhuang ointment, a traditional Chinese medicine, is used to treat it. However, the pharmacological effect of Sanhuang ointment on SSTI and its underlying mechanism remains unclear. Here, we investigate the protective effect of Sanhuang ointment on Methicillin-resistant Staphylococcus aureus (MRSA) infection in the skin and soft tissues and the underlying mechanism by network pharmacological analysis, followed by in vivo experimental validation.Methods: Via network pharmacology, the active components and disease targets of Sanhuang ointment were screened and intersected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A rat model of skin and soft tissue infection was established, and pathological features were observed. Large, medium, and small-dose groups (1 g, 0.5 g, and 0.25 g/animal, with the total amount of Vaseline, dispensed 1 g/animal) of Sanhuang ointment were prepared and Mupirocin ointment was used as a positive control (0.5 g/animal, with the total amount of Vaseline, dispensed 1 g/animal). The expressions of key proteins of the IL-17/NF-κB signaling pathway and downstream inflammatory factors were analyzed by histomorphological analysis, enzyme-linked immunosorbent assay, polymerase chain reaction, and Western blotting.Results: In all, 119 active components and 275 target genes of Sanhuang ointment were identified and intersected with MRSA infection-related genes via network pharmacology analysis, and 34 target genes of Sanhuang ointment were found to be involved in skin and soft tissue infections with MRSA. Sanhuang ointment (1 g/mouse) could effectively ameliorate histopathological changes and significantly inhibit the expression of key proteins involved in the IL-17/NF-κB signaling pathway and downstream inflammatory factors (p < 0.05).Conclusion: Sanhuang ointment has a protective effect on MRSA infection and inhibits inflammation by inhibiting the IL-17/NF-κB signaling pathway. Our findings are important for the secondary development and new drug development of Sanhuang ointment.Plain Language Summary: Sanhuang ointment can significantly inhibit inflammatory response after skin and soft tissue infection with MRSA.Sanhuang ointment may inhibit the inflammatory response induced by MRSA in the skin and soft tissue infections by targeting the IL-17/NF-κB signaling pathway.We study the active components and mechanism of action of Sanhuang ointment on MRSA infection through network pharmacology.Keywords: Sanhuang ointment, MRSA, SSTI, network pharmacology, IL-17, NF-κB

Inmaculada Xu Lou,1,2,&ast; Jiayue Chen,2,3,&ast; Kamran Ali,4,&ast; Qilan Chen2 1Department of Cardiology, International Education College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Department of Cardiology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, 310025, People’s Republic of China; 3Department of Cardiology, Hangzhou Clinical Medical College Internal Medicine of Traditional Chinese Medicine of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 4Department of Oncology, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang, 322000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qilan Chen, Department of Cardiology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, 310025, People’s Republic of China, Email cql13588750941@qq.comAbstract: Sexual dysfunction pertains to any issue that hinders an individual from attaining sexual contentment. This health issue can have a significant impact on the quality of life and psychological health of affected individuals. Sexual dysfunction can generate stress, anxiety, depression, and low self-esteem, which can lead to a reduction in overall life satisfaction and the quality of interpersonal relationships. Sexual dysfunction can manifest as erectile dysfunction in men or lack of sexual desire in women. Although both sexes can experience sexual problems, there are some significant differences in the manifestation of sexual dysfunction between men and women. In men, sexual dysfunction is usually physical and associated with problems such as erectile dysfunction, while in women, sexual dysfunction is usually related to psychological factors. Additionally, there was an association between hypertension and sexual dysfunction in both the sexes. In men, hypertension can cause erection problems, whereas in women, it can cause vaginal dryness and a decrease in sexual desire. Furthermore, antihypertensive drugs can negatively impact sexual function, which can decrease adherence to drug treatment. However, nebivolol, an antihypertensive drug, has beneficial effects on erectile dysfunction in men. This is believed to be because nebivolol improves blood flow to the penis by producing nitric oxide, which can help improve erections.Keywords: sexual dysfunction, hypertension, antihypertensive drugs, erectile dysfunction, beta-blockers, nebivolol

