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Rui Zhang,1,* Yongjian Mai,1,* Huijing Ye,2,* Xiufen Lian,2 Huasheng Yang,2 Yanling Zhu,1 Xiaoliang Gan1 1Department of Anesthesiology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, People’s Republic of China; 2Department of Orbital Diseases and Ocular Oncology, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoliang Gan; Yanling Zhu, Email ganxl@mail.sysu.edu.cn; zhuyling8@mail.sysu.edu.cnBackground and Objectives: Opioid-minimizing strategies are making their appearance in enhanced recovery after surgery. This study is aimed to explore the potential advantages of opioid-free analgesia (OFA) compared to opioid-sparing analgesia (OSA) in patients undergoing orbital fracture reconstruction.Methods: In this prospective, single-center, randomized controlled study, we randomly recruited 122 patients undergoing orbital fracture reconstruction under general anesthesia. Patients received total intravenous anesthesia with a flexible laryngeal mask airway, and multimodal analgesia with either OSA or OFA methods. The OSA group (n = 61) received low doses of fentanyl and nonsteroidal anti-inflammatory drugs (NSAIDs), and the OFA group (n = 61) received medial canthus peribulbar block (MCPB) combined with NSAIDs. The primary outcomes consisted of area-under-the-curve (AUC) of the numerical rating scale (NRS) pain score, and the incidence of postoperative nausea and vomiting (PONV) through the first 24h.Results: Compared to the OSA group, the OFA group demonstrated non-inferiority in postoperative analgesia through the first 24 postoperative hours (difference of the medians, − 6; 95% confidence interval [CI], − 12 to 6), but failed to meet the non-inferiority criterion in the incidence of PONV (difference ratio, 3%; 95% CI, − 7% to 14%). The Quality of Recovery-40 questionnaire (QoR-40) scores on postoperative day 1 was significantly higher in group OFA compared to group OSA (188 [178 to 196] vs 181 [169 to 191], respectively; P = 0.005).Conclusion: In orbital fracture reconstruction, both OFA and OSA strategies provide effective postoperative pain relief, but OFA using MCPB combined NSAIDs enhances the quality of early postoperative recovery.Registered: Chinese Clinical Trial Registry ChiCTR1900028088.Keywords: peribulbar block, opioid-free, opioid-sparing, analgesia, orbital fracture reconstruction

Yuhua Mai,1,2 Liheng Meng,1 Ganlu Deng,2,3 Yingfen Qin1 1Department of Endocrinology, The First Affiliated Hospital of GuangXi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Yingfen Qin, Department of Endocrinology, The First Affiliated Hospital of GuangXi Medical University, Nanning, 530021, Guangxi, People’s Republic of China, Tel/Fax +86-13607862619, Email yingfenq@126.com Ganlu Deng, Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Tel/Fax +86-15676132389, Email dengganlu@gxmu.edu.cnAbstract: With changes in modern lifestyles, type 2 diabetes mellitus (T2DM) has become a global epidemic metabolic disease, and hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. T2DM is a complex metabolic disorder and has been considered an independent risk factor for HCC. Growing evidence supports that T2DM-related risk factors facilitate hepatocarcinogenesis via abundant mechanisms. With the wide implementation of microbiomics, transcriptomics, and immunotherapy, the understanding of the complex mechanisms of intestinal flora and immune cell subsets have advanced tremendously in T2DM-related HCC, uncovering new findings in T2DM-related HCC patients. In addition, reports have indicated the different effects of anti-DM drugs on the progression of HCC. In this review, we summarize the effects of major T2DM-related risk factors (including hyperglycemia, hyperinsulinemia, insulin, chronic inflammation, obesity, nonalcoholic fatty liver disease, gut microbiota and immunomodulation), and anti-DM drugs on the carcinogensis and progression of HCC, as well as their potential molecular mechanisms. In addition, other factors (miRNAs, genes, and lifestyle) related to T2DM-related HCC are discussed. We propose a refined concept by which T2DM-related risk factors and anti-DM drugs contribute to HCC and discuss research directions prompted by such evidence worth pursuing in the coming years. Finally, we put forward novel therapeutic approaches to improve the prognosis of T2DM-related HCC, including exploiting novel diagnostic biomarkers, combination therapy with immunocheckpoint inhibitors, and enhancement of the standardized management of T2DM patients.Keywords: type 2 diabetes mellitus, hepatocellular carcinoma, NAFLD, gut microbiota, inflammatory, immunotherapy

