Search

Qingqing Ma,1,2,&ast; Guoju Luo,1,&ast; Fei Wang,1,&ast; Haolong Li,1 Xiaomeng Li,1,3 Yongmei Liu,1 Zhan Li,1 Ye Guo,1 Yongzhe Li1 1Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Medical Laboratory Innovation Unit, Chinese Academy of Medical Sciences, Shenyang, People’s Republic of China; 3Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye Guo; Yongzhe Li, Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuai-Fu-Yuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Email 4227582@163.com; yongzhelipumch@126.comPurpose: This study investigated potential predictive models associated with natural killer (NK) cell mitochondrial membrane potential (MMP or ΔΨm) in predicting death among critically ill patients with COVID-19.Patients and Methods: We included 97 patients with COVID-19 of different severities attending Peking Union Medical College Hospital from December 2022 to January 2023. Patients were divided into three groups according to oxygen and mechanical ventilation use during specimen collection and were followed for survival and death at 3 months. The lymphocyte subpopulation MMP was detected via flow cytometry. We constructed a joint diagnostic model by integrating identified key indicators and generating receiver operating curves (ROCs) and evaluated its predictive performance for mortality risk in critically ill patients.Results: The NK-cell MMP median fluorescence intensity (MFI) was significantly lower in critically ill patients who died from COVID-19 (p< 0.0001) and significantly and positively correlated with D-dimer content in critically ill patients (r=0.56, p=0.0023). The random forest model suggested that fibrinogen levels and NK-cell MMP MFI were the most important indicators. Integrating the above predictive models for the ROC yielded an area under the curve of 0.94.Conclusion: This study revealed the potential of combining NK-cell MMP with key clinical indicators (D-dimer and fibrinogen levels) to predict death among critically ill patients with COVID-19, which may help in early risk stratification of critically ill patients and improve patient care and clinical outcomes.Keywords: COVID-19, mortality prediction, NK cell, mitochondrial membrane potential, fibrinogen, D-dimer

Geyi Wen,1,&ast; Jinliang Meng,1,&ast; Puxian Peng,2,&ast; Yanyan Xu,1 Ruiqi Wang,1 Wenlong Cui,2 Aihan Wen,2 Guohong Luo,2 Yunhui Zhang,1 Songyuan Tang2 1Department of Pulmonary and Critical Care Medicine, the First People’s Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China; 2Institute of Health Studies, School of Public Health, Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunhui Zhang, Department of Pulmonary and Critical Care Medicine, the First People’s Hospital of Yunnan Province, No. 157 Jinbi Road, Xishan District, Kunming, Yunnan, 650032, People’s Republic of China, Email yunhuizhang3188@126.com Songyuan Tang, Institute of Health Studies, School of Public Health, Kunming Medical University, 1168 West Chunrong Road, Yuhua Street, Chenggong District, Kunming, Yunnan, 650500, People’s Republic of China, Email tsythailand@hotmail.comPurpose: Chronic obstructive pulmonary disease (COPD) is a significant disease impacting health and quality of life. Yunnan Province, a major tobacco producer, lacks comprehensive COPD studies. The purpose of this study is to describe the epidemic situation of COPD in Yunnan province and explore its influencing factors.Methods: This study is a cross-sectional research conducted in a representative sample of adults aged 20 and older from 13 prefectures and cities in Yunnan Province, China. COPD was diagnosed using post-bronchodilator pulmonary function tests. Demographics were analyzed with descriptive statistics. The influencing factors of COPD were examined by using the multivariate logistic regression models.Results: Our study found that high-risk individuals for COPD accounted for 20.30% of the screened population aged 20 and above, with a COPD prevalence of 27.18% among this high-risk group. Male had a higher prevalence (33.01%) than did female (16.35%; p< 0.001 for sex difference). Additionally, the proportion of severe and extremely severe COPD cases in Yunnan Province was higher than the national average and other provinces. After considering the potential confounding variables, male (OR=2.291, 95% CI: 1.584– 3.313), age (OR=1.501, 95% CI: 1.338– 1.685), underweight (OR=1.747, 95% CI: 1.225– 2.491), previous smoking (OR=1.712, 95% CI: 1.182– 2.478), passive smoking (OR=1.444, 95% CI: 1.159– 1.800), and a history of respiratory system diseases in childhood (OR=2.010, 95% CI: 1.346– 3.001) were significantly associated with an increased risk of COPD. Conversely, being overweight (OR=0.636, 95% CI: 0.489– 0.828), and residing in high-altitude counties (OR=0.445, 95% CI: 0.263– 0.754) were negatively correlated with the risk of COPD.Conclusion: There is significant prevalence of COPD (27.18%) among high-risk population aged 20 and above in Yunnan Province, China. Apart from male, smoking, BMI and other known risk factors for COPD. We found that high-altitude residence had a lower prevalence of COPD. There is no significant difference in COPD prevalence between Han and ethnic minority populations.Keywords: chronic obstructive pulmonary disease, epidemiological characteristics, influencing factors, high-risk population, China

Jingwen Xu,1,2 Yue Zhang,1,2 Xiaolin Yao,1 Sijuan Wang,1,2 Kaiqiang Lv,1,2 Guangwen Luo,1,2 Jiaqi Wang,1,2 Guoliang Li1 1School of Food Science and Engineering, School of Biological and Pharmaceutical Sciences, Shaanxi University of Science & Technology, Xi’an, 710021, People’s Republic of China; 2Xi’an Key Laboratory of Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Xi’an, 710021, People’s Republic of ChinaCorrespondence: Guoliang Li, Email 61254368@163.comIntroduction: To improve the bioavailability of trans-resveratrol (trans-Res), it is commonly co-delivered with antioxidant bioactives using a complex synthetic intestinal targeted carrier, however, which makes practical application challenging.Methods: A nanogel (Ngel), as broad-spectrum autonomous ROS scavenger, was prepared using selenized thiolated sodium alginate (TSA-Se) and crosslinked with calcium lactate (CL) for loading trans-Res to obtain Ngel@Res, which maintained spherical morphology in the upper digestive tract but broke down in the lower digestive tract, resulting in trans-Res release.Results: Under protection of Ngel, trans-Res showed enhanced stability and broad-spectrum ROS scavenging activity. The synergistic mucoadhesion of Ngel prolonged the retention time of trans-Res in the intestine. Ngel and Ngel@Res increased the lifespan of Caenorhabditis elegans to 26.00 ± 2.17 and 26.00 ± 4.27 days by enhancing the activity of antioxidases, upregulating the expression of daf-16, sod-5 and skn-1, while downregulating the expression of daf-2 and age-1.Conclusion: This readily available, intestinal targeted selenized alginate-based nanogel effectively improves the bioactivity of trans-Res. Keywords: trans-resveratrol, seleno-alginate, synergistic antioxidant, mucoadhesion, intestinal targeted delivery

