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Wenbin Lu,1,&ast; Xinning Chang,1,&ast; Wei Wu,2– 5 Peipei Jin,1 Shengwei Lin,1 Lize Xiong,2– 5 Xiya Yu2– 5 1Faculty of Anesthesiology, Changhai Hospital, Naval Medical University/Second Military Medical University, PLA, Shanghai, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 4Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 5Clinical Research Centre for Anesthesiology and Perioperative Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lize Xiong; Xiya Yu, Email mzkxlz@126.com; lizexiong@tongji.edu.cn; yuxiyash@163.comObjective: To explore the effect of scalp nerve block (SNB) combined with intercostal nerve block (ICNB) on quality of recovery (QoR) after deep brain stimulation (DBS) in patients with Parkinson’s disease (PD).Methods: We conducted a prospective randomized controlled trial in which 88 patients with PD were randomly assigned to undergo SNB combined with ICNB (SNB group) or not (control group) before surgery. The primary outcome was the 15-item QoR (QoR-15) score 24 h after surgery. The secondary outcomes included QoR-15 scores at 72 h and 1 month after surgery, pain-related events, recovery events in post-anesthesia care unit (PACU), duration of anesthesia and surgery, and nerve block-related adverse events.Results: The QoR-15 score at 24 h after surgery was significantly higher in SNB group than Control group: 122.0 ± 7.6 vs 113.5 ± 11.3 (P = 0.006). SNB combined with ICNB improved QoR-15 scores at 72 h (P = 0.004) but not at 1 month after surgery (P = 0.230). The SNB group was positively related to QoR-15 scores 24 h after surgery (β = 8.92; 95% CI = 4.52~13.32) after adjusting for confounding variables. The numeric rating scale pain scores at PACU discharge and at 24 h, intraoperative opioid consumption, rescue analgesic use, and the incidence of postoperative nausea and vomiting (PONV) in SNB group were significantly lower than Control group (P < 0.05).Conclusion: Preoperative SNB combined with ICNB improved QoR and analgesia after surgery, and reduced intraoperative opioid consumption and the incidence of PONV in patients with PD who underwent DBS.Keywords: deep brain stimulation, intercostal nerve block, Parkinson’s disease, quality of recovery, scalp nerve block

Haoxiang Wen,1,2,&ast; Ruiming Liang,3,&ast; Xiaofei Liu,4 Yang Yu,1 Shuirong Lin,1 Zimin Song,1 Yihao Huang,1 Xi Yu,1 Shuling Chen,5 Lili Chen,6 Baifeng Qian,1 Jingxian Shen,7 Han Xiao,8 Shunli Shen1 1Center of Hepato-Pancreatico-Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Medical Statistics, Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 4Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-senUniversity, Guangzhou, Guangdong Province, People’s Republic of China; 5Precision Medicine Institute, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 6Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 7Department of Radiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 8Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shunli Shen, Center of Hepato-Pancreatico-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhong-Shan Road2, Guangzhou, Guangdong Province, People’s Republic of China, Email Shenshli@mail.sysu.edu.cn Han Xiao, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road2, Guangzhou, Guang- Dong Province, People’s Republic of China, Email xiaoh69@mail.sysu.edu.cnPurpose: Predicting the pathological response after neoadjuvant conversion therapy for initially unresectable hepatocellular carcinoma (HCC) is essential for surgical decision-making and survival outcomes but remains a challenge. We aimed to develop a radiomics model to predict pathological responses.Methods: We included 203 patients with HCC who underwent hepatectomy after neoadjuvant conversion therapy between 2015 and 2023 and separated them into a training set (100 patients from Center A) and a validation set (103 patients from Center B). Pathological complete response (pCR)-related radiomic features were extracted from the largest tumor layer in the arterial and portal vein phases of the CT. A synthetic minority oversampling technique (SMOTE) was used to balance the minority groups in the training set. The SMOTE radiomics model was constructed using a logistic regression model in the SMOTE training set and its performance was verified in the validation set.Results: The AUC of the preoperative modified response evaluation criteria in solid tumors (mRECIST) assessment for pCR was 0.656 and 0.589 in the training and validation sets, respectively. The SMOTE radiomics model was established based on ten radiomic features and showed good pCR-predictive performance in the SMOTE training set (AUC, 0.889; accuracy, 87.7%) and the validation set (AUC: 0.843, accuracy: 86.4%). The RFS of the radiomics-predicted-pCR group was significantly better than that of the predicted-non-pCR group in the training cohort (P = 0.001, 2-year RFS: 69.5% and 30.1% respectively) and the validation cohort (P = 0.012, 2-year RFS: 65.9% and 38.0% respectively).Conclusion: The SMOTE radiomics model has great potential for predicting pathological response and evaluating RFS in patients with unresectable HCC after neoadjuvant conversion therapy.Keywords: hepatocellular carcinoma, radiomics, pathological complete response, neoadjuvant conversion therapy

Nan Lin,1,&ast; Dang Li,1,2,&ast; Si Lin,1 Yilang Ke,1 Jianping Lu,3 Yinrong Wu,1 Tianwen Huang,1,3 Huashan Hong1 1Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Fujian Institute of Geriatrics, Fujian Clinical Research Center for Senile Vascular Aging and Brain Aging, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 2Nursing Department, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 3Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huashan Hong, Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Fujian Institute of Geriatrics, Fujian Clinical Research Center for Senile Vascular Aging and Brain Aging, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86 591 8621 8525, Fax +86 591 8621 8545, Email 15959159898@163.comPurpose: The prevalence of osteoporosis in elderly individuals is high, and osteoporosis is strongly associated with chronic inflammation. The monocyte-to-high-density lipoprotein ratio (MHR) is acknowledged as a marker for assessing systemic inflammation and oxidative stress, and changes in the MHR are associated with many chronic disease prevalent among the elderly population. This study investigated the relationships between the MHR and the incidence of osteoporosis in older adults, along with its predictive value.Patients and Methods: Data from 563 participants aged ≥ 70 years were retrospectively analysed. The haematological parameters were evaluated via established methodologies, utilizing fasting blood samples collected from the participants. The absolute monocyte count was used to calculate the MHR (MHR=monocyte/HDL-C). BMD was measured by dual-energy X-ray absorptiometry. The results were evaluated via comparative statistical analyses, Spearman correlation, logistic regression analyses, and receiver operating characteristic (ROC) curve analysis.Results: The differences in the MHR were statistically significant among the osteoporosis groups (p < 0.001). Spearman correlation analysis revealed a positive correlation between the MHR and BMD. Furthermore, stratifying the sample into four groups on the basis of quartiles of MHR (M1, M2, M3, and M4) revealed a decreased risk of osteoporosis in the highest quartile compared with the lowest quartile (p < 0.001). Multiple logistic regression analysis revealed that BMI and the MHR were independent risk factors for osteoporosis. The area under the ROC curve and the cut-off value of the MHR were 0.710 and 0.308(109/mmol), with specificity and sensitivity of 0.599 and 0.735, respectively (95% CI: 0.668~0.752, p < 0.0001).Conclusion: A low MHR was associated with a greater risk of senile osteoporosis. In clinical practice, the MHR has shown predictive value for senile osteoporosis, contributing to early intervention and treatment of this disease.Keywords: senile osteoporosis, monocyte-to-high-density lipoprotein ratio, bone mineral density, inflammation, senescence

Yawen Pan,1 Mojinzi Chen,2 Lulu Pan,3 Qiuling Tong,4 Zhiqing Cheng,3 Sujin Lin,3 Rongrong Pan,3 Mengyuan Chen,1 Yinghao Zhi3 1Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, 325000, People’s Republic of China; 2Physician,Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, 325000, People’s Republic of China; 3Department of Rehabilitation Medicine, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, 325000, People’s Republic of China; 4The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Yinghao Zhi, Department of Rehabilitation Medicine, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, 325000, People’s Republic of China, Tel +86-13758472924, Email 43914515@qq.comPurpose: The present study aimed to characterize neuroprotective effects of Schisandra Decoction (Sch D) treatment in a mouse model of Parkinson’s disease (PD), and to explore underlying mechanisms focused on the mammalian target of rapamycin (mTOR) signaling pathway.Materials and Methods: 50 male C57 BL/6 mice were randomly assigned to either control (n = 10) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model (n = 40) groups. PD mice were further divided into four groups of ten mice each: MPTP group, LY294002 group, Sch D group, and LY2940002 + Sch D group. Mice from each group were assessed in pole climbing, rotary rod and open field tests. Brain Tyrosine hydroxylase (TH) protein was observed using immunohistochemistry. mRNA levels of PTEN, PI3K and LC3 in brain tissue were measured using RT-PCR. Protein levels of PTEN, PI3K, Akt, p-Akt, mTOR, p-mTOR, p70s6K, p62, LC3II / I, α-synuclein (α-syn), TH in brain tissue were assessed by Western blotting (WB).Results: In behavioral tests, PD mice treated with Sch D showed reduced pole climbing time, longer rotarod duration, and greater distance traveled. In terms of neuroprotection, PD mice in the Sch D group exhibited higher levels of TH protein and enhanced α-syn clearance. Regarding autophagy, compared to the control group, mice in the MPTP group had elevated PTEN protein expression, which inhibited PI3K, p-AKT/AKT, and p-mTOR/mTOR protein levels, decreased LC3II/I protein expression, and increased P62 protein expression. Treatment with Sch D reversed these effects.Conclusion: Sch D reduces α-syn aggregation in the brains of MPTP-induced PD model mice, exerts neuroprotective effects, and improves motor function. Additionally, Sch D inhibits autophagy through the PI3K/AKT/mTOR pathway. The neuroprotective effect of Sch D may involve the suppression of abnormal autophagy and its antioxidant properties, which indirectly reduces α-syn accumulation. Future studies should assess the impact of Sch D on oxidative stress markers to evaluate its antioxidant effects.Keywords: Parkinson’s disease, Shisandra decoction, mTOR signaling pathway, autophagy, traditional Chinese medicine

Xixuan Zhao,1– 4 Yining He,5 Juzhao Zhang,1– 3 Senlin Lin,1– 3 Haidong Zou,1– 4 Yingyan Ma1– 4 1Shanghai Eye Diseases Prevention & Treatment Center/ Shanghai Eye Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2National Clinical Research Center for Eye Diseases, Shanghai, People’s Republic of China; 3Shanghai Engineering Research Center of Precise Diagnosis and Treatment of Eye Diseases, Shanghai, People’s Republic of China; 4Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Biostatistics Office of Clinical Research Unit, Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Yingyan Ma; Haidong Zou, Email mYy_29@163.com; zouhaidong@sjtu.edu.cnAbstract: Myopia is increasingly prevalent in children. Its association with insufficient sleep has been studied, yielding inconsistent findings. This review aims to assess the association of insufficient sleep with myopia and myopia-related refractive parameters in children. A total of 657 articles were identified, of which 40 were included in the systematic review and 33 were included in the meta-analysis. Results showed that insufficient sleep was significantly associated with an increased prevalence of myopia (odds ratio [OR] = 1.59; 95% confidence interval [CI] = 1.31, 1.95; I2 = 99%), and an increased prevalence of high myopia (OR = 3.36; 95% CI = 1.26, 9.00; I2 = 96%). Shorter sleep duration was significantly linked to faster changes in axial length (AL) (β = 0.05; 95% CI = 0.02, 0.08; I2 = 0%). However, correlation between insufficient sleep and the incidence of myopia, spherical equivalent refraction, corneal curvature radius (CR) and AL/CR were insignificant. Moreover, the effect of insufficient sleep on premyopia and astigmatism was not well-studied. The results of this study suggest that insufficient sleep may be an important risk factor for the development of myopia in school-aged children. Therefore, in addition to ensuring sufficient outdoor activities and reducing near work, it is necessary to inform children and parents about the importance of adequate sleep to mitigate the risk of myopia.Keywords: insufficient sleep, myopia, children, axial length, refractive parameters

