Search

Yan-fei Lu,1,* Ji-min Wu,2,* Hai-yan Lan,2 Qiao-min Xu,2 Shu-qi Shi,2 Gong-chen Duan2 1Center for Rehabilitation Medicine, Department of Anesthesiology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, People’s Republic of China; 2Department of Anesthesiology, Lishui People’s Hospital, Wenzhou Medical University Lishui Hospital, Lishui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gong-chen Duan, Department of Anesthesiology, Lishui People’s Hospital, Wenzhou Medical University Lishui Hospital, No. 1188, Liyang Street, Lishui, Zhejiang, 323000, People’s Republic of China, Tel/Fax +8618957093030, Email 981225178@qq.comBackground: Ciprofol is a new intravenous sedative / anesthetic drug. In recent years, many clinical studies have also confirmed the sedative effect of ciprofol. However, more clinical research is still needed on its clinical application characteristics in special populations.Objective: The aim of this study was to compare the clinical effects of ciprofol and propofol in general anesthesia induction of elderly patients.Methods: 60 elderly (aged ≥ 75 years) patients underwent hip fracture surgery were randomly into two groups of a 1:1 ratio. Group C (ciprofol group): 0.3mg/kg ciprofol was infused. Group P (propofol group): 1.5mg/kg propofol was infused. The observation period was from the infusion of test drug to 5 min after endotracheal intubation. The primary outcomes included the incidence of severe hypotension and hypotension during the observation period. The secondary outcomes were as follows: the success rate of general anesthesia induction, the number of additional sedation, the time of loss of consciousness (LOC), Δ MAP, Δ HR, adverse events and the frequency of vasoactive drugs used.Results: Finally, 60 subjects completed the study. Compared with Group P, the incidence of severe hypotension in Group C was lower (26.7% vs 53.3%, P = 0.035), the incidence of hypotension was also lower (36.7% vs 63.3%, P = 0.037), Δ MAP in Group C was significantly lower (31.4 ± 11.4 vs 39.6 ± 15.7, P = 0.025), the frequency of ephedrine used and the incidence of injection pain in Group C were also significantly lower.Conclusion: Ciprofol showed similar efficacy to propofol when used for general anesthesia induction in elderly patients underwent hip fracture surgery and could maintain more stable blood pressure.Keywords: Ciprofol, elderly, Hip fracture surgery, general anesthesia, hypotension

Introdução: A Hemofilia é uma coagulopatia hereditária caracterizada clinicamente por sangramentos em musculatura profunda, articulações, e pós-procedimentos cirúrgicos, sobretudo na boca. O cirurgião dentista desempenha função primordial na equipe inter e multidisciplinar de atendimento a hemofílicos. Objetivo: Relatar um caso clínico definidor para o diagnóstico tardio de hemofilia em paciente adolescente. Relato de caso: Paciente masculino, 14 anos, branco, residente Manaus-AM, foi internado em Pronto Socorro (PS) devido hemorragia bucal, após submetido a exodontia de 1o molar. Como manobra inicial, foi realizada rafia local para o controle hemorrágico e transfusão de CRIO e PFC, prescrição de Ceftriaxona e Clindamicina. Os exames laboratoriais iniciais não apontavam alterações, mas sem o controle adequado do sangramento, o adolescente foi encaminhado ao centro de referência para tratamento de doenças hematológicas e onco-hematológicas, depois dos 23 dias internado. Na anamnese, negou histórico familiar relacionado a coagulopatias e sangramentos espontâneos ou por traumas semelhantes. Paciente apresentava ansiedade elevada, estado psíquico de apreensão e medo, assimetria facial, edema lado esquerdo e usando sonda nasogástrica. No exame intraoral, ferida cirúrgica aberta no palato, estendendo-se da região entre os dentes 22 e 27, sangramento espontâneo e abundante, bordas irregulares, hiperplasiadas, áreas eritematosas, tecido de granulação e coágulos mal formados. O hemograma e coagulograma apresentavam dentro dos padrões de normalidade. O controle hemorrágico, precedeu por higienização técnica da ferida cirúrgica com solução fisiológica e clorexidina 0,12%, tamponamento à base de ácido tranexâmico em forma de pasta, com reposicionamento diário. As manobras foram suficientes para o controle do sangramento local e alta hospitalar depois de 3 dias. Contundo, manteve-se a suspeita de distúrbios da coagulação, pois a transfusão dos hemoderivados, possivelmente, mascarou o resultado. Novos exames foram solicitados 7 dias depois, a fim de ampliar a investigação. O TTPA elevado, 44,60 segundos, foi esclarecedor para guiar a hipótese e confirmar o diagnóstico de Hemofilia A leve (FVIII = 19.4%). Na investigação familiar, um dos irmãos teve o mesmo diagnóstico. Resultados: A interação cirurgião dentista e equipe médica foi essencial para o controle hemorrágico e definição diagnóstica. O adolescente foi incluído no programa integral de acompanhamento e tratamento ao hemofílico. Discussão: A forma leve da hemofilia A pode dificultar o diagnóstico precoce, às vezes sangramentos são discretos ou ocorrerão devido a traumas severos ou complicação cirúrgica. O cirurgião dentista poder ser o primeiro profissional a suspeitar da hemofilia, pelas condições geradas nos procedimentos odontológicos e ainda contribuir no diagnóstico, mesmo que tardio. As condutas são desafiadoras, devido à complexidade do processo diagnóstico, escassez de protocolos padronizados e quiçá profissionais capacitados no atendimento a hemofilia. Conclusão: O conhecimento clínico sobre hemofilia, talvez seja uma dificuldade enfrentada por profissionais de saúde, pois episódios hemorrágicos tendem a ocorrer e agravar se não tomadas as condutas adequadas, o que retarda o diagnóstico, aumenta o tempo de internação e riscos à qualidade de vida do paciente.

Background: This study aimed to compare the number of voids of primary anterior teeth obturated with Endoflas by using three different obturation techniques, namely, endodontic pressure syringe, modified disposable syringe, and reamer using cone-beam computed tomography (CBCT). Materials and Methods: Thirty-six single-rooted primary incisors and canines with lengths ranging within 15–22 mm were randomly divided into three groups (12 teeth/group) according to the obturation techniques used. Group A, endodontic pressure syringe; group B, modified disposable syringe; and group C, reamer. A single operator instrumented and obturated all teeth by using Endoflas. An independent evaluator analysed the quality of the obturation techniques by using CBCT imaging to determine the number of voids in the root canals. Fisher's exact test and multiple pairwise comparisons adjusted by the Dunn–Bonferroni method were used to statistically assess the results. Results: All study groups showed no statistically significant difference in the number of voids (P > 0.05). Comparing the thirds of each group, the coronal and middle thirds of group A contained the maximum number of voids, followed by groups B and C, with no statistically significant difference. For the apical third, voids were highly presented in group C followed by group B. Meanwhile, group A was found to have no voids. Conclusion: Within the limitations of the current research, we concluded that voids existed in all techniques used; however, they were the least when using endodontic pressure syringes. Thus, an endodontic pressure syringe used with an Endoflas obturation material may be preferred as an obturation technique.

Rami Al-Dwairi,1 Ahmad A Ahmad,2 Abdelwahab Aleshawi,1 Areen A Bani-Salameh,2 Ihsan A Aljarrah,2 Qais M Al-Bataineh,2,3 Seren Al Beiruti,1 Ali Omar Alshami,1 Edina Rusen,4 Gabriela Toader5 1Department of Special Surgery, Division of Ophthalmology, Faculty of Medicine, Jordan University of Science & Technology, Irbid, 22110, Jordan; 2Department of Physics, Thin Films and Nanotechnology Laboratory, Faculty of Science and Art, Jordan University of Science & Technology, Irbid, 22110, Jordan; 3Leibniz Institut für Analytische Wissenschaften‐ISAS‐e.V., Dortmund, 44139, Germany; 4Faculty of Chemical Engineering and Biotechnologies, University POLITEHNICA of Bucharest, Bucharest, 011061, Romania; 5Military Technical Academy “Ferdinand I”, Bucharest, 050141, RomaniaCorrespondence: Rami Al-Dwairi, Department of Special Surgery, Division of Ophthalmology, Faculty of Medicine, Jordan University of Science & Technology, P. O. Box: 3030, Irbid, 22110, Jordan, Tel +962799273019, Fax +962 2 7201064, Email ramialdwairi@yahoo.comObjective: Silicone oils have the role in maintaining the attachment of the retina in conditions where the risk of retinal re-detachment is high. However, silicone oils have the tendency to emulsify with subsequent complications. In this work, analyses have been performed to understand changes that occurred to the optical, and physical characteristics of the oil after removal from the vitreous cavity of patients underwent pars plana vitrectomy (PPV) for fibrovascular membranes/tractional retinal detachment (FVM/TRD).Methods: Four samples of silicone oil were allocated from patients who underwent PPV for FVM/TRD. The Fourier-transform infrared (FTIR) spectroscopy, micro-viscometry, and ultraviolet-visible spectrometer analyses were utilized to determine the changes in its chemical bondings, viscosity, absorbance, transmittance, buoyance, and specific gravity.Results: The mean age of the patients was 49.0 years. The mean duration of silicone oil implantation was 18.9 months. FTIR analysis showed significant breaking in the chemical bonding that was related to the lens status during the primary PPV, the presence of significant retinal hemorrhages, the duration of silicone oil implantation, and the degree of silicone oil filling. Similarly, viscosity and contact angle analyses revealed a reduction in the viscosity with similar factors to the FTIR analysis. Moreover, absorbance and transmittance were largely affected by the aggressiveness of FVM/TRD.Conclusion: This study revealed that certain factors such as the age of the patient, duration of silicone oil implantation, lens status, and the presence of retinal hemorrhages, the degree of silicone oil filling and aggressiveness of FVM/TRD may contribute to the emulsification process.Keywords: silicone oil, tractional retinal detachment, emulsification, viscosity