Peng Luo,1,&ast; Yi Zhang,2,3,&ast; Maodi Huang,1 Guochen Luo,1 Yaping Ma,1,4 Xin Wang1,4 1Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, People’s Republic of China; 2Department of Hygiene Toxicology, School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 3Key Laboratory of Maternal & Child Health and Exposure Science of Guizhou Higher Education Institutes, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 4Guizhou Provincial Key Laboratory of Medicinal Biotechnology in Colleges and Universities, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Wang, Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, People’s Republic of China, Tel +86 136 3928 8558, Fax +86-851-2860 8903, Email xin.wang@zmu.edu.cnIntroduction: Osteoporotic-related fractures remains a significant public health concern, thus imposing substantial burdens on our society. Excessive activation of osteoclastic activity is one of the main contributing factors for osteoporosis-related fractures. While polylactic acid (PLA) is frequently employed as a biodegradable scaffold in tissue engineering, it lacks sufficient biological activity. Microdroplets (MDs) have been explored as an ultrasound-responsive drug delivery method, and mesenchymal stem cell (MSC)-derived exosomes have shown therapeutic effects in diverse preclinical investigations. Thus, this study aimed to develop a novel bioactive hybrid PLA scaffold by integrating MDs-NFATc1-silencing siRNA to target osteoclast formation and MSCs-exosomes (MSC-Exo) to influence osteogenic differentiation (MDs-NFATc1/PLA-Exo).Methods: Human bone marrow-derived mesenchymal stromal cells (hBMSCs) were used for exosome isolation. Transmission electron microscopy (TEM) and confocal laser scanning microscopy were used for exosome and MDs morphological characterization, respectively. The MDs-NFATc1/PLA-Exo scaffold was fabricated through poly(dopamine) and fibrin gel coating. Biocompatibility was assessed using RAW 264.7 macrophages and hBMSCs. Osteoclast formations were examined via TRAP staining. Osteogenic differentiation of hBMSCs and cytokine expression modulation were also investigated.Results: MSC-Exo exhibited a cup-shaped structure and effective internalization into cells, while MDs displayed a spherical morphology with a well-defined core-shell structure. Following ultrasound stimulation, the internalization study demonstrated efficient delivery of bioactive MDs into recipient cells. Biocompatibility studies indicated no cytotoxicity of MDs-NFATc1/PLA-Exo scaffolds in RAW 264.7 macrophages and hBMSCs. Both MDs-NFATc1/PLA and MDs-NFATc1/PLA-Exo treatments significantly reduced osteoclast differentiation and formation. In addition, our results further indicated MDs-NFATc1/PLA-Exo scaffold significantly enhanced osteogenic differentiation of hBMSCs and modulated cytokine expression.Discussion: These findings suggest that the bioactive MDs-NFATc1/PLA-Exo scaffold holds promise as an innovative structure for bone tissue regeneration. By specifically targeting osteoclast formation and promoting osteogenic differentiation, this hybrid scaffold may address key challenges in osteoporosis-related fractures. Keywords: bioactive microdroplets, PLA scaffold, MSC-Exo, biocompatibility, osteoclast formation, hBMSCs, osteogenesis

Mei Xiao,1 Guangwen Luo,1 Zhaowei Zhang,1 Yanfen Liu,2 Rui Gong,3 Jianghuan Ke1 1Department of Pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China; 2Department of Endocrinology and Metabolism, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China; 3Department of Clinical Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of ChinaCorrespondence: Guangwen Luo, Department of pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, 321000, People’s Republic of China, Tel +86-0579-82552760, Email lgw2018@126.comPurpose: To investigate the correlation between thyroid-related hormones and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM).Patients and Methods: Patients with T2DM admitted to our hospital between January 2023 and June 2023 were retrospectively analyzed. The patients were divided into DR and non-diabetic retinopathy (NDR) groups according to whether DR occurred. Thyroid function-related hormones (TSH, FT3, and FT4), blood glucose indices (FBG and HbA1c), and blood lipid indices (HDL-C, LDL-C, TC, and TG) of the two groups were analyzed by univariate and multivariate logistic regression to explore the risk factors for DR. Pearson correlation analysis and multiple stepwise regression analysis were used to investigate the correlation of TSH or FT3 with FBG, HbA1c, and TG in DR patients.Results: Of the 286 patients with T2DM included in this study, 101 (35.31%) developed DR and 185 (64.69%) did not. High TG, FBG, HbA1c, and TSH and low FT3 levels were independent risk factors for DR in T2DM patients. TSH positively correlated with TG, whereas FT3 negatively correlated with TG and HbA1c in T2DM patients with DR.Conclusion: Higher TSH and lower FT3 in T2DM patients with normal thyroid function may affect glucose and lipid metabolism, thereby increasing the risk of DR.Keywords: type 2 diabetes mellitus, diabetic retinopathy, thyroid-stimulating hormone, free triiodothyronine, glucose and lipid metabolism

Jiangyan Yong,1,&ast; Hongli Shu,1,&ast; Xiao Zhang,2,&ast; Kun Yang,3 Guining Luo,3 Lu Yu,3 Jiaqi Li,3 Hong Huang4 1Department of Clinical Laboratory, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610072, People’s Republic of China; 2Department of Clinical Laboratory, Chengdu Children Special Hospital, Chengdu, Sichuan, 610031, People’s Republic of China; 3Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People’s Republic of China; 4Department of Clinical Laboratory, the People’s Hospital of Chongqing Liang Jiang New Area, Chongqing, 401121, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Huang, Email hh1643689264@163.comAbstract: Given the unique physiological and pathological characteristics of the lung, the direct, inhalable route is more conducive to pulmonary drug delivery and disease control than traditional systemic drug delivery, significantly circumventing drug loss, off-target effects, systemic and organ toxicity, etc., and is widely regarded as the preferred regimen for pulmonary drug delivery. However, very few lung diseases are currently treated with the preferred inhaled formulations, such as asthma, chronic obstructive pulmonary disease and pulmonary hypertension. And there is a lack of appropriate inhaled formulations for other critical lung diseases, such as lung cancer and pulmonary fibrosis, due to the fact that the physicochemical properties of the drugs and their pharmacokinetic profiles do not match the physiology of the lung, and conventional inhalation devices are unable to deliver them to the specific parts of the lung. Phytochemicals of natural origin, due to their wide availability and clear safety profile, hold great promise for the preparation of inhalable formulations to improve the current dilemma in the treatment of lung diseases. In particular, the preparation of inhalable formulations based on nano- and microparticulate carriers for drug delivery to deep lung tissues, which overcome the shortcomings of conventional inhalation therapies while targeting the drug activity directly to a specific part of the lung, may be the best approach to change the current dilemma of lung disease treatment. In this review, we discuss recent advances in nano- and micron-carrier-based inhalation formulations for the delivery of natural products for the treatment of pulmonary diseases, which may represent an opportunity for practical clinical translation of natural products.Keywords: inhaled nanoformulations, inhalation therapy, natural products, nanomedicine, pulmonary diseases