Hao Wu,1,2,&ast; Qianyu Chen,2,3,&ast; Yanxin Liu,4 Yingdan Tang,5 Yang Zhao,5 Xueying Zhang,6 Xun Chen,2 Xiaoyan Ying,1 Boqun Xu1 1Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Obstetrics and Gynecology, the Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Obstetrics and Gynecology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 4Department of Obstetrics and Gynecology, Pukou Branch of Jiangsu People’s Hospital, Nanjing, Jiangsu, People’s Republic of China; 5Department of Statistics, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 6Department of Obstetrics and Gynecology, the Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Boqun Xu, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, Nanjing, Jiangsu, 210000, People’s Republic of China, Tel +86-13805164016, Email boqun_xu@njmu.edu.cnObjective: The purpose is to establish a model to predict endometrial carcinoma and assess its value in the preliminary diagnosis of endometrial carcinoma.Methods: The data of 381 patients undergoing hysteroscopy were incorporated into the model, including 282 cases in the training cohort and 99 cases in the validation cohort. Significant morphological indexes were selected using the chi-square test and subjected to the binary logistic regression analysis. Besides, the scoring interval was set, and the nomogram of the prediction model was established. Model calibration curves were drawn using the data from the validation cohort. The study was approved by the Ethics Committee of the Affiliated Sir Run Run Hospital of Nanjing Medical University, and written informed consent was obtained from the patients.Results: The sensitivity, specificity, positive predictive value, and negative predictive value of the model were 96.7%, 92.3%, 77.3%, and 99.0%, respectively. Analysis of the receiver operating characteristic curve in the training cohort showed an area under the curve of 0.984 (95% CI: 0.974– 0.995). The receiver operating characteristic curve in the validation cohort revealed an area under the curve of 0.976 (95% CI: 0.950– 1.000). The calibration curve indicated that the probability in the actual setting was consistent with that predicted by the nomogram in the training cohort.Conclusion: Our model has high sensitivity and specificity in predicting endometrial carcinoma, and helps clinicians to make accurate diagnosis.Keywords: hysteroscopy, endometrial carcinoma, morphology, prediction model

Yingli Liu,1 Dan Si,2 Pingping Bai,3 Li Zhu,4 Lili Zhang,1 Qi Chen,5 Yong Qi6 1Department of Pulmonary and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan, 451464, People’s Republic of China; 3Department of Health Management, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan, 450003, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Henan University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Henan University People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of ChinaCorrespondence: Yong Qi, Department of Pulmonary and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Henan University People’s Hospital, No. 7 Weiwu Road, Jinshui District, Zhengzhou, 450003, People’s Republic of China, Tel +8615890110258, Email qiyong@zzu.edu.cnBackground: Although the potential of coronavirus disease 2019 (COVID-19) patients to develop pulmonary embolism (PE) is widely recognized, the underlying mechanism has not been completely elucidated. This study aimed to identify genes common to COVID-19 and PE to reveal the underlying pathogenesis of susceptibility to PE in COVID-19 patients.Methods: COVID-19 genes were obtained from the GEO database and the OMIM, CTD, GeneCards, and DisGeNET databases; PE genes were obtained from the OMIM, CTD, GeneCards, and DisGeNET databases. We overlapped the genes of COVID-19 and PE to obtain common genes for additional analysis, including functional enrichment, protein–protein interaction, and immune infiltration analysis. Hub genes were identified using cytoHubba, a plugin of Cytoscape, and validated using the independent datasets GSE167000 and GSE13535. The genes validated by the above datasets were further validated in clinical samples.Results: We obtained 