Cheng-Yi Hu,1 Wen-Shuai Cui,1 Yi Lei,1 Yu-Wen Tang,1 Yan-Yan Zhang,1 Qi-Min Su,1 Fang Peng,2 Yun-Fei Zeng,1 Jia-Lin Song,1 Cheng-Na Luo,1 Yan Zhou,1 Xin-Yan Li,1 Zhu-Xiang Zhao1 1Department of Infectious Diseases, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 2Department of Critical Care Medicine, the Third Affiliated Hospital of Guang Zhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Zhu-Xiang Zhao, Department of Infectious Diseases, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510515, People’s Republic of China, Email zhaozhuxiang@126.comPurpose: To compare the effectiveness of azvudine and nirmatrelvir/ritonavir for the treatment of coronavirus disease (COVID-19).Patients and Methods: We conducted a retrospective analysis of data from 576 patients with COVID-19, comprising 195 patients without antiviral therapy, 226 patients treated with azvudine, 114 patients treated with nirmatrelvir/ritonavir, and 41 patients were treated with azvudine and nirmatrelvir/ritonavir concurrently. We compared their symptoms, mortality rates, and the length and cost of hospitalization.Results: The incidence of symptoms was similar in patients treated with azvudine and in those treated with nirmatrelvir/ritonavir. However, among patients experiencing weakness, the duration of weakness was significantly shorter in the azvudine group than in the nirmatrelvir/ritonavir group (P=0.029). Mortality did not differ significantly between the azvudine group and the nirmatrelvir/ritonavir group (18.14% vs.10.53%, P=0.068). Among “severe patients”, the mortality rate was markedly lower in patients treated with nirmatrelvir/ritonavir than in patients treated with azvudine (16.92% vs.32.17%, P=0.026). In patients with hepatic insufficiency, those treated with nirmatrelvir/ritonavir had substantially lower mortality than those treated with azvudine (15.09% vs.34.25%, P=0.016). In addition, patients treated with nirmatrelvir/ritonavir had longer hospital stays (P=0.002) and higher hospital costs (P< 0.001) than those receiving azvudine. Compared with patients treated with nirmatrelvir/ritonavir or azvudine alone, patients taking nirmatrelvir/ritonavir and azvudine concurrently had no significant improvement in survival (P> 0.05), length of stay (P> 0.05), or hospital costs (P> 0.05).Conclusion: Azvudine is recommended for patients with non-severe COVID-19 with weakness. Nirmatrelvir/ritonavir is recommended for patients with severe COVID-19, to reduce mortality, and it could be the best choice for patients with hepatic insufficiency. The concurrent use of nirmatrelvir/ritonavir and azvudine in patients with COVID-19 could be not recommended.Keywords: azvudine, nirmatrelvir/ritonavir, COVID-19, SARS-CoV-2

To characterize genomic determinants of response to pembrolizumab in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 study. Associations between biomarkers (tumor mutational burden (TMB), neoantigen load (NL), 18-gene T-cell-inflamed gene expression profile (TcellinfGEP), and PD-L1 combined positive score (CPS)) and clinical outcomes with pembrolizumab were assessed in patients with R/M HNSCC (n=192). Tumor human papillomavirus (HPV) status was also evaluated with the use of p16 immunohistochemistry and whole exome sequencing (WES; HPV+, mapping >20 HPV reads) in pretreatment tumor samples (n=106). TMB, clonality-weighted TMB, and TcellinfGEP were significantly associated with objective response (p=0.0276, p=0.0201, and p=0.006, respectively), and a positive trend was observed between NL and PD-L1 CPS and clinical response (p=0.0550 and p=0.0682, respectively). No correlation was observed between TMB and TcellinfGEP (Spearman ρ=-0.026) or TMB and PD-L1 (Spearman ρ=0.009); a correlation was observed between TcellinfGEP and PD-L1 (Spearman ρ=0.511). HPV status by WES and p16 immunohistochemistry showed concordance (84% ҡ=0.573) among patients whose HPV results were available using both methods. TMB and inflammatory biomarkers (TcellinfGEP and PD-L1) may represent distinct and complementary biomarkers predicting response to anti-programmed death 1 therapies in HNSCC; further study of these relationships in randomized clinical trials is needed. NCT01848834.

Xulin Liao,1,2 Chu Qi Li,1 Qian Min Ge,1 Li Ying Tang,3 Ting Su,4 Qiu Yu Li,1 Yi Cong Pan,1 Hui Ye Shu,1 Li Juan Zhang,1 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong SAR, People’s Republic of China; 3Department of Ophthalmology, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, 361004, People’s Republic of China; 4Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, 02114, USACorrespondence: Yi Shao, Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, Yong Wai Zheng Street, Dong Hu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86 791-88692520, Email freebee99@163.comPurpose: The purpose of this study was to use the percent amplitude of fluctuation (PerAF) to study the changes in brain activity and nerve function of herpes zoster keratitis (HZK) patients.Methods: We recruited 20 HZK patients and 20 healthy controls (HCs). Each of these groups included ten males and ten females and were matched in weight and age. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI). The percent amplitude of fluctuation (PerAF) method was used for analysis and detected differences between the two groups in the neurological function of brain areas. We also applied the receiver operating characteristic (ROC) curve to analyze the two groups and did a correlation analysis between the PerAF value, anxiety and depression score, and visual acuity.Results: The PerAF signal at the right putamen and right precentral gyrus was significantly higher in patients than in HCs. However, the PerAF value of the left inferior temporal was lower in patients than in HCs. In addition, the HZK patients’ anxiety and depression score (HADS) and visual acuity (V.A.) Log MAR negatively correlated with the PerAF value at the left inferior temporal gyrus.Conclusion: HZK patients had some changes in brain regions, and the changes were also related to their mood and visual acuity. These findings might contribute to other studies on the potential pathological mechanism, disease development, prognosis, and brain function in HZK patients.Keywords: herpes zoster keratitis, resting-state functional magnetic resonance imaging, brain activity patterns, brain region, the percent amplitude of fluctuation

Qi Zhang,&ast; Yue-Xiang Ma,&ast; Zheng Dai, Bin Zhang, Shan-Shou Liu, Wen-Xiu Li, Chuan-Qing Fu, Qian-Mei Wang, Wen Yin Department of Emergency, Xijing Hospital, Air Force Medical University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Yin, Department of Emergency, Xijing Hospital, Air Force Medical University, No. 127 Changlexi Road, Xi’an, 710032, People’s Republic of China, Email xjyyyw@fmmu.edu.cnAbstract: Numerous studies on the formulation and clinical applications of novel hemoglobin-based oxygen carriers (HBOCs) are reported in the scientific literature. However, there are fewer scientometric analysis related to HBOCs. Here, we illustrate recent studies on HBOCs using both a scientometric analysis approach and a scope review method. We used the former to investigate research on HBOCs from 1991 to 2022, exploring the current hotspots and research trends, and then we comprehensively analyzed the relationship between concepts based on the keyword analysis. The evolution of research fields, knowledge structures, and research topics in which HBOCs located are revealed by scientometric analysis. The elucidation of type, acting mechanism, potential clinical practice, and adverse effects of HBOCs helps to clarify the prospects of this biological agent. Scientometrics analyzed 1034 publications in this research field, and these findings provide a promising roadmap for further study.Keywords: blood substitutes, trauma, hemorrhagic shock, organ preservation, anemia, risk management

Jipeng Shi,1 Zhen-Qi Lu,1 Qing-Mei Lin,2 Wang Zeng,1 Ping-Jiao Gu,1 Qing Yu,3 Jing Long,1 Da-Gui Huang,1 Yi-Heng Dai1 1Department of Neonatal, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan, Guangdong, 528000, People’s Republic of China; 2Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan, Guangdong, 528000, People’s Republic of China; 3Department of Clinical Laboratory, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan, Guangdong, 528000, People’s Republic of ChinaCorrespondence: Yi-Heng Dai, Email daiyiheng@163.comBackground: There are many difficulties and uncertainties in the early diagnosis of neonatal sepsis. The aim of this study was to determine whether albumin (ALB) is useful for the early diagnosis of neonatal sepsis using ALB, C-reactive protein (CRP) and procalcitonin (PCT) together.Methods: ALB, CRP, PCT and white blood cell (WBC) data from 732 patients with neonatal sepsis and 1317 neonatal infection patients hospitalized in Foshan Maternal and Child Health Hospital from 2011 to 2022 were collected. Receiver operating characteristic (ROC) and logistic regression analyses were performed to assess the diagnostic value of ALB, CRP, PCT and the WBC count for neonatal sepsis. The roles of ALB, CRP, PCT and the WBC count in the diagnosis of neonatal sepsis were analysed by using subject working characteristics (ROC) and areas under the curve (AUCs), and the variables were combined to determine which combination had the best diagnostic efficacy.Results: In the sepsis group, the ALB, CRP, and PCT levels and the WBC count were significantly higher than those in the infection group (P< 0.001). In all infants, the sensitivities and specificities of ALB, CRP, PCT, and WBC count were 0.411, 0.596, 0.483 and 0.411, respectively, and 0.833, 0.846, 0.901 and 0.796, respectively. With a sensitivity of 0.646, a specificity of 0.929, and an AUC of 0.834, the best combination was that of ALB, CRP, and PCT, which was better than that of CRP + PCT, CRP + ALB and PCT + ALB.Conclusion: In neonatal sepsis, in the absence of blood culture results, the combination of ALB, CRP, and PCT is more reliable than CRP, PCT, or CRP+PCT alone. These results suggest that ALB is a useful inflammatory biomarker for the early diagnosis of neonatal sepsis, and can improve the diagnostic efficiency.Keywords: albumin, C-reactive protein, procalcitonin, diagnosis, neonatal sepsis

Bo Wang, Qi-Mao Wang, De-Xin Li Department of Neonatology, The Hospital of Suixi County, Huaibei, People’s Republic of ChinaCorrespondence: Bo Wang, Department of Neonatology, The Hospital of Suixi County, No. 114 of Xihe Road, Suixi County, Huaibei, Anhui, 235000, People’s Republic of China, Tel +86-05616091010, Email bowangwb1908@163.comObjective: To investigate the primary predictive factors for the occurrence of severe neonatal infection, construct a prediction model and assess its effectiveness.Methods: A total of 160 neonates hospitalised in the Department of Neonatology at Suixi County Hospital from January 2019 to June 2022 were retrospectively analysed. Clinical data was analyzed to determine the primary predictive factors for the occurrence of severe neonatal infection. Predictive efficacy was evaluated using a receiver operating characteristic curve, and a nomogram model was constructed according to the predictors. A bootstrap technique was used to verify the accuracy of the model.Results: The neonates were divided, based on the degree of infection, into a mild infection group (n = 80) and a severe infection group (n = 80) according to a 1:1 ratio. Multivariate logistic regression analysis showed that compared with the recovery stage, white blood cell count (WBC) and platelet count (PLT) in the two groups were significantly decreased in the early stage of infection, and the ratio of mean platelet volume to PLT, as well as C-reactive protein (CRP) and procalcitonin levels, was elevated (P

