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The study of distant galaxy groups and clusters at the peak epoch of star formation is limited by the lack of a statistically and homogeneously selected and spectroscopically confirmed sample. Recent discoveries of concentrated starburst activities in cluster cores have opened a new window to hunt for these structures based on their integrated IR luminosities. Here, we carry out a large NOEMA (NOrthern Extended Millimeter Array) program targeting a statistical sample of infrared-luminous sources associated with overdensities of massive galaxies at z > 2, the Noema formIng Cluster survEy (NICE). We present the first result from the ongoing NICE survey, a compact group at z = 3.95 in the Lockman Hole field (LH-SBC3), confirmed via four massive (M∗ ≳ 1010.5 M⊙) galaxies detected in the CO(4-3) and [CI](1-0) lines. The four CO-detected members of LH-SBC3 are distributed over a 180 kpc physical scale and the entire structure has an estimated halo mass of ~1013 M⊙ and total star formation rate of ~4000 M⊙ yr-1. In addition, the most massive galaxy hosts a radio-loud active galactic nucleus with L1.4 GHz, rest = 3.0 × 1025 W Hz-1. The discovery of LH-SBC3 demonstrates the feasibility of our method to efficiently identify high-z compact groups or cluster cores undergoing formation. The existence of these starbursting cluster cores up to z ~ 4 provides critical insights into the mass assembly history of the central massive galaxies in clusters.

Yingxue Sun,1,* Shi Jin,1,* Jun Chen,2,* Jian Zhang,1 Yufei Lu,1 Qiuyu Gu,1 Zhixin Yan,1 Weize Chen,1 Annan Chen,1 Yi Fang,1 Wenye Geng,3 Xialian Xu,1 Nana Song1 1Department of Nephrology, Zhongshan Hospital, Fudan University; Shanghai Medical Center of Kidney; Shanghai Institute of Kidney and Dialysis; Shanghai Key Laboratory of Kidney and Blood Purification; Hemodialysis Quality Control Center of Shanghai, Shanghai, 200032, People’s Republic of China; 2Department of Pathology, Changzheng Hospital, Naval Military Medical University, Shanghai, 200003, People’s Republic of China; 3Scientific Research Department of Shanghai Medical College, Fudan Zhangjiang Institute, Fudan University, Shanghai, 201203, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xialian Xu; Nana Song, Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Tel +86-021-64041990-2138, Fax +86-021-64038038, Email xu.xialian@zs-hospital.sh.cn; song.nana@zs-hospital.sh.cnObjective: This study aimed to investigate the mechanisms and specific targets of cordycepin in the treatment of renal fibrosis using a unilateral ischemia-reperfusion (UIR) model.Methods: A UIR mouse model was established, followed by intraperitoneal injections of cordycepin and Mdivi-1. Masson’s trichrome staining and PAS staining were used to identify renal tubulointerstitial fibrosis and assess the degree of renal injury. Fibrosis markers and mitochondrial dynamics-related proteins were evaluated using Western blotting, while differential gene expression and pathway enrichment were analyzed by RNA-seq. Molecular docking, molecular dynamics simulations and surface plasmon resonance were conducted to validate the specific binding sites of cordycepin on the target protein Drp1. Immunofluorescence and in vitro experiments further elucidated the therapeutic mechanism of cordycepin.Results: In vivo experiments showed that intraperitoneal injection of cordycepin significantly reduced renal inflammation and fibrosis, lowered serum creatinine levels, and decreased collagen deposition. Transcriptome analysis revealed that cordycepin treatment downregulated the mitochondrial fission pathway and upregulated the mitochondrial fusion pathway. Western blotting showed reduced levels of fibrosis markers α-SMA and FN, as well as downregulation of Drp1, MFF, and Fis1, and upregulation of OPA1 and Mfn2. In vitro, cordycepin inhibited TGF-β-induced injury in NRK-52E cells, reducing Drp1 expression and IL-6 secretion. Crosstalk experiments confirmed that decreased IL-6 levels were crucial for cordycepin anti-fibrotic effects by suppressing fibroblast activation.Conclusion: Cordycepin ameliorates renal fibrosis by targeting Drp1 to inhibit mitochondrial fission in injured renal tubular epithelial cells, reducing IL-6 secretion and inhibiting fibroblast activation.Keywords: cordycepin, Drp1, renal fibrosis, mitochondrial fission, UIR, IL-6