Ling Zhou,1,&ast; Yu Gan,1,&ast; Yanjun Wu,1 Dongdong Xue,1 Jianhong Hu,1 Yilan Zhang,2 Yang Liu,3 Siyuan Ma,1 Junyi Zhou,1 Gaoxing Luo,1 Daizhi Peng,1 Wei Qian1 1Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China; 2Department of Oral and Maxillofacial Head and Neck Surgery, Army Medical Center of PLA/Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, People’s Republic of China; 3Department of Urology, Urology Institute of PLA, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daizhi Peng; Wei Qian, Email dzpengpub@126.com; weiqian87@126.comIntroduction: Indocyanine green (ICG) fluorescence imaging has been used in the resection surgery and sentinel lymph node biopsy of many tumors. The aim of the present study is to verify the feasibility and effectiveness of ICG fluorescence imaging used for guiding the biopsy and resection of skin squamous cell carcinoma (SSCC).Methods: Sixty patients were enrolled, including 18 patients of suspected SSCC and 42 patients of diagnosed SSCC on admission. The ICG fluorescence imaging-guided skin biopsy was performed preoperatively in the 18 cases of suspected SSCC. Fifty-three patients underwent ICG fluorescence imaging-guided radical excision.Results: The results showed that 138 skin tissue samples in 60 patients with preoperative or intraoperative ICG fluorescence imaging-guide biopsy were collected. For a total number of 138 biopsies, 122 specimens were squamous cell carcinoma, and the accuracy rate was 88.4%, which was significantly higher than that of the group without preoperative ICG fluorescence imaging (41/62, 66.1%, P < 0.05). Fifty-three patients underwent surgery guided with ICG fluorescence imaging. Residual fluorescent signals in 24 patients were intraoperatively found and the excision was then expanded until the signals disappeared. Follow-up to November 2022, 12 patients died, of which 5 cases died from the tumor recurrence, and the others died due to advanced ages or other reasons. The recurrence rate was 9.4%, which was not significantly different from that of the group received routine radical resection (4/35, 11.4%, P > 0.05). Moreover, sentinel lymph nodes were successfully detected under ICG fluorescence imaging in the 4 patients with suspected lymph node metastases, and the location of lymph nodes can be precisely identified.Conclusion: ICG fluorescence imaging technique can guide the pathology biopsy to improve the accuracy of pathological examination, and help to identify the boundaries of tumor tissues and sentinel lymph nodes to resect tumor radically during operation.Keywords: indocyanine green, ICG, near-infrared fluorescence imaging, skin squamous cell carcinoma, biopsy, radical resection

Liu M, Luo G, Wang Y, et al. Int J Nanomedicine. 2017;12:6827-6840. The authors have advised due to an error that occurred inadvertently at the time of figure assembly, Figure 7B on page 6834 is incorrect. The authors have also advised the magnification in the note section is incorrect. The correct Figure 7 and caption are as follows. Figure 7 Fluorescence microscopy photographes of GFP transgenic fibroblasts on the (A) PCL/DA, (B) PCL/NS0.5, (C) PCL/NS1.0 and (D) PCL/NS2.0 films. (E) The cell viability measured using CCK8 assay at day 1, 3 and 5 post-seeding.Abbreviations: CCK8, Cell Counting Kit-8; DA, dopamine; GFP, green fluorescent protein; NS, nanosilver; PCL, polycaprolactone.Notes: Magnification ×100. *p

Lu Wei,&ast; Jialin Zhang,&ast; Dake Di, Dongmei Wang, Guangpu Luo Department of Traditional Chinese Medicine Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangpu Luo; Dongmei Wang, Department of Traditional Chinese Medicine Dermatology, Dermatology Hospital of Southern Medical University, No. 2, Lujing Road, Yuexiu District, Guangzhou City, Guangdong Province, 510091, People’s Republic of China, Tel +86 13926166004 ; +86 13431086997, Fax +86-20-87257353, Email 102931@163.com; wongdongmei@163.comAbstract: Cutaneous plasmacytosis (CP) is a rare disorder of uncertain etiology. We report an unusual and rare case of CP in a 57‑year‑old male who presented with popular nodules all over the body, accompanied by head plaques. Pathological biopsy of the skin revealed large infiltration of mature plasma cells within the dermis. Elevated serum IgG4 concentrations were found. Immunohistochemical analysis confirmed the polyclonal nature of the plasma cells. The diagnosis of CP was established. Steroid therapy was administered at a dose of 20 mg/day. After 1 month of treatment, the patient’s eruption showed regression. These findings remind dermatologists to include CP in their clinical differential diagnosis of patients with head plaques. Meanwhile, clinicians should carefully that individuals diagnosed with CP at risk for malignant transformation.Keywords: cutaneous plasmacytosis, IgG4-related disease, plasma cell, IgG4

Weiya Zeng,1– 3 Yuan Fang,1– 3 Suifen Mo,1– 3 Caihong Shen,1– 3 Huiling Yang,1– 3 Guihua Luo,1– 3 Luhua Xiao,1– 3 Ruoting Zhan,1– 3 Ping Yan1– 3 1College of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Key Laboratory of Chinese Medicinal Resources from Lingnan (Guangzhou University of Chinese Medicine), Ministry of Education, Guangzhou, People’s Republic of China; 3Joint Laboratory of Nation Engineering Research Center for the Pharmaceutics of Traditional Chinese Medicines, Guangzhou, People’s Republic of ChinaCorrespondence: Ruoting Zhan; Ping Yan, Guangzhou University of Chinese Medicine, No. 232, Outer Ring East Road, Guangzhou, Guangdong, People’s Republic of China, Tel/Fax +86 20-39358045, Email ruotingzhan@vip.163.com; yanping@gzucm.edu.cnPurpose: Rubia cordifolia L. (RC) is a classic herbal medicine for the treatment of rheumatoid arthritis (RA) and has been used since ancient times. The ethanol extract of Rubia cordifolia L. (RCE) showed obvious anti-RA effects in our previous study. However, further potential mechanisms require more exploration. We aimed to investigate the mechanism of RCE for the treatment of RA by integrating metabolomics and network pharmacology in this study.Methods: An adjuvant-induced arthritis (AIA) rat model was established, and we evaluated the therapeutic effects of RCE. Metabolomics of serum and urine was used to identify the differential metabolites. Network pharmacology was applied to determine the key metabolites and potential targets. Finally, the potential targets and compounds of RCE were verified by molecular docking.Results: The results indicated that RCE suppressed foot swelling and alleviated joint damage and also had anti-inflammatory properties by inhibiting the expressions of tumor necrosis factor (TNF)-α, Interleukin (IL)-1β, prostaglandin E2 (PGE2), and P65. Ten and seven differential metabolites were found in the serum and urine, respectively, of rats. Six key targets, ie, phospholipase A2 group IIA (PLA2G2A), phospholipase A2 group X (PLA2G10), cytidine deaminase (CDA), uridine-cytidine kinase 2 (UCK2), charcot-leyden crystal galectin (CLC), and 5′,3′-nucleotidase, mitochondrial (NT5M), were discovered by network pharmacology and metabolite analysis and were found to be related to glycerophospholipid metabolism and pyrimidine metabolism. Molecular docking confirmed that the favorable compounds showed affinities with the key targets, including alizarin, 6-hydroxyrubiadin, ruberythric acid, and munjistin.Conclusion: This study revealed the underlying mechanisms of RCE and provided evidence that will allow researchers to further investigate the functions and components of RCE against RA.Keywords: inflammtion, AIA rats, molecular docking, chronic disease