Jing Guo,&ast; Zhong-Da Liu,&ast; Yin-Ping Feng, Shui-Rong Luo, Qiao-Min Jiang Department of Tuberculosis, Lishui Hospital of Traditional Chinese Medicine, Lishui, 323000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiao-Min Jiang, Department of Tuberculosis, Lishui Hospital of Traditional Chinese Medicine, Lishui, 323000, People’s Republic of China, Tel +86 578-2668397, Email jiangqiaominjqm8@126.comObjective: Compared to younger patients with tuberculosis (TB), elderly and senile-aged patients with TB had a higher incidence of adverse outcomes particularly in terms of lost to follow-up and deaths. Our study aimed to gain insight into the effectiveness of anti-tuberculosis (anti-TB) treatment in the elderly or senile-aged patients and identify the risk factors for adverse outcomes.Methods: The case information was obtained from the “Tuberculosis Management Information System”. From January 2011 to December 2021, this retrospective analysis was conducted in Lishui City, Zhejiang Province to observe and record the outcomes of elderly patients diagnosed with TB who agreed to receive anti-TB and(or) traditional Chinese medicine(TCM) treatment. We also employed a logistic regression model to analyze the risk factors for adverse outcomes.Results: Among the 1191 elderly or senile-aged patients with TB who received the treatment, the success rate was 84.80% (1010/1191). Using logistic regression analysis, several risk factors for adverse outcomes (failure, death, loss to follow-up) were identified, including age ≥ 80 years (OR 2.186, 95% CI 1.517~3.152, P< 0.001), lesion area ≥ 3 lung fields (OR 0.410, 95% CI 0.260~0.648, P< 0.001), radiographic lesions failing to improve after 2 months of treatment (OR 2.048, 95% CI 1.302~3.223, P=0.002), sputum bacteriology failing to turn negative after 2 months of treatment (OR 2.213, 95% CI 1.227~3.990, P=0.008), lack of a standardized treatment plan (OR 2.095, 95% CI 1.398~3.139, P< 0.001), and non-involvement of traditional Chinese medicine (OR 2.589, 95% CI 1.589~4.216, P< 0.001).Conclusion: The anti-TB treatment success rate in the elderly and senile-aged patients is suboptimal. Contributing factors include advanced age, extensive lesions, and low sputum negative conversion rate during the intensive treatment phase. The results will informative and could be useful for policy maker for to control of reemergence of TB in big cities.Keywords: anti-tuberculosis treatment, lung, senile-aged patients, Tuberculosis, risk factors

Quentin M Anstee,1,2 Kate Hallsworth,1,2 Niall Lynch,3 Adrien Hauvespre,4 Eid Mansour,5 Sam Kozma,5 Juliana Bottomley,6 Gary Milligan,7 James Piercy,8 Victoria Higgins9 1Translational & Clinical Research Institute, Faculty of Medical Sciences, University of Newcastle, Newcastle Upon Tyne, UK; 2Liver Unit, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 3Global Value and Access, Gilead Sciences, Hayes, Uxbridge, UK; 4Market Access and Reimbursement, Gilead Sciences, Hayes, Uxbridge, UK; 5Pricing and Market Access (Middle East), Gilead Sciences, Dubai, United Arab Emirates; 6Pricing and Market Access, Gilead Sciences, Hayes, Uxbridge, UK; 7Statistics Department, Adelphi Real World, Bollington, UK; 8Scientific Franchise, Adelphi Real World, Bollington, UK; 9Scientific and NASH Franchise, Adelphi Real World, Bollington, UKCorrespondence: Victoria Higgins, Adelphi Real World, Adelphi Mill, Grimshaw Lane, Bollington, SK10 5JB, UK, Tel +44 1625 577233, Email victoria.higgins@adelphigroup.comObjective: Stratifying disease severity in patients with non-alcoholic steatohepatitis (NASH) is essential for appropriate treatment and long-term management. Liver biopsy is the reference standard for fibrosis severity in NASH, but less invasive methods are used, eg, Fibrosis-4 Index (FIB-4) and vibration-controlled transient elastography (VCTE), for which reference thresholds for no/early fibrosis and advanced fibrosis are available. We compared subjective physician assessment of NASH fibrosis versus reference thresholds to understand classification in a real-world setting.Methods: Data were drawn from Adelphi Real World NASH Disease Specific ProgrammeTM conducted in France, Germany, Italy, Spain and UK in 2018. Physicians (diabetologists, gastroenterologists, hepatologists) completed questionnaires for five consecutive NASH patients presenting for routine care. Physician-stated fibrosis score (PSFS) based on available information was compared with clinically defined reference fibrosis stage (CRFS) determined retrospectively using VCTE and FIB-4 data and eight reference thresholds.Results: One thousand two hundred and eleven patients had VCTE (n = 1115) and/or FIB-4 (n = 524). Depending on thresholds, physicians underestimated severity in 16– 33% (FIB-4) and 27– 50% of patients (VCTE). Using VCTE ≥ 12.2, diabetologists, gastroenterologists and hepatologists underestimated disease severity in 35%, 32%, and 27% of patients, respectively, and overestimated fibrosis in 3%, 4%, and 9%, respectively (p = 0.0083 across specialties). Hepatologists and gastroenterologists had higher liver biopsy rates than diabetologists (52%, 56%, 47%, respectively).Conclusion: PSFS did not consistently align with CRFS in this NASH real-world setting. Underestimation was more common than overestimation, potentially leading to undertreatment of patients with advanced fibrosis. More guidance on interpreting test results when classifying fibrosis is needed, thereby improving management of NASH.Keywords: fibrosis staging, non-alcoholic steatohepatitis, clinically derived reference fibrosis score, physician-stated fibrosis score, real-world evidence

Xin Xiong,1,&ast; Rong Rong,2,&ast; Li-Ying Tang,3,&ast; Tie Sun,1 Yi-Cong Pan,1 Hui-Ye Shu,1 Li-Juan Zhang,1 Qian-Min Ge,1 Rong-Bin Liang,1 Yi Shao1 1Department of Pathology and Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Centre of Natural Ocular Disease Clinical Research Center, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 3Department of Ophthalmology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian Province, 361004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Shao, Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, Yong Wai Zheng Street, Dong Hu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86 791-88692520, Email freebee99@163.comObjective: To explore the risk factors of ocular metastasis (OM) in patients with hepatocellular carcinoma (HCC) by analyzing the demographic characteristics and serum markers.Methods: From July 2002 to December 2012, 1064 HCC patients were included in our study. The chi-squared test and Student’s t-test were used to assess the difference between OM and any other metastasis (NOM). Receiver operating curve (ROC) was used to analyze the diagnostic value of serum biomarkers in HCC patients with OM.Results: The incidence of OM in HCC patients was 1.88% in our research. There are no significant differences in age, gender, or histopathology in the OM group and the group without any metastasis. Binary logistic regression analysis presented that compared with the patients without cancer metastasis, carbohydrate antigen 125 (CA-125) and hemoglobin (Hb) were risk factors in hepatocellular carcinoma patients with OM (P < 0.05). The ROC curve analysis showed that the areas under the CA-125, Hb, and CA125+Hb curves were 0.877, 0.554, and 0.431, and the cutoff values of CA-125 and Hb each were 115.78 u/mL and 120.50 g/L.Conclusion: Our data suggest that CA-125 and Hb are risk indicators in hepatocellular carcinoma patients with OM, and that CA-125+Hb has potentially greater utility in diagnosing hepatocellular carcinoma.Keywords: hepatocellular carcinoma, ocular metastases, CA-125, Hb, risk factors

Objective To estimate the ‘cost of illness’ arising from chronic wounds in Singapore.Design Incidence-based cost of illness study using evidence from a range of sources.Setting Singapore health services.Participants We consider 3.49 million Singapore citizens and permanent residents. There are 16 752 new individuals with a chronic wound in 2017, with 598 venous ulcers, 2206 arterial insufficiency ulcers, 6680 diabetic ulcers and 7268 pressure injuries.Primary outcome measures expressed in monetary terms are the value of all hospital bed days lost for the population; monetary value of quality-adjusted life years (QALYs) lost in the population; costs of all outpatient visits; and costs of all poly clinic, use of Community Health Assist Scheme (CHAS) and emergency departments (EDs) visits. Intermediate outcomes that inform the primary outcomes are also estimated.Results Total annual cost of illness was $350 million (range $72–$1779 million). With 168 503 acute bed days taken up annually (range 141 966–196 032) that incurred costs of $139 million (range 117–161 million). Total costs to health services were $184 million (range $120–$1179 million). Total annual costs of lost health outcomes were 2077 QALYs (range −2657 to 29 029) valued at $166 million (range −212 to 2399 million).Conclusions The costs of chronic wounds are large to Singapore. Costs can be reduced by making positive investments for comprehensive wound prevention and treatment programmes.

The mission of HL-2A is to explore the key physical topics relevant to ITER and to the advanced tokamak operation (e.g. the operation of future HL-2M), such as the access of H-mode, energetic particle physics, edge-localized mode (ELM) mitigation/suppression and disruption mitigation. Since the 2016 Fusion Energy Conference, the HL-2A team has focused on the investigations on the following areas: (i) pedestal dynamics and L-H transition, (ii) techniques of ELM control, (iii) turbulence and transport, (iv) energetic particle physics. The HL-2A results demonstrated that the increase of mean shear flow plays a key role in triggering L-I and I-H transitions, while the change of flow is mainly induced by the ion pressure gradient. Both mitigation and suppression of ELMs were realized by laser blow-off seeded impurity (Al, Fe, W). The 30% Ne mixture supersonic molecular beam injection seeding also robustly induced ELM mitigation. The ELMs were mitigated by low-hybrid current drive. The stabilization of m/n = 1/1 ion fishbone activities by electron cyclotron resonance heating was found on the HL-2A. A new m/n = 2/1 ion fishbone activity was observed recently, and the modelling indicated that passing fast ions dominantly contribute to the driving of 2/1 fishbone. The non-linear coupling between the toroidal Alfven eigenmode and tearing mode (TM) led to the generation of a high frequency mode with the toroidal mode number n = 0. The turbulence was modulated by TM when the island width exceeds a threshold and the modulation is localized merely in the inner area of the islands. Meanwhile, turbulence radial spread took place across the island region.

