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Hanrui Fan,1 Ping Xu,1 Enming Zhang,1 Xi Meng,2 Jianmei Xia,3 Yong Fei,3 Ming Yao3 1Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Sci-Tech University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Anesthesiology and Pain, The First Hospital of Jiaxing, Jiaxing, Zhejiang, People’s Republic of ChinaCorrespondence: Yong Fei, Department of Anesthesiology and Pain, The First Hospital of Jiaxing, 1882 Zhong-Huan-South Road, Jiaxing, 314000, People’s Republic of China, Email jxfy6666662022@163.comBackground: Current studies mostly suggest that hyperhidrosis is caused by relative sympathetic hyperactivity. Sympathetic radiofrequency thermocoagulation is widely used in clinics. Previous studies have demonstrated that surgery at T3 is effective and safe compared with higher levels, so craniofacial hyperhidrosis in our hospital is selected to be treated at T3. However, some patients pursue repeat medical treatment due to an increase in hyperhidrosis at the original site after surgery. Previous studies have demonstrated the significance of Perfusion index (PI) value in the recurrence of palmar hyperhidrosis, but there is no relevant study on craniofacial hyperhidrosis.Methods: Clinical data from patients with craniofacial hyperhidrosis, who underwent T3 sympathetic radiofrequency thermocoagulation at Jiaxing First Hospital (Jiaxing, China) between January 1, 2018 and December 31, 2021, were analyzed. Recurrence in patients 1 year after surgery was recorded through a case search and telephone follow-up system that registered patient information. Clinical data were analyzed using binary logistic regression analysis to investigate risk factors associated with recurrence in patients with craniofacial hyperhidrosis 1 year after surgery.Results: Of 83 patients included in the present study, 34 (40%) experienced increased craniofacial sweating 1 year after surgery. Results of univariate logistic regression analysis revealed that computed tomography (CT) scan count, increase in pulse index (PI) at the fingertips, and differences in forehead temperature were potential risk factors for postoperative recurrence in patients with craniofacial hyperhidrosis (p< 0.2), and the results were consistent on both sides. Three potential risk factors were included in the multivariate logistic regression analysis and results revealed that the risk for recurrence was reduced by 48% (left side) and 67% (right side) for every 1 unit increase in PI value.Conclusion: A small increase in PI was an independent risk factor for recurrence of hyperhidrosis in patients with craniofacial hyperhidrosis after undergoing T3 sympathetic radiofrequency thermocoagulation.Keywords: ephidrosis, craniofacial hyperhidrosis, sympathetic radiofrequency thermocoagulation

Luxia Xiao, Meilin Yao, Hongrui Liu Faculty of Psychology, Beijing Normal University, Beijing, People’s Republic of ChinaCorrespondence: Hongrui Liu, Faculty of Psychology, Beijing Normal University, Beijing, 100875, People’s Republic of China, Email hrliu@bnu.edu.cnPurpose: Drawing upon the cognitive-behavioral model of pathological Internet use (PIU) and tunnel effect, this study aimed to construct a moderated mediation model from the perspective of social ecology. Specifically, the model investigated the relationship between perceived social mobility and smartphone dependence, with a focus on the mediating role of hope and the moderating effect of family socioeconomic status (SES) underlying this relationship.Methods: A cross-sectional study was conducted with 718 Chinese university students (Mage = 19.19, 70.2% female) from Beijing, Henan, and Tianjin, who anonymously filled out the Perceptions of Socioeconomic Mobility Scale, Mobile Phone Addiction Index Scale, Openness to the Future Scale, and family socioeconomic status questionnaire. Preliminary data analysis was executed using SPSS 22.0, and the moderated mediation effect was tested using the latent moderated structural equations approach in Mplus 8.3.Results: The results showed that (a) less perceived social mobility was linked with greater smartphone dependence; (b) hope mediated the aforementioned relationship; and (c) family SES moderated the first-stage path of the indirect effect through hope. For university students with low (rather than high) family SES, their level of hope increased with the improvement of perceived social mobility, and in turn, that of smartphone dependence decreased.Conclusion: These findings suggest that positive perceptions of upward social class mobility and hopeful attitudes toward future opportunities and personal development among disadvantaged university students may alleviate their reliance on smartphones. Researchers and policymakers should pay attention to the role of individuals’ perceptions of the macro environment in motivating specific risky behaviors among university students. Future interventions are essential to mitigate pessimistic environmental perceptions and foster a sense of hope among university students.Keywords: family socioeconomic status, hope, moderated mediation, perceived social mobility, smartphone dependence

Jiayu Yue,1,2 Ming Yao2 1The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University/The Second School of Medicine, Wenzhou Medical University, Wenzhou City, Zhejiang, People’s Republic of China; 2Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or the Affiliated Hospital of Jiaxing University, Jiaxing City, Zhejiang, People’s Republic of ChinaCorrespondence: Ming Yao, Email jxyaoming@zjxu.edu.cnBackground: The neurocutaneous disease caused by the reactivation of varicella-zoster virus (VZV) is called herpes zoster (HZ). The virus remains in the spinal cord back root after the chickenpox disappears. Diminished immune function can reactivate VZV, causing severe neuropathic pain that can last for months or even years, leading to postherpetic neuralgia (PHN), which severely affects the patient’s quality of life. Much literature compares various cytokine levels in the body fluids HZ and PHN patients; however, no studies comprehensively evaluate them.Methods: The Cochrane Library, PubMed, Web of Science, and Medline were screened for studies on cytokine levels in body fluids of HZ and PHN patients in the English language. Healthy individuals were selected as the control group, and the standardized mean difference (SMD) between the case and control groups was imputed using a fixed-effects or random-effects model and expressed as a 95% confidence interval (CI). The Newcastle-Ottawa Scale (NOS) was used to assess article quality.Results: This meta-analysis included 13 articles with 1373 participants. Compared with the control group, the HZ group had significantly higher levels of interleukin (IL)-4, IL-6, IL-10, Hcy, and C-reactive protein (CRP), whereas the levels of CD3+ T and CD4+ T lymphocytes were reduced. Additionally, PHN patients had significantly higher levels of IL-6 and IL-1β compared with the control group.Conclusion: This meta-analysis provides compelling evidence that CRP, Hcy, IL-1β, IL-4, IL-6, IL-8, and IL-10 are associated with the genesis and development of HZ and PHN. These markers can be used to improve the diagnosis and treatment of these diseases.Furthermore, for making the results more convincing, it is necessary to harmonize sample acquisition techniques and analytical methods and also require larger, more rigorously designed studies with broader subgroups and sex/age-matched controls.Keywords: herpes zoster, varicella-zoster virus, neurocutaneous disease, postherpetic neuralgia, biomarker

Mingzheng Yao,1 Dan Liang,2 Xiuli Zeng,1 Xiaomei Xie,1 Jiali Gao,1 Li’an Huang1 1Department of Neurology, The First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of China; 2Department of Neurology, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, People’s Republic of ChinaCorrespondence: Li’an Huang, Department of Neurology, The First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of China, Email huanglian1306@126.comPurpose: Galectin-3 is a key regulator of microglial proliferation and activation and may have dual and time-dependent effects on ischemic stroke. This study aimed to prospectively investigate the dynamic changes in Galectin-3 levels in patients with acute ischemic stroke receiving endovascular therapy and its clinical significance.Patients and Methods: A total of 105 patients with acute ischemic stroke who underwent endovascular therapy were prospectively enrolled. Plasma Galectin-3 was quantitatively detected by an enzyme-linked immunosorbent assay before the operation and at 1 day, 3 days and 7 days after the operation. A linear mixed-effect model, Pearson correlation analysis and receiver operating characteristic (ROC) curve analysis were used to evaluate the dynamic changes in the plasma Galectin-3 concentration and its relationship with clinical outcomes.Results: Increases in plasma Galectin-3 levels at 1 day and 3 days after surgery were associated with early neurological deterioration and death (both P < 0.05). Increased Galectin-3 levels before surgery and at 1 day and 3 days after surgery were associated with poor prognosis (P < 0.05). Pearson correlation analysis revealed that Galectin-3 levels before surgery (r =0.318, P =0.002), at 1 day (r =0.318, P =0.001), 3 days (r =0.429, P < 0.001) and 7 days after surgery (r =0.340, P =0.001) were positively correlated with NIHSS scores. The ROC curve results showed that Galectin-3 concentration had a certain predictive value for death at 1 day (AUC=0.707, P=0.013), 3 days (AUC=0.708, P=0.016) and 7 days after the operation (AUC=0.708, P=0.016), but this predictive value was lower than that of the NIHSS score.Conclusion: In acute ischemic stroke patients receiving endovascular therapy, an increase in the plasma Galectin-3 levels were associated with death, poor prognosis, and early neurological deterioration. Galectin-3 levels were significantly correlated with the NIHSS score and had a certain predictive value for death.Plain Language Summary: Galectin-3 is a key regulator of microglial proliferation and activation and may have dual and time-dependent effects on ischemic stroke. However, relevant clinical studies are less at present. In this study, we found that an increase in the plasma Galectin-3 levels had significant values in death, poor prognosis, and early neurological deterioration in acute ischemic stroke patients receiving endovascular therapy at various times.Keywords: ischemic stroke, Galectin-3, endovascular therapy, inflammation, dynamic change, outcome

Yahui Wang,1,2,&ast; Chengfei Xu,3,&ast; Peng Liu,2 Qiuli He,1 Shihua Zhang,1 Zhihao Liu,1 Chaobo Ni,1 Liping Chen,1 Tong Zhi,1 Longsheng Xu,1 Liang Cheng,3 Xuewu Lin,2 Ming Yao,1 Huadong Ni1,4 1Department of Anesthesiology and Pain Research Center, the Affiliated Hospital of Jiaxing University, Jiaxing, 314001, People’s Republic of China; 2Department of Pain Management, the First Affiliated Hospital of Bengbu Medical College, Bengbu City, 233000, People’s Republic of China; 3Department of Anesthesiology, Bengbu Third People’s Hospital, Bengbu City, 233000, People’s Republic of China; 4Institute of Neuroscience, Soochow University, Suzhou, 215123, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huadong Ni; Ming Yao, Department of Anesthesiology and Pain Research center, the Affiliated Hospital of Jiaxing University, 1882 Zhonghuan South Road, Jiaxing, 314001, People’s Republic of China, Email huadongni@zjxu.edu.cn; jxyaoming@zjxu.edu.cnBackground: Bone cancer pain (BCP) represents one of the most challenging comorbidities associated with cancer metastasis. Long non-coding RNAs (lncRNAs) have garnered attention as potential therapeutic agents in managing neuropathic pain. However, their role in the regulation of nociceptive information processing remains poorly understood. In this study, we observed a significant down-regulation of the spinal lncRNA ENSRNOG00000051325 (lncRNA51325) in a rat model of bone cancer pain. Our study sought to elucidate the potential involvement of lncRNA51325 in the development of BCP by modulating the expression of molecules associated with pain modulation.Methods: We established the BCP model by injecting Walker 256 cells into the tibial plateau of rats. We conducted tests on the pain behaviors and anxiety-like responses of rats through von-Frey test, Gait analysis, and Open Field Test. Spinal lumbar expansion was harvested for molecular biology experiments to explore the relationship between lncRNA51325 and Pumilio RNA binding family member 2 (Pum2).Results: Notably, the overexpression of lncRNA51325 effectively attenuated mechanical allodynia in rats afflicted with BCP, whereas the knockdown of lncRNA51325 induced pain behaviors and anxiety-like responses in naïve rats. Additionally, we observed a time-dependent increase in the expression of Pum2 in BCP-afflicted rats, and intrathecal injection of Pum2-siRNA alleviated hyperalgesia. Furthermore, our investigations revealed that lncRNA51325 exerts a negative modulatory effect on Pum2 expression. The overexpression of lncRNA51325 significantly suppressed Pum2 expression in BCP rats, while the knockdown of lncRNA51325 led to elevated Pum2 protein levels in the spinal cord of naïve rats. Subsequent treatment with Pum2-siRNA mitigated the downregulation of lncRNA51325-induced mechanical allodynia in naïve rats.Conclusion: Our findings indicate that lncRNA51325 plays a role in regulating bone cancer pain by inhibiting Pum2 expression, offering a promising avenue for novel treatments targeting nociceptive hypersensitivity induced by bone metastatic cancer.Keywords: long non-coding RNA, bone cancer pain, Pum2, spinal cord