Abstract Background While the association of chronological age with DNA methylation (DNAm) in whole blood has been extensively studied, the tissue-specificity of age-related DNAm changes remains an active area of research. Studies investigating the association of age with DNAm in tissues such as brain, skin, immune cells, fat, and liver have identified tissue-specific and non-specific effects, thus, motivating additional studies of diverse human tissue and cell types. Results Here, we performed an epigenome-wide association study, leveraging DNAm data (Illumina EPIC array) from 961 tissue samples representing 9 tissue types (breast, lung, colon, ovary, prostate, skeletal muscle, testis, whole blood, and kidney) from the Genotype-Tissue Expression (GTEx) project. We identified age-associated CpG sites (false discovery rate

Xixia Chen,1 Sang Lin,2 Qiwen Jin,1 Lu Zhang,3 Wei Jiang,3 Xin Lu,3 Guochun Wang,1,3 Yongpeng Ge3 1Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China; 2Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Rheumatology, Key Myositis Laboratories, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yongpeng Ge, Department of Rheumatology, China-Japan Friendship Hospital, Yinghua East Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 13716106183, Email gyp2016@163.comObjective: To investigate the prevalence, risk factors and prognosis of invasive pulmonary aspergillosis (IPA) in patients with anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+ DM).Methods: A retrospective analysis was conducted in anti-MDA5+ DM patients diagnosed between January 2016 and March 2023. Patients with lower respiratory tract specimens were categorized into IPA+ and IPA- groups based on the presence of IPA and their clinical characteristics and prognoses then compared.Results: Of the 415 patients diagnosed with anti-MDA5+ DM, 28 cases had IPA (prevalence rate of 6.7%) with Aspergillus fumigatus being the most common species. The patients were categorized into IPA+ (n=28) and IPA- (n=98) groups, with no significant age or gender-related differences (P> 0.05). The IPA+ group had a lower lymphocyte count, particularly the CD4+ T-cell count, and reduced serum albumin and higher serum ferritin levels (P all< 0.05). An elevated bronchoalveolar lavage fluid (BALF) galactomannan level was found to be the sole independent risk factor for the occurrence of IPA (adjusted OR=2.191, P=0.029) with a cut-off value of 0.585 and area under the curve of 0.779. The mortality rate in the IPA+ group was 25%. Compared to survivors, non-survivors in this group exhibited a higher incidence of rapidly progressive interstitial lung disease, lower lymphocyte counts, and increased co-infection with Pneumocystis jirovecii (P all< 0.05).Conclusion: IPA was not rare in patients with anti-MDA5+ DM, with elevated BALF galactomannan levels being an independent risk factor for IPA occurrence. Clinicians must exercise vigilance to identify patients exhibiting the aforementioned risk factors.Keywords: invasive pulmonary aspergillosis, opportunistic infection, anti-MDA5+ dermatomyositis, prevalence, risk factors, prognosis

Jiongfeng Zhang,1,&ast; Xiaohui Luo,1,&ast; Ruiling Zhou,2,&ast; Chong Guo,1 Kai Xu,1 Gaoyang Qu,1 Le Zou,1 Wenye Yao,1 Shifan Lin,1 Zhiping Zhang1 1Department of Orthopedics, the 3rd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330008, People’s Republic of China; 2Department of Dermatology, Jiangxi Provincial Dermatology Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shifan Lin, Email 66031226@qq.com; Zhiping Zhang, Tel +86 791-88862249, Email ndsfy001425@ncu.edu.cnObjective: To explore the suitable population of CT value for predicting low bone mineral density (low-BMD).Methods: A total of 1268 patients who underwent chest CT examination and DXA within one-month period retrospectively analyzed. The CT attenuation values of trabecular bone were measured in mid-sagittal plane from thoracic vertebra 7 (T7). Receiver operating characteristic (ROC) curves were used to evaluate the ability to diagnose low-BMD.Results: The AUC for diagnosing low BMD was larger in women than in men (0.894 vs 0.744, p < 0.05). The AUC increased gradually with the increase of age but decreased gradually with the increase in height and weight (p < 0.05). In females, when specificity was adjusted to approximately 90%, a threshold of 140.25 HU has a sensitivity of 69.3%, which is higher than the sensitivity of 36.5% in males for distinguishing low-BMD from normal. At the age of 70 or more, when specificity was adjusted to approximately 90%, a threshold of 126.31 HU has a sensitivity of 76.1%, which was higher than that of other age groups.Conclusion: For patients who had completed chest CTs, the CT values were more effective in predicting low-BMD in female, elderly, lower height, and lower weight patients.Keywords: bone mineral density, chest computed tomography, dual-energy X-ray absorptiometry, attenuation value

Chen Lin,1 Jing Wang,2 Kexin Cai,2 Yuqing Luo,2 Wensi Wu,1 Siming Lin,2 Zhihong Lin,2 Shaodan Feng2 1Department of Emergency, The Third Affiliated People’s Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, People’s Republic of China; 2Department of Emergency, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of ChinaCorrespondence: Zhihong Lin; Shaodan Feng, Department of Emergency, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China, Tel +86 59187981975, Email fzlinzh@163.com; sdfeng@fjmu.edu.cnPurpose: To address the critical mortality rates among sepsis-associated acute kidney injury (SA-AKI) patients, early prognosis is vital. This study investigates the relationship between coagulation indices and the 28-day mortality rate in patients with SA-AKI.Patients and Methods: This study was a retrospective cohort analysis including patients with SA-AKI admitted to the First Hospital of Fujian Medical University as a training cohort (n = 119) and patients admitted to the Third People’s Hospital of Fujian University of Traditional Chinese Medicine as a validation cohort (n = 51). We examined the relationship between coagulation indices and 28-day mortality in SA-AKI, the cumulative mortality at different activated partial thromboplastin time (APTT) levels, and the nonlinear relationship between APTT and 28-day mortality. Receiver operating characteristic curves were plotted, and the area under the curve was calculated to assess the predictive power of APTT. Finally, subgroup analyses were performed to assess the robustness of the association.Results: Overall, 119 participants with a mean±standard deviation age of 70.47± 15.20 years were included in the training cohort: 54 died, 65 survived. According to univariate and multivariate COX regression analyses, APACHE II score, CRP level, Lac level, and APTT level were independent risk factors for 28-day adverse prognosis. After controlling for some variables, an elevated baseline APTT (≥ 37.7 s) was associated with an elevated risk of 28-day mortality (HR, 1.017; 95% CI, 1.001– 1.032), and Kaplan–Meier analyses further confirmed the increased mortality in the group with a higher APTT. The same results were shown when the validation cohort was analyzed (HR, 1.024; 95% CI, 0.958– 1.096). Subgroup analyses showed the stability of the association between APTT and poor prognosis in SA-AKI.Conclusion: In essence, APTT elevation is synonymous with increased 28-day mortality rates, indicating a poor prognosis in SA-AKI scenarios.Keywords: APTT, prognosis, retrospective studies, critical illness

Suwen Huang,1,&ast; Yanchu Wang,1,2,&ast; Jinrong Zhu,1,3,&ast; Shengqi Li,1,2 Shenyi Lin,1,2 Wei Xie,1,2 Siyao Chen,1,2 Yukai Wang,1,3 Lingsheng Wang,1,2 Qiaoqiao Jin,1,2 Yiyun Weng,1 Dehao Yang4 1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2The First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3The Second School of Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiyun Weng, Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Ouhai District, Wenzhou, Zhejiang, 325000, People’s Republic of China, Tel +86-0577-55579371, Fax +86-0577-55579318, Email wengyiyun2012@126.com Dehao Yang, Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People’s Republic of China, Email dehao_yang@zju.edu.cnPurpose: Myasthenia gravis (MG) is a chronic autoimmune disease caused by neuromuscular junction (NMJ) dysfunction. Our current understanding of MG’s inflammatory component remains poor. The systemic inflammatory response index (SIRI) presents a promising yet unexplored biomarker for assessing MG severity. This study aimed to investigate the potential relationship between SIRI and MG disease severity.Patients and Methods: We conducted a retrospective analysis of clinical data from 171 MG patients admitted between January 2016 and June 2021. Patients with incomplete data, other autoimmune diseases, or comorbidities were excluded. Disease severity was evaluated using the Myasthenia Gravis Foundation of America (MGFA) classification and Myasthenia Gravis Activities of Daily Living (MG-ADL) on admission. The association between SIRI and disease severity was assessed through logistic regression analysis, along with receiver operating characteristic (ROC) curve and decision curve analysis (DCA) comparisons with established inflammation indicators.Results: After exclusion, 143 patients were analyzed in our study. SIRI levels significantly differed between patients with higher and lower disease severity (p < 0.001). Univariate logistic regression showed that SIRI had a significant effect on high disease severity (OR = 1.376, 95% CI 1.138– 1.664, p = 0.001). This association remained significant even after adjusting for age, sex, disease duration, history of MG medication and thymoma (OR = 1.308, 95% CI 1.072– 1.597, p = 0.008). Additionally, a positive correlation between SIRI and MG-ADL was observed (r = 0.232, p = 0.008). Significant interactions were observed between SIRI and immunosuppressor (p interaction = 0.001) and intravenous immunoglobulin (p interaction = 0.005). DCA demonstrated the superior net clinical benefit of SIRI compared to other markers when the threshold probability was around 0.2.Conclusion: Our findings indicate a strong independent association between SIRI and disease severity in MG, suggesting SIRI’s potential as a valuable biomarker for MG with superior clinical benefit to currently utilized markers.Keywords: inflammation, myasthenia gravis foundation of America, MGFA, blood cell count, correlation, systemic inflammatory response index

Abstract Genetic effects on functionally related ‘omic’ traits often co-occur in relevant cellular contexts, such as tissues. Motivated by the multi-tissue methylation quantitative trait loci (mQTLs) and expression QTLs (eQTLs) analysis, we propose X-ING (Cross-INtegrative Genomics) for cross-omics and cross-context integrative analysis. X-ING takes as input multiple matrices of association statistics, each obtained from different omics data types across multiple cellular contexts. It models the latent binary association status of each statistic, captures the major association patterns among omics data types and contexts, and outputs the posterior mean and probability for each input statistic. X-ING enables the integration of effects from different omics data with varying effect distributions. In the multi-tissue cis-association analysis, X-ING shows improved detection and replication of mQTLs by integrating eQTL maps. In the trans-association analysis, X-ING reveals an enrichment of trans-associations in many disease/trait-relevant tissues.