Hai-Ying Chen,1,&ast; Ming-Chao Li,2,&ast; Dan Liao,1 Chi Li,1 Qiu-Ming Ji,1 Ping Guo,1 Zou Su,1 Yu-Hong Yang,1 Wen-Hao Xiao,1 Wen-Hui Zhai1 1Department of Psychiatry, Wuhan Wudong Hospital, Wuhan, People’s Republic of China; 2Department of Psychiatry, Wuhan Mental Health Center, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dan Liao; Chi Li, Department of Psychiatry, Wuhan Wudong Hospital, No. 46 of Wudong Street, Qingshan District, Wuhan, 430084, People’s Republic of China, Tel +86 27 5052 8367, Fax +86 27 8643 8247, Email danliaodr@21cn.comObjective: Our study aimed to investigate the effects of computer-assisted cognitive remediation therapy (CCRT) on cognitive function, social function and quality of life in patients with vascular dementia (VD).Methods: Ninety-eight patients with VD were treated with CCRT in four 45-minute sessions per week over a course of 40 sessions to exercise four cognitive functions, including flexibility, working memory, plan execution and social cognition. The Mini-Mental State Examination (MMSE), Social Disability Screening Schedule (SDSS), Personal and Social Performance Scale (PSP), and Generic Quality of Life Inventory-74 (GQOL-74) were used to assess before and after treatment.Results: (1) The scores of orientation (5.60 ± 1.35), calculation (2.20 ± 0.79), verbal ability (7.10 ± 0.36), spatial ability (0.78 ± 0.42), immediate memory (2.42 ± 0.53), short-term memory (1.17 ± 0.78) and MMSE (23.36 ± 2.98) were all improved after treatment (P < 0.05) compared with those before treatment; (2) The scores of SDSS, PSP and Activities of Daily Living (ADL) after treatment were 8.23 ± 0.94, 81.36 ± 14.23, and 32.7 ± 12.1, and all of which improved (P < 0.05); (3) The scores of physical health were 68.24 ± 7.44, mental health were 69.75 ± 7.15, social function were 69.08 ± 7.43, material life were 37.46 ± 4.85 and the total score were 230.79 ± 9.56, all of which improved (P < 0.05).Conclusion: For patients with VD, CCRT can improve their cognitive function, social function, daily life ability and quality of life.Keywords: computer-assisted cognitive remediation, vascular dementia, cognitive function, social function, daily life ability

Ronnie Thomas,1 Quincy Mariam Jacob,1 Sharon Raj Eliza,2 Malathi Mini,1 Jobinse Jose,3 Sobha A1 1Department of Community Medicine, Government Medical College Kottayam, Kottayam, Kerala, India; 2Department of Community Medicine, Pushpagiri Institute of Medical Sciences and Research Centre, Thiruvalla, Kerala, India; 3Department of Community Medicine, Kasturba Medical College, Mangalore, IndiaCorrespondence: Ronnie Thomas, Department of Community Medicine, Government Medical College Kottayam, Kottayam, Kerala, India, Tel +91 9947014747, Email ronpauloc@gmail.comIntroduction: Catastrophic health expenditure during COVID-19 hospitalization has altered the economic picture of households, especially in low resource settings with high rates of COVID-19 infection. This study aimed to estimate the out of pocket (OOP) expenditure and the proportion of households that incurred catastrophic health expenditure due to COVID-19 hospitalization in Kerala, South India.Materials and Methods: A cross-sectional study was conducted among a representative sample of 155 COVID-19 hospitalized patients in Kottayam district over four months, using a pretested interview schedule. The direct medical and non-medical costs incurred by the study participants during hospitalization and the total monthly household expenditure were obtained from the respective COVID-19 affected households. Catastrophic health expenditure was defined as direct medical expenditure exceeding 40% of the household’s capacity to pay.Results: From the study, median and mean OOP expenditure was obtained as USD 93.57 and USD 502.60 respectively. The study revealed that 49.7% of households had catastrophic health expenditure, with 32.9% having incurred distress financing. Multivariate analysis revealed being below poverty line, hospitalization in private healthcare facility, and presence of co-morbid conditions as significant determinants of catastrophic health expenditure.Conclusion: High levels of catastrophic health expenditure and distress financing revealed by the study have unveiled major unaddressed challenges in the road to universal health coverage.Keywords: COVID-19, financial burden, catastrophic health expenditure, distress financing, Kerala

The digestive physiological characteristics of Chinese giant salamander Andrias davidianus have not been reported in the existing literature, and improving our knowledge in this area could help in the artificial culture of the species. The effect of meal size on the specific dynamic action (SDA) of A. davidianus larvae was assessed in this study at a water temperature of 20°C. The Chinese giant salamander was fed by test diets at meal sizes of 0.5, 1, 2, 4, 8 and 12% of its body mass (4.41 ± 0.07 g), and the postprandial oxygen consumption rate (MO2) was measured at 2 h intervals until the rate returned to its preprandial level. Peak MO2 (MO2peak) increased with meal size but levelled off at larger meal sizes within the studied range (8-12% body mass). The factorial metabolic scope increased from 1.27 to 2.11 when meal size increased from 0.5 to 12%. Time to reach MO2peak was not affected by the relative meal size. The SDA duration increased from 8.89 to 47.33 h as the relative meal size increased from 0.5 to 12%. The amount of energy expended during SDA increased linearly with increasing meal size (R2 = 0.842, p < 0.001, n = 60). There was no significant difference in the SDA coefficient among the different relative meal size groups. These data suggest that (1) A. davidianus larvae increase their energy demands during digestion by prolonging the SDA duration rather than increasing the MO2peak as meal size increases, and (2) A. davidianus showed a smaller factorial metabolic scope in the process of digesting large meal sizes, which may be related to the limited MO2peak of the species.

Xuan Wang,1,&ast; Dan Liao,2,&ast; Qiu-Ming Ji,2 Yu-Hong Yang,2 Ming-Chao Li,3 Xian-Yun Yi,2 Chi Li,2 Yu Chen,2 Hong-Bo Tao,2 Wen-Hui Zhai2 1Institute of Burns, Wuhan Third Hospital, Wuhan University, Wuhan, 430000, People’s Republic of China; 2Department of Psychiatry, Wuhan Wudong Hospital, Wuhan, 430084, People’s Republic of China; 3Department of Psychiatry, Affiliated Wuhan Mental Health Center, Tongji Medical College of Huazhong University Science & Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiu-Ming Ji; Yu-Hong Yang, Department of Psychiatry, Wuhan Wudong Hospital, No. 46 of Wudong Street, Qingshan District, Wuhan, 430084, People’s Republic of China, Tel +86 27 5052 8367, Fax +86 27 8643 8247, Email ji20210826@163.com; yinhua3355@163.comObjective: To examine the bactericidal effects of three different states of medical ozone (liquid, gas, and oil) against drug-resistant strains of common bacteria on burn wounds, which could as a clinical reference.Methods: Three multidrug-resistant strains of methicillin-resistant Staphylococcus aureus, pan-resistant Pseudomonas aeruginosa, and ESBLs Klebsiella pneumoniae were identified from burn wounds. The colonies of the three varieties of bacteria were each carried out using the pour plate method prior to the start of the experiment. Then, depending on the state of ozone, different treatment procedures are applied. Group of ozone gas: in a closed glass jar, the bacterial liquid was injected into a single layer of sterile gauze, and the ozone gas concentration was held at 50 g/mL. The bacterial liquid was diluted and combined directly with ozone water in the ozone water group. Ozone is a type of oil: after the emulsifier was added to the oil group. The gas, water, and oil groups were rapidly neutralized and counted again after 5, 10, and 30 minutes.Results: Ozone gas and oil groups totally eliminated multidrug resistant bacteria in the above study within 30 minutes. (2) At 5 and 10 minutes, the difference in bactericidal effect between ozone gas group and ozone water and oil group was statistically significant (P< 0.05), and there was no significant difference between ozone water and oil groups (P> 0.05); at the time of 30 minutes, the effects of bactericidal effect between ozone water group and ozone gas and oil had no significance (P> 0.05).Conclusion: Ozone has the ability to kill bacteria, depending on the treatment time, different ozone types should be chosen for sterilization and disinfection in clinical application.Keywords: ozone, burn, wound treatment, multidrug resistant bacteria

The choice of chemical composition of lithium- and manganese-rich transition metal oxides used as cathode materials in lithium-ion batteries can significantly impact their long-term viability as storage solutions for clean energy automotive applications. Their structure has been widely debated: conflicting conclusions drawn from individual studies often considering different compositions have made it challenging to reach a consensus and inform future research. Here, complementary electron microscopy techniques over a wide range of length scales reveal the effect of lithium-to-transition metal-ratio on the surface and bulk structure of these materials. We found that decreasing the lithium-to-transition metal-ratio resulted in a significant change in terms of order and atomic-level local composition in the bulk of these cathode materials. However, throughout the composition range studied, the materials consisted solely of a monoclinic phase, with lower lithium content materials showing more chemical ordering defects. In contrast, the spinel-structured surface present on specific crystallographic facets exhibited no noticeable structural change when varying the ratio of lithium to transition metal. The structural observations from this study warrant a reexamination of commonly assumed models linking poor electrochemical performance with bulk and surface structure.