Wanjiao Chen,1 Li Wang,1 Bin Hu,1 Ying Zheng,1 Shuya Zhang,1 Zhong Zhou,2 Yifeng Mai2 1Health Science Center, Ningbo University, Ningbo, 315020 People’s Republic of China; 2The First Affiliated Hospital of Ningbo University, Ningbo, 315020, People’s Republic of ChinaCorrespondence: Zhong Zhou; Yifeng Mai, The First Affiliated Hospital of Ningbo University, 247 Renmin Road, Jiangbei District, Ningbo, Zhejiang Province, 315020, People’s Republic of China, Tel +8613736099999, Email zhouz70@163.com; fymaiyifeng@nbu.edu.cnObjective: This study aimed to compare the predictive value of carotid or femoral artery ultrasound for coronary artery disease (CAD) in type 2 Diabetes mellitus (T2DM) patients free from known CAD, and to assess the relationship with the severity of coronary artery stenosis.Methods: Cross-sectional study in adults with a T2DM duration of at least 5 years and without established CAD. Carotid plaque score (CPS) and Gensini score were used to measure the severity of carotid and coronary artery stenosis, respectively, and patients were divided into no or mild group, moderate group, and severe group according to the tertile of the score. Univariate and multivariate logistic regression analysis was used to explore the possible risk factors for CAD. Receiver operating characteristic (ROC) curves were created to determine the most accurate assessment for detecting significant CAD (≥ 50% stenosis).Results: 245 patients (137 male) aged 68.21± 9.5 years (range: 36– 95 years), with T2DM duration 12.04± 6.17 years (range: 5– 34 years), and without CVD were included. CAD was diagnosed in 165 patients (67.3%). Multiple regression analysis showed that CPS, femoral plaque, and smoking were independently and positively correlated with CAD. CPS yielded the highest area under the curve for detecting significant coronary disease (AUC=0.7323). In contrast, the area under the curve of femoral artery plaque and carotid intima-media thickness was lower than 0.7, which was at a lower prediction level.Conclusion: In patients with long T2DM duration, CPS has a higher ability to predict the occurrence and severity of CAD. However, femoral artery plaque has special value in predicting moderate to severe coronary artery disease in patients with long-term T2DM.Keywords: peripheral atherosclerosis, coronary artery disease, type 2 diabetes mellitus, Gensini score, carotid plaque score, femoral artery plaque

Ruojing Qian,1– 3,* Zhaoyu Xu,4,* Xingyu Hu,1– 3 Suru Liu,1– 3 Yao Mai,1– 3 Xinzhi Tan,1– 3 Xiaofan Su,1– 3 Mingyan Jiang,1– 3 Wei Tang,1– 3 Weidong Tian,1– 3 Li Xie1– 3 1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 4Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weidong Tian; Li Xie, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Engineering Research Center of Oral Translational Medicine, Ministry of Education & National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85502156 ; +86-28-85503499, Email drtwd@sina.com; samuel@163.comPurpose: A synergistic antibacterial system employing photocatalytic performance and low-temperature photothermal effect (LT-PTT) with the potential for infectious skin wound healing promotion was developed.Methods: Ag/Ag2O was synthesized with a two-step method, and its physicochemical properties were characterized. After its photocatalytic performance and photothermal effect were evaluated under 0.5 W/cm2 808 nm NIR laser irradiation, its antibacterial activities in both planktonic and biofilm forms were then studied in vitro targeting Staphylococcus Aureus (S. aureus), and the biocompatibility was tested with L-929 cell lines afterward. Finally, the animal model of dorsal skin wound infection was established on Sprague-Dawley rats and was used to assess infectious wound healing promotion of Ag/Ag2O in vivo.Results: Ag/Ag2O showed boosted photocatalytic performance and local temperature accumulation compared with Ag2O when exposed to 0.5 W/cm2 808 nm NIR irradiation, which therefore endowed Ag/Ag2O with the ability to kill pathogens rapidly and cleavage bacterial biofilm in vitro. Furthermore, after treatment with Ag/Ag2O and 0.5 W/cm2 808 nm NIR irradiation, infectious wounds of rats realized skin tissue regeneration from a histochemical level.Conclusion: By exhibiting excellent NIR-triggered photocatalytic sterilization ability enhanced by low-temperature photothermal effect, Ag/Ag2O was promising to be a novel, photo-responsive antibacterial agent.Keywords: semiconductor/metal hybrid, antibacterial agent, photo-responsive antibacterial activity, reactive oxygen species, infectious wound skin model

Background Elderly population are at increased risk of spinal anesthesia-induced hypotension increasing their risk for postoperative morbidity and mortality. This study aimed to compare the hemodynamic effects of prophylactic infusion of norepinephrine (NE) versus phenylephrine (PE) in elderly patients undergoing hip fracture surgery under spinal anesthesia. Methods Elderly patients scheduled for hip fracture surgery were randomized to receive either NE infusion (8 µg/min) (NE group, n = 31) or PE infusion (100 µg/min) (PE group, n = 31) after spinal anesthesia. Outcomes included mean heart rate, mean blood pressure, cardiac output, incidence of spinal anesthesia-induced hypotension, incidence of bradycardia, and incidence of hypertension. Results Sixty-two patients with a mean age of 71 ± 6 years were included in the final analysis (31 patients in each group). The NE group showed a higher mean heart rate and cardiac output than the PE group. The NE group had a lower incidence of reactive bradycardia (10% vs. 36%, P = 0.031) and hypertension (3% vs. 36%, P = 0.003) than the PE group. No study participant developed hypotension, and the mean blood pressure was comparable between the two groups. Conclusions Both NE and PE infusions effectively prevented spinal anesthesia-induced hypotension in elderly patients undergoing hip fracture surgery. However, NE provided more hemodynamic stability than PE; maintaining the heart rate, higher cardiac output, less reactive bradycardia, and hypertension.