Fardeen Bhimani,1,&ast; Sophie Lin,1,&ast; Maureen McEvoy,1,2 Arianna Cavalli,2 Liane Obaid,2 Yu Chen,1 Anjuli Gupta,1,2 Jessica Pastoriza,1,2 Areej Shihabi,1 Sheldon Feldman1,2 1Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Center for Cancer Care, Bronx, New York, USA; 2Albert Einstein College of Medicine, Bronx, New York, USA&ast;These authors contributed equally to this workCorrespondence: Sheldon Feldman, Department of Surgery, Division of Breast Surgery, Montefiore Medical Center, 1250 Waters Place, 7th Floor, Hutch Tower 1, Bronx, NY, USA, Email sfeldman@montefiore.orgBackground: Positive margins on lumpectomy specimens are associated with a twofold increased risk of local breast tumor recurrence. Prior literature has demonstrated various techniques and modalities for assessing margin status to reduce re-excision rates. However, there is paucity of literature analyzing which margin contributes to the highest re-excision rates. Therefore, the primary aim of the study was to investigate whether the nipple-ward margins resulted in a higher rate of re-excision in our patient population.Methods: A retrospective chart review was performed on patients who had re-excision surgery. Nipple-ward margin was identified by correlating radiological and pathological reports. A cut-off of more than 25% was used to demonstrate correlation between nipple-ward margin and re-excision rate.Results: A total of 98 patients’ data were analyzed, with 41 (41.8%), 14 (14.3%), 5 (5.1%), and 38 (38.8%) diagnosed with DCIS, IDC, ILC, and mixed pathology on their margins, respectively. Overall, 48% (n=47) of the positive margins were nipple-ward, with 44.7% (n=21) reporting DCIS. Upon stratification, 45 (45.9%) cases were single-margin positive, with 26 (57.8%) being nipple-ward. Furthermore, the remaining 53 (54.1%) patients had multiple positive margins, with 21 (39.6.7%) nipple-ward cases.Conclusion: Positive nipple-ward margins significantly contribute to a higher re-excision rate p < 0.001; 48% of re-excision surgeries had positive nipple-ward margins, and 57.8% of positive single-margin cases were nipple-ward. Taking an additional shave during initial lumpectomy decreases re-excision rates. However, planning a lumpectomy procedure with a more elliptical rather than a spherical resection with additional cavity shave (ie, larger volume) in the nipple-ward direction and minimizing the remaining cavity shaves so the total volume resected remains unchanged. Nevertheless, future studies with larger sample sizes are required to bolster our findings.Keywords: nipple-ward, breast cancer, re-excision, nipple-ward positive breast cancer, Shave trial, positive margins

Jin Zhang,1,&ast; Yang Xiao,2,&ast; Shuoxin Bai,3 Shaoqian Lin,2 Shuang Du,1 Zhiping Wang4 1Department of Occupational and Environmental Health, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Center for Disease Control and Prevention, Jinan, Shandong, 250021, People’s Republic of China; 3Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 4School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiping Wang, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong, 250012, People’s Republic of China, Email zhipingw@sdu.edu.cnPurpose: We aimed to examine the association between exercise during pregnancy and preterm birth (PTB).Methods: This study was a baseline survey of the Jinan birth cohort. The study subjects were the mothers one month after giving birth, which were investigated by questionnaires retrospectively containing physical exercise (frequency, time, and primary exercise patterns) during pregnancy and each trimester. Individual time spent on exercise and energy expenditure were assessed based on the questionnaires. PTB was clinically defined as a newborn born on or before the last day of the 37th week. Adjusted odds ratios (OR) were estimated using logistic regression to assess the relationship between exercise during pregnancy and the risk of PTB. Variable selection for the multivariate models was guided by the directed acyclic graph. The median effect was analyzed by the sequential test.Results: The prevalence of PTB in this study was 4.38% (285/6501). The adjusted OR (95% CI) for the risk of PTB related to exercise during pregnancy was 0.74 (0.58– 0.95). During the 1st and 2nd trimesters, the ORs (95% CI) for 2.5 to 7 hours of exercise per week were 0.77 (0.59– 0.99) and 0.74 (0.57– 0.96). During the 3rd trimester, the ORs (95% CI) for 2.5 to 7 hours and more than 7 hours of exercise per week were 0.74 (0.56– 0.96) and 0.65 (0.44– 0.94). After stratifying the subjects, the association was only found among subjects without pregnancy complications. Pregnancy complications partially mediated (52.40%) the relationship between exercise during pregnancy and PTB.Conclusion: Exercise during pregnancy can reduce the risk of PTB for women without pregnancy complications. 2.5 to 7 hours of exercise (like walking) per week may be appropriate in three trimesters of pregnancy, and the time could be extended in the 3rd trimester.Keywords: pregnant women, exercise, trimester, mediation analysis

Shiyu Lin,&ast; Xiaojuan Li,&ast; Yuning Zhang,&ast; Wei Zhang, Gang Shu, Haohuan Li, Funeng Xu, Juchun Lin, Hualin Fu Innovative Engineering Research Center of Veterinary Pharmaceutics, Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hualin Fu, Tel +86 28 82691162, Fax +86 28 82652669, Email fuhl2005@sohu.comIntroduction: Biofilm is highly resistant to antibiotics due to its heterogeneity and is implicated in over 80% of chronic infections; these refractory and relapse-prone infections pose a huge medical burden.Methods: In this study, rhamnolipid (RHL), a biosurfactant with antibiofilm activity, was loaded with the antibiotic azithromycin (AZI) to construct a stable nanomicelle (AZI@RHL) that promotes Staphylococcus aureus (S. aureus) biofilm disruption.Results: AZI@RHL micelles made a destruction in biofilms. The biofilm biomasses were reduced significantly by 48.2% (P< 0.05), and the main components polysaccharides and proteins were reduced by 47.5% and 36.8%, respectively. These decreases were about 3.1 (15.9%), 7.3 (6.5%), and 1.9 (19.5%) times higher compared with those reported for free AZI. The disruption of biofilm structure was observed under a confocal microscope with fluorescent labeling, and 48.2% of the cells in the biofilm were killed. By contrast, the clearance rates of cells were only 20% and 17% when treated alone with blank micelles or free AZI. Biofilm formation was inhibited up to 92% in the AZI@RHL group due to effects on cell auto-aggregation and eDNA release. The rates for the other groups were significantly lower, with only 27.7% for the RHL group and 12% for the AZI group (P< 0.05). The low cell survival and great formation inhibition could reduce biofilm recolonization and re-formation.Conclusion: The antibiofilm efficacy of rhamnolipid was improved through micellar nanoparticle effects when loading azithromycin. AZI@RHL provides a one-step solution that covers biofilm disruption, bacteria inactivation, recolonization avoidance, and biofilm re-formation inhibition. Keywords: Staphylococcus aureus, antibiofilm, rhamnolipid, biosurfactant, nanomicelle

Wenbin Lu,&ast; Shengwei Lin,&ast; Cheng Wang, Peipei Jin, Jinjun Bian Faculty of Anesthesiology, Changhai Hospital, Naval Medical University/Second Military Medical University, PLA, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peipei Jin; Jinjun Bian, Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, 168, Changhai Road, Shanghai, 200433, People’s Republic of China, Tel/Fax +86-021-31161886 ; +86-021-31161841, Email kingpei89@163.com; jinjunbicu@163.comPurpose: To explore the relationship between the systemic inflammation response index (SIRI) and postoperative delirium (POD) in older patients with hip arthroplasty surgery.Patients and Methods: Older patients who underwent elective hip arthroplasty surgery were included in this retrospective study. SIRI, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were collected from blood routine examination at admission. Binary logistic regression analysis was performed to evaluate the association between SIRI levels and POD was analyzed.Results: Ultimately, 116 older patients who met the inclusion criteria were assessed. Thirty-four (29%) of 116 patients diagnosed with POD were defined as the POD group, and the rest consisted of the Non-POD group. Compared with non-POD patients, POD patients showed significantly higher levels of SIRI (P < 0.001) and NLR (P = 0.002) at admission. There was no significance in the levels of PLR between two groups. SIRI was independently associated with the occurrence of POD in multivariate logistic regression analysis [odds ratio (OR) = 3.34, 95% confidence interval (95% CI) = 1.26– 8.85, P = 0.016]. Receiver operating characteristic curve analysis indicated that SIRI with an optimal cutoff value of 0.987 predicted the POD with a sensitivity of 88.2% and specificity of 74.4%, and the area under the curve was 0.82 (95% CI, 0.74– 0.90, P < 0.01).Conclusion: Preoperative SIRI and NLR levels in the blood are associated with the occurrence of POD. Moreover, preoperative SIRI level is a useful candidate biomarker to identify delirium after elective hip arthroplasty surgery in older patients.Keywords: geriatric, hip arthroplasty, neutrophil to lymphocyte ratio, postoperative delirium, platelet to lymphocyte ratio, systemic inflammation response index

Hui Xiao,&ast; Ni Guo,&ast; Junyi Li, Ling Jin, Yuan Liu, Shufen Lin, Lei Fang, Xing Liu, Chengguo Zuo State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xing Liu; Chengguo Zuo, Zhongshan Ophthalmic Center, Sun Yat-sen University, 7 Jinsui Road, Guangzhou, 510000, People’s Republic of China, Email liuxing@mail.sysu.edu.cn; zuochengguo@mail.sysu.edu.cnPurpose: To report the prevalence, clinical characteristics and risk factors for paracentral acute middle maculopathy (PAMM) following acute primary angle closure (APAC) and acute primary angle closure glaucoma (APACG).Methods: This retrospective study consecutively recruited patients diagnosed with APAC or APACG. Based on the spectral domain optical coherence tomography characteristics, PAMM eyes were divided into three stages. Characteristics of different stages such as the time from symptoms to treatment (TST), retinal thickness and BCVA improvement were analyzed. The risk factors of PAMM were evaluated by binary logistic regression models.Results: A total of 781 eyes of 781 APAC or APACG patients were included, and PAMM was found in 22 (2.9%) of them. Stage III eyes had a significantly longer TST than stage I eyes (P = 0.008) while exhibiting significantly thinner retinal thicknesses (P < 0.0001). The BCVA improvement was significantly worse in the eyes treated in stage III than in those treated in stage I (P = 0.008). Older age, longer axial length and without type 2 diabetes were associated with a lower risk of incident PAMM (OR = 0.95, P = 0.028; OR = 0.52, P = 0.019; OR = 3.92, P = 0.022).Conclusion: PAMM can be secondary to APAC or APACG at a rate of 2.9%. Different visual outcomes were observed in patients who received the intervention at different stages of PAMM. Younger patients with a shorter axial length and type 2 diabetes were found to be more susceptible to PAMM.Keywords: paracentral acute middle maculopathy, acute primary angle closure, acute primary angle closure glaucoma, risk factors, spectral domain optical coherence tomography

Yanmei Luo,1,&ast; Jie Liu,2,&ast; Zhihui Jiang,3,&ast; Xinghai Yang,1 Song Lin,1 Xiaowen Mao1 1Department of Pediatric Surgery, Maternal and Child Health Hospital of Hubei, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pediatric Surgery, Yijishan Hospital of Wannan Medical College, Wannan Medical College, Wuhu, People’s Republic of China; 3Department of General Surgery, Qingdao Women and Children’s Hospital, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaowen Mao; Song Lin, Department of Pediatric Surgery, Maternal and Child Health Hospital of Hubei, Tongji Medical College, Huazhong University of Science and Technology, No. 58 Guanggu Third Road, Donghu New Technology Development Zone, Wuhan City, 430070, Hubei Province, People’s Republic of China, Email xiaowenmao0927@163.com; yes888111@sina.cnPurpose: To compare and analyze the therapeutic effects of endoscopy-assisted laparoscopic surgery (EALS) and laparoscopic surgery (LS) in the treatment of gastric duplication cysts (GDCs).Patients and Methods: We reviewed the clinical data of children with GDCs who underwent surgical treatment at Hubei Maternal and Child Health Hospital, Yijishan Hospital of Wannan Medical College, and Qingdao Women and Children’s Medical Center from September 2014 to November 2022.Results: The study comprised 29 children with GDCs, including 14 in the EALS group and 15 in the LS group. There was no significant difference between the two groups in terms of age, sex, weight, and cyst size characteristics. There was a significant difference between the two groups in terms of average surgical time (P> 0.05), which was 1.100 ± 0.833 hours in the EALS group and 1.933 ± 0.159 hours in the LS group. There was a significant difference between the two groups (P< 0.05) in average intraoperative blood loss, which was 7.93 ± 3.81 milliliters in the EALS group and 11.80 ± 2.72 milliliters in the LS group. There was a significant difference between the two groups (P< 0.05) in average postoperative fasting time, which was 73.79 ± 8.36 hours in the EALS group and 114.1 ± 9.24 hours in the LS group. There was a significant difference between the two groups (P< 0.05) in average postoperative hospital stay, which was 10.21 ± 4.25 days in the EALS group and 14.47 ± 4.36 days in the LS group.Conclusion: EALS technology can not only shorten surgical time, accurately locate GDCs, reduce injuries, and decrease the probability of complications but also achieve treatment goals safely and reliably.Keywords: gastric duplication cyst, laparoscopic, endoscopic, surgery, children