Yuhan Wang,1,&ast; Ping Zhang,1,&ast; Yu Lv,1 Yu Deng,2 Ming Yao,3 Lin Wang,1 Guangtao Pan3 1College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei Province, People’s Republic of China; 2Department of Encephalopathy, Guangzhou Hospital of Integrated Traditional and West Medicine Affiliated to Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Department of Dermatology, Yancheng Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangtao Pan, Department of Dermatology, Yancheng Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, No. 53, Renmin North Road, Tinghu District, Yancheng, Jiangsu Province, People’s Republic of China, Tel +86-17612738767, Email panguangtaowuhan@foxmail.comAbstract: This literature review systematically searched relevant literature from the past 10 years using various medical databases, including PubMed, Medline, Cochrane, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu. As a chronic inflammatory disease, psoriasis is associated with various cells and cytokines of the body’s immune system, making them more susceptible to various systemic comorbidities than the general population. At a time when conventional regimens are ineffective and there is a lack of personalized treatment options for such comorbidities, the development of biologics has revolutionized the treatment of psoriasis comorbidities, and a number of biologic combination therapies have been incorporated into first-line treatments in many countries. The focus of this review was to investigate the relationship between psoriasis and comorbidities, such as metabolic syndrome, psoriatic arthritis, cardiovascular diseases, mental disorders, infectious diseases, digestive system diseases, and renal diseases. Furthermore, the study explored the significance of biologic therapies in the management of these comorbidities. Also this paper suggests current conditions and precautions for the use of biologic therapies to minimize the occurrence of adverse effects. This review was performed to provide guidance for clinical drug selection in patients with psoriasis and comorbidities, as well as serve as a reference for the development and application of biologic therapies.Keywords: psoriasis, biologics, comorbidity, research advancements

Mengying Yao,1– 3,&ast; Dawei Lian,1– 3,&ast; Meizhu Wu,1– 3 Yuting Zhou,1– 3 Yi Fang,1– 4 Siyu Zhang,1– 3 Wenqiang Zhang,1– 3 Yanyan Yang,1– 4 Renfeng Li,1– 3 Hong Chen,1– 3 Youqin Chen,5 Aling Shen,1– 4 Jun Peng1– 3 1Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 2Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 3Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, Fujian, People’s Republic of China; 4Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 5Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children’s Hospital, Cleveland, OH, USA&ast;These authors contributed equally to this workCorrespondence: Aling Shen; Jun Peng, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China, Tel +86 18050286255 ; +86 15806070011, Email saling86@hotmail.com; pjunlab@hotmail.comPurpose: This study aimed to investigate the molecular mechanisms of isoliensinine, a kind of bibenzyl isoquinoline alkaloid which isolated from a TCM named Lotus Plumule (Nelumbo nucifera Gaertn), in treating renal interstitial fibrosis (RIF) by using RNA sequencing, KEGG analysis and in vivo experimental approaches.Methods: Spontaneous hypertension rats (SHRs) were randomly assigned into five groups, consisting of SHR, SHR+Isoliensinine-L (2.5 mg/kg/day), SHR+Isoliensinine-M (5 mg/kg/day), SHR+Isoliensinine-H (10 mg/kg/day), and SHR+Valsartan (10 mg/kg/day) groups (n = 6 for each group). A control group of Wistar Kyoto rats (n = 6) was also included. Rats were treated intragastrically with isoliensinine, valsartan, or double-distilled water of equal volume for 10 weeks. To examine the therapeutic impact on hypertensive renal injury, fibrosis, and its underlying mechanisms, multiple techniques were employed, including hematoxylin and eosin staining, Masson trichrome staining, RNA sequencing, gene ontology (GO) function and pathway enrichment analysis and immunohistochemistry.Results: Resultantly, the use of isoliensinine at different concentrations or valsartan showed significant improvement in renal pathological injury in SHRs. RNA sequencing and KEGG analysis uncovered 583 differentially expressed transcripts and pathways enriched in collagen formation and ECM–receptor interaction after treatment with isoliensinine. There was also a reduction in the increase of collagen and upregulation of collagen I & III, TGF-β 1, p-Smad2, and p-Smad3 in the renal tissue of SHRs. Thus, isoliensinine ameliorated renal injury and collagen deposition in hypertensive rats, and inhibiting the activation of the TGF-β 1/Smad2/3 pathway might be one of the underlying mechanisms.Conclusion: This study showed that treatment with isoliensinine effectively reduced the renal injury and fibrosis in SHRs. In addition, isoliensinine inhibited the TGF-β 1/Smad2/3 signaling in-vivo. These findings provided strong evidence for the therapeutic benefits of isoliensinine in combating renal injury and fibrosis.Graphical Abstract: Keywords: isoliensinine, RNA sequencing, hypertension, renal injury, TGF-β 1/Smad2/3 pathway, collagen deposition

Xu Yang,1 Mi Yao,2 Delu Yin,3 Na Zhang,1 Jing Li,1 Yan Jiang,1 Rundong Fu,1 Yi Qian1 1Department of General Practice, Donghuashi Community Health Service Center, Beijing, People’s Republic of China; 2Department of General Practice, Peking University Health Science Center, Beijing, People’s Republic of China; 3Department of Health Development, Capital Institute of Pediatrics, Beijing, People’s Republic of ChinaCorrespondence: Xu Yang, Department of General Practice, Donghuashi Community Health Service Center, 33 Donghuashi Street, Dongcheng District, Beijing, 100062, People’s Republic of China, Tel +86 13693088802, Fax +86 1067120077, Email xuyang8799@163.comBackground: Chronic obstructive pulmonary disease (COPD) has a high incidence rate in China, but the diagnosis rate remains insufficient. This study aimed to explore and compare COPD screening tools for primary healthcare institutions in China.Purpose: Exploring COPD Screening Tools and Their Combined Use for Primary Healthcare Institutions in China.Patients and Methods: From September 2022 to March 2023, a screening for COPD was conducted among residents aged 35 years and above in primary healthcare institutions in Beijing, China. The screening involved the use of the CAPTURE scale, COPD-SQ scale, and peak expiratory flow rate test. Any positive results from these screening tests were followed by further pulmonary function testing to confirm the diagnosis. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic (ROC) curves were calculated for each screening tool alone and in combination.Results: A total of 986 individuals completed the screening tests. The positive rates for the CAPTURE scale, COPD-SQ scale, and peak flow meter screening were 41.78%, 29.11%, and 52.03%, respectively. Of the participants, 166 (24.09%) underwent pulmonary function tests, with an average age of 61.69± 13.68 years. The peak flow meter screening showed the highest sensitivity (83.78%) when used alone, while the COPD-SQ scale exhibited the best specificity (59.69%), positive predictive value (31.58%), and negative predictive value (58.56%). Significant differences (P< 0.05) were observed between any two of the three screening tools. Among the combinations, the peak flow meter screening + COPD-SQ scale showed the highest accuracy, with a Youden index of 0.277 and an AUC of 0.638.Conclusion: There is variation in the accuracy of existing screening tools for COPD when used alone. For primary healthcare institutions, the optimal COPD screening tool is the combination of peak flow meter screening and the COPD-SQ questionnaire. If limited by screening equipment conditions, the COPD-SQ questionnaire can be used alone for screening.Keywords: primary health care institutions, chronic obstructive pulmonary disease, COPD, screening questionnaire, peak flow rate test, pulmonary function tests

Jiaji An,1 He Di,2 Zixuan Yang,3 Meifang Yao2 1School of Finance, Jilin University of Finance and Economics, Changchun, People’s Republic of China; 2School of Business and Management, Jilin University, Changchun, People’s Republic of China; 3Shenzhen Finance Institute, School of Management and Economics, Chinese University of Hong Kong, Shenzhen, People’s Republic of ChinaCorrespondence: He Di, School of Business and Management, Jilin University, 2699 Qianjin Ave, Changchun, 130012, People’s Republic of China, Email dihe@jlu.edu.cnPurpose: Silence is a typical negative behaviour exhibited by employees when they are faced with tension and stress and is influenced by a number of factors. Leaders have an important influence on employees’ emotions and behaviour, but the research is not yet clear enough. In this paper, we focus on the research frontier of self-deprecating humour of leaders, aiming to analyse its effect on employee silence and discuss the mechanism of the role of leader-member exchange (LMX) in it, based on social exchange theory.Methods: We conducted a regression analysis and bootstrap test for mediating effects based on 2531 data from 151 financial institutions in mainland China. A simple random sampling was taken of the target population to ensure an unbiased sample. Using Harman’s single-factor test to check the data for common method bias. Regression analysis and Bootstrap test were used to analyze the correlation between variables and mediating effect models.Findings: (a) Leader self-deprecating humour significantly reduces employee silence and effectively improves the quality of LMX; (b) There is a significant negative relationship between LMX and employee silence; (c) LMX plays a mediating role in the process of self-deprecating humour influencing employee silence and this mediating effect is complete; (d) Affective exchange between leaders and employees appears to be an essential factor in reducing stress from leaders and reducing employee silence.Originality/Value: We attempt to open the black box of the mechanism of action between leader self-deprecating humour and employee silence, enrich and expand the application of social exchange theory to negative employee behavior, and provide new theoretical knowledge and empirical evidence from developing countries.Practical Implications: The results of the study indicated that self-deprecating humor of leaders can significantly inhibit employee silence through high levels of LMX. Moreover, the mediating role played by LMX was complete. Therefore, organizations should not only focus on the role of leadership humor, but also to achieve mutual respect and trust between leaders and subordinates, and an emotional exchange that goes beyond economic relationships.Keywords: leader self-deprecating humour, employee silence, leader-member exchange, mediating effect

Ling Ma,1,&ast; Yi Wang,2,&ast; Ming Yao,1 Bing Huang,1 Jiajia Deng,1 Huaichang Wen2 1Department of Anesthesiology and Pain Research Center, The Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 2Department of Anesthesiology, First Affiliated Hospital of Wannan Medical College, Wuhu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaichang Wen, No. 2 Zhe shan Street, Wuhu, People’s Republic of China, Email wenhc19851207@163.comObjective: To verify the injectate dispersal patterns (IDP) and therapeutic outcome of ultrasound-guided cervical selective nerve root block (UG-SCNRB) in treating cervical radiculopathy (CR).Methods: Overall, 18 CR patients were recruited to undergo UG-SCNRB in the CT room. Following placement of the puncture needle tip between the target nerve root and posterior tubercle, 3 mL of the drug was administered per root (0.33% lidocaine 0.5 mL + Compound betamethasone injection 0.5mL + methylcobalamin injection 1mL + iohexol 1mL). Subsequently, the IDP was assessed on postintervention CT scan images.Results: In all, 18 participants were analyzed. We injected 21 target cervical nerve roots, namely, 1 C4 nerve, 9 C5 nerves, and 11 C6 nerves. Among the IDPs on postintervention CT scan images, two IDPs were most prevalent, namely, the contrast spread into the extraforaminal spaces (Zone I, the interscalene) in 100% (21/21) of cases, and the foraminal space spread (Zone II) in 61.90% (13/21) of cases. The injectate spread into the epidural spaces (Zone III) in only 2 out of 21 cases (9.52%). The pain relief was significantly improved two hours after surgery, compared to the preoperative VAS pain scores (2 hours, 1.39± 0.50 vs VAS at baseline, P< 0.01). The VAS pain scores during follow-up were significantly lower than preoperation (1 weeks, 1.94± 0.54 vs VAS at baseline; 2 weeks, 2.61± 0.70, P< 0.01 vs VAS at baseline; 4 weeks, 2.67± 0.59, P< 0.01 vs VAS at baseline).Conclusion: We verified, via CT imaging, that the UG-SCNRB drug diffusion was within safe range (the injectate mainly spread to the extraforaminal spaces), and without any serious complications, such as, intravascular drug injection, extensive diffusion of the epidural space, and general spinal anesthesia.Keywords: ultrasound-guided, cervical radiculopathy, selective nerve root block, efficacy, tomography