Qi-Ming Pang,1,2 Si-Yu Chen,1 Sheng-Ping Fu,1,2 Hui Zhou,3 Qian Zhang,4 Jun Ao,2 Xiao-Ping Luo,1 Tao Zhang1,2 1Key Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine Centre, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China; 2Department of Orthopedics, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China; 3The First School of Clinical Medicine, Zunyi Medical University, Zunyi, People’s Republic of China; 4Department of Human Anatomy, Zunyi Medical University, Zunyi, People’s Republic of ChinaCorrespondence: Tao Zhang; Qian Zhang, Email oceanzt@163.com; zmczq@163.comAbstract: Spinal cord injury (SCI) is a catastrophic condition with high morbidity and mortality that still lacks effective therapeutic strategies. It is well known that the most important stage in SCI pathogenesis is secondary injury, and among the involved mechanisms, the inflammatory cascade is the main contributor and directly influences neurological function recovery. In recent years, increasing evidence has shown that mesenchymal stem cells (MSCs) transplantation is a promising immunomodulatory strategy. Transplanted MSCs can regulate macrophage-, astrocyte-, and T lymphocyte-mediated neuroinflammation and help create a microenvironment that facilitates tissue repair and regeneration. This review focuses on the effects of different types of immune cells and MSCs, specifically the immunoregulatory capacity of MSCs in SCI and repair. We will also discuss how to exploit MSCs transplantation to regulate immune cells and develop novel therapeutic strategies for SCI.Keywords: spinal cord injury, mesenchymal stem cells, immune cells, neuroinflammation, immunoregulation, macrophage, astrocyte, T cell

Fei Zhou,1,2,&ast; Ou Dai,1,2,&ast; Cheng Peng,1,2 Liang Xiong,1– 3 Hui Ao,1,4 Fei Liu,1– 3 Qin-Mei Zhou1,3,4 1State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 2School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 3Institute of Innovative Medicine Ingredients of Southwest Specialty Medicinal Materials, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 4Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cheng Peng; Qin-Mei Zhou Tel +86 28 61800005; +86 28 61800231Email pengchengchengdu@126.com; zhqmyx@sina.cnPurpose: Perilla frutescens (L.) Britt., a traditional edible-medicinal herb in China, has been used to treat cardiovascular and cerebrovascular (cardio-cerebrovascular) diseases for thousands of years. However, knowledge of the mechanisms underlying the effects of essential oil from P. frutescens (EOPF) in the treatment of cardio-cerebrovascular diseases is lacking. The promotion of angiogenesis is beneficial in the treatment of ischemic cardio-cerebrovascular diseases. The current study investigated the pro-angiogenic role of EOPF and its main component perillaldehyde in sunitinib-injured transgenic Tg (flk1:EGFP) zebrafish embryos and human umbilical vein endothelial cells (HUVECs) for the first time.Materials and Methods: The pro-angiogenic effects of EOPF and perillaldehyde were observed in vivo using transgenic Tg (flk1:EGFP) zebrafish embryos and in vitro using HUVECs. Cell viability, proliferation, migration, tube formation, and protein levels were detected by MTT, EdU staining, wound healing, transwell chamber, and Western blot assays, respectively.Results: EOPF and perillaldehyde exerted a significant stimulatory effect on the formation of zebrafish intersegmental vessels (ISVs). Moreover, EOPF and perillaldehyde promoted proliferation, migration, and tube formation in sunitinib-treated HUVECs. Additionally, our findings uncovered that the pro-angiogenic effects of EOPF and perillaldehyde were mediated by increases in the expression ratios of p-ERK1/2 to ERK1/2 and Bcl-2 to Bax.Conclusion: The present study is the first report to provide clear evidence that EOPF and perillaldehyde promote angiogenesis by stimulating repair of sunitinib-injured ISVs in zebrafish embryos and promoting proliferation, migration, and tube formation in sunitinib-injured HUVECs. The underlying mechanisms are related to increased p-ERK1/2 to ERK1/2 and Bcl-2 to Bax expression ratios. EOPF and perillaldehyde may be used in the treatment of cardio-cerebrovascular diseases, which is consistent with the traditional application of P. frutescens.Keywords: Perilla frutescens, essential oil, perillaldehyde, pro-angiogenesis, HUVECs, zebrafish

Background With improved survival among People Living with HIV (PLHIV), many are confronted with age associated comorbidities and geriatric syndromes. Neurocognitive impairment is one of the three most frequent conditions that affects quality of life of PLHIV despite achieving viral suppression. Healthcare providers face challenges in early identification of neurocognitive impairment, performing comprehensive assessment and managing older PLHIV. Objectives This paper aims to review available evidence regarding aetiology and management of older PLHIV who develop neurocognitive impairment, suggest improvements on current management and postulate future study direction. Methods A PubMed search for original articles and Clinical Guidelines was conducted from September 2021 to August 2022 using a combination of keywords related to neurocognitive impairment in PLHIV. The citations from all selected articles were reviewed for additional studies. Results Older PLHIV tend to be frailer than their uninfected counterparts, are plagued with multi-morbidity and are at increased risk of cognitive impairment. The aetiologies for neurocognitive impairment are multifactorial, multi-dimensional and complex. The management of neurocognitive impairment in older PLHIV involves identifying and optimizing predisposing factors, physical function, social and psychological health with appropriate care navigation. Conclusion Identification and management of neurocognitive impairment in older PLHIV through interdisciplinary collaboration among stakeholders is important. This exemplifies an integrated model of care for older PLHIV and promotes the notion of living well beyond viral suppression.

The Gemini Planet Imager Exoplanet Survey (GPIES) is a multiyear direct imaging survey of 600 stars to discover and characterize young Jovian exoplanets and their environments. We have developed an automated data architecture to process and index all data related to the survey uniformly. An automated and flexible data processing framework, which we term the Data Cruncher, combines multiple data reduction pipelines (DRPs) together to process all spectroscopic, polarimetric, and calibration data taken with GPIES. With no human intervention, fully reduced and calibrated data products are available less than an hour after the data are taken to expedite follow up on potential objects of interest. The Data Cruncher can run on a supercomputer to reprocess all GPIES data in a single day as improvements are made to our DRPs. A backend MySQL database indexes all files, which are synced to the cloud, and a front-end web server allows for easy browsing of all files associated with GPIES. To help observers, quicklook displays show reduced data as they are processed in real time, and chatbots on Slack post observing information as well as reduced data products. Together, the GPIES automated data processing architecture reduces our workload, provides real-Time data reduction, optimizes our observing strategy, and maintains a homogeneously reduced dataset to study planet occurrence and instrument performance.

Hai-Yun Zhang,1– 3 Qiu-Meng Xie,1– 3 Cui-Cui Zhao,1– 3 Jia-Feng Sha,1– 3 Ya Ruan,1– 3 Hui-Mei Wu1– 3 1Anhui Geriatric Institute, Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Key Laboratory of Geriatric Molecular Medicine of Anhui Province, Hefei, Anhui, People’s Republic of China; 3Key Laboratory of Respiratory Disease Research and Medical Transformation of Anhui Province, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Hui-Mei WuAnhui Geriatric Institute, Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaTel +86 551 65120742Email wuhm@ahmu.edu.cnPurpose: CpG-ODN has been found to attenuate allergic airway inflammation in our previous study. Here, we aimed to further investigate whether CpG-ODN exerts such effect via regulating endoplasmic reticulum (ER) stress and revealed the underlying mechanism.Methods: Five-week-old C57BL/6 mice were randomly grouped and treated with or without CpG-ODN or/and SP600125. Meantime, RAW264.7 cells were used to investigate the effect of CpG-ODN on OVA-induced ER stress in vitro. The cellularity of bronchoalveolar lavage fluid (BALF) was classified and counted after Wright–Giemsa staining. HE and PAS staining methods were applied to analyze airway inflammation. The protein levels of IL-4, IL-5, IL-13, p-JNK, JNK, CHOP, XBP1, ATF6α and GRP78 in lung tissues were detected by Western blotting. Correspondingly, the ER stress markers were detected by Western blotting and immunofluorescence in RAW264.7 cells.Results: In OVA-induced allergic airway inflammation, CpG-ODN significantly suppressed inflammatory cells infiltration, goblet cell hyperplasia and the protein expression of Th2 cytokines. Moreover, OVA exposure strongly increased the activation of ER stress with higher protein expressions of CHOP, XBP1, ATF6α and GRP78. However, these OVA-induced increase of ER stress markers were markedly suppressed by CpG-ODN treatment. In addition, exposure to OVA significantly increased the phosphorylation of JNK, which was significantly reduced by CpG-ODN treatment. Remarkably, single treatment of SP600125, an antagonist of JNK, functioned similarly as CpG-ODN in mitigating allergic airway inflammation and suppressing OVA-induced activation of ER stress; however, no significant synergistic effect was evidenced by combined treatment of SP600125 and CpG-ODN. Furthermore, in OVA-stimulated RAW264.7 cells, we also found that OVA stimulation increased the expressions of ER stress markers, and CpG-ODN significantly reduced their expression levels via suppressing the phosphorylation of JNK.Conclusion: These results indicated that CpG-ODN mitigates allergic airway inflammation via suppressing the activation of JNK-medicated ER stress.Keywords: asthma, CpG-ODN, SP600125, endoplasmic reticulum homeostasis

Xiao-Yan Chen,1,2 Qing-Mei Yang,1,2 Jian-Xiu Fang,1,2 Hai-Feng Guo1,2 1Department of Ultrasound, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, People’s Republic of China; 2Department of Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Xiao-Yan ChenDepartment of Ultrasound, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, No. 99 Longcheng Street, Taiyuan, 030032, People’s Republic of ChinaTel +8613934200119Email che_xiaoyan2@126.comBackground: Patients with hypertension complicated by acute myocardial infarction (AMI) have a generally poor prognosis. The identification of powerful predictors for recurring cardiovascular events (RCEs) is vital. This study seeks to evaluate the predictive value of three-dimensional (3D) strain parameters for RCEs in patients with hypertension complicated by AMI.Methods: We successfully followed up patients with hypertension and AMI from April 2015 to December 2015 in this retrospective study. Participants previously underwent 3D echocardiography, one week, and one month after percutaneous coronary intervention (PCI). The left ventricular structural function parameters, as well as 3D strain parameters including 3D global longitudinal strain (3D-GLS), 3D global circumferential strain, 3D global radial strain, and 3D global area strain (3D-GAS), were acquired. A Cox model was used to determine the relationships between these parameters and RCEs.Results: In total, 62 patients were enrolled in the analysis. During follow-up (41.27 ± 20.45 months), 20 patients (32.3%) had RCEs that were independently predicted one month after PCI by 3D-GLS (HR: 1.481, 95% CI: 1.202– 1.824, P < 0.001) and 3D-GAS (HR: 1.254, 95% CI: 1.093– 1.440, P = 0.001). The optimal cutoffs for 3D-GLS and 3D-GAS in predicting cardiac events were ≥ 12.5% (area under the receiver operating characteristic curve [AUC]: 0.736, 95% CI: 0.611– 0.862, P = 0.003), and > 20.5% (AUC: 0.685, 95% CI: 0.551– 0.818, P = 0.020), respectively.Conclusion: The assessed values of 3D-GLS and 3D-GAS one month after PCI can predict RCEs in patients with hypertension complicated by AMI.Keywords: hypertension, acute myocardial infarction, three-dimensional speckle tracking echocardiography, strain, cardiovascular events