36 genes shared by PE and COVID-19. Functional enrichment and immune infiltration analyses revealed the involvement of cytokines and immune activation. Five genes (CCL2, CXCL10, ALB, EGF, and MKI67) were identified as hub genes common to COVID-19 and PE. CXCL10 was validated in both independent datasets (GSE167000 and GSE13535). Serum levels of CXCL10 in the COVID-19 group and the COVID-19 combined with PE group were significantly higher than those in the healthy control group (P< 0.001). In addition, there were significant differences between the COVID-19 group and the COVID-19 combined with PE group (P< 0.01).Conclusion: Our study reveals common genes shared by PE and COVID-19 and identifies CXCL10 as a possible cause of susceptibility to PE in COVID-19 patients.Graphical Abstract: Keywords: pulmonary embolism, coronavirus disease 2019, bioinformatics, CXCL10

Xiaofei Huang,1 Lihua Shi,1 Yin Lin,1 Cong Zhang,1 Penghui Liu,1 Ran Zhang,2 Qiqi Chen,1 Xudong Ouyang,3 Yuanyuan Gao,2 Yingshuai Wang,3,&ast; Tongyi Sun1,&ast; 1Shandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biological Medicine, School of Life Science and Technology, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 2School of Pharmacy, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 3School of Life Science and Technology, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tongyi Sun, Shandong Key Laboratory of Proteins and Peptides Pharmaceutical Engineering, Shandong Universities Key Laboratory of Biological Medicine, School of Life Science and Technology, Weifang Medical University, Baotong Road, Weifang, Shandong, 261053, People’s Republic of China, Tel/Fax +86-536-8462067, Email sd_sty@126.com Yingshuai Wang, School of Life Science and Technology, Weifang Medical University, Baotong Road, Weifang, Shandong, 261053, People’s Republic of China, Tel/Fax +86-536-8462052, Email yingshuaiwang1987@163.comPurpose: Diabetic foot ulcers (DFU) are severe complications of diabetes, posing significant health and societal challenges. Elevated levels of reactive oxygen species (ROS) at the ulcer site hinder wound healing in most patients, while individuals with diabetes are also more susceptible to bacterial infections. This study aims to synthesize a comprehensive therapeutic material using polysaccharides from Pycnoporus sanguineus to promote DFU wound healing, reduce ROS levels, and minimize bacterial infections.Methods: Polysaccharides from P.sanguineus were employed as reducing and stabilizing agents to fabricate polysaccharide-based composite particles (PCPs) utilizing silver ions as templates. PCPs were characterized via UV-Vis, TEM, FTIR, XRD, and DLS. The antioxidant, antimicrobial, and cytotoxic properties of PCPs were assessed through in vitro and cellular experiments. The effects and mechanisms of PCPs on wound healing were evaluated using a diabetic ulcer mouse model.Results: PCPs exhibited spherical particles with an average size of 57.29± 22.41 nm and effectively combined polysaccharides’ antioxidant capacity with silver nanoparticles’ antimicrobial function, showcasing synergistic therapeutic effects. In vitro and cellular experiments demonstrated that PCPs reduced cellular ROS levels by 54% at a concentration of 31.25 μg/mL and displayed potent antibacterial activity at 8 μg/mL. In vivo experiments revealed that PCPs enhanced the activities of superoxide dismutase (SOD) and catalase (CAT), promoting wound healing in DFUs and lowering the risk of bacterial infections.Conclusion: The synthesized PCPs offer a novel strategy for the comprehensive treatment of DFU. By integrating antioxidant and antimicrobial functions, PCPs effectively promote wound healing and alleviate patient suffering. The present study demonstrates a new strategy for the integrated treatment of diabetic wounds and expands the way for developing and applying the polysaccharide properties of P. sanguineus.Keywords: Pycnoporus sanguineus, polysaccharide, injury, antioxidant, antibacterial