Bingyue Xin, Keyue Xie, Bing Huang, Ming Yao Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of ChinaCorrespondence: Ming Yao, Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, No. 1882 South Zhonghuan Road, Nanhu District, Jiaxing, Zhejiang Province, People’s Republic of China, Email jxyaoming666@163.comObjective: To investigate the effectiveness and safety of computed tomography (CT)-guided radiofrequency thermocoagulation (RFTC) of the thoracic sympathetic nerve versus chemical resection (CTS) for the treatment of pain caused by Raynaud’s disease.Methods: Patients who underwent CTS or thoracic sympathetic nerve RFTC between March 2012 and March 2021 were enrolled in this retrospective study. There were 28 cases in the alcohol group (Group A) and 44 in the radiofrequency group (Group R). Visual analog scores (VAS) were collected from patients at different time points, as well as preoperative and postoperative finger end perfusion index (PI) and hand temperature (T). The efficiency, postoperative recurrence rate, complications, and improvement in postoperative quality of life were observed in both groups.Results: Pain scores at different follow-up times after surgery decreased in both groups compared to the preoperative period (P < 0.05). Postoperative T and PI were higher in both groups than preoperatively all (P < 0.05). The recurrence rate was higher in the R group than in the A group. Postoperative complications were observed in 13.6% and 25% of patients in groups R and A, respectively. Meanwhile, the postoperative quality of life improved in both groups, but the radiofrequency (RF) group was better than the alcohol group in terms of improvement in quality of life (P < 0.05).Conclusion: Both CT-guided CTS and RFTC of the thoracic sympathetic nerve provided good treatment outcomes. However, the RF group was superior to the alcohol group in terms of complication rate and quality of life improvement.Keywords: Raynaud’s disease, sympathetic nerve, radiofrequency thermocoagulation, chemical thoracic sympathectomy, CT guidance

Ziwen Mao,1,2 Weyland Cheng,1,2 Zhenwei Li,2 Manye Yao,2 Keming Sun2 1Henan Provincial Key Laboratory of Children’s Genetics and Metabolic Diseases, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, Henan, People’s Republic of China; 2Department of Orthopaedic Surgery, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Weyland Cheng, Henan Provincial Key Laboratory of Children’s Genetics and Metabolic Diseases, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, 33 Longhu Waihuan East Road, Zhengzhou, Henan, People’s Republic of China, Tel +86 18502758200, Email wey_c@hotmail.comAbstract: Bitter taste receptors (T2Rs) consist of 25 functional receptors that can be found in various types of cells throughout the human body with responses ranging from detecting bitter taste to suppressing pathogen-induced inflammation upon activation. Numerous studies have observed clinical associations with genetic or phenotypic variants in bitter taste receptors, most notably that of the receptor isoform T2R38. With genetic variants playing a role in the response of the body to bacterial quorum-sensing molecules, bacterial metabolites, medicinal agonists and nutrients, we examine how T2R polymorphisms, expression levels and bitter taste perception can lead to varying clinical associations. From these genetic and phenotypic differences, healthcare management can potentially be individualized through appropriately administering drugs with bitter masking to increase compliance; optimizing nutritional strategies and diets; avoiding the use of T2R agonists if this pathway is already activated from bacterial infections; adjusting drug regimens based on differing prognoses; or adjusting drug regimens based on T2R expression levels in the target cell type and bodily region.Keywords: bitter taste receptors, TAS2R38, chronic rhinosinusitis, obesity, oral health, cancer

Jingxia Wang,1,2,&ast; Qiangqiang Xiang,1,2,&ast; Silan Gu,1,&ast; Yudan Gu,3 Mingfei Yao,1 Weixin Huang,4,5 Wang Gao,4 Ling-Ling Tang1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Shulan International Medical College, Hangzhou, People’s Republic of China; 3Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4Jinan Microecological Biomedicine Shandong Laboratory, Jinan, People’s Republic of China; 5Shaoxing Tongchuang Biotechnology Co., Ltd, Shaoxing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling-Ling Tang, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Shulan International Medical College, Hangzhou, People’s Republic of China, Email lingling.tang@shulan.comBackground: Antibiotics are the first line of treatment for infectious diseases. However, their overuse can increase the spread of drug-resistant bacteria. The present study analyzed the impact of different types of antibiotics on the gut microbiome and cytokines level of mice.Methods: A total of five groups of 8-week-old male BALB/c mice (n = 35) were treated with piperacillin-tazobactam (TZP), ceftriaxone (CRO), tigecycline (TGC), levofloxacin (LEV) or normal saline (Ctrl), respectively, for up to 4 weeks. Fecal samples were analyzed by bacterial 16S rRNA gene sequencing for bacterial identification. Blood samples were used for the determination of 23 serum cytokines using multiplex immunoassay.Results: Exposure to antibiotics was shown to affect the normal weight gain of mice. Significant changes in gut composition caused by TZP, CRO and TGC treatment included the decreased abundance of Bacteroidetes (p < 0.01), Muribaculaceae (p < 0.01) and Lachnospiraceae (p < 0.01), and the increased abundance of Proteobacteria (p < 0.05), Enterobacteriaceae (including Klebsiella and Enterobacter) (p < 0.01) and Enterococcaceae (including Enterococcus) (p < 0.01). After 4-week treatment, the TZP, CRO and LEV groups had significantly lower concentrations of several serum cytokines. Correlation analysis of the top 30 bacterial genera and cytokines showed that Enterococcus and Klebsiella were strongly positively correlated with tumor necrosis factor-α (TNF-α), interleukins (IL) IL-12p70 and IL-1β. Desulfovibrio, Candidatus Saccharimonas, norank_f__norank_o__Clostridia_UCG-014, Lactobacillus, and Roseburia were strongly negatively correlated with these cytokines.Conclusion: This study demonstrates the effects of various antibiotics on the intestinal microflora and immune status of mice. Compared with TZP, CRO and TGC, LEV had minimal impact on the gut microbiota. In addition to TGC, long-term TZP, CRO and LEV intervention can lead to a decrease in serum cytokine levels, which may depend on the intestinal microflora, antibiotic used and the duration of treatment.Keywords: gut microbiota, piperacillin-tazobactam, ceftriaxone, tigecycline, levofloxacin, cytokine, immunity

Meixue Yao,1,&ast; Mengda Liu,2,&ast; Xia Chen,3 Jianjun Li,4 Yan Li,5 Yu Run Wei,2 Yong Liu,3 Kang Long Yang,3 Xiaoxiao Duan,5 Weixing Shao,2 Xiangxiang Sun,2 Xiaoxu Fan,2 Shufang Sun,2 Lili Tian,2 Dehui Yin,1 Mingjun Sun2 1Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Laboratory of Zoonoses, China Animal Health and Epidemiology Center, Qingdao, 266032, People’s Republic of China; 3Yubei Animal Husbandry and Aquatic Products Station, Chongqing, 401120, People’s Republic of China; 4School of Animal Science and Veterinary Medicine, Tianjin Agriculture College, Tianjin, 300384, People’s Republic of China; 5Qingdao Animal Disease Prevention and Control Center, Qingdao, 266000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingjun Sun, Laboratory of Zoonoses, China Animal Health and Epidemiology Center, No. 369 Nanjing Road, Qingdao, 266032, People’s Republic of China, Email sunmingjun@cahec.cn Dehui Yin, Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China, Email yindh16@xzhmu.edu.cnBackground: Brucellosis is one of the most important zoonotic diseases in the world. Canine brucellosis, caused mainly by Brucella canis, is seriously neglected, and there is a lack of accurate diagnostic tools.Methods: In this study, to compare BP26, Omp25, Omp31 and a multiepitope-based fusion protein in the serological detection of canine brucellosis, using 34 brucellosis-positive dog sera and 62 negative control sera, the Brucella outer membrane proteins Omp31, BP26, Omp25 and a multiepitope-based fusion protein were evaluated by iELISA for their potential use as antigens in the serological diagnosis of canine brucellosis.Results: The results showed that the multiepitope-based fusion protein performed best in distinguishing brucellosis-positive and brucellosis-negative dog sera, with a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 98.41%. BP26 and Omp31 showed excellent sensitivity in detecting brucellosis-positive dog sera, but their cross reaction to sera infected with Vibrio parahaemolyticus and Listeria monocytogenes may hinder their application as diagnostic reagents. Omp25 lacked sufficient sensitivity and showed limited ability in distinguishing positive and negative dog sera.Conclusion: The multiepitope-based fusion protein can be used as an ideal antigen for serologically diagnosing canine brucellosis currently prevalent worldwide.Keywords: Brucella, outer membrane protein, multiepitope, canine brucellosis

Meixue Yao,1,2,&ast; Xiaohan Guo,1,2,&ast; Xiling Wu,1,2 Qiongqiong Bai,1,2 Mingjun Sun,3 Dehui Yin1,2 1Center for Medical Statistics and Data Analysis, School of Public Health, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Laboratory of Zoonoses, China Animal Health and Epidemiology Center, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dehui Yin, Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, No. 129 Tongshan Road, Xuzhou, 221004, People’s Republic of China, Email yindh16@xzhmu.edu.cnBackground: Brucellosis is a zoonotic disease that causes substantial public health problems and endangers the development of animal husbandry in endemic areas. Early diagnosis of infected animals and humans is a crucial step in reducing the incidence of brucellosis. In this study, we designed different combinations of Brucella major outer membrane proteins (omps) including omp10, omp16, omp19, omp25, omp31 and BP26 as antigens and evaluated their efficiency in serodiagnosis for brucellosis. The efficiency assay was conducted using the method of indirect enzyme-linked immunosorbent assay (iELISA) together with a collection of brucellosis-positive sera and healthy sera from multiple species (161 from human, 120 from goat and 144 from cattle). The diagnostic effectiveness of each omp combination was analyzed by receiver operating characteristic (ROC) curve with the software GraphPad Prism version 6.05.Results: The omp25/omp31/BP26 combination showed the best efficiency in diagnosis for human brucellosis. The area under the ROC curve (AUC) was 0.995 and, compared with the serum tube agglutination test (SAT) and the Rose Bengal plate agglutination test (RBPT), the positive and negative diagnostic accuracies of iELISA were 94.59% (105/111) and 100.0% (50/50), respectively. Evaluation of the 120 goat and 144 cattle serum samples showed that the best combination for diagnosing both omp31/BP26, the AUC was 0.9262 in goat and 0.9344 in cattle, and compared with those of SAT and RBPT, the positive and negative diagnostic accuracies in goat were 72.73% (48/66) and 100.0% (54/54), respectively. The positive and negative diagnostic accuracies in cattle were 79.79% (75/94) and 100.0% (50/50), respectively. Cross-reaction assays showed that omp25/omp31/BP26 and omp31/BP26 do not cross with other common pathogens.Conclusion: The results indicated that combinations of omps, as protein antigens, can be used to diagnose brucellosis with high accuracy in human, goat and cattle.Keywords: brucellosis, diagnosis, outer membrane proteins, iELISA