Wei Ju,1,2,&ast; Guan-fa Luo,1,&ast; Yuan-yuan Shi,3 Fei-jun Zhou,1 Meng-qi Li,1 Jian-hui Xu,1 Zhi-xin Yan,2 Xi-hu Yang1 1Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China; 2Department of Burn and Plastic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi-hu Yang, Email yangxihu1981@126.comObjective: Sebaceous carcinoma (SC) of the submandibular gland is extremely rare. Owing to the low morbidity and nonspecific clinical manifestations, diagnosis is commonly delayed, which increases metastasis and mortality. To date, there have been five reported cases of SC of the submandibular gland. Here, we present a new case and review the relevant literature.Methods and Results: A 36-year-old woman presented with an enlarged left submandibular gland. Clinical features included a non-tender solitary nodular mass with normal overlying skin. There were no special findings on computed tomography or ultrasound examination except for a swollen mass in the left submandibular gland. The patient underwent surgical resection. Pathological examination confirmed the diagnosis of SC with nerve infiltration. Immunohistochemical examination of this case showed positive staining for P63, P40, CK7, CK8/18, MLH1, MSH2, MSH6, and PMS2. The specimen was negative for androgen receptor, CEA, S-100, CK5/6, SOX-10, SOX-11, SMA, and GCDFP-15. The KI-67 labeling index was determined to be 15%. PAS and anti-epithelial membrane antigen were positive in partial area. The patient is still undergoing follow-up, and no metastasis or recurrence has been observed for 2 months.Conclusion: This case highlighted the fact that despite its rarity, SC should be considered as a differential diagnosis for masses located in the head and face. Early and accurate diagnosis, followed by wide surgical excision, has a favorable prognosis. Therefore, clinicians should be familiar with the clinical and pathological features of this disease.Keywords: sebaceous carcinoma, salivary gland neoplasms, submandibular gland, androgen receptor, P63, P40

Siyuan Ma,1,&ast; Yali Gong,1,&ast; Xiaoqiang Luo,1,&ast; Yuan Peng,2 Cheng Zhang,1 Xiaorong Zhang,1 Xiaohong Hu,1 Peng Tang,3 Zhiqiang Yuan,1 Gaoxing Luo,1 Haisheng Li1 1State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Key Laboratory for Proteomics Disease, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Clinical Laboratory, the Second Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haisheng Li, Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Tel +86-023-68765952, Email lee58427@163.comBackground: Elizabethkingia meningoseptica infections have gradually emerged as life-threatening nosocomial infections worldwide, accompanied by increasing incidence, multidrug resistance and poor outcomes. However, the epidemiology and clinical features of E. meningoseptica infection are still limited in mainland China.Methods: Patients with E. meningoseptica infections from 2011 to 2019 in southwestern China were retrospectively analyzed. The clinical features, infection patterns and outcomes were extracted from medical records and analyzed. A comprehensive systematic review was performed in accordance with PRISMA guidelines from conception to August 23, 2021.Results: Ninety-two patients were ultimately included, with the prevalence rapidly rising from 0 in 2011 to 0.19 per 1000 inpatients in 2019. A total of 93.48% of E. meningoseptica isolates were multidrug resistant, including 100% resistance to carbapenem. Furthermore, 75% of E. meningoseptica infections were concomitant with other pathogens. The mortality of our cohort was 36.96%, with risk factors for mechanical ventilation (OR=9.51, P=0.004), male sex (OR=0.27, P=0.031) and more concomitant pathogens. After propensity score matching, central venous catheters, exposure to carbapenem and antifungal drugs, and underlying tumors were associated with E. meningoseptica infection. Sixteen articles were also summarized, with reported mortality rates ranging from 11.0% to 66.6%. Blood and respiratory tract were the common sources. Piperacillin/tazobactam, trimethoprim/sulfamethoxazole, fluoroquinolone and minocycline were the most sensitive antibiotics. Inappropriate antibiotic treatment was the most commonly reported risk factor for mortality.Conclusion: Nosocomial infection with E. meningoseptica has become an emerging problem with high mortality in southwestern China. Inappropriate antibiotic treatment and central venous catheters are risk factors for infection and death and should receive adequate attention.Keywords: meningoseptica, nosocomial infection, epidemiology, risk factor, multidrug resistance, infection control

Ye Tian,1,2 Heng Zhang,1,2 Ying Cao,2 Lu Yang,3 Guangheng Luo1 1Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of China; 2Guizhou University School of Medicine, Guiyang, People’s Republic of China; 3Department of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Guangheng Luo, Tel +86-173-8501-5539, Fax +86-851-8562 1836, Email luoguangheng1975@163.comPurpose: Transurethral resection of the prostate (TURP) is often indicated for benign prostatic hyperplasia (BPH). Some patients, however, fail to adequately respond to these interventions. Accordingly, a powerful prediction model for TURP efficacy is warranted. This study aimed to create a nomogram with preoperative parameters for the prediction of individual TURP efficacy.Methods: Clinical data from 356 BPH subjects who underwent TURP were retrospectively collected between November 2015 and June 2021 for nomogram development. The prediction model was developed using multivariable logistic regression analysis and presented as a nomogram. Nomogram performance was assessed through calibration curves and the concordance index (C-index). An independent validation cohort containing 177 consecutive patients in the corresponding period was used for external validation. The optimal cutoff value was determined through receiver operating characteristic curve (ROC) analysis by maximizing the Youden index, and its accuracy was assessed through sensitivity, specificity and predictive values.Results: In multivariate analysis of the primary cohort, the independent factors for TURP efficacy were age, International Prostate Symptom Score (IPSS), intravesical prostatic protrusion (IPP), bladder wall thickness (BWT), peripheral zone thickness (PT) and transitional zone thickness (TT), all of which were included in the nomogram. The calibration curve for survival probability showed good agreement between the nomogram predictions and actual observations. The C-index for predicting TURP efficacy was 0.860 (95% confidence interval [CI], 0.808– 0.911). The optimal cutoff total nomogram score was 177, with a maximum Youden index of 0.643. The sensitivity, specificity, positive predictive value, and negative predictive value for predicting TURP efficacy were 70.6%, 75.6%, 90.6%, and 43.7% in the validation cohort, respectively. Logistic regression analysis in the validation cohort demonstrated that the area under the curve (AUC) was 0.806 (95% CI, 0.733– 0.879).Conclusion: The P.R.OS.T.A.T.E nomogram objectively and accurately predicted TURP efficacy, thereby facilitating the clinical decision-making process.Keywords: nomogram, benign prostatic hyperplasia, lower urinary tract symptoms, transurethral resection of prostate, efficacy