Qianqian Gu,* Lingren Zhou,* Xiaofei Shen, Le Xu, Guixian Wu, Weijia Pan, Wenxia Lin, Dongqing Lv, Ling Lin, Shuangquan Yan Department of Respiratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, 317000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling Lin; Shuangquan Yan, Hospital of Zhejiang Province affiliated to Wenzhou Medical University, 150 Ximen Street, Taizhou, 317000, People’s Republic of China, Email Linling@enzemed.com; ysq25908712@163.comAbstract: Nocardiosis caused by Nocardia otitidiscaviarum is exceptionally rare and characterized by a high mortality rate. It typically affects immunocompromised patients, resulting in severe pulmonary or disseminated infections, and is notorious for abscess formation. Empyema resulting from nocardiosis is even less common. Early clinical signs and imaging findings lack specificity, culture growth is sluggish, and the absence of an effective serological detection method can delay treatment. We report an 81-year-old patient with chronic obstructive pulmonary disease treated by long-term inhalation of high-dose salmeterol fluticasone. The initial empirical anti-infection treatment proved ineffective, resulting in rapid disease progression before the confirmation of nocardiosis with empyema through cultures of pleural fluid and sputum. Despite active treatment measures, the patient succumbed to severe pulmonary infection, sepsis, and multiple organ failure. A review of the literature, together with clinical experience, indicates that conventional empirical treatment for Nocardia otitidiscaviarum infection may not always be effective due to the escalating rate of drug resistance. Therefore, the primary step in the management of the infection is timely diagnosis using different methods. Furthermore, the identification of the responsible strain followed by conducting drug sensitivity tests is paramount for the successful treatment of this disease.Keywords: severe nocardia pneumonia, empyema, drug resistance rate, drug sensitivity test

Bowen Wei,1,2,* Siwei Wang,1,2,* Suiran Li,1,2,* Qingxiang Gu,3 Qingyun Yue,4 Zhuo Tang,1,2 Jiamin Zhang,1,2 Wei Liu1,2 1Department of Rheumatism and Immunity, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China; 3Center of Preventive Treatment of Disease, Cangzhou Hospital of Integrated Traditional Chinese and Western of Hebei Province, Cangzhou, Hebei, People’s Republic of China; 4School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Liu, Email fengshiliuwei@163.comBackground: Ankylosing spondylitis (AS) is a chronic autoimmune disease characterized by inflammation of the sacroiliac joints and spine. Cuproptosis is a newly recognized copper-induced cell death mechanism. Our study explored the novel role of cuproptosis-related genes (CRGs) in AS, focusing on immune cell infiltration and molecular clustering.Methods: By analyzing the peripheral blood gene expression datasets obtained from GSE73754, GSE25101, and GSE11886, we identified the expression patterns of cellular factors and immune infiltration cell related to cuproptosis. Subsequently, we employed weighted gene co-expression network analysis (WGCNA) to identify differentially expressed genes (DEGs) within each cluster and utilized the “GSVA” and “GSEABase” software packages to examine variations in gene sets enriched across various CRG clusters. Finally, we selected the best-performing machine learning model to predict genes associated with AS. Datasets (GSE25101 and GSE73754) and ELISA to assess the expression levels of the five genes and their corresponding proteins.Results: Seven cuproptosis-related DEGs and four immune cell types were identified, revealing significant immune heterogeneity in the immune cell infiltration between the two cuproptosis-related molecular clusters in AS. The eXtreme Gradient Boosting (XGB) model showed the highest predictive accuracy, achieving an area under the receiver operating characteristic curve (AUC) of 0.725, and 5-gene prediction models were established. It showed satisfactory performance in the GSE25101 dataset (AUC = 0.812). According to the blood serum samples of AS patients and controls, PELI1 had a higher expression level (AUC = 0.703, p = 0.07), while ICAM2 and RANGAP1 had lower expression levels (AUC = 0.724, 0.745, and p = 0.011, 0.000, respectively) in AS patients.Conclusion: We explored the correlation of cuproptosis in AS, and developed the optimal machine learning model to identify high-risk genes associated with AS. We also explored the pathogenesis and treatment strategies of AS, targeting PELI1, ICAM2, and RANGAP1.Keywords: ankylosing spondylitis, cuproptosis, immune cell infiltration, machine learning model