Anna H Green,1 Julianne M Forlizzi,2 Joseph Boyle,3 Wilfrido J Castillo,3 Daniel Mascarenhas,1 Meizhen Yao,4 Geza Kiss,5 Carlos Sagebien1 1Department of Orthopedic Surgery, Rutgers Robert Wood Johnson University Hospital, New Brunswick, NJ, USA; 2Department of Orthopedic Surgery, OrthoConnecticut, Norwalk, CT, USA; 3Rutgers Robert Wood Johnson University School of Medicine, New Brunswick, NJ, USA; 4Rutgers University Biostatistics and Epidemiology Services Center, New Brunswick, NJ, USA; 5Department of Anesthesiology, Rutgers Robert Wood Johnson University Hospital, New Brunswick, NJ, USACorrespondence: Anna H Green, Department of Orthopedic Surgery, Rutgers Robert Wood Johnson University Hospital, 1 RWJ Place, MEB 422A, New Brunswick, NJ, 08901, USA, Tel +1 571 228 2234, Fax +1 732 235 6002, Email annagreen7@gmail.comPurpose: To estimate the risk of hospital-acquired COVID-19 transmission in a population of orthopaedic trauma patients during the first wave of the pandemic.Patients and Methods: This is a retrospective cohort study of 109 patients who underwent an emergent orthopedic procedure by a single orthopedic traumatologist between March 1, 2020 and May 15, 2020 during the first peak of the pandemic. After applying inclusion and exclusion criteria, a total of 82 patients (67 inpatients and 15 ambulatory) were identified for final analysis. The primary outcome measured was postoperative Coronavirus (COVID-19) status. Secondary outcome measures included length of stay and discharge disposition.Results: The mean age and length of stay in the hospital group was 59.5 years (± 21.7) and 4.3 days (± 4.6), respectively, versus 47.9 years (± 9.8) in the ambulatory group. 7.3% (6/82) of the inpatients subsequently tested or screened positive for COVID-19 at 2 weeks post-operatively, compared to 0/15 ambulatory patients (P=0.58). Of the 6 inpatients who tested positive, 4 (66.7%) were discharged to a rehabilitation center. Diabetes (P=0.05), hypertension (P=0.02), and congestive heart failure (P=0.005) were associated with transmission.Conclusion: In this analysis, there was a nosocomial transmission rate of 7% compared to zero in the ambulatory surgery center, however this was not found to be statistically significant. This data supports the use of precautions such as frequent screening, hand washing, and masks to reduce transmission when COVID-19 rates are high. There is a lower risk of nosocomial COVID-19 transmission for patients treated as an outpatient and elective surgical procedures may be safer in this setting.Keywords: coronavirus, pandemic, infection, hospital transmission

Pei Chen, Mengyun Yao, Tao Fang, Chaoshuang Ye, Yongjiang Du, Yang Jin, Ruijin Wu Department of Obstetrics and Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Ruijin Wu, Department of Obstetrics and Gynecology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China, Tel +86 571-8706223, Email wurj@zju.edu.cnBackground: Endometriosis (EMS) is a common and highly recurrent gynecological disease characterized by chronic pain and infertility. There are no definitive therapies for endometriosis since the pathogenesis remains undetermined. This study aimed to identify EMS-related functional modules and hub genes by integrated bioinformatics analysis.Methods: Three endometriosis expression profiling series (GSE25628, GSE23339, and GSE7305) were obtained from Gene Expression Omnibus (GEO). The EMS-related module was constructed by weighted gene co-expression network analysis (WGCNA), followed by Gene Ontology (GO) enrichment analyses. Cytohubba and the MCODE plug-ins of Cytoscape were used to screen out the hub genes, which were verified via receiver operating characteristic (ROC) curves. Immunohistochemistry was performed to verify the protein expression of the hub genes in ectopic endometrial tissues. Moreover, CIBERSORT was used to analyze the relationship between the abundance of immune cells infiltration and the expression of hub genes.Results: Among the 18 modules obtained, the darkmagenta module was identified as the EMS-related module, genes of which were significantly enriched to terms referring to cell migration and neurogenesis. NFASC and CHL1 were screened out and prioritized as hub genes through Cytoscape and confirmed to be differentially upregulated in ectopic endometrial samples. Finally, the expression of hub genes was related to the abundance of immune cells infiltration. The higher expression of NFASC or CHL1 correlated with increased M2 macrophages and decreased natural killer (NK) cells in ectopic lesions.Conclusion: This study provided new insights into the molecular factors underlying the pathogenesis of endometriosis and provided a theoretical basis for the potential that the two hub genes, NFASC and CHL1, might be novel biomarkers and therapeutic targets in the future.Keywords: endometriosis, bioinformatics analysis, WGCNA, immune cell infiltration

Yiqiu Zhang,1,* Chenlu Song,1,* Wei Ni,1,2 Qing Pei,1 Caixia Wang,1 Youguo Ying,3 Min Yao1 1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Intensive Care Unit, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min Yao; Youguo Ying, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People’s Republic of China, Email my058@vip.sina.com; yingyouguo@sina.comPurpose: Acute kidney injury (AKI) is one of the most severe complications of sepsis, the pathological features of which are excessive inflammation and programmed cell death of resident renal cells. Heat shock protein 70 (HSP70) is a critical stress protein for repressing inflammation, however, its role in AKI is not fully understood. The current study aimed to determine the protective effect of HSP70 on septic AKI and its underlying mechanisms.Methods: Hsp70.1 knockout and wildtype mice were used for creating sepsis model by cecal ligation and puncture (CLP). Renal function, histological changes, pro-inflammatory cytokines, and apoptosis were analyzed with H&E, PAS, ELISA, western-blot, and immunofluorescence. Moreover, the effects of HSP70 on renal proximal tubular epithelial (HK-2) cells with LPS were assessed by measuring the levels of nuclear factor kappa B (NF-κB) signaling and downstream cytokines, viability, and apoptosis using western-blot, qRT-PCR, flow-cytometry, and immunofluorescence. Immunoprecipitate and immunoblotting were used for determining the interaction of HSP70 with tumor necrosis factor receptor-associated factor 6 (TRAF6). Exogenous HSP70 was applied to further identify its biological significance at the cellular and animal level.Results: Hsp70.1 deficiency significantly aggravated renal dysfunction with increasing serum levels of BUN, SCr, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL), and shortened survival in CLP mice. Furthermore, hsp70.1 knockout caused renal-tissue structural damage, especially proximal tubular, and inflammatory cascade and increased apoptotic cells, along with elevated Bax, caspase 3 and cleaved caspase 3, as well as decreased Bcl2 in vivo and vitro. Significantly, HSP70 directly interacted with TRAF6 in HK-2 cells, leading to suppression of inflammatory response and apoptosis. Moreover, exogenous HSP70 alleviated renal damage, decreased apoptosis and elevated survival rate in septic AKI in vivo and vitro.Conclusion: Our findings demonstrated that HSP70 played a critical role in sepsis-induced AKI via interaction with TRAF6 and inhibiting inflammation and apoptosis.Keywords: heat shock protein 70, sepsis, acute kidney injury, tumor necrosis factor receptor-associated factor 6, nuclear factor kappa B, apoptosis

Mengxin Yao,1 Yue Xiao,1 Zhuoqiao Yang,1 Wenxin Ge,1 Fei Liang,1 Haoyue Teng,1 Yingjie Gu,2 Jieyun Yin1 1Department of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaCorrespondence: Jieyun Yin, School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou, Jiangsu, People’s Republic of China, Tel/Fax +86 0512 6588036, Email jyyin@suda.edu.cnBackground: Preeclampsia (PE) is a significant cause of maternal and neonatal morbidity and mortality worldwide. However, the pathogenesis of PE is unclear and reliable early diagnostic methods are still lacking. The purpose of this review is to summarize potential metabolic biomarkers and pathways of PE, which might facilitate risk prediction and clinical diagnosis, and obtain a better understanding of specific metabolic mechanisms of PE.Methods: This review included human metabolomics studies related to PE in the PubMed, Google Scholar, and Web of Science databases from January 2000 to November 2021. The reported metabolic biomarkers were systematically examined and compared. Pathway analysis was conducted through the online software MetaboAnalyst 5.0.Results: Forty-one human studies were included in this systematic review. Several metabolites, such as creatinine, glycine, L-isoleucine, and glucose and biomarkers with consistent trends (decanoylcarnitine, 3-hydroxyisovaleric acid, and octenoylcarnitine), were frequently reported. In addition, eight amino acid metabolism-related, three carbohydrate metabolism-related, one translation-related and one lipid metabolism-related pathways were identified. These biomarkers and pathways, closely related to renal dysfunction, insulin resistance, lipid metabolism disorder, activated inflammation, and impaired nitric oxide production, were very likely to contribute to the progression of PE.Conclusion: This study summarized several metabolites and metabolic pathways, which may be associated with PE. These high-frequency differential metabolites are promising to be biomarkers of PE for early diagnosis, and the prominent metabolic pathway may provide new insights for the understanding of the pathogenesis of PE.Keywords: gestational hypertension, metabolite, biomarker, prediction

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

Ling Ma, Ming Yao Department of Anesthesiology and Pain Medicine, The Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of ChinaCorrespondence: Ling Ma Tel +8619883372886Email 1319108@qq.comBackground: Herpes zoster neuralgia has a considerable impact on people’s quality of life, especially after the development of postherpetic neuralgia. There are many clinical reports on the treatment of herpes zoster neuralgia, but there have been no special reports on the treatment of herpes zoster involving the neck. Our research focuses on a posterior and upper quarter of the cervical foramina puncture approach for herpes zoster involving the cervical 3– 8 (C3-8) nerve region and to consider the safety and efficacy of pulsed radiofrequency combined with steroid injection and ozone injection in this puncture path under CT guidance.Materials and Methods: A total of 104 patients with herpes zoster neuralgia involved in the cervical 3– 8 nerve region use a posterior and upper quarter of the cervical foramina puncture approach received pulsed radiofrequency combined with steroid and ozone injection to the dorsal root ganglion. The total number of injection procedures, complications, NRS collection (preprocedure, postprocedure at once, two, four and 12 weeks) and drug dose decreases were documented.Results: During a total of 257 procedures, 254 procedures successfully completed PRF (3 cases failed to reach the C8 aim points), and the rate of puncture failure was 1.17%. Drug injection was successfully performed in 252 procedures (the injection success rate was 99.21%); the NRSs (preprocedure, postprocedure at once, two, four and twelve weeks) were 5.75 ± 0.682, 2.6 ± 1.023, 2.21 ± 0.925, 1.89 ± 1.162, and 1.43 ± 1.369, and the difference among them was statistically significant. Drug dosages decreased before and after operation and showed statistically significant differences.Conclusion: Pulsed radiofrequency combined with steroid and ozone injection for herpes zoster neuralgia involving the C3-8 nerves under CT guidance through a posterior superior quarter approach showed safety and efficacy and had a high success rate, and the NRS decreased significantly.Keywords: pulsed radiofrequency, herps zoster neuralgia, steroid, ozone

Ziyuan Shen,1,&ast; Fei Wang,2,&ast; Chenlu He,1,&ast; Dashan Li,3 Shanlin Nie,3 Zhenzhen Bian,3 Mingkang Yao,4 Yuhao Xue,5 Ying Wang,6 Weiying Gu,2 Taigang Zhu,7 Yuye Shi,5 Hao Zhang,4 Shuiping Huang,1,8 Yuqing Miao,9 Wei Sang3 On behalf of the Huaihai Lymphoma Working Group1Department of Epidemiology and Biostatistics, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Hematology, The First People’s Hospital of Changzhou, Changzhou, Jiangsu, People’s Republic of China; 3Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4Department of Hematology, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China; 5Department of Hematology, The First People’s Hospital of Huaian, Huaian, Jiangsu, People’s Republic of China; 6Department of Personnel, Suqian First Hospital, Suqian, Jiangsu, People’s Republic of China; 7Department of Hematology, The General Hospital of Wanbei Coal-Electric Group, Suzhou, People’s Republic of China; 8Center for Medical Statistics and Data Analysis, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 9Department of Hematology, Yancheng First People’s Hospital, Yancheng, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei SangDepartment of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of ChinaTel +8613645207648Email xyfylbl515@xzhmu.edu.cnYuqing MiaoDepartment of Hematology, Yancheng First People’s Hospital, Yancheng, Jiangsu, People’s Republic of ChinaTel +8613851342032Email miaomiaomyq@163.comIntroduction: Immunonutritional status is associated with the survival of DLBCL. This multicenter retrospective study aimed to explore the prognostic value of Prognostic Nutrition Index (PNI) in DLBCL patients by using propensity score matched analysis (PSM).Methods: A total of 990 DLBCL cases were recruited from 5 centers of Huaihai Lymphoma Working Group (HHLWG). A 1:1 PSM analysis was performed using the nearest-neighbor method, with a caliper size of 0.02. Cox regression analysis was used to examine factors associated with survival.Results: The median age at diagnosis was 62 years and 52.5% were males, with the 3-y overall survival of 65.1%. According to the MaxStat analysis, 44 was the optimal cut-off point of PNI. After PSM analysis, a total of 282 patients in PNI < 44 group could be propensity matched to PNI ≥ 44 patients, creating a group of 564 patients. Multivariable analysis revealed that PNI, age, central nervous system involvement and International Prognostic Index (IPI) were independent prognostic factors for DLBCL. Kaplan–Meier analysis indicated that patients with low PNI in Ann Arbor Stage (III/VI), ECOG (< 2), IPI (LR+LIR), GCB, and BCL-2 negative groups had a poor prognosis.Discussion: PNI could accurately stratify the prognosis of DLBCL after PSM analysis.Keywords: diffuse large B-cell lymphoma, prognostic nutrition index, propensity score matched, prognosis