Jiayi Tang,1,2 Jiachun Tao,2 Ge Luo,2 Jianjun Zhu,2 Ming Yao2 1The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing and The Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of ChinaCorrespondence: Ming YaoDepartment of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing and The Affiliated Hospital of Jiaxing University, No. 1882 South Zhonghuan Road, Nanhu District, Jiaxing City, Zhejiang Province, People’s Republic of China, Tel +86 573 13456218632, Email jxyaoming666@163.comObjective: To analyze the influencing factors of motor dysfunction in patients with limb herpes zoster and to construct a nomogram to predict the risk of this complication.Methods: A total of 213 patients with limb herpes zoster in the First Hospital of Jiaxing from January 2015 to June 2020 were enrolled. The muscle strength of the affected limb was evaluated by the Medical Research Council (MRC) score. The muscle strength of the affected limb was less than grade 5, and lower than that of the contralateral limb (normal side) was defined as motor dysfunction. Univariate and multivariate logistic regression analyses were used to determine the influencing factors of motor dysfunction in patients with limb herpes zoster. The nomogram of the risk of motor dysfunction was drawn by R software. Discrimination and calibration of the prediction model were assessed by using the C-index and calibration plot. Internal validation was assessed by using bootstrapping validation.Results: There were 58 cases in the motor dysfunction group and 155 cases in the nonmotor dysfunction group, and univariate analysis showed that the location of involvement (OR = 4.095, 95% CI: 2.097– 8.466, P = 0.017), whether or not diseases were combined (OR = 0.520, 95% CI: 0.281– 0.959, P = 0.036) and the number of affected centrums (OR = 0.336, 95% CI: 0.177– 0.632, P = 0.001) were associated with the occurrence of motor dysfunction in patients with limb herpes zoster. Multivariate logistic regression analysis showed that upper limb involvement (OR = 3.811, 95% CI: 1.829– 8.387, P = 0.001), noncombined diseases (OR = 0.493, 95% CI: 0.249– 0.969, P = 0.041) and the number of affected centrums ≤ 3 (OR = 0.439, 95% CI: 0.218– 0.881, P = 0.020) were independent influencing factors of this complication. The prediction model displayed good discrimination with a C-index of 0.72 and good calibration. A high C-index value of 0.71 could still be reached in the interval validation.Conclusion: This study used the clinical data available to establish a nomogram model for motor dysfunction of limb herpes zoster and found that motor dysfunction is more likely to occur in patient who meets upper limb involvement, combined diseases and the number of affected centrums > 3. This kind of high-risk group should be intervened as soon as possible.Keywords: herpes zoster, motor dysfunction, prediction model, nomogram

Gang Luo, Jialing Chen, Zhanjun Ren College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, People’s Republic of ChinaCorrespondence: Zhanjun RenCollege of Animal Science and Technology, Northwest A&F University, Yangling, Shannxi, 712100, People’s Republic of ChinaEmail Renzhanjun@nwsuaf.edu.cnAbstract: N6-methyladenosine (m6A) is the most prevalent and abundant type of internal post-transcriptional RNA modification in eukaryotic cells. METTL3 is a methylation modifying enzyme, which can directly or indirectly affect biological processes, such as RNA degradation, translation and splicing. In addition, it was found that 67% of 3’-UTR regions containing m6A sites had at least one miRNA binding site, and the number of m6A at 3’-UTR sites was closely related to the binding sites of miRNA. With the improvement of human living standards, obesity has become a very serious and urgent problem. The essence of obesity is the accumulation of excess fat. Exploring the origin and development mechanisms of adipocyte from the perspective of fat deposition has always been a hotspot in the field of adipocyte research. The aim of the present review is to focus on METTL3 regulating fat deposition through mRNA/adipocyte differentiation axis and pri-miRNA/pre-miRNA/target genes/adipocyte differentiation and to provide a theoretical basis according to the currently available literature for further exploring this association. This review may provide new insights for obesity, fat deposition disease and molecular breeding.Keywords: METTL3, m6A methylation, miRNA, adipocyte differentiation, intramuscular fat

Jing Yang,1,&ast; Jinzhe Zhou,2,&ast; Yingying Zhao,1 Liangchen Zhu,2 Guanghong Luo,3 BuJun Ge2 1Department of Gastroenterology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of China; 2Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Department of Radiation Oncology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanghong Luo; Bujun Ge Email luo.guanghong@szhospital.com; gbj109@126.comIntroduction: Excessive production of reactive oxygen species (ROS) to induce high oxidative stress is one of the main causes of colitis; thus, it has been regarded as a therapeutic target for colitis treatment. And the nanomaterial-based therapeutic strategies are effective against colitis. However, the previous elaborately designed materials exhibit limited application due to the uncertain biocompatibility and complicated manufacturing processes.Methods: In this study, the highly monodisperse hollow CeO2 nanoparticles (H-CeO2) with uniform morphology were obtained by in situ growing CeO2 on solid silica nanoparticles and subsequently removing the silica core. The H-CeO2 was further modified with PEG, which owned excellent biological stability and biocompatibility. The experimental model of colitis induced by dextran sulfate sodium (DSS) was used to investigate the anti-inflammatory effect of H-CeO2-PEG.Results: The H-CeO2-PEG showed good ROS scavenging efficacy and decreased the levels of proinflammatory cytokines (IL-6, IL-1β, IL-18, and TNF-α) in DSS-induced colitis mice. Furthermore, H-CeO2-PEG inhibited the activation of the MAPK signalling pathway to alleviate colitis.Conclusion: This study reveals the therapeutic effects of CeO2-based nanomedicine toward colitis and elucidates the specific signalling pathway involved, which provides potential alternative therapeutic options for patients with inflammation tissue.Keywords: hollow CeO2, ROS, inflammation, colitis, MAPK signalling pathway

Inflammation and loss of articular cartilage are considered the major cause of temporomandibular joint osteoarthritis (TMJOA), a painful condition of the temporomandibular joint (TMJ). To determine the cause of TMJ osteoarthritis in these patients, synovial fluid of TMJOA patients was compared prior to and after hyaluronic lavage, revealing substantially elevated levels of interleukin (IL) 1β, reactive oxidative stress (ROS), and an overload of Fe3+ and Fe2+ prior to lavage, indicative of ferroptosis as a mode of chondrocyte cell death. To ask whether prolonged inflammatory conditions resulted in ferroptosis-like transformation in vitro, we subjected TMJ chondrocytes to IL-1β treatment, resulting in a shift in messenger RNA sequencing gene ontologies related to iron homeostasis and oxidative stress–related cell death. Exposure to rat unilateral anterior crossbite conditions resulted in reduced COL2A1 expression, fewer chondrocytes, glutathione peroxidase 4 (GPX4) downregulation, and 4-hydroxynonenal (4-HNE) upregulation, an effect that was reversed after intra-articular injections of the ferroptosis inhibitor ferrostatin 1 (Fer-1). Our study demonstrated that ferroptosis conditions affected mitochondrial structure and function, while the inhibitor Fer-1 restored mitochondrial structure and the inhibition of hypoxia-inducible factor 1α (HIF-1α) or the transferrin receptor 1 (TFRC) rescued IL-1β–induced loss of mitochondrial membrane potential. Inhibition of HIF-1α downregulated IL-1β–induced TFRC expression, while inhibition of TFRC did not downregulate IL-1β–induced HIF-1α expression in chondrocytes. Moreover, inhibition of HIF-1α or TFRC downregulated the IL-1β–induced MMP13 expression in chondrocytes, while inhibition of HIF-1α or TFRC rescued IL-1β–inhibited COL2A1 expression in chondrocytes. Furthermore, upregulation of TFRC promoted Fe2+ entry into chondrocytes, inducing the Fenton reaction and lipid peroxidation, which in turn caused ferroptosis, a disruption in chondrocyte functions, and an exacerbation of condylar cartilage degeneration. Together, these findings illustrate the far-reaching effects of chondrocyte ferroptosis in TMJOA as a mechanism causing chondrocyte death through iron overload, oxidative stress, and articular cartilage degeneration and a potential major cause of TMJOA. [ABSTRACT FROM AUTHOR]