Qian Wang,1,2,&ast; Guimin Huang,3,&ast; Ruikun Wang,4 Zhilong Cao,5 Jieqiong Liang,1 Mengyao Li,1 Qinglong Gu1,2 1Department of Otolaryngology-Head and Neck Surgery, Capital Institute of Pediatrics, Beijing, People’s Republic of China; 2Graduate School of Peking Union Medical College, Beijing, People’s Republic of China; 3Child Health Big Data Research Center, Capital Institute of Pediatrics, Beijing, People’s Republic of China; 4Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, People’s Republic of China; 5School of Software, Beihang University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qinglong Gu, Department of Otolaryngology-Head and Neck Surgery, Capital Institute of Pediatrics, No. 2 Yabao Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86-13146836613, Email gql71@163.comPurpose: This study investigates the prevalence, risk factors, and clinical characteristics of positional obstructive sleep apnea (POSA) among pediatric patients diagnosed with obstructive sleep apnea (OSA).Patients and Methods: A total of 1,236 children aged 0 to 17 years who underwent nocturnal polysomnography (PSG) and completed the Sleep Questionnaire were included. After excluding those with an AHI < 1, neurological or muscular disorders, or insufficient sleep time in specific positions, 908 patients remained: 158 with POSA and 750 with non-positional OSA (NPOSA). Propensity score matching (PSM) was applied at a 1:2 ratio, resulting in a final sample of 153 POSA and 306 NPOSA patients. Data analyses were performed using R software (version 4.2.3).Results: The prevalence of POSA was 12.8%. After PSM, patients with POSA had a lower overall AHI (8.66 vs 10.30), REM-AHI (14.30 vs 17.40), and NREM-AHI (7.43 vs 8.77) compared to those with NPOSA. POSA patients also had a shorter total sleep time (411 vs 427 minutes), spent less time in the supine position (168 vs 225 minutes), and more time in non-supine positions (241 vs 202 minutes) than NPOSA patients. Additionally, while the supine AHI was higher in POSA patients (15.60 vs 10.30), the non-supine AHI was lower (5.00 vs 11.00) compared to NPOSA patients. The minimum oxygen saturation was slightly higher in POSA patients (0.88 vs 0.87). All differences were statistically significant (P < 0.05). Risk factors for POSA included mild OSA, allergic rhinitis, non-allergic rhinitis, and obesity.Conclusion: The prevalence of POSA in children is lower than in adults, and its severity is less than that of NPOSA. Compared to NPOSA patients, POSA patients had significantly higher AHI during supine sleep and lower AHI during non-supine sleep. POSA patients also spent more time in non-supine positions, suggesting that avoiding supine sleep may help reduce apnea events. These findings highlight the importance of monitoring and managing sleep posture in POSA patients.Keywords: obstructive sleep apnea, pediatric patients, risk factors, polysomnography, sleep position, sleep-disordered breathing

Yuexi Liu,&ast; Qiuying Gu,&ast; Yao Xiao, Xing Wei, Jinlong Wang, Xiaolan Huang, Hua Linghu Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Linghu, Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email linghuhua@cqmu.edu.cnPurpose: To evaluate Ki67 expression and prognostic value during neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer (EOC).Patients and Methods: 95 patients with advanced EOC receiving NACT followed by interval debulking surgery (IDS) were available for tissue samples from matched pre- and post-therapy specimens. The expression of Ki-67 was evaluated by immunohistochemistry and classified by percentage of stained cells. The optimal cutoff values of the Ki67 were assessed by receiver operating characteristic analysis. Kaplan-Meier analysis, the Log rank test, and Cox regression analysis were carried out to analyze survival.Results: Post-NACT Ki67 was an independent prognostic factor for recurrence by univariate (HR: 1.8, 95% CI: 1.1– 3.0, P-value: 0.023) and multivariate (HR: 1.88, 95% CI: 1.08– 3.26, P-value: 0.025) analysis. Residual disease > 1cm (HR: 2.69, 95% CI: 1.31– 5.54, P-value: 0.0070) and pre-treatment CA125 ≥ 1432 U/mL (HR: 2.00, 95% CI: 1.13– 3.55, P-value: 0.017) were also independent risk factors for progression-free survival (PFS) in multivariate analysis. Post-NACT Ki67 ≥ 20% was an independent risk factor for PFS, however, baseline Ki67 and Ki67 change did not suggest prognostic significance. In patients with high CA125, the median PFS for patients with high postKi67 (median PFS: 15.0 months, 95% CI: 13.4– 16.6 months) was significantly (P-value: 0.013) poorer compared to patients with low postKi67 (median PFS: 30.0 months, 95% CI: 13.5– 46.5 months).Conclusion: Post-NACT Ki67 ≥ 20% was an independent factor associated with poorer PFS in patients with advanced-stage EOC undergoing NACT followed by IDS. The combination of post-NACT Ki67 and pretreatment CA125 could better identify patients with poorer PFS in NACT-administered patients.Keywords: interval debulking surgery, progression-free survival, overall survival, tumor marker