Qing-Min Liu,1,&ast; Yi-Yu He,2,&ast; Li-Li Liu,3 Li-Kun Wang4 1Intensive Care Unit, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of China; 2Department of Cardiovascular Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 3Department of Pathology, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of China; 4Infection Control Center, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Li LiuDepartment of Pathology, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of ChinaEmail 13505495928@126.comLi-Kun WangInfection Control Center, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of ChinaEmail Lkwang999@163.comIntroduction: Chronic hepatitis B (CHB) virus (HBV) infection has emerged as a global health burden affecting nearly 292 million people. Tenofovir alafenamide (TAF) is an effective treatment for CHB patients. However, the detailed mechanism underlying the antiviral activity of TAF remains unclear.Methods: In this study, we investigated the antiviral effect of exosomes derived from the serum of CHB patients treated with TAF (Exo-serum) and TAF-treated macrophages (MP) (Exo-MP(TAF)).Results: RNAseq analysis was also performed to determine the associated long non-coding RNAs (lncRNAs). The results demonstrated that both Exo-serum and Exo-MP(TAF) could be taken up by HepAD38 cells and exhibited potent antiviral activities, as manifested by significantly downregulating the levels of hepatitis B surface antigen, hepatitis B e antigen, HBV DNA, and covalently closed circular DNA. The antiviral effect of Exo-serum was more potent than those of TAF treatment alone. RNAseq analysis revealed that lncRNA HOTTIP was upregulated significantly in Exo-serum. Further, lncRNA HOTTIP knockdown reversed the antiviral effect of Exo-MP(TAF) on HepAD38 cells, whereas lncRNA HOTTIP knockdown exerted the opposite roles.Discussion: Taken together, these results suggest that exosomal lncRNA HOTTIP is essential for the antiviral activity of TAF and provide a novel understanding of the exosome-mediated mechanism underlying HBV infection.Keywords: chronic hepatitis B, tenofovir alafenamide, exosome, lncRNA HOTTIP

Li-Hong Lu, Yu-Qing Song, Qi-Ming Wu, Zhao Wang, Yong-Fu Chen, Qian Dong, Xiao-Tao Han Department of Cardiology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaCorrespondence: Qi-Ming WuDepartment of Cardiology, Beijing Ditan Hospital, Capital Medical University, No. 8 of Jingshun Street, Chaoyang District, Beijing, 100015, People’s Republic of ChinaTel +86 138 0100 9058Fax +86 10-84322988Email lulihong1954@163.comObjective: To improve our knowledge of cardiac manifestations caused by brucellosis through analyzing abnormal electrocardiograms of patients infected with brucella.Methods: A total of 108 cases were enrolled, and their electrocardiograms were analyzed and summarized retrospectively.Results: Among 108 cases, 77 (71.3%) had a normal electrocardiogram, and 31 (28.7%) had an abnormal electrocardiogram. There were 13 cases with nodal tachycardia (12%), 9 cases with sinus bradycardia (8%), 7 cases with sinus arrhythmia (6%), 8 cases with left ventricular high voltage (7%), 13 cases with abnormal ST segment and T wave (12%), 2 cases with abnormal Q wave (1.85%), 3 cases with complete right bundle branch block (2.78%), 3 cases with ventricular premature beat (2.78%), 1 case with left anterior fascicular block (0.9%), 1 case with first degree a-v block (0.9%), 1 case with QT internal prolongation (0.9%), 1 case with poor R wave progression (0.9%), and 1 case with short PR interval (0.9%).Conclusion: The cardiac manifestations of brucellosis were rare, but the mortality was high. Patients with abnormal electrocardiogram should have improved echocardiography in time. Early detection of the abnormal electrocardiogram could give a hint of cardiac damage to avoid the serious consequences.Keywords: brucella, brucellosis, ECG, manifestations, cardiac manifestations

The temporal-spatial structures of plasma flows and turbulence around tearing mode islands are presented. The experiments were performed using Langmuir probe arrays in the edge plasmas of J-TEXT tokamak. The correlation analyses clearly show that the flows have similar structures of m/n = 3/1 as the magnetic island does (m and n are the poloidal and toroidal mode numbers, respectively). The sign of the potential fluctuations for the flows inverses and the powers significantly reduce at q = 3 surface. Approaching to the last closed flux surface for the magnetic islands, the radially elongated flow structure forms. The flows are concentrated near separatrix and show quadrupole structures. The turbulence is concentrated near X-point and partly trapped inside the magnetic islands.

We present new observations of the low-mass companion to HD 984 taken with the Gemini Planet Imager (GPI) as a part of the GPI Exoplanet Survey campaign. Images of HD 984 B were obtained in the J (1.12-1.3 μm) and H (1.50-1.80 μm) bands. Combined with archival epochs from 2012 and 2014, we fit the first orbit to the companion to find an 18 au (70-year) orbit with a 68% confidence interval between 14 and 28 au, an eccentricity of 0.18 with a 68% confidence interval between 0.05 and 0.47, and an inclination of 119°with a 68% confidence interval between 114°and 125°. To address the considerable spectral covariance in both spectra, we present a method of splitting the spectra into low and high frequencies to analyze the spectral structure at different spatial frequencies with the proper spectral noise correlation. Using the split spectra, we compare them to known spectral types using field brown dwarf and low-mass star spectra and find a best-fit match of a field gravity M6.5 ±1.5 spectral type with a corresponding temperature of K. Photometry of the companion yields a luminosity of log(Lbol/L⊙)=2.88 ± 0.07 dex with DUSTY models. Mass estimates, again from DUSTY models, find an age-dependent mass of 34 ±1 to 95 ±4 M Jup. These results are consistent with previous measurements of the object.

Sun P, Huang W, Kang L, Jin M, Fan B, Jin H, Wang Q, Gao Z. Int J Nanomedicine. 2017;12:3221–3234 At the authors request, the Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. An investigation by the Publisher found overlap in images from Figure 5. Specifically, The image from Figure 5, 0 h, Blank, has been duplicated with the same image for Figure 5, 0 h, H6R6-NP. The image from Figure 5, 0h, Naked siRNA, has been duplicated with the same image for Figure 5, 0 h, H6R6-NP. The image from Figure 5, 24 h, Naked siRNA, has been duplicated with the same image for Figure 5, 24 h, H6R6-NP. The image from Figure 5, 48 h, Naked siRNA, has been duplicated with the image for Figure 5, 48 h, CS-NP. The authors cooperated with the investigation and provided data associated with the study. However, despite the authors’ assistance, they were unable to provide a satisfactory explanation for how the images came to be duplicated, and the validity of the published work could not be verified. The decision was made to retract the article and the authors agreed with this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Xin Xin, Wei Liu, Zhe-Ao Zhang, Ying Han, Ling-Ling Qi, Ying-Ying Zhang, Xin-Tong Zhang, Hong-Xia Duan, Li-Qing Chen, Ming-Ji Jin, Qi-Ming Wang, Zhong-Gao Gao, Wei Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People’s Republic of ChinaCorrespondence: Zhong-Gao Gao; Wei HuangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, People’s Republic of ChinaTel +86-10-63026505Email zggao@imm.ac.cn; huangwei@imm.ac.cnBackground: Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood–brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration.Methods: Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly.Results: The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and − 15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect.Conclusion: Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.Keywords: glioma, blood–brain barrier, RVG15, liposome, paclitaxel

David R Powell,1 Jean-Pierre Revelli,1 Deon D Doree,1 Christopher M DaCosta,1 Urvi Desai,1 Melanie K Shadoan,1 Lawrence Rodriguez,2 Michael Mullens,2 Qi M Yang,1 Zhi-Ming Ding,1 Laura L Kirkpatrick,3 Peter Vogel,1 Brian Zambrowicz,1– 3 Arthur T Sands,1– 3 Kenneth A Platt,3 Gwenn M Hansen,3 Robert Brommage1 1Department of Pharmaceutical Biology, Lexicon Pharmaceuticals, Inc, The Woodlands, TX, USA; 2Department of Information Technology, Lexicon Pharmaceuticals, Inc, The Woodlands, Tx, USA; 3Department of Molecular Biology, Lexicon Pharmaceuticals, Inc, The Woodlands, Tx, USACorrespondence: David R PowellDepartment of Pharmaceutical Biology, Lexicon Pharmaceuticals, Inc, 2445 Technology Forest Boulevard, The Woodlands, Tx, 77381, USATel +1 713 249 3972Fax +1 281 863 8115Email dpowell@lexpharma.comPurpose: Obesity is a major public health problem. Understanding which genes contribute to obesity may better predict individual risk and allow development of new therapies. Because obesity of a mouse gene knockout (KO) line predicts an association of the orthologous human gene with obesity, we reviewed data from the Lexicon Genome5000TM high throughput phenotypic screen (HTS) of mouse gene KOs to identify KO lines with high body fat.Materials and Methods: KO lines were generated using homologous recombination or gene trapping technologies. HTS body composition analyses were performed on adult wild-type and homozygous KO littermate mice from 3758 druggable mouse genes having a human ortholog. Body composition was measured by either DXA or QMR on chow-fed cohorts from all 3758 KO lines and was measured by QMR on independent high fat diet-fed cohorts from 2488 of these KO lines. Where possible, comparisons were made to HTS data from the International Mouse Phenotyping Consortium (IMPC).Results: Body fat data are presented for 75 KO lines. Of 46 KO lines where independent external published and/or IMPC KO lines are reported as obese, 43 had increased body fat. For the remaining 29 novel high body fat KO lines, Ksr2 and G2e3 are supported by data from additional independent KO cohorts, 6 (Asnsd1, Srpk2, Dpp8, Cxxc4, Tenm3 and Kiss1) are supported by data from additional internal cohorts, and the remaining 21 including Tle4, Ak5, Ntm, Tusc3, Ankk1, Mfap3l, Prok2 and Prokr2 were studied with HTS cohorts only.Conclusion: These data support the finding of high body fat in 43 independent external published and/or IMPC KO lines. A novel obese phenotype was identified in 29 additional KO lines, with 27 still lacking the external confirmation now provided for Ksr2 and G2e3 KO mice. Undoubtedly, many mammalian obesity genes remain to be identified and characterized.Keywords: obesity, druggable, homologous recombination, gene trapping