Shengming Deng,1– 4,* Zhiyao Fan,1– 4,* Huanyu Xia,1– 4,* Yitao Gong,1– 4 Yunzhen Qian,1– 4 Qiuyi Huang,1– 4 He Cheng,1– 4 Kaizhou Jin,1– 4 Zhiwen Xiao,1– 4 Guopei Luo,1– 4 Xianjun Yu,1– 4 Chen Liu1– 4 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Pancreatic Cancer Institute, Shanghai, People’s Republic of China; 4Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chen Liu; Xianjun YuShanghai Pancreatic Cancer Institute, 270 Dong an Road, Shanghai 200032, People’s Republic of ChinaTel/Fax +86-21-6403-1446Email liuchen@fudanpci.org; yuxianjun@fudanpci.orgBackground: The fibrinogen/albumin ratio (FAR) has been widely reported to be a possible biomarker for predicting prognosis in several types of tumors, but the prognostic value of the FAR in pancreatic neuroendocrine neoplasms (Pan-NENs) has not been systematically studied.Patients and Methods: In total, 324 patients with Pan-NENs were recruited. The patients were divided into 2 subgroups according to the FAR cutoff value, and clinicopathological characteristics of the 2 subgroups were compared. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The prognostic value of the FAR was analyzed in univariate and multivariate analyses.Results: The optimal cutoff value for the FAR was calculated to be 0.08 for OS. The patients with a FAR ≥ 0.08 had higher proportions of nonfunctioning tumors, Pan-NECs, grade 3 tumors, and stage IV tumors than those with a FAR < 0.08. In the univariate analysis, a FAR ≥ 0.08 was associated with poor OS (hazard ratio (HR) = 2.37, P < 0.001) and PFS (HR = 2.37, P < 0.001). In the multivariate analysis, a FAR ≥ 0.08 was an independent risk factor for poor OS (HR = 4.70, P < 0.001) and PFS (HR = 1.80, P = 0.006).Conclusion: The pretreatment FAR, which includes fibrinogen and albumin, was a feasible and predictive biomarker for prognosis in patients with Pan-NENs. An elevated FAR, based on a cutoff value of 0.08, was an independent risk factor for poor OS and PFS.Keywords: pancreatic neuroendocrine neoplasms, survival, fibrinogen/albumin ratio

Yanhong Wang,1,2 Qian Wang,1 Xibei Li,3 Gongwen Luo,2 Mou Shen,2 Jia Shi,4 Xueliang Wang,5 Lu Tang6 1Department of Basic Medicine, Medical College of Yunnan University of Economics and Management, Kunming, Yunnan 650000, People’s Republic of China; 2Second Department of Internal Medicine, Chongming Branch of Yueyang Integrated Hospital of Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Chongming, Shanghai, 202150, People’s Republic of China; 3Department of Stomatology, Jining Medical College, Jining, Shandong 272000, People’s Republic of China; 4Department of Information, The First Affiliated Hospital of Naval Military Medical University (Shanghai Changhai Hospital), Shanghai 200433, People’s Republic of China; 5Department of Nephrology and Rheumatology, Zhaotong Traditional Chinese Medicine Hospital of Yunnan Province, Zhaotong, Yunnan 657000 People’s Republic of China; 6Department of Traditional Chinese Medicine, Kunming Second People’s Hospital, Kunming, Yunnan, 650000 People’s Republic of ChinaCorrespondence: Lu TangDepartment of Traditional Chinese Medicine, Kunming Second People’s Hospital, No. 672 Longquan Road, Panlong District, Kunming, Yunnan 650000, People’s Republic of ChinaEmail tanglu11610@163.comBackground: Paeoniflorin (Pae) possesses anti-tumor activity in various malignancies. However, it is unclear whether Pae plays a sensitizer role in breast cancer (BC) and the molecular mechanisms involved in this process. Our oligonucleotide microarray revealed that microRNA (miR)-15b is the most significantly downregulated miRNA in MCF-7/4-hydroxytamoxifen (4-OHT) cells treated with Pae. This paper summarized the relevance of Pae in BC cell endocrine resistance to tamoxifen (Tam) and the molecular mechanisms involved miR-15b expression.Materials and Methods: 4-OHT-resistant BC cell lines were developed and treated with different concentrations of Pae. Flow cytometry, lactose dehydrogenase activity, caspase-3 activity, colony formation, and EdU assays were carried out to assess the impact of Pae on BC cells. Differentially expressed miRNAs in BC cells treated with Pae were analyzed by microarray. Targeting mRNAs of screened miR-15b as well as the binding of forkhead box O1 (FOXO1) to the cyclin D1 (CCND1) promoter sequence were predicted through bioinformatics analysis. Finally, the expression of β-catenin signaling-related genes in cells was detected by Western blotting.Results: Pae (100 μg/mL) inhibited the clonality and viability of BC cells, while enhancing apoptosis in vitro. Pae also repressed miR-15b expression. Overexpression of miR-15b restored the growth and resistance of BC cells to 4-OHT. Moreover, Pae promoted FOXO1 expression by downregulating miR-15b, thereby transcriptionally inhibiting CCND1 and subsequently blocking β-catenin signaling.Conclusion: Pae inhibits 4-OHT resistance in BC cells by regulating the miR-15b/FOXO1/CCND1/β-catenin pathway.Keywords: paeoniflorin, breast cancer, tamoxifen, microRNA-15b, FOXO1

Hong Liu,1,2 Yan-li Zhan,2,3 Guo-jing Luo,2,4 Ling-ling Zou,2,5 Yun Li,2 Hong-yun Lu2,4 1Department of Nutrition, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Endocrinology & Metabolism, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 3Department of Rheumatology, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 4Department of Endocrinology & Metabolism, Zhuhai Hospital Affiliated with Jinan University, Zhuhai People’s Hospital, Zhuhai, Guangdong, People’s Republic of China; 5Department of Endocrinology, The Second People’s Hospital of Hefei, Anhui, People’s Republic of ChinaCorrespondence: Hong-yun LuDepartment of Endocrinology & Metabolism, The Fifth Affiliated Hospital of Sun Yat-Sen University, No. 52 Meihua East Road, Zhuhai, Guangdong 519000, People’s Republic of ChinaTel +86 756-252 8741Fax +86 75 6252 8300Email luhongy@mail.sysu.edu.cnBackground: Glucagon-like peptide-1 (GLP-1) has been reported to have beneficial impacts on improving human’s metabolism and ameliorating insulin resistance. While insulin is another important and conventional drug in diabetes treatment, but it has an adverse effect on weight gain.Purpose: To make sure whether GLP-1 and insulin play different roles in human adipose-derived stem cells (hADSCs).Methods: We examined the in vitro roles and molecular mechanisms of liraglutide, a GLP-1 analogue, and human insulin on hADSCs isolated from subcutaneous adipose tissue. Different concentrations (0, 0.1, 1, 10, 100nM) of liraglutide and insulin were added to proliferation and differentiation medium of hADSCs, respectively.Results: Liraglutide inhibits while insulin promotes the proliferation and differentiation at the concentration of 100nM. Moreover, the levels of GSK-3 increase during differentiation and liraglutide could down-regulate it when compared with insulin. We also find that the activation of phosphorylated GSK-3α and GSK-3β is involved in the differentiation roles. And classical and non-classical Wnt pathways all play roles in the differentiation, which are characterized with the up/down-regulation of the expression of adipogenesis genes such as PPAR-γ and CEBP-α.Conclusion: Liraglutide and insulin have contrary effects on the proliferation and adipogenesis via Wnt pathway in primary cultured ADSCs. Those effects could partly explain the different roles of GLP-1 and insulin on weight gain and insulin resistance.Keywords: liraglutide, insulin, human adipose-derived stem cells, obesity, Wnt signaling pathway