Yong Fei, Bing Huang, Jiajia Deng, Longsheng Xu, Ming Yao Department of Anesthesiology and Pain Medicine, Affiliated Hospital of Jiaxing University, Jiaxing, 314001, People’s Republic of ChinaCorrespondence: Longsheng Xu; Ming YaoDepartment of Anesthesiology and Pain Medicine, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314001, People’s Republic of ChinaEmail xlsh2468@163.com; jxyaoming666@163.comObjective: The purpose of this study was to investigate the clinical efficacy of dorsal root ganglion (DRG) pulsed radiofrequency combined with paravertebral injection of recombinant human interferon-α 2b in the treatment of patients with acute herpes zoster neuralgia and its preventive effectiveness on postherpetic neuralgia (PHN).Methods: A retrospective analysis of 62 patients with acute herpes zoster neuralgia was implemented. All patients were divided into two groups: pulsed radiofrequency paraspinal injection of recombinant human interferon-α 2b (group P); pulsed radiofrequency combined with paravertebral injection of saline (group C). The numerical rating scales (NRS) scores were used for pain assessment, and the dose of the analgesic drug was recorded. Gal-3 and IL-6 levels in blood were compared between the two groups before treatment and at 1 week, 2, and 4 weeks after treatment. The incidence of PHN was recorded in both groups.Results: The pain intensity, the levels of Gal-3 and IL-6 in blood and the dose of oral administration of gabapentin capsules and morphine were reduced in all patients after treatment. Compared with group C, patients in group P had lower NRS scores, blood levels of Gal-3 and IL-6, and dosages of oral gabapentin capsules and morphine hydrochloride immediate-release tablets after treatment. The incidence of PHN was significantly lower at 8 and 12 weeks.Conclusion: DRG pulsed radiofrequency combined with paravertebral injection of recombinant human interferon-α 2b for acute stage herpes zoster neuralgia is a more effective treatment, and can effectively prevent the incidence rate of PHN.Keywords: pulsed radiofrequency, dorsal root ganglion, recombinant human interferon-α 2b, herpes zoster, postherpetic neuralgia

Zhengbo Wei,1 Mengwei Yao,2 Sisi Ning,2 Yuan Wu,2 Xunzhao Zhou,2 Changtao Zhong,2 Kui Yan,2 Ying Xie3,4 1Department of Head and Neck Tumor Surgery, Cancer Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Graduate School of Guangxi Medical University, Nanning, People’s Republic of China; 3Life Science Institute of Guangxi Medical University, Nanning, People’s Republic of China; 4Key Laboratory of High-Incident-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Ying XieKey Laboratory of High-Incident-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of ChinaEmail xieying@gxmu.edu.cnObjective: We examined whether the single-nucleotide polymorphism (SNP) rs13181 in the gene encoding excision repair cross complementation group 2 (ERCC2) is associated with the risk and prognosis of nasopharyngeal carcinoma (NPC).Methods: SNPs at rs13181 were genotyped in 439 NPC patients (NPC group) and 431 age- and gender-matched cancer-free controls (control group) from a region of China where NPC is endemic, and frequencies of GG, GT and TT genotypes were compared between the two groups in the case–control study. In a subset of 365 NPC cases, SNPs were examined for potential correlation with tumor-free survival time (TFS) and overall survival (OS).Results: Relative to NPC risk with a TT genotype, NPC risk was similar with GT + GG genotypes (OR 1.052, 95% CI 0.656– 1.688), after adjusting for gender, age, smoking history, and immunoglobin A against Epstein-Barr virus capsid antigen (EBV-VCA-IgA) status. Univariate analysis showed that the GG or GT genotype was associated with significantly worse TFS (p< 0.001) and OS (p=0.010) than the TT genotype. Prognosis was significantly worse for men than for women (TFS, p=0.045; OS, p=0.031), for T3–T4 classification than for T1–T2 (TFS, p=0.009; OS, p=0.007), for N3 than for N0+N1+N2 (TFS, p< 0.001; OS, p< 0.001). Based on multivariate analysis, independent risk factors for poor TFS were GG or GT genotype (HR 2.629, 95% CI 1.625– 4.254, p< 0.001), T3–T4 classification (HR 2.146, 95% CI 1.244– 3.701, p=0.006) and N3 (HR 2.527, 95% CI 1.574– 4.059, p< 0.001). GG or GT genotype (HR 2.217, 95% CI 1.283– 3.832, p=0.004), gender (HR 1.989, 95% CI 1.046– 3.785, p=0.036), T3–T4 (HR 2.431, 95% CI 1.306– 4.526, p=0.005) and N3 (HR 2.693, 95% CI 1.637– 4.432, p< 0.001) were independent risk factors for poor OS.Conclusion: The rs13181 SNP in ERCC2 does not appear to be associated with NPC risk, but it may serve as an independent prognostic factor for NPC recurrence and death.Keywords: single nucleotide polymorphism, rs13181, nasopharyngeal carcinoma, excision repair cross complementation group 2, tumor-free survival, overall survival

Pan Gao,1,2,* Hongtao Liu,3,* Zhenzhen Yang,1,2 Yiran Hui,2,4 Zhuangzhuang Shi,2 Zhen Yang,2 Min Song,2 Menghui Yao,2 Wenfei Fan,1 Jinhua Yang,1 Yibin Hao,1 Tianli Fan2 1People’s Hospital of Zhengzhou, Zhengzhou, Henan, 450001, People’s Republic of China; 2Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 3Laboratory for Cell Biology, College of Life Sciences of Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 4University of Chinese Academy of Sciences-Shenzhen Hospital, Shenzhen, Guangdong, 518106, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tianli FanDepartment of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of ChinaEmail fantianli@zzu.edu.cnPurpose: Increasing evidence has demonstrated that animal models are imperative to investigate the potential molecular mechanism of metastasis and discover anti-metastasis drugs; however, efficient animal models to unveil the underlying mechanisms of metastasis in esophageal squamous cell carcinoma (ESCC) are limited.Methods: ESCC cell EC9706 with high invasiveness was screened by repeated Transwell assays. Its biological characteristics were identified by flow cytometry as well as by the wound healing and CCK-8 assays. Besides, the levels of epithelial–mesenchymal transition-related markers were examined using Western blotting. Parental (EC9706-I0) and subpopulation (EC9706-I3) cells were employed to establish the renal capsule model. Next, the tumor growth was detected by a live animal imaging system, and hematoxylin and eosin staining was applied to evaluate the metastatic status in ESCC.Results: EC9706-I3 cells showed rapid proliferation ability, S phase abundance, and high invasive ability; obvious upregulation in N-cadherin, Snail, Vimentin, and Bit1; and downregulation in E-cadherin. EC9706-I3 cells were less sensitive to the chemotherapy drug 5-fluorouracil than EC9706-I0 cells; however, both cell lines reached a tumorigenesis rate of 100% in the renal capsule model. The live animal imaging system revealed that the tumors derived from EC9706-I0 cells grew more slowly than those from EC9706-I3 cells at weeks 3– 14. The EC9706-I3 xenograft model displayed a spontaneous metastatic site, including kidney, heart, liver, lung, pancreas, and spleen, with a distant metastatic rate of 80%.Conclusion: Our data suggested that the metastatic model was successfully established, providing a novel platform for further exploring the molecular mechanisms of metastasis in ESCC patients.Keywords: esophageal squamous cell carcinoma, renal capsule model, spontaneous metastasis, epithelial–mesenchymal transition process

Weyland Cheng,1,2 Manye Yao,1 Fangna Liu1 1Department of Orthopaedic Surgery, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, Henan, People’s Republic of China; 2Henan Provincial Key Laboratory of Children’s Genetics and Metabolic Diseases, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Weyland Cheng Tel +86 18502758200Email wey_c@hotmail.comAbstract: Non-gustatory, extraoral bitter taste receptors (T2Rs) are G-protein coupled receptors that are expressed throughout the body and have various functional responses when stimulated by bitter agonists. Presently, T2Rs have been found to be expressed in osteoclasts and osteocytes where osteoclasts were capable of detecting bacterial quorum-sensing molecules through the T2R38 isoform. In the innate immune system, stimulating T2Rs induces anti-inflammatory and anti-pathogenic effects through the phospholipase C/inositol triphosphate pathway, which leads to intracellular calcium release from the endoplasmic reticulum. The immune cells with functional responses to T2R activation also play a role in bone inflammation and orthopaedic disorders. Furthermore, increasing intracellular calcium levels in bone cells through T2R activation can potentially influence bone formation and resorption. With recent studies finding T2R expression in bone cells, we examine the potential of targeting this receptor to treat bone inflammation and to promote bone anabolism.Keywords: TAS2R, calcium signaling, osteoblasts, drug target, bone inflammation

Mingyan Yao,1,2,* Hongzhou Liu,1,* Bing Li,1 Yang Liu,1 Yiming Mu1 1Department of Endocrinology, Chinese People’s Liberation Army General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Endocrinology, Baoding NO.1 Central Hospital, Baoding, 071000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiming MuDepartment of Endocrinology, Chinese People’s Liberation Army General Hospital, No. 28 Fuxing Road, Beijing, 100853, People’s Republic of ChinaEmail muyiming@301hospital.com.cnPurpose: There is a close correlation between menopausal age and cardiovascular disease (CVD) risk. Some research suggests that this risk is attributable to an elevated urinary albumin-creatinine ratio (UACR), but further work is needed to explore the link between UACR and age at time of menopause.Patients and Methods: Data analyzed in the present study were derived from seven regional centers participating in the REACTION study. A total of 21,672 postmenopausal women met with our study inclusion and exclusion criteria, and were split into three groups based upon their age at onset of natural menopause. A UACR ≥ 30 mg/g was the primary outcome measure for this study. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a logistic regression approach.Results: Relative to women who were 46– 50 years old at time of natural menopause, those with an earlier onset of menopause (≤ 45 years) exhibited an increased risk of UACR elevation following adjustment for confounding variables (OR: 1.18, 95% CI: 1.04– 1.33), whereas the opposite was true for women with a later age of menopause onset (> 50 years) (OR: 0.86, 95% CI: 0.78– 0.94). For every 1-year delay in the onset of menopause, UACR risk fell by 3% (OR: 0.97, 95% CI: 0.96– 0.98).Conclusion: In summary, early menopause (≤ 45 years old) was linked to a higher risk of UACR elevation in postmenopausal women. However, further work will be needed to understand the mechanistic basis for these findings.Keywords: age, urinary albumin-creatinine ratio, menopause

Hui Lyu,1 Ming Yao,2 Danying Zhang,3 Xueying Liu4 1Pain Department & Urology Department, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 2Dean Office, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 3Cardiology Department, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 4Department of Nursing, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of ChinaCorrespondence: Xueying Liu Tel +86 13456280706Email 2925917086@qq.comPurpose: To explore how the organizational identity and psychological resilience affect work engagement of the front-line nurses in the prevention and control of coronavirus disease 2019 (COVID-19) and to establish the relationship model based on these factors.Material and Methods: Convenience sampling was applied to collect questionnaire samples from 216 nurses (from 12 cities in 6 provinces). General information questionnaires, organizational identity scale (OIQ), psychological resilience scale (CD-RISC), and Utrecht Work Engagement Scale (UWES) were used as tools for data collection.Results: Both organizational identification and psychological resilience had a positive impact on work engagement (r=0.457∼ 0.669). The structural equation model indicated that psychological resilience had a significant partial mediating effect on the relationship between organizational identity and work engagement; the mediating effect value was 0.25, the overall effect value of work engagement was 0.73, and the mediating effect accounted for 34.2%.Conclusion: Our results revealed that organizational identity could directly affect nursing. It can also indirectly affect nurses’ work engagement through the intermediary role of psychological resilience. In face of the COVID-19 epidemic, hospitals and nursing managers could improve the level of nurses’ job involvement by improving organizational identity, which in turn may have a positive effect on psychological resilience.Keywords: coronavirus disease, COVID-19, pneumonia, nurses, organizational identity, psychological resilience, work engagement