Shan Lin,1 Caihong Liu,2 Jingting Sun,1 Yinghui Guan1 1Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Yinghui Guan, Email guanyh@jlu.edu.cnPurpose: Exosomes are able to exchange their bioactive RNA cargo to recipient cells. In COPD, exosomes can be controlled and engineered for its use as targeted diagnostic and therapeutic tool. Our study explored novel lncRNAs and mRNAs in plasma exosomes that could be involved in the pathogenesis of COPD.Methods: High-throughput sequencing was conducted to detect the alterations in the expression of exosomal lncRNAs and mRNAs. Gene ontology (GO) functional analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to determine the significant functions and pathways associated with differentially expressed (DE) lncRNAs. The mRNA expression profile dataset, GSE76925, and microRNA expression profile dataset, GSE70080, were obtained from the GEO database. Venn diagrams were used to find common DE mRNAs between my mRNAs dataset and GSE76925. These common DEGs were subjected to PPI analyses to identify Hub genes. Subsequently, Venn diagrams were used to identify common genes between the target genes of DE-miRNAs and Hub genes as well as DE-miRNAs and my lncRNAs dataset. Finally, a lncRNA–miRNA–mRNA co-expression network was constructed by prediction using proprietary software. The lncRNA and mRNA expressions were then validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR).Results: We identified 1578 differentially regulated lncRNAs and 3071 differentially regulated mRNAs. GO and KEGG pathway analyses suggested that the DE lncRNAs are involved in the pathogenesis of COPD. A lncRNA–miRNA–mRNA meshwork was established to predict the potential interactions among these RNAs. RP3-329A5.8 and MRPS11 expression was then subjected to qRT-PCR for validation. Correlations between MRPS11 and clinic-pathological features were explored.Conclusion: Our study provided a set of lncRNAs and mRNAs that may be involved in the pathogenesis of COPD, thereby highlighting the need for further research on both diagnostic biomarkers and molecular mechanisms.Keywords: stable COPD, plasma, exosomes, lncRNA, mRNA

Wanshan Zhu, Lexia Wu, Jiaming Wu, Sihong Lin, Cantu Fang, Huatang Zhang Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, Guangdong Province, People’s Republic of ChinaCorrespondence: Huatang Zhang, Email paul201503@163.comAbstract: Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and is on the rise annually. It is characterized by low differentiation, high malignancy, and rapid growth. Consequently, treatment options are limited, and the patient’s prognosis is poor. The emergence of immunotherapy has partially improved the survival and prognosis of SCLC patients. However, a unique response known as “pseudoprogression” during immunotherapy has raised concerns. The occurrence of tumor enlargement despite a positive response to immune checkpoint inhibitor therapy undoubtedly affects the assessment of clinical drug efficacy and the selection of subsequent treatment strategies. In this article, we analyze a clinical case of pseudoprogression in a patient with SCLC who received immune therapy (Durvalumab). Currently, there is insufficient evidence-based medicine to guide the diagnosis, differentiation and subsequent treatment strategies for pseudoprogression in SCLC following immunotherapy. Through this case report and literature review, we aim to provide diagnostic and therapeutic insights for the clinical use of immunotherapy in advanced SCLC. Additionally, we hope that fellow readers of this article can engage in further collaborative discussions through more clinical research.Keywords: small cell lung cancer, immunotherapy, pseudoprogression

Xiaohang Chen,1,2 Shuaiqi Ji,1,2 Yuxiang Yan,1 Shuoqi Lin,1,2 Lianghang He,1,2 Xiaoyu Huang,2 Lin Chang,2 Dali Zheng,1 Youguang Lu1,2 1Fujian Key Laboratory of Oral Diseases, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Preventive Dentistry, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, People’s Republic of ChinaCorrespondence: Youguang Lu; Dali Zheng, Email fjlyg63@fjmu.edu.cn; dalizheng@fjmu.edu.cnAbstract: Tumors are the second-most common disease in the world, killing people at an alarming rate. As issues with drug resistance, lack of targeting, and severe side effects are revealed, there is a growing demand for precision-targeted drug delivery systems. Plant-derived nanovesicles (PDNVs), which arecomposed of proteins, lipids, RNA, and metabolites, are widely distributed and readily accessible. The potential for anti-proliferative, pro-apoptotic, and drug-resistant-reversing effects on tumor cells, as well as the ability to alter the tumor microenvironment (TME) by modulating tumor-specific immune cells, make PDNVs promising anti-tumor therapeutics. With a lipid bilayer structure that allows drug loading and a transmembrane capacity readily endocytosed by cells, PDNVs are also expected to become a new drug delivery platform. Exogenous modifications of PDNVs enhance their circulating stability, tumor targeting ability, high cell endocytosis rate, and controlled-release capacity. In this review, we summarize PDNVs’ natural antitumor activity, as well as engineered PDNVs as efficient precision-targeted drug delivery tools that enhance therapeutic effects. Additionally, we discuss critical considerations related to the issues raised in this area, which will encourage researchers to improve PDNVs as better anti-tumor therapeutics for clinic applications.Graphical Abstract: Keywords: plant-derived nanovesicles, cancer therapy, natural bioactivity, drug delivery platform, engineered EVs, targeted precision therapy

Wanyang Dong,1,&ast; Qi Peng,1,&ast; Xiaohua Tang,1,2,&ast; Tian Zhong,1 Shunan Lin,1 Ziling Zhi,1 Jingyi Ye,1 Bixia Yang,1 Ning Sun,1,3 Wenchang Yuan1 1Guangzhou Key Laboratory for Clinical Rapid Diagnosis and Early Warning of Infectious Diseases, KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, 510180, People’s Republic of China; 2Third Affiliated Hospital of Guangzhou Medical University, Department of Clinical Laboratory, Guangzhou, 510150, People’s Republic of China; 3Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Sun; Wenchang Yuan, Email ning.sun@connect.polyu.hk; yuanwenchang95@163.comBackground: Staphylococcus haemolyticus is an opportunistic pathogen that belongs to coagulase-negative Staphylococci (CoNS). Increasing infection and multi-drug resistance cases caused by this strain have been reported and thus it poses a great health threat.Methods: The third-generation sequencing technology was performed on a S. haemolyticus SH-1 isolated from a clinical sample to analyze the drug resistance genes, which included vancomycin resistance related genes. In addition, antimicrobial susceptibility tests, transmission electron microscopy and Triton X-100 stimulated autolysis were conducted to understand its biological characteristics.Results: The study shows that this clinical isolate is a vancomycin intermediate-resistant strain. Genome comparison also revealed that WalK(N70K) and WalK(R280Q) mutations may contribute to the vancomycin resistant phenotype. Besides, S. haemolyticus SH-1 exhibit common features of thicker cell wall and decreased autolytic activity.Conclusion: S. haemolyticus SH-1 with WalKR mutations shows typical characteristics of vancomycin resistant strains. Combining the genome features and biological properties, our findings may provide important information for the understanding of the molecular mechanism of S. haemolyticus to vancomycin intermediate-resistance.Keywords: Staphylococcus haemolyticus, drug resistance gene, vancomycin intermediate-resistance, whole genome sequencing

Han Tang,1,2 Ruibo Wang,3 Pei Yan,1,4 Wei Zhang,1 Feng Yang,1 Shengjie Guo,3 Ting Li,3 Luanxing Yi,5 Xue Bai,6 Shan Lin,7 Yuhai Zhang,1 Lei Shang1 1Department of Health Statistics, School of Public Health, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 2Department of Clinical Nursing, School of Nursing, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 3School of Nursing and Health, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 4Department of Operation Room, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 5School of Nursing, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, People’s Republic of China; 6Puyang Oilfield General Hospital, Puyang, Henan, 457001, People’s Republic of China; 7Department of Neurology, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, Fujian, 350025, People’s Republic of ChinaCorrespondence: Lei Shang, The Fourth Military Medical University, Changle West Road 169&num;, Xi’an, Shaanxi, People’s Republic of China, Tel +86 029-84774853, Email shanglei@fmmu.edu.cnBackground: Chemotherapy often negatively impacts the nutritional status of breast cancer patients, and healthy dietary behaviors are important for patient wellbeing. With the guidance of the “Knowledge, Attitude and Practice model” (KAP model), the objective of this survey was to determine the frequency with which patients engage in healthy dietary behaviors and to explore the association between healthy dietary behaviors and nutrition literacy and dietary attitudes.Methods: This study included a total of 284 breast cancer patients undergoing chemotherapy from three hospitals spanning three cities in China. Face-to-face interviews were conducted to collect demographic and clinical characteristics as well as the Dietary Nutritional Knowledge, Attitude and Practice Questionnaire (DNKAPQ) and the Nutrition Literacy Measurement Scale for Chinese Adult (NLMS-CA).Results: Participants exhibited medium to high scores for nutrition literacy, dietary attitude and dietary behavior. Nutrition literacy (r = 0.505, p < 0.001) and dietary attitude (r= 0.326, p < 0.001) scores were both positively correlated with the total dietary behavior score. The total nutrition literacy score was positively correlated with the total dietary behavior score (r = 0.286, p < 0.001). In the univariate analysis, age, body mass index, living environment, education level, monthly family income, work status, menopausal status, number of comorbidities, relapse and endocrine therapy were significantly associated with dietary behavior (p < 0.05). In the multiple linear regression analysis, patients’ dietary behavior was significantly associated with nutrition literacy (β = 0.449, p < 0.001) and dietary attitude (β = 0.198, p < 0.001). These two factors accounted for 28.6% of the variation in the patients’ dietary behavior scores.Conclusion: There is an important need for targeted dietary and nutritional interventions designed and implemented by health professionals to improve dietary behaviors. Intervention design and content should take the patients’ nutrition literacy and dietary attitudes into consideration. In particular, women who are older, overweight, unemployed, and postmenopausal and live in rural areas, exhibit fewer comorbidities, have a lower family income and education level, have not relapsed and are currently receiving endocrine therapy are in urgent need of diet-specific intervention.Keywords: attitude, behavior, breast cancer, chemotherapy, dietary, nutrition literacy

Qi Lou,1,&ast; Lu Pan,1,&ast; Shengjin Xiang,1,2,&ast; Yueting Li,1 Jiahui Jin,1 Jingyang Tan,1 Baoshan Huang,1,2 Kaihui Nan,1,2 Sen Lin1,2 1National Engineering Research Center of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China; 2State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaihui Nan; Sen Lin, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China, Tel +86-577-88067962, Email lin_sen@wmu.edu.cn; nankh@l63.comIntroduction: Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED).Methods: The TAT was chemically grafted onto the Mal-PEG2000-DSPE by Michael’s addition between the sulfhydryl group in TAT and the maleimide group in Mal-PEG2000-DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction.Results: After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experimental animals by inhibiting tissue inflammation and preventing the loss of the corneal epithelium and conjunctival goblet cells. Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis. TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission.Conclusion: NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis is involved in the development of BAC-DED. The present study provided new insights into the adverse effects of BAC, which can serve as a new target for protecting corneal epithelium when applying BAC as a preservative in eye drops. The developed TAT-MT-LIPs can efficiently inhibit BAC-DED and give great potential to be developed as a new DED treatment.Keywords: melatonin liposome, dry eye disease, benzalkonium chloride, pyroptosis, NLRP3/Caspase-1/GSDMD signaling axis