Hui Wu,1– 3 Gui Zhen Weng,1 Li Na Sun,2 Zhang Chi Pan,1 Lu Zhang,4 Qiang Chen,1,3 Chun Mei Shi1,3 1Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 2Department of Oncology, Lishui Central Hospital and Fifth Affiliated Hospital of Wenzhou Medical College, Lishui, Zhejiang, 323000, People’s Republic of China; 3Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian, 350001, People’s Republic of China; 4Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of ChinaCorrespondence: Chun Mei Shi, Email shichunmei@tom.comPurpose: Immune checkpoint inhibitors (ICIs) have been developed for clinical application and proven effective for non-small cell lung cancer (NSCLC). Blockade of the programmed cell death 1 (PD-1) protein can partially reinvigorate circulating exhausted-phenotype CD8+ T cells (Tex cells) in preclinical models, however the clinical implication in anti-PD-1-based immunotherapy in NSCLC is unknown.Methods: Serum specimens were obtained before and during treatment from 145 patients with NSCLC patients who received anti-PD-1 treatment and their prognoses were followed-up. Indicators such as cell subpopulations, T cell invigoration were detected by clinical laboratory testing. Survival curves were estimated by the Kaplan-Meier method, Cox regression analysis was used to identify factors associated with prognoses of NSCLC patients.Results: The expressions of Ki-67 in PD-1+/CD8+ T cells in most NSCLC patients (97 of 145 cases) increased after treatment. The responding Ki-67+/CD8+ T cell population was mainly CD45RAlo CD27hi, containing cells with high expression of CTLA-4, PD-1, and 2B4 and low expression of NKG2-D (P < 0.0001). The maximum fold change of Ki-67+/PD-1+/CD8+T cells in treatment cycles and the tumor burden determined by imaging may be associated with survival. Patients with higher Ki-67 expression on PD-1+CD8+ T-cells (pretreatment) had statistically significant increased progression-free survival (PFS). A Ki-67 expression to tumor burden ratio greater than 0.6 at the 1st cycle of anti-PD-1 immunotherapy was associated with improvement of PFS and overall survival (P < 0.05).Conclusion: Activation of circulating Tex cells before or during therapy related to tumor burden may be associated with clinical efficacy of anti-PD-1 immune therapy in NSCLC.Keywords: non-small cell lung cancer, immunotherapy, T cell invigoration, prognosis

Taoying Li,1,2 Long Zheng,3 Jianjiang Zhang,1 Qiang Chen1 1Law School, Xinjiang University, Urumqi, People’s Republic of China; 2Department of Law, Jiangxi Police College, Nanchang, People’s Republic of China; 3Graduate School and Open Learning College, Cavite State University, Indang, PhilippinesCorrespondence: Jianjiang Zhang, Law School, Xinjiang University, No. 666 Shengli Road, Tianshan District, Urumqi, People’s Republic of China, Tel +8618099276105, Email zjjzqc@163.comPurpose: Reproductive rights represent an intrinsic and pivotal human entitlement, encompassing legal protection for procreation. Essential to this framework is the recognition that single women equally deserve reproductive rights. Although Chinese legislation refrains from overtly disallowing reproductive rights for single women, the interplay of conventional marriage norms and family planning policies has inadvertently tied these rights to marital status, consequently constraining single women’s ability to assert them. The establishment of a robust legal structure to ensure reproductive rights for single women would profoundly contribute to advancing a harmonious evolution of China’s population dynamics.Patients and Methods: We employ meticulous textual scrutiny to analyze comprehensively the stipulations concerning women’s reproductive liberties within the framework of Chinese jurisprudence. Furthermore, we engage in empirical inquiry to enumerate and elucidate the multifarious constraints placed upon the reproductive freedoms of unmarried women in the Chinese context. This endeavor entails a detailed exposition and incisive examination of China’s limitations imposed upon the reproductive rights of single women, encompassing both legal strictures and policy dimensions.Results: The absence of legal endorsement and safeguarding has given rise to substantial impediments to the exercise of reproductive rights among single women in China. Not only do endeavors to assert reproductive rights on behalf of single women encounter intricate challenges in judicial implementation, but they also encounter manifold barriers within national policies. This predicament not only subjects single women to considerable psychological strain but also contradicts the overarching objective of achieving a harmonized population development trajectory in China.Conclusion: China should expedite the development of a legal framework for protecting reproductive rights that includes provisions for supporting single women to have children. This legal apparatus should efficaciously enshrine and shield the reproductive rights of single women, thus playing a pivotal role in advancing a more equitable and well-balanced trajectory of population development.Keywords: single women, reproductive rights, reproductive limitations, psychological, reproductive justice, Chinese law