Ang Xiao,1,&ast; Qian-Min Ge,1,&ast; Hui-Feng Zhong,2 Li-Juan Zhang,1 Hui-Ye Shu,1 Rong-Bin Liang,1 Yi Shao,1 Qiong Zhou1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Ocular Disease Clinical Research Center, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Department of Intensive Care, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, 341000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Shao; Qiong ZhouDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Ocular Disease Clinical Research Center, No. 17, YongWaiZheng Street, DongHu District, Nanchang, 330006, Jiangxi, People’s Republic of ChinaTel/Fax +86 791-88692520; +86 791-88694639Email freebee99@163.com; qiongz-ms@126.comObjective: To explore the changes in gray matter volume (GMV) and white matter volume (WMV) in proliferative diabetic retinopathy (PDR) patients using voxel-based morphometry (VBM).Participants and Methods: In total, 15 patients (10 males, 5 females) with PDR were enrolled to the patient group and 15 healthy controls (10 males, 5 females) to the control group, matched for age, sex, handedness, and education status. All individuals underwent voxel-based morphometry scans. GMV and WMV were compared between the two groups.Results: GMV in bilateral superior temporal gyrus, sixth area of left cerebellum, left middle temporal gyrus, left orbital inferior frontal gyrus and left middle cingulum gyrus and WMV in left thalamus and left precuneus were significantly lower in patients than controls (P< 0.01). Conversely, WMV was significantly higher in bilateral lenticular putamen of patients than controls (P< 0.01).Conclusion: Abnormal GMV and WMV in many specific areas of the cerebrum provide new insights for exploration of the occurrence and development of DR and its pathophysiology.Keywords: voxel-based morphometric, white matter, gray matter, proliferative diabetic retinopathy

Yue Chen,1,&ast; Yan-Chang Yang,2,&ast; Li-Ying Tang,3,&ast; Qian-Min Ge,4 Wen-Qing Shi,1,4 Ting Su,3,5 Hui-Ye Shu,1,4 Yi-Cong Pan,1,4 Rong-Bin Liang,4 Qiu-Yu Li,4 Yi Shao4 1Department of Dermatology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangzhou, 518033, People’s Republic of China; 2Department of Anesthesiology, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 3Department of Ophthalmology, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province, 361102, People’s Republic of China; 4Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 5Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, 02114, USA&ast;These authors contributed equally to this workCorrespondence: Yi ShaoDepartment of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, YongWaiZheng Street, DongHu District, Nanchang, Jiangxi, 330006, People’s Republic of ChinaTel/Fax +86 791-88692520Email freebee99@163.comObjective: Gastric adenocarcinoma originates from the glands in the superficial layer or mucosa of the stomach. It is prone to metastases, of which ocular metastasis (OM) is rare, but once it occurs the disease is considered more serious. The aim of this study was to investigate the risk factors for OM in gastric adenocarcinoma.Methods: Patients with gastric adenocarcinoma were recruited to this study between June 2003 and July 2019. Demographic data and serological indicators (SI) were compared between patients with and without OM, and binary logistic regression was used to explore whether the relevant SI may be risk factors for OM of gastric adenocarcinoma. Receiver operating characteristic (ROC) curves were used to analyze different SIs for OM in gastric cancer patients.Results: Chi-square tests showed significant between-groups difference in gender composition (P < 0.05), but not in age or histological grade (P > 0.05). t-test results showed that low-density lipoprotein (LDL) and carbohydrate antigen-724 (CA724) were significantly higher in patients with than without OM (P < 0.05). Binary logistic regression analysis showed that LDL was an independent risk factor for OM (P < 0.001). ROC curve analysis showed that the areas under the curves (AUC) for LDL and CA724 were 0.903 and 0.913 respectively, with higher AUC for combined LDL and CA724 (0.934; P < 0.001).Conclusion: LDL and CA724 have value as predictors for OM in patients with gastric adenocarcinoma, with higher predictive value when these factors are combined.Keywords: gastric adenocarcinoma, serological indicators, ocular metastases, risk factors, ROC curve

Zi-Long Zhang,1,2,* Jun-Song Yang,1,* Ding-Jun Hao,1 Tuan-Jiang Liu,1 Qi-Ming Jing2,* 1Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Graduate School of Xi’an Medical University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ding-Jun HaoDepartment of Spine Surgery, HongHui Hospital, Xi’an Jiaotong University, Xi’an City, Shaanxi Province, People’s Republic of ChinaEmail 1684047601@qq.comPurpose: To analyze the risk factors for new vertebral fractures after percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fractures (OVCFs).Patients and Methods: We retrospectively reviewed the records of patients with symptomatic OVCFs who underwent PVP in our hospital, from January 2014 to January 2019. Demographic and lifestyle data on the presence of underlying chronic disease, preoperative bone mineral density, details of vertebral fractures, postoperative osteoporosis treatment, and new fracture development were collected. Patients were divided into postoperative fracture and non-fracture groups. To identify the independent risk factors for new vertebral fracture development, variables significant on univariate analysis were included in a multivariate regression model.Results: Of the 2202 patients treated with PVP, 362 (16.43%) had a new postoperative vertebral fracture. All patients were followed up for > 12 months (mean 14.7 months). Univariate analysis revealed no significant difference in height; body weight; preoperative bone mineral density; number of fractured vertebrae; injection volume of bone cement in a single vertebra; leakage rate of bone cement; or presence of hypertension, coronary heart disease, and chronic obstructive pulmonary disease between the fracture and non-fracture groups (P> 0.05). Age, sex, smoking, alcohol consumption, diabetes mellitus, postoperative exercise, and postoperative osteoporosis treatment were associated with new vertebral fractures (all P< 0.05). A multivariate analysis showed that age (odds ratio [OR]=1.212, P< 0.0001), female sex (OR=1.917, P< 0.0001), smoking (OR=1.538, P=0.026), and diabetes (OR=1.915, P< 0.0001) were positively correlated with new vertebral fracture development, whereas postoperative exercise (OR=0.220, P< 0.0001) and osteoporosis treatment (OR=0.413, P< 0.0001) were negatively correlated.Conclusion: Elderly patients, females, and those with a history of smoking and diabetes are at high risk of new vertebral fracture after PVP. Patients should be encouraged to stop smoking and consuming alcohol, control blood glucose level, participate in sufficient physical activity, and adhere to osteoporosis treatment to prevent new vertebral fractures.Keywords: aged, fractures, compression, osteoporosis, risk factors, spinal fractures, vertebral body

Jian-Xiu Fang, Xiao-Yan Chen, Qing-Mei Yang, Meng-Hua Xue Department of Ultrasound, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, 030032, People’s Republic of ChinaCorrespondence: Jian-Xiu FangDepartment of Ultrasound, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, No. 99 Longcheng Street, Xiaodian District, Taiyuan, Shanxi Province, 030032, People’s Republic of ChinaTel/ Fax +86 139 34534690Email fangjx_sd@163.comObjective: Glomerulosclerosis and tubulointerstitial fibrosis are associated with lower renal parenchymal resilience. The purpose of this study is to determine the factors influencing renal resilience in patients with diabetic nephropathy (DN).Methods: We recruited 56 healthy volunteers and 187 patients with DN. All the participants were evaluated using shear-wave elastography (SWE), and the size of their kidneys and Young’s modulus values for the parenchyma were recorded. A total of 187 patients with DN are allocated to three groups according to their urinary albumin-to-creatinine ratio: normoalbuminuric (< 30 mg/g creatinine), microalbuminuric (30– 300 mg/g), and macroalbuminuric (≥ 300 mg/g) groups. Renal resilience is compared between the stages of diabetic nephropathy and the healthy control group, and the factors affecting the stiffiness of the renal parenchyma in DN are analyzed.Results: The renal parenchyma is harder in participants with DN than in healthy participants (P < 0.001), and the stiffiness increases with the progression of the disease (P < 0.001). Multivariate logistic regression analysis shows that disease stage (β = 0.789, P < 0.001), duration of diabetes (β = 0.028, P < 0.001), and serum creatinine (SCr) concentration (β = 0.001, p < 0.001) influence the stiffiness of the renal parenchyma.Conclusion: We show that SWE can be used to measure changes in the stiffiness of the renal parenchyma in patients with DN. Furthermore, Young’s modulus of the renal parenchyma is related to the duration of diabetes, urinary albumin excretion, and SCr concentration. Thus, SWE can be used to objectively and non-invasively stage DN.Keywords: diabetic nephropathy, shear-wave elastography, Young’s modulus, parenchymal stiffiness

Giao Huynh,1 Tap Van Nguyen,2 Dung Dang Nguyen,1 Quang Minh Lam,1 Tuan Nhat Pham,1 Han Thi Ngoc Nguyen3 1Faculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Faculty of Medicine, Tra Vinh University, Tra Vinh City, Tra Vinh Province, Vietnam; 3Infection Control Department, University Medical Center Ho Chi Minh City, Ho Chi Minh City, VietnamCorrespondence: Tap Van NguyenTra Vinh University, 126 Nguyen Thien Thanh Street, Tra Vinh City, Tra Vinh Province, VietnamTel +84914064340Email nvtap@tvu.edu.vnGiao HuynhUniversity of Medicine and Pharmacy at Ho Chi Minh City, 217 Hong Bang Street, District 5, Ho Chi Minh City, VietnamTel +84908608338Email hgiaoytcc@ump.edu.vnBackground: Vaccination is one of the best ways to control a pandemic such as COVID-19. However, identifying community apprehensions towards vaccination needs to be understood in detail. This study aims to determine the factors that can predict the acceptance of the COVID-19 vaccine.Methods: A cross-sectional study was considered by systematic random sampling of 425 adults with chronic illnesses in Ho Chi Minh City. Data were collected between December 2020 and January 2021 via a self-administered, structured questionnaire. The main outcome was the acceptance of future COVID-19 vaccinations.Results: A total of 425 eligible adults responded to the survey, whose mean age was 52.9± 15.6 years; 67.8% of them were women, more than a half of them had high school education level or higher (57.4%) and received COVID-19 information mainly via television and social media accounted for 82.4% and 58.1%, respectively. Overall, knowledge of COVID-19 was reported as relatively good, with a mean score of 7.11 ± 1.77 (0– 9). Determinants of vaccination acceptance were knowledge and cues to action. Accordingly, there was a 1.2-fold increase in the odds of acceptance of COVID-19 vaccination for a 1-unit increase in “the total knowledge score” (AOR 1.2, 95% CI: 1.1– 1.3, p< 0.05), and there was a 3.2-fold increase in the odds of vaccination acceptance for a 1-unit increase in “cues to action” (AOR 3.2, 95% CI: 1.7– 5.8, p< 0.001).Conclusion: Determinants that influence the intention to have the COVID-19 vaccination are identified, which can be applied to future health education interventions that should focus on enhanced knowledge towards COVID-19 via mass media messages and cues to action from healthcare workers’ recommendations to promote vaccine acceptance.Keywords: beliefs, COVID-19, health belief model, knowledge, vaccination