Shuchi Lin,1,&ast; Xiaofan Huang,1,&ast; Ying Zhang,1 Xiaohan Zhang,1 Erhong Cheng,1 Jindong Liu1– 4 1Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 3Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jindong Liu, Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, Huaihai Road West, Quanshan District, Xuzhou, Jiangsu, People’s Republic of China, Tel +86-13951355136, Email liujindong1818@163.comPurpose: Myocardial injury after non-cardiac surgery is closely related to major adverse cardiac and cerebrovascular event and is difficult to identify. This study aims to investigate how to predict the myocardial injury of thoracic surgery and whether intraoperative variables contribute to the prediction of myocardial injury.Methods: The prospective study included adult patients with high cardiovascular risk who underwent elective thoracic surgery from May 2022 to October 2022. Multivariate logistic regression was used to establish a model with baseline variables and a model with baseline and intraoperative variables. We compare the predictive performance of two models for postoperative myocardial injury.Results: In general, 31.5% (94 of 298) occurred myocardial injury. Age ≥ 65 years old, obesity, smoking, preoperative hsTnT, and one-lung ventilation time were independent predictors of myocardial injury. Compared with baseline model, the intraoperative variables improved model fit, modestly improved the reclassification (continuous net reclassification improvement 0.409, 95% CI, 0.169 to 0.648, P< 0.001, improved integrated discrimination 0.036, 95% CI, 0.011 to 0.062, P< 0.01) of myocardial injury cases, and achieved higher net benefit in decision curve analysis.Conclusion: The risk stratification and anesthesia management of high-risk patients are essential. The addition of intraoperative variables to the baseline predictive model improved the performance of the overall model of myocardial injury and helped anesthesiologists screen out the patients at the greatest risk for myocardial injury and adjust anesthesia strategies.Keywords: prediction model, myocardial injury, thoracic surgery, cardiovascular risk, hsTnT

Ziran Wang,1 Jintu Chen,2 Jingjing Song,3 Lingjun Kong,1 Xuanzhi Wang,4 Tengda Xu,5 Songbai Lin,5 Yaling Dou1 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, People’s Republic of China; 3Department of Clinical Laboratory, Anhui Provincial Maternal and Child Health Hospital, Hefei, Anhui, People’s Republic of China; 4Department of Medical Laboratory, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 5Department of Health Management, Peking Union Medical College Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yaling Dou, Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Email douyl@pumch.cnObjective: To determine the plasminogen activator inhibitor-1 (PAI-1) 4G/5G (rs1799889) genotype of the subjects in a robust detection method and to explore the association of the PAI-1 4G/5G polymorphism with susceptibility to diabetes mellitus (DM) and hypertension (HTN) as well as clinical characteristics.Methods: This study recruited 208 patients (68 patients were diagnosed with DM, 70 patients with HTN and 70 patients with DM combined with HTN) and 132 healthy controls (HC). A subset of the population was selected to evaluate the accuracy of the Real-time PCR (RT-PCR) method for detecting PAI-1 4G/5G polymorphism by using the sequencing method as the gold standard. Furthermore, the association of the PAI-1 4G/5G polymorphism with genetic susceptibility to DM and HTN was explored. Moreover, variations in clinical characteristics among individuals with various PAI-1 genotypes were also analyzed in the DM group, the HTN group and the DM+HTN group.Results: There was a high concordance between the RT-PCR method and the sequencing method in determining the PAI-1 4G/5G polymorphism. No association was observed between the PAI-1 4G/5G polymorphism and susceptibility to DM, HTN and DM+HTN, respectively. There were no statistical differences in all study indicators among individuals that carrying various genotypes in the HC group. There were several variations in clinical characteristics among individuals harboring different PAI-1 4G/5G genotypes in the DM group, the HTN group and the DM+HTN group.Conclusion: The RT-PCR method can accurately identify the PAI-1 4G/5G genotype in different individuals. The PAI-1 4G/5G polymorphism may not be associated with genetic susceptibility to DM, HTN and DM+HTN, but differences in clinical characteristics among individuals with various genotypes may provide a reference for disease assessment and personalized treatment of patients.Keywords: diabetes mellitus, hypertension, plasminogen activator inhibitor-1, gene polymorphism

Simin Wan,1,&ast; Shuwei Lin,1,&ast; Yirimuwen,2 Sijie Li,3 Guihua Qin1 1School of Psychology, Zhejiang Normal University, Jinhua, Zhejiang, People’s Republic of China; 2Department of Education, Hetao College, Bayannur, Inner Mongolia, People’s Republic of China; 3Nanchong Central Hospital, North Sichuan Medical University, Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guihua Qin, Email qyaqi0220@163.comBackground: As the role of emotional intelligence has been increasingly explored, researchers generally agree that emotional intelligence is a better predictor of individual success. And fortunately, emotional intelligence is somewhat easily shaped. Schools are important microsites for the shaping of an individual’s emotional intelligence. Good teacher-student relationship contribute to the shaping and development of students’ emotional intelligence.Objective: Based on the theory of developmental contextualism, the current study aims to identify the relationship between good teacher-student relationship and students’ emotional intelligence, and the mediating roles of students’ openness and emotional intelligence.Methods: In this study, a total of 352 adolescents (11– 15 years old) from two schools were surveyed using the teacher-student relationship scale, big five inventory openness subscale, and emotional intelligence scale.Results: Teacher-student relationship were positively correlated with students’ openness, empathy, and emotional intelligence. Teacher-student relationship positively predicted students’ emotional intelligence; students’ openness and empathy played a fully mediating role in teacher-student relationship and emotional intelligence.Conclusion: The closeness and supportiveness of the teacher-student relationship were positively related to students’ openness, empathy, and emotional intelligence were positively correlated.Keywords: teacher–student relationship, openness, empathy, emotional intelligence, adolescents

Jie Wang,&ast; Bin Cao,&ast; Sihao Lin, Yong Wang, Qifa Zhang, Yang Jiang, Wei Li, Yingjian Zhu Department of Urology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201803, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingjian Zhu; Wei Li, Department of Urology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 800 Huangjiahuayuan Road, Shanghai, 201803, People’s Republic of China, Tel +8613764490868 ; +8618117094957, Email zhuyingjian_sjtu@126.com; croma_shh@126.comPurpose: Urologic chronic pelvic pain syndrome has attracted a lot of attention in the new century, and an increasing number of relevant studies have been published. Therefore, we performed a bibliometric analysis of these publications, hoping to show the current research hotspots and future research trends.Methods: The articles on were selected from the Web of Science Core Collection. Countries, authors, references and keywords in the field were visualized and analyzed using CiteSpace and VOSViewer software.Results: A total of 1014 articles on urologic chronic pelvic pain syndrome were identified, with “chronic pelvic pain syndrome” being the most common keyword, with a strong association with “interstitial cystitis” and “chronic prostatitis”. The hotspot of urologic chronic pelvic pain syndrome research has gradually shifted from chronic prostatitis / urologic chronic pelvic pain syndrome to cystitis/bladder pain syndrome over the past few years. Future research tends to focus on urologic chronic pelvic pain syndrome etiology, including oxidative stress and inflammation.Conclusion: Research on urologic chronic pelvic pain syndrome is steadily growing. The United States has made the most prominent contribution in this area, and the share of China’s contribution is expected to grow further. The etiology of urologic chronic pelvic pain syndrome, including inflammation and oxidative stress, have been the focus of current research and developmental trends in the future research.Keywords: bibliometric analysis, chronic pelvic pain syndrome, interstitial cystitis, chronic prostatitis, mechanisms, treatments

Shuchi Lin,1,&ast; Ying Zhang,1,&ast; Xiaofan Huang,1,&ast; Xiaohan Zhang,1 Erhong Cheng,1 Zhaoyun Zhou,2 Jindong Liu1,3– 5 1Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, People’s Republic of China; 3Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 5NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jindong Liu, Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Huaihai Road West, Quanshan District, Xuzhou, Jiangsu, People’s Republic of China, Tel +86-13951355136, Email liujindong1818@163.comPurpose: This study aims to investigate whether the administration of salbutamol/budesonide reduced the incidence of myocardial injury in thoracic surgery.Methods: The randomized controlled trial included 298 patients over 45 and at high-risk for cardiovascular complications after lobectomy. Patients in the experimental group were treated with salbutamol/budesonide after anesthesia induction with fiberoptic bronchoscope. The primary outcome was the incidence rates of myocardial injury, assessed before and three days after the operation. The secondary outcome was respiratory function at each time point during the operation, including lung compliance and arterial partial pressure of oxygen, postoperative pulmonary and cardiovascular complications, hospital stay, pain score, and analgesic dosage.Results: In the control group, the incidence of myocardial injury was 57/150 (38%), while that in the experimental group was 33/148 (22%); compared between the two groups, the difference in the incidence of myocardial injury was statistically significant. The dynamic compliance and static compliance at half an hour after the start of surgery in the experimental group were significantly improved. Before leaving the operating room, the difference in arterial oxygen partial pressure between the two groups was statistically significant.Conclusion: Intraoperative administration of salbutamol/budesonide reduced the incidence of myocardial injury after thoracic surgery, improved lung function, and reduced the incidence of postoperative pulmonary complications.Keywords: salbutamol/budesonide, myocardial injury, thoracic surgery, cardiovascular risk, hsTnT, prediction model

Huan Shi,1,&ast; Lan Chen,2,&ast; Yanlin Liu,1,&ast; Qinglian Wen,1 Sheng Lin,1 Qian Wen,1 Yun Lu,1 Jie Dai,1 Jianmei Li,1 Susu Xiao,1 Shaozhi Fu1 1Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Department of Oncology, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaozhi Fu, Tel +86 830-3165698, Fax +86 830-3165690, Email shaozhifu513@163.comBackground: Chemotherapy still plays a dominant role in cancer treatment. However, the inability of conventional chemotherapeutic drugs to reach the hypoxic zone of solid tumors significantly weakens their efficacy. Bacteria-mediated drug delivery systems can be an effective targeting strategy for improving the therapeutic outcomes in cancer. Anaerobic bacteria have the unique ability to selectively transport drug loads to the hypoxic regions of tumors.Methods: We designed a Bifidobacterium infantis (Bif)-based biohybrid (Bif@PDA-PTX-NPs) to deliver polydopamine (PDA)-coated paclitaxel nanoparticles (PTX-NPs) to tumor tissues.Results: The self-driven Bif@PDA-PTX-NPs maintained the toxicity of PTX as well as the hypoxic homing tendency of Bif. Furthermore, Bif@PDA-PTX-NPs significantly inhibited the growth of A549 xenografts in nude mice, and prolonged the survival of the tumor-bearing mice compared to the other PTX formulations without any systemic or localized toxicity.Conclusion: The Bif@PDA-PTX-NPs biohybrids provide a new therapeutic strategy for targeted chemotherapy to solid tumors.Keywords: tumor hypoxia, bifidobacterium infantis, paclitaxel, nanoparticles, lung cancer