Sanjay K Agarwal,1 Sukhbir S Singh,2 David F Archer,3 Yabing Mai,4 Kristof Chwalisz,5 Keith Gordon,6 Eric Surrey7 1Department of Obstetrics and Gynecology and Reproductive Sciences, Center for Endometriosis Research and Treatment, UC San Diego, La Jolla, CA, USA; 2Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; 3Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA; 4 Statistics, AbbVie Inc, North Chicago, IL, USA; 5Clinical Development, AbbVie Inc, North Chicago, IL, USA; 6Medical Affairs, AbbVie Inc, North Chicago, IL, USA; 7Colorado Center for Reproductive Medicine, Lone Tree, CO, USACorrespondence: Sanjay K AgarwalDepartment of Obstetrics and Gynecology and Reproductive Sciences, Center for Endometriosis Research and Treatment, UC San Diego, 9500 Gilman Drive, #0633, La Jolla, CA, USATel +1 (858) 534-8930Email skagarwal@ucsd.eduObjective: In this post hoc analysis, we evaluated the impact of elagolix on dysmenorrhea and nonmenstrual pelvic pain across menstrual period (bleeding days) and nonmenstrual (nonbleeding) days.Methods: Data from two randomized, 6-month, placebo-controlled trials (Elaris Endometriosis (EM)-I and EM-II) of elagolix (150 mg once daily (QD) and 200 mg twice daily (BID)) in premenopausal women with moderate to severe endometriosis-associated pain (N = 1686) were pooled. Women recorded the presence of menstrual period and severity of dysmenorrhea or nonmenstrual pelvic pain in a daily electronic diary.Results: At baseline, women in the placebo group and both elagolix treatment groups reported moderate or severe dysmenorrhea, on average, 81% of their menstrual period days and moderate/severe nonmenstrual pelvic pain, on average, 56% of their nonmenstrual (nonbleeding) days. Compared with placebo at month 6, elagolix-treated women had a significantly lower mean (standard deviation (SD)) percentage of menstrual period days with moderate or severe dysmenorrhea (elagolix 150 mg QD = 52.4 (38.9), p = 0.002; elagolix 200 mg BID = 38.5 (43.6), p < 0.001, placebo = 61.3 (33.7)) and a significantly lower mean (SD) percentage of nonmenstrual (nonbleeding) days with moderate or severe nonmenstrual pelvic pain (elagolix 150 mg QD = 31.1 (35.8), p < 0.001; elagolix 200 mg BID = 19.7 (29.9), p < 0.001; placebo = 35.6 (33.9)).Conclusion: Following 6 months of elagolix treatment, women who still menstruated had a lower proportion of menstrual period days with moderate or severe dysmenorrhea compared with placebo, demonstrating pain reduction despite continued menses. Additionally, pain did not shift from dysmenorrhea to nonmenstrual pelvic pain, as the percentage of days with moderate or severe nonmenstrual pelvic pain was also reduced for elagolix-treated women compared with placebo.Trial Registration: The Elaris EM-I study is registered with the US National Library of Medicine, www.ClinicalTrials.gov, NCT01620528. The Elaris EM-II study is registered with the US National Library of Medicine, www.ClinicalTrials.gov, NCT01931670. Both studies are registered with the EU Clinical Trial Register, www.clinicaltrialsregister.ed, 2011-004295-11.Keywords: bleeding, dysmenorrhea, elagolix, endometriosis, nonmenstrual pelvic pain

Objective The aim of this study was to investigate early atherosclerotic changes in juvenile-onset systemic lupus erythematosus (jSLE) patients and its relation with disease activity. Patients and methods Thirty patients suffering from jSLE diagnosed according to the 2012 SLICC SLE criteria were included in the study. Clinical and laboratory parameters, disease activity, and traditional risk factors for atherosclerosis were assessed. B-mode ultrasound was performed to measure carotid intima–media thickness (CIMT) and the number and size of plaque deposits in both the left and the right common carotid arteries. A total of 20 healthy volunteers were taken as a control group. Results The mean±SD age of the patients was 18.93±2.81. The mean±SD disease duration was 4.33±2.25. The mean±SD CIMT differed significantly between the patient and control (n=20) groups (0.74±0.21 vs. 0.38±0.05; P