Qingqing Gu, Mingzhi Zhu, Yanyan Wang, Yuanting Gu The Second Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Yuanting Gu; Yanyan Wang, The Second Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China, Tel +86-371-66913114, Fax +86-371-66964992, Email guyuanting2009@163.com; fccwangyy22@zzu.edu.cnPurpose: To evaluate the efficacy and safety of a pyrotinib-based therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) in the real world.Methods: Clinical data of 218 patients with HER2-positive MBC who received a pyrotinib-based therapy from January 2020 to March 2023 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.Results: Finally, 195 patients were included in the efficacy cohort. The median progression-free survival (PFS) in the total population is 12.4 months (95% CI, 9.8– 15.0 months). More than half of the patients in the efficacy cohort received pyrotinib mono-targeted therapy (103 cases, 52.8%). Among the remaining patients, 74 (37.9%) patients chose a combined trastuzumab-targeted therapy and 17 (8.7%) chose to combine inetetamab. Median PFS in the pyrotinib group vs pyrotinib plus trastuzumab group was 10.5 months vs 20.1 months (P< 0.001). The median PFS of primary trastuzumab resistance population reached to 20.1 months in pyrotinib plus trastuzumab group. Double-targets’ advantage was also observed in the brain metastases subgroup (17.9 months vs 10.0 months, P=0.386). The patients who received pyrotinib plus inetetamab as second and higher-line treatment reached a median PFS of 7.9 months (95% CI, 4.0– 11.8 months). Forty-one (19.8%) of 207 patients included in the safety cohort experienced grade 3 or higher diarrhea, the most common adverse event in safety analysis, and no adverse event-related deaths.Conclusion: The combination of pyrotinib and trastuzumab demonstrated promising efficacy in the treatment of HER2-positive metastatic breast cancer, including those who had primary resistance to trastuzumab and brain metastases. Pyrotinib plus trastuzumab is expected to be a potent option in the first-line. Additionally, the concurrent administration of pyrotinib and inetetamab could be an alternative to consider in the second and higher-line treatment for metastatic breast cancer. The adverse reactions of pyrotinib were tolerable in general.Keywords: pyrotinib, HER2, metastatic breast cancer, trastuzumab, inetetamab

Yihua Fan,1– 3,&ast; Wei Liu,1,2,&ast; Yue Jin,1,2,&ast; Hang Lu,1,2 Chunliu Liu,1,2 Aihua Wang,1,2 Qingxiang Gu,1,2 Yuxiu Ka1,2 1Department of Rheumatism and Immunity, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China; 3Department of Rheumatism and Immunity, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Liu, Email fengshiliuwei@163.comBackground: Acute gouty arthritis (AGA) is characterized by the accumulation of monosodium urate crystals within the joints, leading to inflammation and severe pain. Western medicine treatments have limitations in addressing this condition. Previous studies have shown the efficacy of Qinpi Tongfeng formula (QPTFF) in treating AGA, but further investigation is needed to understand its mechanism of action.Methods: We used ultra-high-performance liquid chromatography tandem Q-Exactive Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-MS) to identify compounds in QPTFF. Target proteins regulated by these compounds were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Chemistry Database, and Swiss Target Prediction Database. AGA-related targets were searched and screened from various databases, including Genecards, PharmGKB, Drugbank, etc. Intersection targets of QPTFF and AGA were analyzed for protein–protein interaction networks, GO function enrichment, and KEGG pathway enrichment. We then verified QPTFF’s mechanism of action using an AGA rat model, assessing pathological changes via H&E staining and target expression via ELISA, RT-qPCR, and Western blot.Results: UHPLC-Q-Orbitrap-MS identified 207 compounds in QPTFF, with 55 selected through network pharmacology. Of 589 compound-regulated targets and 1204 AGA-related targets, 183 potential targets were implicated in QPTFF’s treatment of AGA. Main target proteins included IL-1β, NFKBIA, IL-6, TNF, CXCL8, and MMP9, with the IL-17 signaling pathway primarily regulated by QPTFF. Experimental results showed that medium and high doses of QPTFF significantly reduced serum inflammatory factors and MMP-9 expression, and inhibited IL-17A, IL-6, IKK-β, and NF-κB p65 mRNA and protein expression in AGA rats compared to the model group.Conclusion: Key targets of QPTFF include IL-1β, NFKBIA, IL-6, TNF-α, CXCL8, and MMP9. QPTFF effectively alleviates joint inflammation in AGA rats, with high doses demonstrating no liver or kidney toxicity. Its anti-inflammatory mechanism in treating AGA involves the IL-17A/NF-κB p65 signaling pathway.Keywords: acute gouty arthritis, Qinpi Tongfeng formula, network pharmacology, UHPLC-Q-Orbitrap-MS, IL-17 signaling pathway