Ling Wei,1,&ast; Qiyan Chen,2,3,&ast; Lu Yang,2,3 Tongzhen Ji,4 Wenjing Peng,5 Bing Shao,2 Hui Li2 1Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing, People’s Republic of China; 3National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China; 4Department of Clinical Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 5College of Animal Husbandry and Veterinary Medicine, Jinzhou Medical University, Jinzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Li; Bing Shao, Email lihui@bjcdc.org; shaobingch@sina.comObjective: The emerging epidemic of extended-spectrum β-lactamase-producing E. coli (ESBL-EC) is a global public health crisis. ESBL-EC infections are increasing worldwide and contribute to morbidity and mortality among newborn infants. However, the antimicrobial resistance characteristics and clonal transmission of maternal and neonatal ESBL-EC isolates need to be further deciphered.Materials and Methods: We performed phenotypic and genotypic characterization of 33 ESBL-EC isolates from pregnant women and newborn during 2019– 2020.Results: Minimum inhibitory concentrations of 17 antimicrobial agents showed that all isolates were multidrug-resistant (MDR) and had a resistance rate of 100% to ampicillin, and mild resistance to florfenicol, gentamicin, ceftazidime, and amoxicillin-clavulanate. Additionally, imipenem, meropenem, polymyxin, and tigecycline exhibited good activity against the tested ESBL-EC isolates with low MIC50 (0.06– 1 μg/mL) and MIC90 (0.06– 1 μg/mL). Whole genome sequencing indicated that ESBL-EC isolates contained diverse antimicrobial resistant genes (blaCTX-M, blaTEM, blaSHV, tetA, etc.) and toxin genes (ompA, csg, fimH, hybtA, etc.). blaCTX-M genes were the main ESBL genotype. ST1193 (18.2%) was the second most abundant ST among the ESBL-EC isolates (ST131 was the most common, with 30.3%), and this is the first report of its mother-to-infant colonization transmission in China.Conclusion: These findings revealed the occurrence of high-risk ST1193 clone among ESBL-EC isolates from pregnant women and newborn colonization in China. Further national or regional multicenter studies are needed to assess the dissemination and evolution of ESBL-EC ST1193 clone as a nosocomial pathogen in China.Keywords: ESBL, E. coli, antibiotic resistance, colonization transmission, ST1193 clone

Chunxiang He,1,2 Ze Li,1,2 Miao Yang,1,2 Wenjing Yu,1,2 Rongsiqing Luo,1,2 Jinyong Zhou,1,2 Jiawei He,1,2 Qi Chen,1,2 Zhenyan Song,1,2 Shaowu Cheng1,2 1School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Zhenyan Song; Shaowu Cheng, Tel +86 073188458257, Email songzhenyan2013@hnucm.edu.cn; scheng@hnucm.edu.cnAbstract: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by complex pathophysiological features. Amyloid plaques resulting from extracellular amyloid deposition and neurofibrillary tangles formed by intracellular hyperphosphorylated tau accumulation serve as primary neuropathological criteria for AD diagnosis. The activation of microglia has been closely associated with these pathological manifestations. Non-coding RNA (ncRNA), a versatile molecule involved in various cellular functions such as genetic information storage and transport, as well as catalysis of biochemical reactions, plays a crucial role in microglial activation. This review aims to investigate the regulatory role of ncRNAs in protein expression by directly targeting genes, proteins, and interactions. Furthermore, it explores the ability of ncRNAs to modulate inflammatory pathways, influence the expression of inflammatory factors, and regulate microglia activation, all of which contribute to neuroinflammation and AD. However, there are still significant controversies surrounding microglial activation and polarization. The categorization into M1 and M2 phenotypes may oversimplify the intricate and multifaceted regulatory processes in microglial response to neuroinflammation. Limited research has been conducted on the role of ncRNAs in regulating microglial activation and inducing distinct polarization states in the context of neuroinflammation. Moreover, the regulatory mechanisms through which ncRNAs govern microglial function continue to be refined. The current understanding of ncRNA regulatory pathways involved in microglial