Jianjun Zhu,1,2,* Yong Fei,2,* Jiajia Deng,2 Bin Huang,2 Ming Yao2 1The Second 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 or The Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming YaoDepartment of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, No. 1882 South Zhonghuan Road, Nanhu District, Jiaxing City, Zhejiang Province, People’s Republic of ChinaTel +86 573 13456218632Email jxyaoming666@163.comPurpose: In CT-guided dorsal root ganglion puncture, especially T1–T3, it is often difficult to reach the target due to obstruction of the lamina, transverse process, and ribs. Therefore, a safe and effective puncture method with high success rate is urgently needed to guide us in our clinical work.Patients and Methods: A total of 44 patients with dorsal root ganglion underwent pulsed radiofrequency therapy for pain T1–T3 herpes zoster neuralgia at the pain department of Affiliated Hospital of Jiaxing University from January 2019 to February 2020 were retrospectively reviewed. Each patient underwent the same surgical method. The patient’s operation time, CT filming times, nerve electrophysiological tests, the NRS scores before and after operation at one, four, eight, and 12 weeks, Pittsburgh Sleep Disorder Index (PSQI), dosage of gabapentin capsules and tramadol hydrochloride sustained-release tablets, surgical complications and incidence of postherpetic neuralgia (PHN) were recorded.Results: The success rate of 44 patients who underwent puncturing of the costal transverse process to T1 target was 88.46%, to T2 target was 90.68%, and to T3 target was 90.68%, respectively. The NRS score of patients before surgery was 5.48± 0.59, and those at one, four, eight, and 12 weeks after surgery were 3 (3,3), 1 (1,2), 0 (0, 1), and 0 (0, 0). The difference of NRS score between preoperation and postoperation is statistically significant. No intraoperative and postoperative complications occurred. Two patients developed PHN after standard treatment, and the incidence of it was 4.55%.Conclusion: CT-guided puncturing of the costal transverse process in the dorsal root ganglion of patients who underwent pulsed radiofrequency treatment of T1–T3 herpes zoster neuralgia showed a high success rate and is considered to be safe and effective.Keywords: costotransverse joint, pulsed radiofrequency, dorsal root ganglion, herpes zoster neuralgia

Lanqing Cao, Ping-Li Sun, Yangyang He, Min Yao, Hongwen Gao Department of Pathology, The Second Hospital of Jilin University, Changchun, Jilin 130041, People’s Republic of ChinaCorrespondence: Min YaoDepartment of Pathology, The Second Hospital of Jilin University, 218 Ziqiang Road, Changchun, Jilin 130041, People’s Republic of ChinaTel/Fax +86-431-81136933Email yaomin@jlu.edu.cnPurpose: An accurate risk assessment system for disease metastasis or recurrence could improve the cancer management practice in cervical squamous cell carcinoma (CxSCC) patients, which has few definite prognostic predictors. Previous studies have indicated the important utility of stromal features in determining cancer biological behavior; however, it lacks histopathologic or morphologic criteria for its evaluation. Therefore, this present study aimed to comprehensively catalog histopathological features of mesenchymal stroma to determine the prognostic value of these features in CxSCC.Patients and methods: We histologically and immunohistochemically evaluated the stromal features in the primary tumors of 122 CxSCC patients. The follow-up duration was 41.25 months (range: 3–80.77 months). Multivariate proportional hazard regression models were used to identify the top classifier for distant metastasis-free survival (DMFS) prediction.Results: Lymph-vascular invasion (LVI), lymph node metastasis (LNM), tumor-node-metastasis (TNM) stage and tumor budding were positively correlated with distant metastasis (P < 0.001, P < 0.001, P < 0.001 and P = 0.012, respectively). Distant metastasis was also associated with the immature desmoplastic reaction (DR) (P = 0.002), high level of cancer-associated fibroblasts (P = 0.003), vasohibin-1 (VASH1)-positive microvessels (P = 0.027), and the VASH1/CD31 ratio (P = 0.004). Multivariate COX proportional hazard regression models revealed that LVI, LNM, and DR were independent predictors of poor DMFS in CxSCC patients.Conclusion: Primary tumor histologic stromal features, especially DR, may be useful in predicting distant metastasis in patients with CxSCC.Keywords: stromal features, squamous cell carcinoma, distant metastasis, desmoplastic reaction

Yin Shi, Shanshan Gao, Ying Zheng, Mukun Yao, Fan Ruan Department of Gynecology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Fan RuanDepartment of Gynecology, Tongde Hospital of Zhejiang Province, No. 234 Gucui Road, Xihu District, Hangzhou City, Zhejiang Province, People’s Republic of ChinaTel +86 571-89972000Email ruanfan@zjtdhospital.com.cnBackground: LncRNA cancer susceptibility candidate 15 (CASC15) has been demonstrated to act as an oncogene in different cancers; however, its role in ovarian cancer remains elusive.Methods: Quantitative real-time PCR (qRT-PCR) was performed to examine the expression of lncRNA CASC15. Kaplan–Meier survival analysis was performed to evaluate the prognostic significance of lncRNA CASC15. CCK-8, soft-agar colony-formation, flow cytometry, transwell migration and invasion assays were used to analyze the biological behavior of lncRNA CASC5 in ovarian cancer. Furthermore, the potential mechanism of lncRNA CAC15 was investigated by bioinformatics analysis, luciferase reporter assay, and biotin pull-down assay.Results: In this study, we found that the expression of CASC15 was lower in ovarian cancer tissues and cells by qRT-PCR. In addition, low expression of CASC15 was closely correlated with advanced TNM stage, moderate/poor differentiation, and larger size. Moreover, Kaplan–Meier survival analysis showed that patients with low CASC15 expression level had poorer overall survival and progression-free survival than those with high CASC15 expression. Meanwhile, ROC analysis found that CASC15 had diagnostic values to distinguish tumor tissues from nontumorous tissues. Overexpression of CASC15 prohibited the malignancy of ovarian cancer cells, including proliferation, colony formation, cell cycle, migration, and invasion, and promoted cell apoptosis. In addition, bioinformatics analysis, luciferase reporter assay, and biotin pull-down assay confirmed that CASC15 straightly interacted with miR-221. We also observed that ARID1A was a downstream target of miR-221 and CASC15 subsequently exerted its tumor-suppressive effects by regulating the expression of ARID1A in ovarian cancer cells.Conclusion: Overall, this study firstly elucidated that CASC15 could play a tumor-suppressive role in ovarian cancer by the regulation of CASC15/miR-221/ARID1A axis, which may provide a ponderable prognostic biomarker and promising therapeutic target for treatment of patients with ovarian cancer.Keywords: long non-coding RNA, CASC15, ovarian cancer, miR-221, ARID1A

Bing Huang,1 Ming Yao,1 Qianying Liu,1 Yajing Chen,1 Huadong Ni,1 Zhang Li,1 Keyue Xie,1 Yong Fei,1 Langping Li21Department of Anesthesiology and Pain Medical Center, First Affiliated Hospital of Jiaxing University, Jiaxing 314001, People’s Republic of China; 2Department of Anesthesiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, People’s Republic of ChinaBackground: The computed tomography (CT)-guided radiofrequency ablation (RFA) of the maxillary nerve (V2) via foramen rotundum (FR) approach has been reported to offer the highest rates of pain relief in V2 trigeminal neuralgia (TN). However, the access to FR may be obstructed by the greater wing of the sphenoid bone.Objectives: We report on an optimized CT-guided percutaneous infrazygomatic of maxillary nerve through the foramen rotundum (FR) to treat V2 trigeminal neuralgia (TN) using personalized RFA needles based on patient’s individual CT-image parameters.Patients and methods: 176 patients with isolated V2 TN were included. If the entry of the percutaneous needle into the FR canal was blocked by the greater wing of the sphenoid bone, straight RFA needles was bent at the tip with an angle α (the angle between the straight line from the external opening of FR to the skin entry point and the long axis of the FR canal). The maxillary nerve RFA was performed after confirmation with electrophysiological tests. Pain relief in the V2 territory and TN recurrence rate were followed for up to 60 months.Results: Fifty-two patients (29.55%) required needle bending. The maxillary nerve thermal RFA resulted in analgesia in the V2 territory without affecting the V1 or V3 zone. TN recurrence rate at 6, 12, 24, 36, 48 and 60 months was 2.55%, 7.64%, 17.20%, 24.41%, 30.28% and 33.77%, respectively.Conclusion: The personalized needle modification technique for maxillary nerve RFA through FR is safe and effective to treat V2 TN.Keywords: trigeminal neuralgia, maxillary nerve, foramen rotundum, radiofrequency ablation

Qixia Luo,1,* Tianshui Niu,1,* Yuan Wang,1 Jianhua Yin,2 Fen Wan,3 Mingfei Yao,1 Haifeng Lu,1 Yonghong Xiao,1 Lanjuan Li11State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou, The First Affiliated Hospital, College of Medicine, Zhejiang University, People’s Republic of China; 2College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, People’s Republic of China; 3College of Laboratory Medicine, Hangzhou Medical College, Hangzhou, People’s Republic of China*These authors contributed equally to this work Objectives: Although resistance to colistin is increasingly reported from clinical settings, the genetic mechanisms that lead to colistin resistance in Escherichia coli have not been fully characterized. Here, we assess the evolution of colistin resistance in clinical isolates of mobilized colistin resistance (MCR)-negative and MCR-positive Escherichia coli.Methods: Spontaneously mutated colistin-resistant progeny were evolved using a step-wise reduction of colistin susceptibility. Resistance phenotypes were confirmed by minimum inhibitory concentration (MIC) determination, and the probable resistance mechanisms were investigated using PCR and reverse transcription-quantitative PCR. Mutated genes of the laboratory-evolved mutants were identified by whole-genome sequencing and comparative genomics. Fitness costs and serum resistance of the mutants were also compared to the corresponding wild types.Results: MCR-negative isolates displayed higher increases in MICs than did MCR-positive isolates following colistin exposure. Upregulation of pmrAB and associated genes was evident among MCR-negative isolates but not MCR-positive isolates. Comparative genomic analysis of mutants and their corresponding wild-types (WTs) revealed numerous mutations in genes encoding membrane transporters and two-component systems. Additionally, MCR-negative mutants exhibited higher fitness costs than MCR-positive mutants compared with their corresponding WTs but displayed similar serum resistance.Conclusion: Our findings reveal multiple differences between MCR-positive and MCR-negative E. coli strains following colistin exposure, which provide reference values for clinical medication.Keywords: colistin resistance, MCR, comparative genomic, Escherichia coli

Bing Huang,1 Keyue Xie,1 Yajing Chen,1 Jiang Wu,2 Ming Yao11Department of Anesthesiology and Pain Medicine, The First Affiliated Hospital, Jiaxing University, Jiaxing, Zhejiang 314000, People’s Republic of China; 2Department of Anesthesiology and Pain Medicine, University of Washington Medical Center, University of Washington, Seattle, WA 98195, USABackground: Percutaneous trans-foramen ovale (FO) radiofrequency ablation (RFA) of Gasserian ganglion (GG) is commonly used to treat V3 trigeminal neuralgia (TN). However, this intracranial approach is less selective and safe.Objectives: To report a novel percutaneous within-FO RFA of the V3 under CT-guidance and outcomes with both bipolar and monopolar techniques.Patients and methods: Twenty-six patients with isolated V3 primary TN and FO >6 mm in diameter underwent either monopolar (n=12) or bipolar RFAs (n=14) based on their preference. Successful analgesia over V3, residual pain, recurrent pain, and complications were compared between the two groups. The ex vivo egg albumen model was used to demonstrate the size difference in the thermocoagulation lesion created by monopolar vs bipolar electrodes.Results: In the bipolar group, there were more cases of masticatory atonia as compared to the monopolar (P=0.104), but no residual pain was observed. In the monopolar group, there were two cases of residual pain found, which led to immediate repeat RFAs. Therefore, during the immediate post-operative period, both groups obtained 100% complete V3 analgesia with a similar risk of facial hematoma (P=0.641). During up to 27-months of post-operative follow-up, in the bipolar group, complete pain relief persisted in all patients; in the monopolar group, 1 case of recurrent pain was found at 14 months. Ex vivo study demonstrated that, at 90 °C/90 seconds of RFA, the width of lesions is significantly larger by the 6-mm spacing parallel-tip bipolar electrodes compared to the monopolar electrode (9.5±0.567 vs 5.5±0.07 mm).Conclusion: In treating patients with isolated V3 TN and FO >6mm in diameter, this percutaneously within-FO RFA of the V3 under CT guidance is both clinically practical and effective, while bipolar RFA is associated with a lower incidence of residual and recurrent pain likely due to larger lesion sizes.Keywords: trigeminal neuralgia, mandibular nerve, foramen ovale, radiofrequency ablation, bipolar