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

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

Zhu-Xi Yu, Yang Pi, Mei-Kai Chen, Dan-Jiang Dong, Qin Gu Department of Critical Care Medicine, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 21008, People’s Republic of ChinaCorrespondence: Qin Gu, Department of Critical Care Medicine, the Affiliated Drum Tower Hospital of Nanjing University Medical school, Nanjing, Jiangsu, 21008, People’s Republic of China, Tel +86-13705150348, Email guqin123456202206@163.comAbstract: Hemodynamic instability in patients with clozapine intoxication can indirectly reflect the serum concentration of clozapine.We have described a case of a 32-year-old pregnant woman who developed life-threatening clozapine toxicity at 28 weeks of gestation. The levels of clozapine and norclozapine in the serum were high. We initiated hemoperfusion(HP) and other detoxification therapies to remove the drug. The patient had severely dilated peripheral blood vessels, which led to cardiac symptoms such as fatal hypotension and uncontrollable tachycardia, resulting in very high cardiac output and elevated Central venous oxygen saturation (ScvO2). Pharmacological intervention significantly improved the hemodynamics.In light of our observations in the ongoing case, we posit that evaluating hemodynamic parameters before and after blood detoxification could serve as a valuable means to gauge effectiveness and provide guidance for treatment.Keywords: clozapine, toxicity, pulse index continuous cardiac output, PICCO, hemoperfusion, HP

Chang Tang,1,2,&ast; Lanting Wang,1,2,&ast; Zihua Chen,1,2,&ast; Jin Yang,1,2 Haiqing Gao,1,2 Chenggong Guan,1,2 Qiaozhi Gu,1,2 Shan He,1,2 Fanping Yang,1,2 Shengan Chen,1,2 Li Ma,1,2 Zhen Zhang,1,2 Ying Zhao,1,2 Lin Tang,1,2 Yu Xu,1,2 Yue Hu,3 Xiaoqun Luo1,2 1Department of Allergy & Immunology, Huashan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Department of Dermatology, Huashan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Department of Clinical Laboratory, Huashan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqun Luo, 12 Wulumuqi Zhong Road, Jing’an District, Shanghai, People’s Republic of China, Tel +86 13918825230, Email luoxiaoqun913@126.comPurpose: Several in vivo experiments have shown that molecular hydrogen is a promising therapeutic agent for interstitial lung diseases (ILD). In this study, hydrogen therapy was investigated to determine whether it is superior to N-Acetylcysteine (NAC) for the treatment of patients with early-stage ILD.Patients and Methods: A prospective, single-center, randomized, controlled clinical trial was conducted in 87 patients with early-stage ILD. Hydrogen or NAC therapy was randomly assigned (1:1 ratio) to the eligible patients. The primary endpoint was the change in the high-resolution computed tomography (HRCT) and composite physiologic index (CPI) scores from baseline to week 48. Pulmonary function was evaluated as a secondary endpoint, and adverse events were recorded for safety analysis.Results: The rate of HRCT image improvement from the baseline in the HW group (63.6%) was higher than that in the NAC group (39.5%). A significant decrease in CPI and improvement in DLCO-sb were observed in the hydrogen group compared with those in the control group. Changes in other pulmonary function parameters, including FVC, FEV1, FEV1/FVC%, and TLC, were not significantly different between the two groups. Adverse events were reported in 7 (15.9%) patients in the HW group and 10 (23.3%) patients in the NAC group, but the difference was not significant (P=0.706).Conclusion: Hydrogen therapy exhibits superior efficacy and acceptable safety compared with NAC therapy in patients with early-stage ILD.Keywords: hydrogen, N-acetylcysteine, interstitial lung disease, therapeutic effects