Yanxiong Huang,1 Zhilong Zhang,2 Shihao Lin,3 Haobin Zhou,4 Guiyun Xu5 1Department of Clinical Psychology, Affiliated Longhua People’s Hospital, Southern Medical University (Longhua People’s Hospital), Shenzhen, Guangdong, People’s Republic of China; 2The First People’s Hospital of Huizhou City, Huizhou, Guangdong, People’s Republic of China; 3The Second Clinical College, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 4The First Clinical College, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 5The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Guiyun Xu, Department of Affective Disorder, the Affiliated Brain Hospital of Guangzhou Medical University, 36 Mingxin Road, Guangzhou, Guangdong Province, 510370, People’s Republic of China, Tel +86-81268189, Email 13650774898@163.comAbstract: Bipolar disorder (BD) is a common chronic mental disorder usually characterized by manic, hypomanic and depressive episodes. Patients diagnosed with BD have cognitive impairments in both the mood attack and remission stages, that is impairment of attention, memory and executive function. Up till the present moment, the causative mechanisms of cognitive impairment in BD patients remain poorly understood. Several studies have demonstrated that cognitive impairment in patients with bipolar disorder is not associated with a single factor, but with gene polymorphism, brain structural and functional variables, inflammatory and metabolic factors. Herein, we reviewed and summarized the recent reports on cognitive impairment mechanisms in patients with BD. To prevent or alleviate cognitive damage at an early stage, we propose that future research should focus on investigating the pathological mechanism of specific cognitive dimension damage as well as the pathological mechanism network between the damage of each dimension. It is crucial to recognize mechanisms of cognitive impairment for improving the symptoms and prognosis of BD patients, restoring their social function and integration.Keywords: bipolar disorder, cognitive impairment, mechanism, attention impairment, memory impairment, impairment of executive function

Ningfang Lian,1,&ast; Jiawei Wu,1,&ast; Biying Wang,1 Su Lin,2 Jiefeng Huang,1 Jia Chen,1 Qichang Lin1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University; Fujian Provincial Sleep-Disordered Breathing Clinic Center; National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University; Institute of Respiratory Disease, Fujian Medical University, Fuzhou, People’s Republic of China; 2Liver Research Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qichang Lin, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, Fujian Province, 350005, People’s Republic of China, Tel +86-591-87981698, Fax +86-591-83318716, Email linqc_fy@126.comPurpose: Liver injury in non-obese obstructive sleep apnea (OSA) patients has received much attention in recent years. This study aimed to investigate risk factors of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis in non-obese patients with OSA.Methods: A retrospective study was conducted in the Sleep Center of the First Affiliated Hospital of Fujian Medical University. All consecutive non-obese patients with suspected sleep apnea admitted to the center were enrolled. The clinical characteristics of patients with simple snoring and with different severity OSA were compared. Multivariate logistic regression models were used to analyze the risk factors of NAFLD and liver fibrosis.Results: A total of 410 patients were enrolled. The levels of triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased with the aggravation of OSA (All p< 0.05). Among non-obese patients with OSA, 17 (5%) were diagnosed with liver fibrosis and 228 (65%) with NAFLD; Apnea‑hyponea index (AHI) was an independent predictor for NAFLD and liver fibrosis [OR (95% CI): 1.02 (1.00– 1.03), 1.04 (1.00– 1.07), both p< 0.05]; hypertriglyceridemia was an independent predictor for NAFLD [OR (95% CI): 1.13 (1.12– 1.99), p< 0.05].Conclusion: NAFLD and liver fibrosis were common in non-obese OSA patients and the severity of OSA was an independent risk factor for them.Keywords: obstructive sleep apnea, non-alcoholic fatty liver disease, liver fibrosis

Zengxin Jiang,1,&ast; Zeng Zhang,1,&ast; Shuo Li,2,&ast; Sen Lin,3 Hengfeng Yuan1 1Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Joint Bone Disease Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 3National Engineering Research Center, East China University of Science and Technology, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sen Lin; Hengfeng Yuan, Email linsen@ecust.edu.cn; yuanhf@shsmu.edu.cnBackground: Degenerative joint disease or osteoarthritis (OA) is a leading cause of disability worldwide. Intra-articular injection is the mainstay nonsurgical treatment for OA. However, dense cartilage and a lack of vasculature often limit the ability of drugs to reach cell or tissue targets at the concentrations necessary to elicit the desired biological response. Kartogenin (KGN), a small molecular compound, possesses a strong capacity to promote chondrogenic differentiation of mesenchymal stem cells (MSCs). However, the rapid clearance of KGN from the intra-articular cavity limits its feasibility.Materials and Methods: We constructed a magnetically guided biodegradable nanocarrier system (MNP) which enabled intracartilaginous delivery of KGN to promote chondrogenic differentiation by MSCs embedded within the articular matrix. Moreover, in preclinical models of OA, KGN-loaded MNPs exhibited increased tissue penetration and retention within the joint matrix under external magnetic guidance.Results: Histological examination showed that compared with KGN alone, KGN-loaded MNPs enhanced chondrogenic differentiation and improved the structural integrity of both articular cartilage and subchondral bone.Conclusion: This study demonstrates a practical method for intracartilaginous delivery using engineered nanocarriers, thus providing a new strategy to improve the efficacy of molecular therapeutic agents in the treatment of OA.Graphical Abstract: Keywords: osteoarthritis, kartogenin, magnetic nanoparticles, intracartilaginous

Mendelian randomization uses genetic variation to study the causal effect of exposure on outcome, but results can be biased by confounders, such as horizontal pleiotropy. Here, the authors present MR-CUE, a method to determine causal effects by accounting for correlated and uncorrelated horizontal pleiotropic effects.

Shufang Lin,1 Shuzhen Wei,1 Yong Zhao,1 Zhisong Dai,1 Jian Lin,1 Yu Pang2 1Fujian Provincial Key Laboratory of Zoonosis Research, Fujian Center for Disease Control and Prevention, Fuzhou, People’s Republic of China; 2Department of Bacteriology and Immunology, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of ChinaCorrespondence: Shuzhen Wei, Fujian Center for Disease Control and Prevention, No. 386, Chong’an Road, Jin’an District, Fuzhou, Fujian, 350012, People’s Republic of China, Tel/Fax +86 591 8343 1464, Email 499277975@qq.com Yu Pang, Beijing Chest Hospital, Capital Medical University, No. 97, Machang, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel/Fax +86 10 8950 9359, Email pangyupound@163.comBackground: Here, we aimed to determine the population structure of Mycobacterium tuberculosis (MTB) genotypes in Fujian and explore risk factors associated with infection with the Beijing genotype. We also explored the association between Beijing genotype and drug resistance.Methods: Representative MTB isolates obtained during provincial-level routine anti-tuberculosis drug resistance surveillance conducted since 2013 in 11 Fujian counties were analyzed using McSpoligotyping. In vitro drug susceptibilities to anti-tuberculosis drugs were determined using the standard Löwenstein–Jensen proportion method.Results: Overall, 477 MTB isolates were included in the study, of which 245 isolates belonged to the Beijing genotype family and 232 possessed non-Beijing genotypes. Ultimately, a total of 204 spoligotypes were identified that included 58 spoligotype international types (SITs) from the SITVITWEB database and 146 novel spoligotypes. As compared to patients < 25 years of age (control group), elderly patients (≥ 65 years of age) were more likely to be infected with non-Beijing genotypes [aOR 18.69, 95% CI (5.80– 60.26)], with risk of infection with non-Beijing genotypes increasing with age [aOR 3.73, 95% CI (1.67– 8.30) for patients 45– 64 years of age]. Additionally, as compared to isolates with Beijing and other non-Beijing genotypes, significantly greater proportions of isolates with novel spoligotypes exhibited PTO- and PAS-resistance. Moreover, a markedly higher proportion of isolates with novel spoligotypes exhibited OFX-resistance as compared to isolates with other non-Beijing genotypes.Conclusion: Our data demonstrated that the Beijing genotype is the predominant MTB sublineage in Fujian and that the prevalence rate of infection with this MTB genotype decreases with advancing patient age. Notably, the prevalence rate of this genotype in Fujian TB patients is relatively lower than in other regions of China. In addition, the emergence of novel spoligotypes of highly drug-resistant MTB isolates highlights the urgent need for ongoing molecular genotyping surveillance in Fujian.Keywords: Mycobacterium tuberculosis, genotype, spoligotype, drug resistant

Jing Li1 &ast;, Zheng Xu2 &ast;, Tengda Xu,1 Songbai Lin1 1Department of Health Management, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 2Department of AI Research, Digital Health China Technologies Co. Ltd, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Songbai Lin, Department of Health Management, Peking Union Medical College Hospital, 1&num; Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86 10 6915 9901, Fax +86 10 6915 9901, Email linsb@pumch.cnPurpose: To evaluate the performance of machine-learning models based on multiple years of continuous data to predict incident diabetes among patients with metabolic syndrome.Patients and Methods: The dataset comprises the health records from 2008 to 2020 including 4510 nondiabetic participants with metabolic syndrome (MetS) at baseline and with at least 6 years of records. MetS was defined according to the International Diabetes Federation (IDF) criteria. Overall, 332 patients developed incident diabetes during the 7± 1.4 years of follow-up. Three popular classification algorithms were evaluated on the dataset: logistic regression, random forest, and Xgboost. Five models including single-year models (year 1, year 2, and year 3) and multiple-year models (year 1– 2 and year 1– 3) were developed for each algorithm.Results: The model performances improved with the increasing longitudinal dataset as the area under the receiver operating characteristic curve (AUROC) was boosted for both random forest (year 1– 3: AUROC=0.893; year 3: AUROC=0.862; year 1– 2: AUROC=0.847; year 2: AUROC=0.838) and Xgboost (year 1– 3: AUROC=0.897; year 3: AUROC=0.833; year 1– 2: AUROC=0.856; year 2: AUROC=0.823) model. In the multiple-year models, the highest fasting plasma glucose, followed by the mean or lowest level of HbA1c and BMI had the most important predictive value for the onset of diabetes. In the “ 1– 3” year model, “delta weight” which reflects the fluctuations of yearly change of weight was the fourth-most important feature.Conclusion: This study demonstrated improved performance with the accumulation of longitudinal data when using machine learning for diabetes prediction in MetS patients. For individuals with similar clinical parameters, the variation trends of these parameters could change the risk of future diabetes. This result indicated that models based on longitudinal multiple years’ data may provide more personalized assessment tools for risk evaluation.Keywords: diabetes, metabolic syndrome, machine-learning method, prevention

Huiyun Zhang,1 Wenya Hua,1 Siran Lin,1 Yu Zhang,1 Xinchang Chen,1 Shiyong Wang,1 Jiazhen Chen,1 Wenhong Zhang1– 3 1Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Key Laboratory of Medical Molecular Virology (MOE/MOH), Shanghai Medical College, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Jiazhen Chen, Department of Infectious Diseases, Huashan Hospital, Fudan University, Rm 524, Building No. 5, No. 12 Middle Wulumuqi Road, Shanghai, 200040, People’s Republic of China, Email jiazhen_chen@163.comObjective: Nontuberculous mycobacteria (NTM) can cause pulmonary and extrapulmonary diseases. Tedizolid (TZD) is a new oxazolidinone with in vitro activity against NTM such as Mycobacterium avium complex (MAC), Mycobacterium fortuitum, and Mycobacterium abscessus complex. The aim of this study was to evaluate the TZD susceptibility profiles of clinical isolates of NTM.Methods: The microdilution method was used to identify the minimum inhibitory concentration (MIC) of TZD and linezolid (LZD) for 133 clinical NTM isolates. Broth microdilution chequerboard assays were used to investigate the synergistic effects of TZD and three antibiotics on two reference isolates and eleven clinical isolates of NTM.Results: The TZD MIC50 and MIC90 for M. abscessus complex were 2 and 4 μg/mL, 16 and > 32 μg/mL for MAC, respectively. TZD exhibited lower MICs than that of LZD for most NTM, which were positively correlated. Due to the high MIC values of TZD against MAC, it is necessary to conduct drug sensitivity tests before TZD administration. TZD-clarithromycin combination had synergistic response on M. abscessus complex in 3 of the 8 isolates, which lasted only 3– 5 days. TZD-cefoxitin had synergistic effect against all five M. fortuitum isolates.Conclusion: Our study demonstrates that TZD had greater in vitro potency than LZD, and synergy studies suggested that TZD may be an important component of multi-drug treatment regimen.Keywords: tedizolid, susceptibility testing, nontuberculous mycobacteria, linezolid, oxazolidinone