activation remains incomplete and may be influenced by spatial, temporal, and tissue-specific factors. Therefore, further in-depth investigations are warranted. In conclusion, there are ongoing debates and uncertainties regarding the activation and polarization of microglial cells, particularly concerning the categorization into M1 and M2 phenotypes. The study of ncRNA regulation in microglial activation and polarization, as well as its mechanisms, is still in its early stages and requires further investigation. However, this review offers new insights and opportunities for therapeutic approaches in AD. The development of ncRNA-based drugs may hold promise as a new direction in AD treatment.Keywords: Alzheimer’s disease, non-coding RNA, neuroinflammation, microglia activation, miRNA, circRNA, lncRNA

Qitao Chen, Qiuwei Tao, Qilin Zhu, Jing Zhu, Xufeng Du Department of Dermatology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of ChinaCorrespondence: Xufeng Du, Department of Dermatology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, No. 299 Qingyang Road, Wuxi, People’s Republic of China, Tel +86 19952290906, Email docdxf@126.comPurpose: Androgenetic alopecia (AGA) is a common dermatological condition, with reported associations between serum vitamin D and sex hormone levels. However, the relationship between these factors and the severity of hair loss remains unclear.Patients and Methods: Our cross-sectional study included 310 AGA patients who visited the dermatology clinic and underwent trichoscopy examinations throughout 2021. We collected data on serum sex hormones and 25(OH)D levels during their consultations. TrichoScan analysis was used to characterize and quantify AGA severity based on hair density and vellus hair proportions in the central scalp area, which were then correlated with the collected indicators.Results: The study findings reflect the basic demographic characteristics of AGA patients in the Chinese population. We discovered a significant negative correlation between serum SHBG levels and AGA severity in women, but no association was found in men. Serum testosterone, estradiol, dehydroepiandrosterone sulfate, and 25(OH)D levels showed no significant correlation with the severity of androgenetic alopecia, regardless of gender.Conclusion: To our knowledge, this is the first study to investigate the relationship between serum sex hormones, vitamin D, and AGA severity using trichoscopic scalp hair features.Keywords: androgenetic alopecia, TrichoScan, vitamin D, sex hormones

Jiaoquan Chen,&ast; Nanji Yu,&ast; Weihong Wu, Shanshan Ou, Quan Chen, Huilan Zhu Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, 510095, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huilan Zhu, Department of Dermatology Guangzhou Institute of Dermatology, 56 Hengfu Road, Guangzhou, 510095, People’s Republic of China, Email zhlhuilan@126.comBackground: Although dupilumab is an effective treatment approach for chronic actinic dermatitis (CAD) in some cases, its effectiveness and safety in CAD have not been sufficiently assessed.Purpose: Evaluation of the effectiveness and safety of dupilumab in patients with recalcitrant CAD was performed.Methods: We retrospectively reviewed the medical records of CAD patients treated with dupilumab. Data regarding demographics were collected, and disease severity scores were assessed using the following: Clinical Severity Score of CAD (CSS-CAD), Atopic Dermatitis Control Tool (ADCT), Dermatology Life Quality Index (DLQI), and Numeric Rating Scale (NRS)-itch scores.Results: After 12 weeks of treatment, there was a significant decrease in disease severity scores of 16 CAD patients. Only one patient achieved a good response and most of the patients (62.5%, 10/16) had no significant symptom improvement after 4 weeks of treatment. However, after 12 weeks of treatment, 43.75% (7/16) of the patients reached excellent response (> 75% improvement of CSS-CAD), 31.25% (5/16) good response (50%– 75% improvement of CSS-CAD), 6.25% (1/16) partial response (25%– 50% improvement of CSS-CAD), and only 18.75% (3/16) no response (< 25% improvement of CSS-CAD). One patient complained of injection site reaction at the first injection.Conclusion: This study supports dupilumab as an effective and safe treatment option for patients with recalcitrant CAD. Patients may require at least 4 weeks of treatment before the partial response is noted.Keywords: chronic actinic dermatitis, dupilumab, photodermatitis, atopic dermatitis