Fangqing Zhu,1 Sheng Li,2 Qiuping Gu,1 Ningsheng Xie,1 Yinxia Wu3 1Department of Gastroenterology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of China; 2Department of Gastroenterology, Yuebei People’s Hospital, Shantou University Medical College, Shaoguan, Guangdong, 512026, People’s Republic of China; 3Department of Rehabilitation, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of ChinaCorrespondence: Fangqing Zhu; Yinxia Wu, Email wanliqingkong0707@163.com; xiaflora0608@163.comBackground: Pyroptosis is a form of proinfammatory gasdermin-mediated programmed cell death. Abnormal infammation in the intestine is a critical risk factor for Ulcerative colitis (UC). However, at present, it is not clear whether pyroptosis of colonic fibroblasts is involved in the pathogenesis and progression of UC.Methods: In this study, key genes associated with UC were identified by bioinformatics analysis. Datasets were downloaded from the Gene Expression Omnibus (GEO) database (GSE193677). The differentially expressed genes were analyzed, and the hub genes were screened by weighted gene co-expression network analysis (WGCNA) and differentially expressed genes. We also downloaded the dataset from GEO for single-cell RNA sequencing (GSE231993). The expression of key genes was verified by immunohistochemistry, immunofluorescence and Western blot, and the specific pathways of key genes inducing pyroptosis in cell lines were explored.Results: The results of bioinformatics analysis showed that the expression of APOL1 and CXCL1 in UC tissues was significantly higher than that in normal tissues. The results of single-cell analysis showed that the two genes were co-localized to fibroblasts. These results were consistent with the results of immunohistochemistry and immunofluorescence colocalization in human intestinal mucosa specimens. Furthermore, APOL1 overexpression induced NLRP3-caspase1-GSDMD-mediated pyroptosis of fibroblasts, which was confirmed by Western blot.Conclusion: APOL1 induces pyroptosis of fibroblasts mediated by NLRP3-Caspase1-GSDMD signaling pathway and promote the release of chemokines CXCL1. Fibroblasts may play a crucial role in the pathogenesis and progression of UC.Keywords: apolipoprotein L1, pyroptosis, fibroblasts, gasdermin-D, Ulcerative colitis

Zhiming Kuang,1 Qiuping Gu1,2 1Department of Critical Care Medicine, Ganzhou People’s Hospital, Ganzhou, Jiangxi Province, 341000, People’s Republic of China; 2Department of Gastroenterology, Ganzhou People’s Hospital, Ganzhou, Jiangxi Province, 341000, People’s Republic of ChinaCorrespondence: Qiuping Gu, Department of Gastroenterology, Ganzhou People’s Hospital, No. 16, Meiguan Avenue, Zhanggong District, Ganzhou City, Jiangxi Province, People’s Republic of China, Tel +86-18214932018, Email zhangdi2@mail.sdufe.edu.cnObjective: To investigate the correlation between the expression of cereblon (CRBN) protein in peripheral blood and the severity and prognosis of sepsis.Methods: A total of 130 patients with sepsis admitted to our hospital were selected as the observation subjects (sepsis group). The patients were divided into mild group, moderate group and severe group according to their conditions. The patients were divided into survival group and death group according to their living conditions within 28 days after admission. 130 health individuals were selected as the control group. The levels of CRBN mRNA, CRP and PCT in peripheral blood were detected.Results: The levels of serum CRBN mRNA, CRP, and PCT in patients with sepsis were higher than those in the control group (P< 0.05); As the condition worsens, the levels of CRBN mRNA, CRP, and PCT gradually increase, and there are statistically significant differences among patients with mild, moderate, and severe sepsis; Correlation analysis showed that the expression of CRBN mRNA in sepsis patients was positively correlated with CRP, PCT levels, APACHE II score and SOFA score (P< 0.05); the 28-day cumulative survival rate of patients with high CRBN mRNA expression was significantly lower than that of patients with low CRBN mRNA expression (P< 0.05); compared with the survival group, the levels of serum CRBN mRNA, CRP and PCT in the death group were significantly higher (P< 0.05); the AUC of death in sepsis patients diagnosed by CRBN mRNA, CRP and PCT was 0.961, the combined diagnostic efficacy was higher than that of single detection (P< 0.05).Conclusion: The expression level of CRBN in the peripheral blood of patients with sepsis is increased, which is related to the severity and prognosis of the patients. The combination of CRP and PCT has certain diagnostic value for the death of sepsis patients.Keywords: sepsis, cereblon protein, prognosis, severity