Yitao Gong,1– 4,* Zhiyao Fan,1– 4,* Guopei Luo,1– 4,* Qiuyi Huang,1– 4 Yunzhen Qian,1– 4 He Cheng,1– 4 Kaizhou Jin,1– 4 Quanxing Ni,1– 4 Xianjun Yu,1– 4 Chen Liu1– 4 1Department of Pancreatic Surgery, 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; 3Shanghai Pancreatic Cancer Institute, Shanghai 200032, People’s Republic of China; 4Pancreatic Cancer Institute, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xianjun Yu; Chen LiuDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai 200032, People’s Republic of ChinaTel + 86 21-64175590 ext 1307Fax + 86 21-64031446Email yuxianjun@fudanpci.org; liuchen@fudanpci.orgPurpose: Pancreatic neuroendocrine tumours (panNETs) are rare tumours of pancreas. Lymphocyte subsets in the peripheral blood are reported to reflect tumour prognosis and progression. The objective of the study is to investigate the hypotheses that the levels of peripheral lymphocytes may reflect tumour progression and may predict the prognosis of pancreatic neuroendocrine tumours (panNETs).Patients and Methods: A retrospective cohort study consisting of 73 patients diagnosed with panNETs was conducted. Kaplan–Meier methods and Log rank tests were used to compare the survival rates, and a Cox regression model was used to perform multivariate analyses.Results: panNET patients with distant metastasis were associated with lower peripheral total T cell (p = 0.039) and CD4+ T cell (p = 0.006) counts. Lower peripheral B cells (p = 0.007) and higher peripheral NK cell (p = 0.001) counts indicated worse progression-free survival (PFS) in Log rank tests. In multivariate analyses, low B cell count (hazard ratio (HR): 6.769, 95% confidence interval (CI): 2.158 to 21.228, p = 0.001) and high NK cell count (HR: 3.715, 95% CI: 1.164 to 11.855, p = 0.027) were independent risk factors for progression. NK cells and B cells were also significantly associated with PFS following radical surgical resection.Conclusion: Peripheral total T cell and CD4+ T cell counts may reflect the distant metastasis status in panNET patients. The absolute count of peripheral B cells and NK cells may independently predict the progression of panNET patients, making them promising prognostic indicators and potential targets for treatment of panNETs.Keywords: pancreatic neuroendocrine tumours, panNETs, lymphocyte subsets, progression-free survival, B cells

Qingjuan Chen,1,* Chenjing Zhu,2,* Yingying Jin,3 Xiaomin Si,4 Wan Jiao,4 Wenjing He,4 Wei Mao,4 Ming Li,1 Guomin Luo1 1Department of Oncology, Yongchuan Hospital of Chongqing Medical University, Chongqing 40016, People’s Republic of China; 2Department of Radiation Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, People’s Republic of China; 3Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province 710004, People’s Republic of China; 4Department of Oncology, Xianyang Center Hospital, Xi’an, Shaanxi Province 712000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingjuan ChenDepartment of Oncology, Yongchuan Hospital of Chongqing Medical University, Chongqing 40016, People’s Republic of ChinaEmail dr.qingjuan.chen@outlook.comBackground: Lung cancer is one of the most common malignancies around the world. The lack of early diagnosis and effective treatment strategies contributes to the poor prognosis of patients with lung cancer. Recent studies have implied the role of long non-coding RNAs (lncRNAs) in oncogenesis. The purpose of our study was to identify specific lncRNAs which were correlated with non-small cell lung cancer (NSCLC) and their potential functions.Materials and Methods: The global plasma lncRNA profiling was performed using LncPathTM Human Cancer Array, and 11 lncRNAs were then selected for quantitative reverse transcription PCR (qRT-PCR) validation in 138 plasma samples from 69 NSCLC patients and 69 healthy controls (HCs). A noteworthy lncRNA, RP11-438N5.3, the function of which was previously unknown, was further explored on the aspect of the correlation of its expression level with clinicopathological factors.Results: The results revealed that plasma level of RP11-438N5.3 was significantly lower in NSCLCs than that in HCs (p < 0.01). Receiver operating characteristic (ROC) analyses showed that the area under the ROC curve (AUC) for plasma RP11-438N5.3 was 0.814 (95% CI, 0.743– 0.885; p< 0.01). High expression of RP11-438N5.3 in plasma correlated with favorable prognosis for NSCLC patients (Hazard ratio = 2.827; 95% CI: 1.036 to 7.718; p = 0.024; Cox regression analysis). Moreover, we found that the plasma level of stromal interaction molecule 1 (STIM1) mRNA was remarkably higher in NSCLC compared with HC (p< 0.01), and the AUC for STIM1 was 0.753 (95% CI, 0.673– 0.833; p< 0.01), RP11-438N5.3 and STIM1 were inversely correlated with each other.Conclusion: Our results indicated that RP11-438N5.3 and STIM1 might provide a new strategy for NSCLC diagnosis. Furthermore, increased circulating RP11-438N5.3 level holds great potential in indicating a beneficial prognosis in NSCLC patients.Keywords: long non-coding RNA, biomarker, non-small cell lung cancer, RP11-438N5.3, stromal interaction molecule 1

Iron acquisition is a virulence factor for Staphylococcus aureus. We assessed the efficacy of the iron chelator, deferasirox (Def), alone or in combination with vancomycin (Van) against two methicillin-resistant S. aureus (MRSA) strains in vitro and in a murine bacteremia model. In vitro time-kill assays were carried out against MRSA or vancomycin-intermediate S. aureus (VISA) strains. The impact of Def on Van binding to the surface of S. aureus was measured by flow cytometry. Furthermore, we compared the efficacy of Def, Van, or both drugs in treating S. aureus bacteremia in a murine model. Combination therapy reduced MRSA and VISA viability in vitro versus either drug alone or untreated controls (p < 0.005); this outcome was correlated with enhanced Van surface binding to S. aureus cells. In vivo, Def + Van combination therapy significantly reduced the bacterial burden in mice kidneys (p = 0.005) and spleen (p < 0.001), and reduced the severity of infection with MRSA or VISA strains compared to placebo-treated mice. Our results show that Def enhances the in vitro and in vivo capacity of Van-mediated MRSA killing via a mechanism that appears to involve increased binding of Van to the staphylococcal surface. Iron chelation is a promising, novel adjunctive therapeutic strategy for MRSA and VISA infections.