Ge-Di Zhang,1,* Xi-Xi Liu,2,* Jia-Lang Liang,3 Qi-Ming Hu4 1Department of Endocrinology, Yuncheng Hospital of Traditional Chinese Medicine, Yuncheng, 274700, People’s Republic of China; 2Department of Endocrinology, Yichun Hospital of Traditional Chinese Medicine, Yichun, 336000, People’s Republic of China; 3Department of Endocrinology, Guangdong Integrated Traditional Chinese and Western Medicine Hospital, Foshan, 528000, People’s Republic of China; 4Department of Endocrinology, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, 330000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qi-Ming HuDepartment of Endocrinology, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, No. 445 of Bayidadao Street, Donghu District, Nanchang, 330000, People’s Republic of ChinaTel +86 79107702803Email huqimingqw_as@163.comObjective: This study aimed to summarize the distribution pattern of traditional Chinese medicine (TCM) syndromes in patients with type 2 diabetes mellitus (T2DM).Methods: The frequency, characteristics and distribution of all TCM syndromes of 549 patients with T2DM were analyzed.Results: The average age of T2DM onset was higher in women than in men (ie, men experienced earlier onset). The distribution of TCM syndromes, in order of frequency, was as follows: damp-heat trapping spleen (including spleen deficiency and dampness, damp heat due to spleen deficiency, and qi weakness due to spleen deficiency) (58.29%), qi-yin deficiency (16.03%), deficiency of yin and excessive heat (12.93%), blood stasis in collaterals (9.41%), and yin-yang deficiency (3.21%). The physical intensity of patients’ occupational activity was mainly light (49.6%), followed by heavy (31.4%) and moderate (19.0%).Conclusion: Damp-heat trapping spleen is the most common TCM syndrome in patients with T2DM, with damp heat due to spleen deficiency the most significant subtype. This syndrome tends to occur in people over the age of 60 and those undertaking too much or too little physical activity in their occupational activities. The traditional “three more and one less” symptoms do not adequately describe the clinical symptoms of T2DM.Keywords: type 2 diabetes, TCM syndrome differentiation, damp heat due to spleen deficiency, epidemiology, clinical symptoms

Si-Wen Tan,1,2,* Guo-Qian Cai,3,* Qiu-Yu Li,1,* Yu Guo,3 Yi-Cong Pan,1 Li-Juan Zhang,1 Qian-Min Ge,1 Hui-Ye Shu,1 Xian-Jun Zeng,3 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China; 2The First Clinical Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, YongWaiZheng Street, DongHu District, Nanchang, 330006, Jiangxi, People’s Republic of ChinaTel/Fax +86 791-88692520Email freebee99@163.comXian-Jun ZengDepartment of Radiology, The First Affiliated Hospital of Nanchang University, No. 17, YongWaiZheng Street, DongHu District, Nanchang, 330006, Jiangxi, People’s Republic of ChinaTel/Fax +86 791-88694639Email 375135747@qq.comPurpose: Previous research suggests that diabetic optic neuropathy (DON) can cause marked anatomical and functional variations in the brain, but to date altered functional synchronization between two functional hemispheres remains uncharacterized in DON patients. Voxel mirrored homotopic connectivity (VMHC) is a voxel-based method to evaluate the synchronism between two mirrored hemispheric by determining the functional connectivity between each voxel in one hemisphere and its counterpart. In this study, we aim to assess abnormal changes in interhemispheric functional connectivity in DON patients via the VMHC method.Methods: The study included 28 adult DON patients (12 male, 16 female) and 28 healthy controls (12 male, 16 female) who were closely matched for sex and age. Participants were examined using resting-state functional magnetic resonance imaging. The VMHC method was applied to investigate the abnormal state in bilateral hemispheres in DON patients and the same regions in healthy controls, as well as the receiver operating characteristic (ROC) curves were used to evaluate characteristics. Associations between altered VMHC values in distinct cerebral regions and clinical features were assessed via correlational analysis.Results: Markedly lower VMHC values were evident in the right temporal inferior, the left temporal inferior, the right mid-cingulum, the left mid-cingulum, the right supplementary motor region, and the left supplementary motor region in DON patients compared with healthy controls. ROC curve analysis suggested that the application of VMHC is reliable for the diagnosis of DON.Conclusion: Anomalous interhemispheric functional connectivity in specific brain areas caused by DON may indicate neuropathologic mechanisms of vision loss and blurry vision in patients with DON.Keywords: diabetes, diabetic optic neuropathy, magnetic resonance imaging, resting-state functional MRI

Daniel Geh,1 Quentin M Anstee,2,3 Helen L Reeves2– 4 1Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; 2Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; 3The Liver Unit, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK; 4Hepatopancreatobiliary Multidisciplinary Team, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UKCorrespondence: Helen L ReevesTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UKTel +44 191 208 4423Fax +44 191 208 4301Email h.l.reeves@ncl.ac.ukAbstract: Due to an increase in the obesity-associated metabolic syndrome of epidemic proportions, nonalcoholic fatty liver disease (NAFLD) is becoming a leading cause of hepatocellular carcinoma (HCC) in western countries. This presents added challenges, as NAFLD-associated HCC tends to present at an advanced stage in older patients with co-morbidities. Their prognosis is generally poor with the benefits of standard therapies less certain. The pathogenesis of NAFLD-associated HCC is multifactorial and not well understood, although the risk of HCC developing undoubtedly increases as NAFLD progresses to steatohepatitis and cirrhosis. Recent advances in our understanding of the drivers of NAFLD and HCC will hopefully lead to the development of clinically relevant biomarkers, tools and strategies to aid the identification of high-risk patients, inform preventive measures, and introduction of better tolerated targeted therapies. Lifestyle modification and chemoprevention with drugs such as anti-platelets, statins and anti-diabetics are being evaluated for HCC prevention. The landmark IMBrave150 study introducing the combination of atezolizumab and bevacizumab has recently transformed the landscape of systemic therapies in HCC, with follow-up analyses and real-world data for patients with NAFLD-associated HCC eagerly anticipated. While responses may vary in ways not yet appreciated, the rate of discovery and progress suggests imminent change and opportunities.Keywords: hepatocellular carcinoma, HCC, nonalcoholic fatty liver disease, NAFLD, liver cirrhosis, biomarkers, prevention, systemic therapy, immunotherapy

Bai-Rong Wang,1,2 Jun-Teng Yao,2 Hui Zheng,1 Quan-Min Li1 1Department of Endocrinology, Medical College of Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China; PLA Rocket Force Characteristic Medical Center, Beijing, 100088, People’s Republic of China; 2Department of Endocrinology, Jinjiang Municipal Hospital, Jinjiang, 362200, People’s Republic of ChinaCorrespondence: Quan-Min LiPLA Rocket Force Characteristic Medical Center, Beijing, 100088, People’s Republic of ChinaTel +86 10 66927601Email liquanming369@163.comObjective: This study aimed to investigate the association of the glycated albumin (GA)/glycosylated hemoglobin (HbA1c) ratio with the mean amplitude of glycemic excursion (MAGE) in type 2 diabetes mellitus (T2DM).Methods: A total of 102 patients with T2DM who were first treated in Jinjiang Hospital of Fujian Province were enrolled in this study. The patients’ general clinical data, including HbA1c, GA, fasting blood glucose, and fasting and peak C-peptide values upon diagnosis and after one year of follow-up, were collected, and their MAGE was calculated.Results: With the increase of the GA/HbA1c ratio at baseline, the patients’ fasting and peak C-peptide values decreased gradually from baseline to follow-up, while their MAGE, HbA1c, and fasting blood glucose increased gradually. A regression analysis demonstrated that the baseline MAGE was independently positively correlated with the GA/HbA1c ratio. A Cox regression analysis demonstrated that a baseline GA/HbA1c ratio of > 2.78 was an independent risk factor for poor fasting blood glucose and HbA1c.Conclusion: The GA/HbA1c ratio is closely related to the MAGE and islet function in patients with T2DM.Keywords: type 2 diabetes mellitus, glycated albumin, glycosylated hemoglobin, blood glucose control, blood glucose fluctuation

IntroductionFirst-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment of advanced non-small-cell lung cancer with EGFR-activating mutations improves outcomes compared with chemotherapy, but resistance develops in most patients. Compensatory signaling through type 1 insulin-like growth factor 1 receptor (IGF-1R) may contribute to resistance; dual blockade of IGF-1R and EGFR may improve outcomes.Patients and methodsWe performed a randomized, double-blind, placebo-controlled phase II study of linsitinib, a dual IGF-1R and insulin receptor tyrosine kinase inhibitor, plus erlotinib versus placebo plus erlotinib in chemotherapy-naive patients with EGFR-mutation positive, advanced non-small-cell lung cancer. Patients received linsitinib 150 mg twice daily or placebo plus erlotinib 150 mg once daily on continuous 21-day cycles. The primary end point was progression-free survival.ResultsAfter randomization of 88 patients (44 each arm), the trial was unblinded early owing to inferiority in the linsitinib arm. The median progression-free survival for the linsitinib versus the placebo group was 8.4 months versus 12.4 months (hazard ratio, 1.37; P = .29). Overall response rate (47.7% vs. 75.0%; P = .02) and disease control rate (77.3% vs. 95.5%; P = .03) were also inferior. Whereas most adverse events were ≤ grade 2, linsitinib plus erlotinib was associated with increased adverse events that led to decreased erlotinib exposure (median days, 228 vs. 305). No drug-drug interaction was suggested by pharmacokinetic and pharmacodynamic results.ConclusionAdding linsitinib to erlotinib resulted in inferior outcomes compared with erlotinib alone. Further understanding of the signaling pathways and a biomarker that can predict efficacy is needed prior to further clinical development of IGF-1R inhibitors in lung cancer.