Zihan Hu,1,&ast; Danjiang Dong,2,&ast; Fei Peng,1,&ast; Xing Zhou,1 Qin Sun,1 Hui Chen,1,3 Wei Chang,1 Qin Gu,2,&ast; Jianfeng Xie,1,&ast; Yi Yang1,&ast; 1Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2Department of Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 3Department of Critical Care Medicine, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfeng Xie; Qin Gu, Department of Critical Care Medicine, Zhongda Hospital, School of medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People’s Republic of China, Tel/Fax +00862583262500, Email xie820405@126.com; guqinicu012323@126.comPurpose: Immune dysfunction plays a pivotal role in sepsis pathogenesis. Previous studies have revealed the crucial role of T cells and human leukocyte antigen-DR (HLA-DR) in sepsis. However, the function of natural killer (NK) cells remains unclear. This study aimed to investigate whether NK cells are associated with sepsis prognosis. In addition, we aimed to explore the interrelation and influence between NK and other immunological features in patients with sepsis.Patients and Methods: This retrospective, observational study included patients with sepsis from two hospitals in mainland China. The clinical characteristics and immune results during the early phase were collected. Patients were classified according to the level of immune cells to analyze the relationship between immunological features and 28-day mortality.Results: A total of 984 patients were included in this study. Non-survivors were older and had lower levels of lymphocytes, monocytes, NK cells, HLA-DR, and T cells. Patients were classified into eight groups according to their levels of NK cells, HLA-DR, and T cells. Only patients with decreased NK and T cell counts showed a significant increase in 28-day mortality. An increase in CD8+ T cells was correlated with the alleviation of 28-day mortality only among patients with high NK cell levels.Conclusion: This study provides novel insights into the association between NK cells and 28-day mortality as well as the interrelation between NK cells and other immune cells in sepsis. The relationship between CD8+ T cells and 28-day mortality in sepsis is dependent on NK cell count.Keywords: sepsis, immune dysfunction, natural killer cell, HLA-DR, T cell

Alcohol oxidation by O2 to carboxylic acid can be operated in water using noble-metal catalysts, but relies on the undesirable addition of a base such as sodium hydroxide. Using periodic density functional theory (DFT), we built a model including the chemisorption of hydroxide anion at the metal/water interface to rationalize the pivotal role of the added base on the catalytic activity. We demonstrate that the role of the base is to polarize the surface and that a similar promotion could be obtained by tuning the electronic properties of additives, alloy, and support.

An open question in single molecule nanoarrays is how the chemical and morphological heterogeneities of the solid support affect the properties of biomacromolecules. We generated arrays that allowed individually-resolvable DNA molecules to interact with tailored surface heterogeneities and revealed how molecular conformations are impacted by surface interactions.

Sufang Zhang,1,* Liyan Huang,1,* Qingshan Huang,2,* Weili Wei,1 Lijun Xie,1 Jinshu Zeng,1 Qiuyang Gu,1 Ling Chen,1 Shuqiang Chen1 1Department of Ultrasound, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 2Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuqiang ChenDepartment of Ultrasound, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of ChinaTel/Fax +86-591-87981961Email chenshu0518@163.comPurpose: Ultrasonography as the first choice for thyroid nodules is still difficult to distinguish between solid follicular thyroid neoplasm (FTN) and solid nodular goiter (NG). We tried to investigate the value of relative size (M/S, M: the maximum diameter of target nodule, S: the maximum diameter of the largest of the remaining nodules) that may help to differentiate FTN from NG.Methods: T test and chi-square test were used to retrospectively analyze the differences of the clinical and ultrasonographic characteristics between FTN and NG in 422 cases in our hospital. T test was used to analyze the difference of M/S value in the two kinds of nodules. ROC was used to evaluate the accuracy of M/S value in distinguishing the two.Results: There were statistically significant differences in age, echogenicity, calcification, peripheral halo and blood supply between the two. The M/S value is not only significantly different in the two kinds of nodules but also can be used as a quantitative indicator to guide ultrasound diagnosis. ROC analysis showed that the cutoff point and AUC of M/S value were 1.94 and 0.709, respectively.Conclusion: In the ultrasound diagnosis of multiple thyroid nodules, the M/S value can better distinguish FTN and NG. We need to be aware of FTN when the M/S value of the nodule is greater than 2.Keywords: follicular thyroid neoplasm, nodular goiter, size, ultrasonography