Xiaotong Yan,1,* Mingjie Yao,2,* Xiajie Wen,2 Yiwei Zhu,3 Erjiang Zhao,4 Xiangjun Qian,2 Xiangmei Chen,2 Weiquan Lu,4 Quanjun Lv,3 Ling Zhang,5 Fengmin Lu1,2 1Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China; 2Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; 3Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou 450001, China; 4Department of Medical Records, Henan Cancer Hospital, Zhengzhou 450008, China; 5Department of Hepatobiliary Surgery, Henan Cancer Hospital, Zhengzhou 450008, China *These authors contributed equally to this work Aims: To date, curative resection remains to be the most optimal therapeutic choice of hepatocellular carcinoma (HCC), though the overall survival (OS) remains extremely unsatisfactory. To better manage the HCC patients, we evaluated the prognosis predicting values of apolipoprotein B (ApoB) and low-density lipoprotein cholesterol (LDL-C) on the long-time survival of patients who underwent surgical treatment in this study. Methods: A subgroup of 164 patients from our previously described follow-up cohort were enrolled in this study, of whom the pre-surgery ApoB and LDL-C measurements were available. They had been followed until January 2017, with a 19.5 months median survival time. The prognosis predicting values of serum ApoB, LDL-C, and other clinical variables were evaluated through Cox univariate and multivariate analyses, meanwhile, Kaplan–Meier analysis was conducted to obtain the OS curves. Results: Pre-surgery ApoB was an independent prognosis predicting factor with HR as 1.396 (P=0.033), elevated ApoB was associated with worse postsurgery prognosis in HCC patients. Concordantly, Spearman’s correlation analysis revealed that value of pre-surgery ApoB was to some extent correlated with tumor size (r=0.355, P

Wenjie Zheng,1,2,* Junling Yang,2,* Zhizhen Dong,3,* Li Wang,1 Miao Fang,1 Wei Wu,2 Dengfu Yao,1,2 Min Yao1 1Medical School of Nantong University, Nantong 226001, Jiangsu, China; 2Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China; 3Department of Diagnostics, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China *These authors contributed equally to this work Purpose: High mobility group box 3 (HMGB3) is associated with hepatocytes malignant transformation by our previous work. We continued to investigate the diagnostic and prognostic values of HMGB3 for hepatocellular carcinoma (HCC). Patients and methods: Circulating HMGB3 levels were quantitatively detected in a cohort of 225 patients with chronic liver diseases by ELISA and compared with alpha-fetoprotein by the receiver operating characteristic curve. HMGB3 expression in tissues of 170 HCC was detected by tissue microarray and immunohistochemistry. Relationship between HMGB3 level and HCC prognosis was evaluated by the Kaplan–Meier curves and Cox regression model. Results: The incidence of serum HMGB3 >2.0 ng/mL was 75.6% in HCC (96/127), 20.8% in liver cirrhosis (10/48), 16.0% in chronic hepatitis (8/50), and none in healthy controls (0/49). Significant difference (P30.6% in their paracancerous tissues (52/170). HMGB3 expression was closely related to tumor size, TNM stage, poor survival, and high recurrence, suggesting an independent prognosis factor for HCC. Conclusion: HMGB3 with aberrant expression could be a novel diagnostic and prognostic marker for HCC. Keywords: hepatocellular carcinoma, HMGB3, diagnosis, prognosis, biomarker

Sisi Ning,1,* Mengwei Yao,1,* Yuan Wu,1 Xunzhao Zhou,1 Changtao Zhong,1 Kui Yan,1 Zhengbo Wei,2 Ying Xie3,4 1Graduate School of Guangxi Medical University, Nanning, China; 2Department of Head and Neck Tumor Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China; 3Life Sciences Institute of Guangxi Medical University, Nanning, China; 4Key Laboratory for High-Incidence Tumor Prevention and Treatment, Guangxi Medical University, Ministry of Education, Nanning, China *These authors contributed equally to this work Objective: To evaluate the potential association of variations in the number of tandem repeats in the dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin-related (DC-SIGNR) neck region with susceptibility to nasopharyngeal carcinoma (NPC).Methods: Variations in the number of repeats in the genotypes and alleles in the neck region of DC-SIGN/DC-SIGNR were analyzed in 477 unrelated NPC patients and 561 cancer-free controls.Results: Genotypes and alleles in the DC-SIGN neck region did not differ significantly between NPC patients and controls, but the 9-repeat genotype in the DC-SIGNR neck region was significantly more frequent among patients (OR 1.339, 95% CI 1.018–1.760, P=0.037). The association between this genotype and NPC remained significant after adjusting for sex, age, smoking history, and presence of immunoglobulin against Epstein–Barr virus viral capsid antigen (OR 1.625, 95% CI 1.134–2.329, P=0.0082).Conclusion: These results suggest that genotypes/alleles in the DC-SIGN neck region are not associated with NPC susceptibility, whereas the 9-repeat variant in the neck region of DC-SIGNR may increase the risk of NPC. Keywords: nasopharyngeal carcinoma, DC-SIGN, DC-SIGNR, genetic polymorphism, neck region repeat variation

Li Zhang,1,* Mengchu Yao,2,3,* Wei Yan,4,* Xiaoning Liu,5 Baofei Jiang,6 Zhaoye Qian,2,3 Yong Gao,2,3 Xiao-jie Lu,7 Xiaofei Chen,2 Qi-long Wang2,3,5 1Department of Hematology, 2Department of Clinical Oncology, 3Huai’an Key Laboratory of Esophageal Cancer Biobank, 4Department of Gastroenterology, 5Department of Central Laboratory, 6Department of Gastrointestinal Surgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, 7Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China *These authors contributed equally to this work Abstract: Low toxicity and high efficacy are the key factors influencing the real-world clinical applications of nanomaterial-assisted drug delivery. In this study, novel hollow carbon spheres (HCSs) with narrow size distribution were developed. In addition to demonstrating their ease of synthesis for large-scale production, we also demonstrated in vitro that the HCSs possessed high drug-loading capacity, lower cell toxicity, and optimal drug release profile at low pH, similar to the pH in the tumor microenvironment. The HCSs also displayed excellent immunocompatibility and could rapidly distribute themselves in the cytoplasm to escape lysosomal clearance. More importantly, the HCSs could efficiently deliver doxorubicin (a representative chemotherapeutic drug) to tumor sites, which resulted in significant inhibition of tumor growth in an esophageal xenograft cancer model. This also prolonged the circulation time and altered the biodistribution of the drug. In conclusion, this study revealed a novel drug delivery system for targeted tumor therapy. Keywords: hollow carbon spheres, drug delivery, doxorubicin, esophagus carcinoma

Meiqi Yao, Jinhua Chen, Jiyong Jing, Han Sheng, Xing Tan, Jingfen Jin Nursing Department, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China Background: Patient adherence is a crucial determinant of rehabilitation in the long term after stroke. However, adherence is inconstant and fluctuates along a time course, and the underlying regular pattern of adherence variation remains to be clarified. Objective: We aimed to describe the longitudinal pattern of adherence to rehabilitation exercises in stroke patients and to determine different adherence phases based on formulated rehabilitation adherence curve. Patients and methods: Rehabilitation adherence levels were prospectively collected using the Questionnaire of Exercise Adherence (EAQ) among patients diagnosed with first-onset stroke since the second week of stroke onset, with a follow-up of 24 weeks. SPSS19.0 was used to formulate a fitting curve based on a scatter diagram. Possible causal factors for the different adherence phases are also discussed from the psychological, socioeconomic, and behavioral aspects. Results: A total of 98 patients were included in this study. General adherence of the included subjects was classified as low to medium during follow-up. The adherence fitting curve was an “S” curve, with the fitting function y =0.005x3-0.211x2+1.963x+52.345. Three phases, namely, rapid increase phase, slow decrease phase, and stable phase, were identified based on the adherence curve, and relevant theories are explored. Conclusion: Rehabilitation adherence of stroke patients is a dynamic behavioral process that continuously changes along a time course, with a regular pattern of an “S” curve and includes a rapid increase phase, a slow decrease phase, and a stable phase. Keywords: cerebrovascular disease, rehabilitation pattern, early rehabilitation

Mingjuan Liu,1 Ming Yao,1,2 Hanqi Wang,1 Longsheng Xu,1 Ying Zheng,1 Bing Huang,1 Huadong Ni,1 Shijie Xu,1 Xuyan Zhou,1 Qingquan Lian2 1Department of Anesthesiology and Pain Medicine, The First Hospital of Jiaxing, The First Affiliated Hospital of Jiaxing University, Jiaxing, 2Department of Anesthesiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China Background: Cancer-induced bone pain (CIBP) is one of the most challenging clinical problems due to a lack of understanding the mechanisms. Recent evidence has demonstrated that activation of microglial G-protein-coupled P2Y12 receptor (P2Y12R) and proinflammatory cytokine production play an important role in neuropathic pain generation and maintenance. However, whether P2Y12R is involved in CIBP remains unknown.Methods: The purpose of this study was to investigate the role of P2Y12R in CIBP and its molecular mechanisms. Using the bone cancer model inoculated with Walker 256 tumor cells into the left tibia of Sprague Dawley rat, we blocked spinal P2Y12R through intrathecal administration of its selective antagonist MRS2395 (400 pmol/µL, 15 µL).Results: We found that not only the ionized calcium-binding adapter molecule 1 (Iba-1)-positive microglia in the ipsilateral spinal cord but also mechanical allodynia was significantly inhibited. Furthermore, it decreased the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and the production of proinflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6), whereas it increased tumor necrosis factor-α (TNF-α).Conclusion: Taken together, our present results suggest that microglial P2Y12R in the spinal cord may contribute to CIBP by the activation of spinal microglia and p38MAPK pathway, thus identifying a potential therapeutic target for the treatment of CIBP. Keywords: P2Y12 receptor, cancer-induced bone pain, p38MAPK pathway, cytokines

Yinbo Peng,1 Chenlu Song,1 Chuanfeng Yang,1 Qige Guo,1 Min Yao1,2 1Department of Burns and Plastic Surgery, Shanghai Ninth People’s Hospital, Institute of Traumatic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Dermatology, Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA Abstract: Silver nanoparticles (AgNPs) are being widely applied as topical wound materials; however, accumulated deposition of silver in the liver, spleen, and other main organs may lead to organ damage and dysfunction. We report here that low molecular weight chitosan-coated silver nanoparticles (LMWC-AgNPs) are effective against methicillin-resistant Staphylococcus aureus (MRSA), have better biocompatibility, and have lower body absorption characteristics when compared with polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) and silver nanoparticles without surface stabilizer (uncoated-AgNPs) in a dorsal MRSA wound infection mouse model. LMWC-AgNPs were synthesized by reducing silver nitrate with low molecular weight chitosan as a stabilizer and reducing agent, while PVP-AgNPs were synthesized using polyvinylpyrrolidone as a stabilizer and ethanol as a reducing agent. AgNPs with different surface stabilizers were identified by UV-visible absorption spectrometry, and particle size was determined by transmission electron microscopy. UV-visible absorption spectra of LMWC-AgNPs, PVP-AgNPs and uncoated-AgNPs were similar and their sizes were in the range of 10–30 nm. In vitro experiments showed that the three types of AgNPs had similar MRSA-killing effects, with obvious effect at 4 µg/mL and 100% effect at 8 µg/mL. Bacteriostatic annulus experiments also showed that all the three types of AgNPs had similar antibacterial inhibitory effect at 10 µg/mL. Cell counting kit-8 assay and Hoechst/propidium iodide (PI) staining showed that LMWC-AgNPs were significantly less toxic to human fibroblasts than PVP-AgNPs and uncoated-AgNPs. Treatment of mice with MRSA wound infection demonstrated that the three types of AgNPs effectively controlled MRSA wound infection and promoted wound healing. After continuous application for 14 days, LMWC-AgNPs-treated mice showed significantly reduced liver dysfunction as demonstrated by the reduced alanine aminotransferase and aspartate aminotransferase levels and liver deposition of silver, in comparison to mice treated with uncoated-AgNPs or PVP-AgNPs. Our results demonstrated that LMWC-AgNPs had good anti-MRSA effects, while harboring a better biocompatibility and lowering the body’s absorption characteristics. Keywords: silver nanoparticles, LMWC-AgNPs, MRSA, PVP-AgNPs, PVP, biocompatibility