Siyang Lin,1,2,&ast; Fang Wang,2– 4,&ast; Jiaxin Zheng,1,2 Yin Yuan,1,2,5,6 Feng Huang,1,2,5,6 Pengli Zhu1,2,5,6 1Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Geriatric Medicine, Fujian Provincial Hospital, Fuzhou, Fujian, People’s Republic of China; 3Fujian Health College, Fuzhou, Fujian, People’s Republic of China; 4Nursing School of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 5Fujian Provincial Center for Geriatrics, Fuzhou, Fujian, People’s Republic of China; 6Fujian Provincial Key Laboratory of Geriatrics, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Huang; Pengli Zhu, Shengli Clinical Medical College of Fujian Medical University, No. 134 Dongjie Road, Gulou District, Fuzhou, 350001, Fujian, People’s Republic of China, Tel/Fax +86-591-88216023, Email wmhf0327@126.com; zpl7755@hotmail.comPurpose: Intrinsic capacity (IC) reflects the overall health status of older adults and has great public health significance. But few studies described the related biomarkers for IC. The aim of this study was to investigate the association between homocysteine (Hcy) and IC in older adults.Participants and Methods: This cross-sectional study included 1927 community-dwelling Chinese older adults aged 60– 98 years from May 2020 to December 2020. Data were collected through interviews, physical examinations, and laboratory tests. IC involved five domains of cognition, locomotion, sensory, vitality, and psychology evaluated by the Mini-cog scale, 4-m walk test, self-reported visual and hearing conditions, MNA-SF scale, and GDS-4 scale, respectively. The score of each domain dichotomized as 0 (normal) and 1 (impaired) was added together to an IC total score. Low IC was defined as a score of 3– 5, and high IC as 0– 2. Hcy was measured by a two-reagent enzymatic assay. A restricted cubic spline regression model was used to explore the non-linear relationship between Hcy and low IC.Results: Hcy was higher in the low IC group than in the high IC group. Restricted cubic spline analysis revealed a J-shaped nonlinear association between Hcy and low IC. The risk of IC decline was slowly decreased until 8.53 μmol/L of Hcy (OR=0.753, 95% CI=0.520– 1.091, P=0.132), and increased with elevations of per 5 μmol/L Hcy afterwards (OR=1.176, 95% CI=1.059– 1.327, P=0.005). Among the five domains of IC, Hcy had ORs of 1.116 (1.009– 1.247) for cognition impairment, 1.167 (1.055– 1.305) for vitality, and 1.160 (1.034– 1.303) for psychology per 5 μmol/L increase in Hcy above the change point. Additional sensitivity analysis also demonstrated the nonlinear association between Hcy and low IC.Conclusion: Hcy had a J-shaped association with low IC. Higher Hcy (Hcy ≥ 8.53μmol/L) might provide clinical implications for early identifying the risk of low IC.Keywords: homocysteine, intrinsic capacity, older adults, frailty

Ying Zhao,1,&ast; Shiyuan Lin,1,2,&ast; Ruiyue Fang,1 Yaling Shi,1 Wei Wu,1 Wei Zhang,1 Hui Chen1 1College of Pharmacy, Guilin Medical University, Guilin, 541199, People’s Republic of China; 2Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Chen; Wei Zhang, College of Pharmacy, Guilin Medical University, No. 1 Zhiyuan Road, Guilin, 541199, People’s Republic of China, Email chenhui_gl@163.com; 22437564@qq.comIntroduction: In the previous study, nanoparticles coated with trimethyl chitosan (TMC) derivatives (PPTT-NPs) could promote the oral bioavailability of panax notoginseng saponins (PNS). Herein, we chose PPTT-NPs as a model drug to study the property and mechanism of intestinal absorption in vitro and in vivo.Methods: The stability of PPTT-NPs was evaluated using simulated gastric fluid and simulated intestinal fluid. The uptake and transport of PPTT-NPs were investigated in Caco-2 and Caco-2&HT29 co-culture cells. The biosafety, intestinal permeability, adhesion, and absorption mechanism of PPTT-NPs were investigated using SD rats in vivo. The live imaging and biodistribution of PPTT-NPs were observed by IVIS. Furthermore, the effects on CYP3A4 of PPTT-NPs were investigated using testosterone as the probe substrate.Results: The results of the stability assay showed that PPTT-NPs had a strong tolerance to the pH and digestive enzymes in the gastrointestinal environment. In vitro cell experiments showed that the uptake of drugs exhibited a time-dependent. When the ratio of TMC-VB12 and TMC-Cys was 1:3, the uptake capacity of PPTT-NPs was the highest. PPTT-NPs could enhance the paracellular transport of drugs by reversibly opening a tight junction. Animal experiments demonstrated that PPTT-NPs have good biological safety. PPTT-NPs had good adhesion and permeability to small intestinal mucosa. Meanwhile, PPTT-NPs needed energy and various protein to participate in the uptake of drugs. The live imaging of NPs illustrated that PPTT-NPs could prolong the residence time in the intestine. Moreover, TMC-VB12 and TMC-Cys could reduce the metabolism of drugs by inhibiting CYP3A4 to a certain extent.Conclusion: The results show that TMC-VB12 and TMC-Cys are effective in the transport of PPTT-NPs. PPTT-NPs can increase the intestinal adhesion of drugs and exert high permeation by intestinal enterocytes which demonstrate significant and efficient potential for oral delivery of the BCS III drugs.Graphical Abstract: Keywords: Panax notoginseng saponins, TMC derivatives, nanoparticles, oral absorption, Caco-2&HT29 co-culture cells

Jian Lin,1,2 Yong Zhao,1,2 Shuzhen Wei,1,2 Zhisong Dai,1,2 Shufang Lin1,2 1Institute of Tuberculosis Control and Prevention, Fujian Center for Disease Control and Prevention, Fuzhou, People’s Republic of China; 2Fujian Provincial Key Laboratory of Zoonosis Research, Fujian Center for Disease Control and Prevention, Fuzhou, People’s Republic of ChinaCorrespondence: Shufang Lin; Jian Lin, Institute of Tuberculosis Control and Prevention, Fujian Center for Disease Control and Prevention, No. 386, Chong’an Road, Xindian Town, Jin’an District, Fuzhou, Fujian, 350011, People’s Republic of China, Tel/Fax +86 591 8343 1464, Email zqszl@163.com; 13665033307@126.comPurpose: The purpose of this study was to evaluate a new commercial kit for Mycobacterium species identification and compare its results with that of the commonly used GenoType Mycobacterium CM assay. In addition, we were committed to identifying the main frequent species of nontuberculous mycobacteria (NTM) in Fujian.Methods: A total of 261 clinical strains, collected at the Center for Disease Control and Prevention of Fujian Province, China, were preliminarily identified as NTM based on p-nitrobenzoic acid (PNB) growth test. The genomic DNA of all 261 strains was extracted and subjected to species identification using MeltPro Myco assay and GenoType Mycobacterium CM assay. The results of the latter were used as a control to calculate the positive agreement, negative agreement, agreement and the total agreement of the former. For samples with inconsistent detection results, sequencing was performed for verification.Results: Compared to GenoType Mycobacterium CM assay, the total agreement of MeltPro Myco assay was 96.55% (252/261 strains). Both the positive and negative agreement of MeltPro Myco assay in identifying M. intracellulare, M. abscessus, M. kansasii, M. fortuitum, M. avium, M. gordonae, M. scrofulaceum, and mixed infections were higher than 99.00%, but the positive agreement of M. chelonae was relatively low at only 33.33%. In Fujian, the predominant strain of NTM was M. intracellulare (64.36%, 130/202 strains), followed by M. abscessus (19.31%, 39/202 strains), M. kansasii (4.46%, 9/202 strains), and M. fortuitum (3.96%, 8/202 strains).Conclusion: The reliability of MeltPro Myco assay for identifying mycobacterium species was strongly demonstrated in this study, which greatly supports its usage for the clinical identification of mycobacteria. The present study also showed that the distribution of mycobacteria in Fujian, China, was significantly different from that in other regions and provided important data for future epidemiological study of NTM.Keywords: evaluation, line probe assay, nontuberculous mycobacteria, species identification

Suipeng Chen,1,&ast; Mengjiao Kuang,1,&ast; Ying Qu,1,2 Shirui Huang,1 Binbin Gong,1 Suzhen Lin,1 Huiyan Wang,1 Guiye Wang,1 Hongqun Tao,1 Jian Yu,1 Zuqin Yang,3 Minghua Jiang,1 Qipeng Xie1 1Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China; 2Department of Clinical Laboratory, Wenzhou People’s Hospital, The Third Affiliated Hospital of Shanghai University, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China; 3Newborn Department of Pediatrics, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qipeng Xie, Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China, Tel +86 15157787159, Email pandon2002@163.comObjective: Sepsis remains a major cause of neonatal death. To better characterize the inflammatory response during neonatal sepsis, we compared the differences in serum cytokines and chemokines between full-term neonates with sepsis and without infection.Methods: We enrolled 40 full-term neonates with sepsis and 26 full-term neonates without infection as controls between October 2016 and June 2018. Forty cytokines /chemokines in serum were analyzed using the Luminex Bead Immunoassay System.Results: Our results showed that serum IL-6, IL-8, TNF-α, IL-1β, MIF, CXCL13, CXCL1, CXCL2, CXCL5, CXCL6, CXCL16, CCL27, CCL2, CCL8, CCL3, CCL20, CCL23, and CX3CL1 levels were significantly increased in neonates with sepsis compared to those in the control group (all p< 0.05). The levels of serum CCL20, and IL-17 were higher in late-onset sepsis (LOS) than those in early-onset sepsis (EOS) (all p< 0.05). Conversely, serum CXCL16 was lower in LOS than that in EOS (p< 0.05).Conclusion: Our findings revealed that excessive pro-inflammatory cytokines might be involved in neonatal sepsis. In addition, chemokines significantly increased the recruitment of immune cells after infection to participate in the anti-infection defense of neonates, but this could lead to damage.Keywords: neonatal sepsis, cytokines, chemokines