Qihua Gu,1,2 Xinhao Deng,1,2 Zhao Li,1,2 Jing Wang,3 Chengping Hu,1,2 Shuhua Lei,1,2 Xiaoling Cai1,2 1Department of Respiratory Medicine, Xiangya Hospital Affiliated to Central South University, Changsha, Hunan Province, 410008, People’s Republic of China; 2Key Cite of National Clinical Research Center for Respiratory Disease, Changsha, Hunan Province, 410008, People’s Republic of China; 3Department of Pathology, Xiangya Hospital Affiliated to Central South University, Changsha, Hunan Province, 410008, People’s Republic of ChinaCorrespondence: Qihua Gu Tel +86 15973196025Email guqh06@163.comBackground: Simple signs of local pleural adhesion are often found in people during a physical examination. In the present study, we aimed to clarify whether the merely localized pleural adhesion was just caused by previous pleural inflammation or physiological variation.Materials and Methods: Chest X-ray image materials were collected to analyze the incidence of simple pleural adhesions. Moreover, the causes of these simple pleural adhesions were further analyzed using thoracoscopy under direct vision and biopsy data.Results: In all 2218 chest X-ray images, 68 cases were found to have pleural lesions (3.07%), including 15 cases of localized pleural adhesion only. Subsequently, we analyzed the characteristics of 70 cases of pleural lesions using thoracoscopy. In two lung cancer patients with pleural metastasis, we found an unusual pleural junction. This connective strip was smooth and free of inflammation, resembling the normal pleura.Conclusion: Some of these purely localized pleural adhesions might be attributed to previous inflammation. However, there was still at least a possibility that there must be a physiological pleural junction, which could be the cause of the purely localized pleural adhesion shown in the chest radiograph.Keywords: pleural adhesion, bridge connection, physiological variation, image, thoracoscope

Yongwei Gu,1– 3,* Qing Gu,4,* Qing Yang,1,2 Meng Yang,3 Shengzhang Wang,5 Jiyong Liu1– 3 1Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, People’s Republic of China; 4Department of Pharmacy, Jingan District Zhabei Central Hospital, Shanghai 200070, People’s Republic of China; 5Institute of Biomechanics, Department of Aeronautics and Astronautics, Fudan University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shengzhang WangDepartment of Aeronautics and Astronautics, Institute of Biomechanics, Fudan University, Shanghai 200433, People’s Republic of ChinaTel/Fax +86-21-65647825Email szwang@fudan.edu.cnJiyong LiuDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of ChinaTel/Fax +86-21-64175590Email liujiyong@fudan.edu.cnBackground: Skin pharmacokinetics is an indispensable indication for studying the drug fate after administration of transdermal drug delivery systems (TDDS). However, the heterogeneity and complex skin structured with stratum corneum, viable epidermis, dermis, and subcutaneous tissue inevitably leads the drug diffusion coefficient (Kp) to vary depending on the skin depth, which seriously limits the development of TDDS pharmacokinetics in full thickness skin.Methods: A multilayer geometry skin model was established and the Kp of drug in SC, viable epidermis, and dermis was obtained using the technologies of molecular dynamics simulation, in vitro permeation experiments, and in vivo microdialysis, respectively. Besides, finite element analysis (FEA) based on drug Kps in different skin layers was applied to simulate the paeonol nanoemulsion (PAE-NEs) percutaneous dynamic penetration process in two and three dimensions. In addition, PAE-NEs skin pharmacokinetics profile obtained by the simulation was verified by in vivo experiment.Results: Coarse-grained modeling of molecular dynamic simulation was successfully established and the Kp of PAE in SC was 2.00× 10− 6 cm2/h. The Kp of PAE-NE in viable epidermis and in dermis detected using penetration test and microdialysis probe technology, was 1.58× 10− 5 cm2/h and 3.20× 10− 5 cm2/h, respectively. In addition, the results of verification indicated that PAE-NEs skin pharmacokinetics profile obtained by the simulation was consistent with that by in vivo experiment.Discussion: This study demonstrated that the FEA combined with the established multilayer geometry skin model could accurately predict the skin pharmacokinetics of TDDS.Keywords: nano transdermal drug delivery system, skin pharmacokinetics, finite element analysis, multilayer geometry model, diffusion coefficient, paeonol nanoemulsion