This paper evaluates the current status of global modeling of the organic aerosol (OA) in the troposphere and analyzes the differences between models as well as between models and observations. Thirty-one global chemistry transport models (CTMs) and general circulation models (GCMs) have participated in this intercomparison, in the framework of AeroCom phase II. The simulation of OA varies greatly between models in terms of the magnitude of primary emissions, secondary OA (SOA) formation, the number of OA species used (2 to 62), the complexity of OA parameterizations (gas-particle partitioning, chemical aging, multiphase chemistry, aerosol microphysics), and the OA physical, chemical and optical properties. The diversity of the global OA simulation results has increased since earlier AeroCom experiments, mainly due to the increasing complexity of the SOA parameterization in models, and the implementation of new, highly uncertain, OA sources. Diversity of over one order of magnitude exists in the modeled vertical distribution of OA concentrations that deserves a dedicated future study. Furthermore, although the OA / OC ratio depends on OA sources and atmospheric processing, and is important for model evaluation against OA and OC observations, it is resolved only by a few global models. The median global primary OA (POA) source strength is 56 Tg a-1 (range 34-144 Tg a-1) and the median SOA source strength (natural and anthropogenic) is 19 Tg a-1 (range 13-121 Tg a-1). Among the models that take into account the semi-volatile SOA nature, the median source is calculated to be 51 Tg a-1 (range 16-121 Tg a-1), much larger than the median value of the models that calculate SOA in a more simplistic way (19 Tg a-1; range 13-20 Tg a-1, with one model at 37 Tg a-1). The median atmospheric burden of OA is 1.4 Tg (24 models in the range of 0.6-2.0 Tg and 4 between 2.0 and 3.8 Tg), with a median OA lifetime of 5.4 days (range 3.8-9.6 days). In models that reported both OA and sulfate burdens, the median value of the OA/sulfate burden ratio is calculated to be 0.77; 13 models calculate a ratio lower than 1, and 9 models higher than 1. For 26 models that reported OA deposition fluxes, the median wet removal is 70 Tg a-1 (range 28-209 Tg a-1), which is on average 85% of the total OA deposition. Fine aerosol organic carbon (OC) and OA observations from continuous monitoring networks and individual field campaigns have been used for model evaluation. At urban locations, the model-observation comparison indicates missing knowledge on anthropogenic OA sources, both strength and seasonality. The combined model-measurements analysis suggests the existence of increased OA levels during summer due to biogenic SOA formation over large areas of the USA that can be of the same order of magnitude as the POA, even at urban locations, and contribute to the measured urban seasonal pattern. Global models are able to simulate the high secondary character of OA observed in the atmosphere as a result of SOA formation and POA aging, although the amount of OA present in the atmosphere remains largely underestimated, with a mean normalized bias (MNB) equal to -0.62 (-0.51) based on the comparison against OC (OA) urban data of all models at the surface, -0.15 (+0.51) when compared with remote measurements, and -0.30 for marine locations with OC data. The mean temporal correlations across all stations are low when compared with OC (OA) measurements: 0.47 (0.52) for urban stations, 0.39 (0.37) for remote stations, and 0.25 for marine stations with OC data. The combination of high (negative) MNB and higher correlation at urban stations when compared with the low MNB and lower correlation at remote sites suggests that knowledge about the processes that govern aerosol processing, transport and removal, on top of their sources, is important at the remote stations. There is no clear change in model skill with increasing model complexity with regard to OC or OA mass concentration. However, the complexity is needed in models in order to distinguish between anthropogenic and natural OA as needed for climate mitigation, and to calculate the impact of OA on climate accurately.

Zhiyao Fan,1–4,* Kun Fan,1–4,* Yitao Gong,1–4,* Qiuyi Huang,1–4 Chao Yang,1–4 He Cheng,1–4 Kaizhou Jin,1–4 Quanxing Ni,1–4 Xianjun Yu,1–4 Guopei Luo,1–4 Chen Liu1–4 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Pancreatic Cancer Institute, Shanghai, People’s Republic of China; 4Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guopei Luo; Chen LiuDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, People’s Republic of ChinaTel +86-21-6403-1446Fax +86-21-6403-1446Email luoguopei@fudanpci.org; liuchen@fudanpci.orgPurpose: The CRP/albumin (Alb) ratio, a recently reported predictor, has shown value for prognosis in various human cancers. This study aimed to determine the prognostic value of baseline CRP/Alb and to explore the relevance between postchemotherapy CRP/Alb and the efficacy of chemotherapy in advanced pancreatic cancer patients.Patients and methods: Five hundred and ninety-five patients diagnosed with locally advanced or metastatic adenocarcinoma of the pancreas were enrolled. Cut-off Finder was used to calculate the best cut‑off value for baseline CRP/Alb. The primary endpoint was overall survival, which was analyzed by Kaplan-Meier survival curves with 95% confidence intervals. The log rank test and Cox proportional hazard model were used to evaluate the univariate and multivariate analyses.Results: The optimal cut-off value for baseline CRP/Alb was determined to be 0.18. Both the baseline CRP/Alb (CRP/Alb≥0.18 vs. CRP/Alb

Hanyu Cao,1,* Lin Li,1,* Bowen Yang,2 Gupo Luo,2 Jiangyan Lou,1 Mingrong Xi1,*1Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu City, Sichuan Province, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second Hospital, Sichuan University, Chengdu City, Sichuan Province, People’s Republic of China*These authors contributed equally to this workObjectives: We conducted this study to explore the clinical characteristics, prognosis, and prevalence of unexpected uterine sarcoma (UUS) after hysterectomy and myomectomy for presumed leiomyoma.Study design: The records of women who underwent hysterectomy or myomectomy through laparoscopy or laparotomy for preoperatively presumed uterine leiomyomas from January 2009 to December 2016 were reviewed and data were retrospectively analyzed.Results: Eleven patients had morcellation of uterine sarcoma. Eighty-eight patients were diagnosed with uterine sarcomas (total prevalence: 0.33%) including 29 leiomyosarcomas (LMS), 48 endometrial stromal sarcomas (ESS), and 11 adenosarcomas. ESS patients with advanced stage were significantly associated with worse overall survival (p

Menglong Liu,1 Tengfei Liu,1 Xiaorong Zhang,1 Zhiwen Jian,2 Hesheng Xia,2 Jiacai Yang,1 Xiaohong Hu,1 Malcolm Xing,1,3 Gaoxing Luo,1 Jun Wu1,41Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, People’s Republic of China; 2State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Chengdu, 610065, People’s Republic of China; 3Department of Mechanical Engineering, University of Manitoba, Winnipeg, MB R3T 2N2, Canada; 4Department of Burns, the First Affiliated Hospital, SunYat-Sen University, Guangzhou 510080, People’s Republic of ChinaBackground: Designing a wound dressing that effectively prevents multi-drug-resistant bacterial infection and promotes angiogenesis and re-epithelialization is of great significance for wound management.Methods and results: In this study, a biocompatible composite membrane comprising biomimetic polydopamine-modified eggshell membrane nano/microfibres coated with KR-12 antimicrobial peptide and hyaluronic acid (HA) was developed in an eco-friendly manner. The physicochemical properties of the composite membrane were thoroughly characterized, and the results showed that the surface hydrophilicity and water absorption ability of the composite membrane were improved after the successive conjugation of the HA and the KR-12 peptide. Furthermore, the in vitrobiological results revealed that the composite membrane had excellent antibacterial activity against Gram-positive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli, and it could prevent MRSA biofilm formation on its surface. Additionally, it promoted the proliferation of keratinocytes and human umbilical vein endothelial cells and increased the secretion of VEGF. Finally, an in vivo animal study indicated that the composite membrane could promote wound healing via accelerating angiogenesis and re-epithelialization, which were demonstrated by the enhanced expression of angiogenetic markers (CD31 and VEGF) and keratinocyte proliferation marker (PCNA), respectively.Conclusion: These results indicated that the composite membrane is a potential candidate of wound dressingsKeywords: antimicrobial peptides, hyaluronic acid, fibrous eggshell membrane, antibacterial activity, angiogenesis, re-epithelialization