Roger Shen,1 Jane J Kim,2 Mingyi Yao,2,3 Tamer A Elbayoumi2,3 1Department of Family Medicine, Northeastern Health Systems-Tahlequah City Hospital, Tahlequah, OK, USA; 2Department of Pharmaceutical Sciences, College of Pharmacy-Glendale, Midwestern University, 3Nanomedicine Center of Excellence in Translational Nanomedicine, Midwestern University, Glendale, AZ, USA Abstract: Berberine (Brb) is an active alkaloid occurring in various common plant species, with well-recognized potential for cancer therapy. Brb not only augments the efficacy of antineoplastic chemotherapy and radiotherapy but also exhibits direct antimitotic and proapoptotic actions, along with distinct antiangiogenic and antimetastatic activities in a variety of tumors. Despite its low systemic toxicity, several pharmaceutical challenges limit the application of Brb in cancer therapy (ie, extremely low solubility and permeability, very poor pharmacokinetics (PKs), and oral bioavailability). Among lipid-based nanocarriers investigated recently for Brb, stealth amphiphilic micelles of polymeric phospholipid conjugates were studied here as a promising strategy to improve Brb delivery to tumors. Specifically, physicochemically stable micelles made of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (PEG-PE) mixed with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) (PEG-succinate ester of vitamin E), in a 3:1 M ratio, increased Brb solubilization by 300%. Our PEG-PE/TPGS-mixed micelles firmly retained the incorporated Brb, displaying extended-release profile in simulated media, with up to 30-fold projected improvement in simulated PKs of Brb. Owing to the markedly better uptake of Brb-containing mixed micelles in vitro, our Brb-mixed micelles nanoformulation significantly amplified apoptosis and overall cytotoxic effectiveness against monolayer and spheroid cultures of human prostate carcinomas (16- to 18-fold lower half-maximal inhibitory concentration values in PC3 and LNPaC, respectively), compared to free Brb. Mixed PEG-PE/TPGS micelles represent a promising delivery platform for the sparingly soluble anticancer agent, Brb, encouraging further pharmaceutical development of this drug for cancer therapy. Keywords: mixed micelles, polymer–phospholipid conjugates, vitamin E TPGS, berberine hydrochloride, apoptosis, prostatic adenocarcinoma

Ying Xie,2 Yuan Wu,3 Xunzhao Zhou,3 Mengwei Yao,3 Sisi Ning,3 Zhengbo Wei1 1Department of Head and Neck Tumor Surgery, Affiliated Tumor Hospital of Guangxi Medical University, 2Guangxi Key Laboratory for High-Incidence Tumor Prevention and Treatment, Experimental Center of Medical Science of Guangxi Medical University,3Graduate School of Guangxi Medical University, Nanning, People’s Republic of China Abstract: This case–control study investigates the possible relationships between the single-nucleotide polymorphisms rs1052133 in the human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene and rs3219472 in the human MutY glycosylase homologue (hMUTYH) gene and the risk of nasopharyngeal carcinoma (NPC). The two polymorphisms were genotyped in 488 unrelated NPC patients and 573 cancer-free controls. Genotype GG at rs1052133 was associated with significantly lower NPC risk than genotypes GC + CC (odds ratio [OR] 0.770, 95% confidence interval [CI] 0.595–0.996, P=0.012). In subgroup analyses, subjects with genotype GG at rs1052133 were at lower risk of NPC than those with GC or CC among individuals older than 40 years (OR 0.706, 95% CI 0.524–0.950), women (OR 0.571, 95% CI 0.337–0.968), and those with no smoking history (OR 0.634, 95% CI 0.463–0.868). No significant association was seen between polymorphisms at hMUTYH rs3219472 and the risk of NPC. However, gene–gene interaction analysis showed that subjects with genotype CC at rs1052133 and genotype AA at rs3219472 (CC/AA) were at 2.887-fold higher risk of NPC than those with GG/GG, 3.183-fold higher risk than those with GG/GA, and 3.392-fold higher risk than those with GG/AA. Our results suggest that hOGG1 rs1052133 polymorphism may play an important role in NPC pathogenesis, especially among women, >40 years old, and those with no smoking history. The hMUTYH rs3219472 polymorphism may interact with hOGG1 rs1052133 polymorphism to influence susceptibility to NPC. Keywords: nasopharyngeal carcinoma, base excision repair pathway, human 8-oxoguanine DNA glycosylase 1, human MutY glycosylase homologue, single-nucleotide polymorphism

BACKGROUND:Togo has conducted annual, integrated, community-based mass drug administration (MDA) for soil-transmitted helminths (STH) and schistosomiasis since 2010. Treatment frequency and target populations are determined by disease prevalence, as measured by baseline surveys in 2007 and 2009, and WHO guidelines. Reported programmatic treatment coverage has averaged over 94%. Togo conducted a cross-sectional survey in 2015 to assess the impact of four to five years of MDA on these diseases. METHODOLOGY/PRINCIPAL FINDINGS:In every sub-district in the country outside the capital, the same schools were visited as at baseline and a sample of fifteen children age 6 to 9 years old was drawn. Each child submitted urine and a stool sample. Urine samples were tested by dipstick for the presence of blood as a proxy measure of Schistosoma haematobium infection. Stool samples were analyzed by the Kato-Katz method for STH and Schistosoma mansoni. At baseline, 17,100 children were enrolled at 1,129 schools in 562 sub-districts; in 2015, 16,890 children were enrolled at the same schools. The overall prevalence of both STH and schistosomiasis declined significantly, from 31.5% to 11.6% for STH and from 23.5% to 5.0% for schistosomiasis (p

Guo-Jun Wei,1 Meng Yao,1 Yan-Song Wang,1 Chang-Wei Zhou,1 De-Yu Wan,1 Peng-Zhen Lei,1 Jian Wen,1 Hong-Wei Lei,2 Da-Ming Dong1 1Department of Orthopaedics, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China; 2Department of Rheumatology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China Background: Peripheral nerve injury is a common trauma, but presents a significant challenge to the clinic. Silk-based materials have recently become an important biomaterial for tissue engineering applications due to silk’s biocompatibility and impressive mechanical and degradative properties. In the present study, a silk fibroin peptide (SF16) was designed and used as a component of the hydrogel scaffold for the repair of peripheral nerve injury. Methods: The SF16 peptide’s structure was characterized using spectrophotometry and atomic force microscopy, and the SF16 hydrogel was analyzed using scanning electron microscopy. The effects of the SF16 hydrogel on the viability and growth of live cells was first assessed in vitro, on PC12 cells. The in vivo test model involved the repair of a nerve gap with tubular nerve guides, through which it was possible to identify if the SF16 hydrogel would have the potential to enhance nerve regeneration. In this model physiological saline was set as the negative control, and collagen as the positive control. Walking track analysis and electrophysiological methods were used to evaluate the functional recovery of the nerve at 4 and 8 weeks after surgery. Results: Analysis of the SF16 peptide’s characteristics indicated that it consisted of a well-defined secondary structure and exhibited self-assembly. Results of scanning electron microscopy showed that the peptide based hydrogel may represent a porous scaffold that is viable for repair of peripheral nerve injury. Analysis of cell culture also supported that the hydrogel was an effective matrix to maintain the viability, morphology and proliferation of PC12 cells. Electrophysiology demonstrated that the use of the hydrogel scaffold (SF16 or collagen) resulted in a significant improvement in amplitude recovery in the in vivo model compared to physiological saline. Moreover, nerve cells in the SF16 hydrogel group displayed greater axon density, larger average axon diameter and thicker myelin compared to those of the group that received physiological saline. Conclusion: The SF16 hydrogel scaffold may promote excellent axonal regeneration and functional recovery after peripheral nerve injury, and the SF16 peptide may be a candidate for nerve tissue engineering applications. Keywords: peripheral nerve injury, silk fibroin, peptide, hydrogel, scaffold

Airen Xu,1,* Mingfei Yao,2,* Guangkui Xu,3 Jingyan Ying,1 Weicheng Ma,1 Bo Li,2 Yi Jin21Clinical Pharmacology Research Center, Ningbo Urinary and Renal Diseases Hospital, Ningbo, 2College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 3Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing, China *These authors contributed equally to this workBackground: The aim of this work was to improve oral bioavailability. The uptake of a series of quaternary ammonium salt didodecyl dimethylammonium bromide (DMAB)-modified nanoparticles (with uniform sizes ranging from 50 nm to 300 nm) into heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2) and human colon adenocarcinoma cells (HT-29) was investigated.Methods: Coumarin-6 (C6) loaded poly (lactide-co-glycolide) (PLGA) nanoparticles were prepared with DMAB using the emulsion solvent diffusion method. The physicochemical properties and cellular uptake of these nanoparticles were studied. Deserno’s model was applied to explain the experimental observations.Results: The results showed that the surface modification of PLGA nanoparticles with DMAB notably improved the cellular uptake. The cellular uptake was size-dependent and had an optimal particle size of 100 nm. The experimental data was integrated numerically, and was in agreement with the theoretical model.Conclusion: These results indicated that the interactions between the charged nanoparticles and the cells resulted from various forces (eg, electrostatic forces, hydrophobic forces, bending and stretching forces, and limited receptor-mediated endocytosis), and the uptake of the nanoparticles occurred as a result of competition.Keywords: coumarin-6, nanoparticles, cellular uptake, Deserno’s model

Bo Li1, Hui Xu2, Zhen Li1, Mingfei Yao1, Meng Xie1, Haijun Shen1, Song Shen1, Xinshi Wang1, Yi Jin11College of Pharmaceutical sciences, Zhejiang University, Hangzhou, 2No. 202 Hospital of People's Liberation Army, Shenyang, ChinaBackground: Multidrug resistance (MDR) mediated by the overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), remains one of the major obstacles to effective cancer chemotherapy. In this study, lipid/particle assemblies named LipoParticles (LNPs), consisting of a dimethyldidodecylammonium bromide (DMAB)-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticle core surrounded by a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) shell, were specially designed for anticancer drugs to bypass MDR in human breast cancer cells that overexpress P-gp.Methods: Doxorubicin (DOX), a chemotherapy drug that is a P-gp substrate, was conjugated to PLGA and encapsulated in the self-assembled LNP structure. Physiochemical properties of the DOX-loaded LNPs were characterized in vitro. Cellular uptake, intracellular accumulation, and cytotoxicity were compared in parental Michigan Cancer Foundation (MCF)-7 cells and P-gp-overexpressing, resistant MCF-7/adriamycin (MCF-7/ADR) cells.Results: This study found that the DOX formulated in LNPs showed a significantly increased accumulation in the nuclei of drug-resistant cells relative to the free drug, indicating that LNPs could alter intracellular traffic and bypass drug efflux. The cytotoxicity of DOX loaded-LNPs had a 30-fold lower half maximal inhibitory concentration (IC50) value than free DOX in MCF-7/ADR, measured by the colorimetric cell viability (MTT) assay, correlated with the strong nuclear retention of the drug.Conclusion: The results show that this core-shell lipid/particle structure could be a promising strategy to bypass MDR.Keywords: chemotherapy, drug delivery, polymeric nanoparticles, multidrug resistance