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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]