Ming Yang,1– 3 Qi Zhang,1– 3 Yizhong Ge,1– 4 Meng Tang,1– 3 Chunlei Hu,1– 3 Ziwen Wang,1– 3 Xi Zhang,1– 3 Mengmeng Song,1– 3 Guotian Ruan,1– 3 Xiaowei Zhang,1– 3 Tong Liu,1– 3 Hailun Xie,1– 3 Heyang Zhang,1– 3 Kangping Zhang,1– 3 Qinqin Li,1– 3 Xiangrui Li,1– 3 Xiaoyue Liu,1– 3 Shiqi Lin,1– 4 Hanping Shi1– 3 1Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, People’s Republic of China; 3Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, People’s Republic of China; 4The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Hanping Shi, Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China, Tel/Fax +86 10 6392 6983, Email shihp@ccmu.edu.cnPurpose: The incidence, progression, and prognosis of cancer could be affected by inflammation and nutrition. Female patients have different inflammatory and nutritional states depending on their age and tumor types. It is important to screen for suitable prognostic indicators in female patients with cancer of different ages and tumor types.Patients and Methods: Baseline clinicopathologic and laboratory characteristics of 1502 female patients with cancer were obtained from a multicenter cohort study. Concordance indices (C-indices) were used to evaluate the prediction accuracy of following inflammation- and nutrition-based indicators: advanced lung cancer inflammation index (ALI), systemic immune inflammation index (SII), modified geriatric nutritional risk index (mGNRI), albumin-to-globulin ratio (AGR), prognostic nutritional index (PNI), lymphocyte-to-C-reactive protein ratio (LCR), controlling nutritional status score (CONUT), modified Glasgow prognostic score (mGPS), and lymphocyte-to-C-reactive protein score (LCS).Results: The most suitable indicators in different female populations with cancer had C-indices as follows: LCR (0.668; 95% CI, 0.644– 0.693) for all females; AGR (0.681; 95% CI, 0.619– 0.743) for young females; LCR (0.667; 95% CI, 0.628– 0.706) for middle-aged females; ALI (0.597; 95% CI, 0.574– 0.620) for elderly females; LCR (0.684; 95% CI, 0.621– 0.747) for females with reproductive system cancer; and ALI (0.652; 95% CI, 0.624– 0.680) for females with non-reproductive system cancer.Conclusion: The most suitable indicators for the different female populations with cancer are summarized as follows: LCR for all females, AGR for young females, LCR for middle-aged females, ALI for elderly females, LCR for females with reproductive system cancer, and ALI for females with non-reproductive system cancer.Keywords: female, cancer, prognosis, inflammation, nutrition

Duming Zhong, Dan Chen, Guangquan Zhang, Shaobai Lin, Runhong Mei, Xuefeng Yu Department of Orthopedics, The Fourth Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Xuefeng Yu; Runhong Mei, Email yxf_1958@sina.com; 1255946311@qq.comBackground: Ewing’s sarcoma (ES) is a common bone cancer in children and adolescents. There are ethnic differences in the incidence and treatment effects. People have made great efforts to clarify the cause; however, the molecular mechanism of ES is still poorly understood.Methods: We download the microarray datasets GSE68776, GSE45544 and GSE17674 from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) of the three datasets were screened and enrichment analysis was performed. STRING and Cytoscape were used to carry out module analysis, building a protein–protein interaction (PPI) network. Finally, a series of analyses such as survival analysis and immune infiltration analysis were performed on the selected genes.Results: A total of 629 differentially expressed genes were screened, including 206 up-regulated genes and 423 down-regulated genes. The pathways and rich-functions of DEGs include protein activation cascade, carbohydrate binding, cell-cell adhesion junctions, mitotic cell cycle, p53 pathway, and cancer pathways. Then, a total of 10 hub genes were screened out. Biological process analysis showed that these genes were mainly enriched in mitotic nuclear division, protein kinase activity, cell division, cell cycle, and protein phosphorylation.Conclusion: Survival analysis and multiple gene comparison analysis showed that CDCA8, MAD2L1 and FANCI may be involved in the occurrence and prognosis of ES. The purpose of our study is to clarify the DEG and key genes, which will help us know more about the molecular mechanisms of ES, provide potential pathway or targets for the diagnosis and treatment.Keywords: Ewing sarcoma, biomarkers, microarray, differentially expressed genes, protein interaction

Feng Su,1,&ast; Yong Fang,1,&ast; Jinjie Yu,1 Tian Jiang,1 Siyun Lin,1 Shaoyuan Zhang,1 Lu Lv,2 Tao Long,2 Huiwen Pan,2 Junqing Qi,2 Qiang Zhou,3 Weifeng Tang,4 Guowen Ding,2 Liming Wang,5 Lijie Tan,1 Jun Yin1 1Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Jiangsu, People’s Republic of China; 3Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan, People’s Republic of China; 4Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, Jiangsu, People’s Republic of China; 5Department of Respiratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Yin; Lijie Tan, Zhongshan Hospital of Fudan University, 180 Fenglin road, Xuhui District, Shanghai, 200032, People’s Republic of China, Email jun_yin@fudan.edu.cn; tan.lijie@zs-hospital.sh.cnBackground: The σ 1A subunit of the adaptor protein 1 (AP1S1) participates in various intracellular transport pathways, especially the maintenance of copper homeostasis, which is pivotal in carcinogenesis. It is therefore rational to presume that AP1S1 might also be involved in carcinogenesis. In this hospital-based case-control study, we investigated the genetic susceptibility to ESCC in relation to SNPs of AP1S1 among Chinese population.Methods: A database containing a total of 1303 controls and 1043 ESCC patients were retrospectively studied. The AP1S1 SNPs were analyzed based on ligation detection reaction (LDR) method. Then, the relationship between ESCC and SNPs of AP1S1 was determined with a significant crude P< 0.05. Then the logistic regression analysis was used for the calculation for adjusted P in the demographic stratification comparison if a significant difference was observed in the previous step.Results: AP1S1 rs77387752 C>T genotype TT was an independent risk factor for ESCC, while rs4729666 C>T genotype TC and rs35208462 C>T genotype TC were associated with a lower risk for ESCC, especially in co-dominant model and allelic test for younger, male subjects who are not alcohol-drinkers nor cigarette smokers.Conclusion: AP1S1 rs77387752, rs4729666 and rs35208462 polymorphisms are associated with susceptibility to ESCC in Chinese individuals. AP1S1 SNPs may exert an important role in esophageal carcinogenesis and could serve as potential diagnostic biomarkers.Keywords: AP1S1, single nucleotide polymorphism, SNP, esophageal squamous cell carcinoma, ESCC

Ou L, Lin H, Song Y, et al. Int J Nanomedicine. 2020;15:5131–5146. The Editor and Publisher of International Journal of Nanomedicine are retracting the published article. The authors requested to correct the image used for Figure 8D, p-PTEN, Inhibitor, however it was found the image had been duplicated with that from Figure 7E, p-PTEN, inhibitor from Ou L, Sun T, Liu M, et al. Efficient miRNA Inhibitor Delivery with Graphene Oxide-Polyethylenimine to Inhibit Oral Squamous Cell Carcinoma. Int J Nanomedicine. 2020;15:1569–1583. https://doi.org/10.2147/IJN.S220057. The authors cooperated with our queries and provided some data from their study, but they were unable to provide a satisfactory explanation for the image duplication. As the findings could not be adequately verified the Editor and Publisher made the decision to retract the article. The authors did not agree with this decision. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Guochao Mao,&ast; Jianhua Wu,&ast; Hanxiao Cui, Luyao Dai, Li Ma, Zhangjian Zhou, Baobao Liang, Shuqun Zhang, Shuai Lin Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuai Lin; Shuqun Zhang, Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi, 710004, People’s Republic of China, Email voyage420@163.com; shuqun_zhang1971@163.comPurpose: We aimed to characterize the expression patterns of glycolysis and hypoxia genes in colon cancers as well as their value in prognosis and immune microenvironment.Methods: The expression profiles were acquired from the Cancer Genome Atlas database. Enrichment of hypoxia and glycolysis gene sets in colon cancer was identified by gene set enrichment analysis. Then, a prognostic signature was built up after Cox regression analyses, and overall survival analysis validated the predictive ability. Immune status and infiltration in cancer tissues were explored using the single sample gene set enrichment analysis and CIBERSORT algorithm. A nomogram model integrating clinical variables and the gene signature was established and assessed.Results: Altogether, 378 cancer and 39 control cases were enrolled. Three glycolysis gene sets and two hypoxia gene sets were enriched in colon cancer (P < 0.05). Five independent genes (ENO3, GPC1, P4HA1, SPAG4, and STC2) were significantly correlated with prognosis of colon cancer patients. Patients with higher risks had significantly better prognosis than those with lower risks (P = 0.002 and AUC = 0.750), which was also observed in the elderly, female and stage I–II subgroups (P < 0.05). In high-risk cases, proportion of NK cells resting increased (P < 0.05) while that of dendritic cells activated (P < 0.05), dendritic cells resting (P < 0.01) and monocytes (P < 0.01) decreased. Besides, expressions of 22 checkpoint genes were found abnormal in groups with different risks (P < 0.05). The predictive nomogram presented satisfactory performance with C-index of 0.771 (0.712– 0.830). The area under ROC curve was 0.796 and 0.803 for 3- and 5-year survival prediction, respectively.Conclusion: A glycolysis and hypoxia combined gene signature was a promising method to evaluate the prognosis and immune infiltration of colon cancer patients, which may provide a new tool for cancer management.Keywords: colon cancer, gene signature, glycolysis, hypoxia, prognosis

Hailun Xie,1– 3,&ast; Guotian Ruan,1– 3,&ast; Qi Zhang,1– 3,&ast; Yizhong Ge,1– 3 Mengmeng Song,1– 3 Xi Zhang,1– 3 Xiaoyue Liu,1– 3 Shiqi Lin,1– 3 Xiaowei Zhang,1– 3 Xiangrui Li,1– 3 Kangping Zhang,1– 3 Ming Yang,1– 3 Meng Tang,1– 3 Minghua Cong,4 Hanping Shi1– 3 1Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, 100038, People’s Republic of China; 3Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, 100038, People’s Republic of China; 4Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hanping Shi, Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China, Email shihp@ccmu.edu.cnPurpose: The nutritional risk index (NRI) and handgrip strength (HGS) are useful indicators of nutritional and physical status, respectively, both of them can predict the prognosis of many cancers; however, the predictive accuracy of a single indicator is unsatisfactory. Whether the combination of NRI and HGS could enhance the stratification of the prognosis of patients with cancer cachexia.Patients and Methods: The study population was randomly divided into training and validation cohorts. We combined NRI and HGS and constructed the NRI–HGS score. Restricted cubic splines were used to assess the associations between NRI, HGS, and all-cause mortality. The Kaplan–Meier method was used to calculate the survival probability of the patients. The Cox proportional hazards risk model was used to analyze survival and prognostic factors.Results: Low NRI and low HGS were independent predictors of poor prognosis in patients with cancer cachexia. The NRI–HGS score showed a better prognostic stratification than either NRI or HGS. The co-occurrence of low NRI and low HGS was associated with an approximately 1.8-fold increased risk of mortality. The NRI–HGS score could effectively distinguish patients with a poor prognosis at different pathological stages. Furthermore, we constructed a novel prognostic nomogram based on NRI and HGS. The concordance index and calibration plot confirmed that the nomogram had good prognostic accuracy. The area under the receiver operating characteristic curve of the nomogram reached > 0.8, which was much higher than that of the traditional tumor–node–metastasis staging system. The nomogram provided better prognostic stratification for patients with cancer cachexia.Conclusion: Low NRI and low HGS are independent prognostic indicators in cancer cachexia. The combination of NRI and HGS improve prognostic stratification for patients with cancer cachexia. Our study suggests combining nutritional and physical status in future cachexia research.Keywords: nutritional risk index, handgrip strength, cancer cachexia, prognostic

Dianna Liu,1 Shicheng Lin,2 Yuan Li,2 Tian Zhou,1 Kaiwen Hu,1 Quanwang Li1 1Oncology Department, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100071, People’s Republic of China; 2Graduate School, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of ChinaCorrespondence: Kaiwen Hu; Quanwang Li, Email kaiwenh@163.com; quanwangli@126.comPurpose: Yin-Huo-Tang (YHT) is a classic traditional Chinese prescription, used to prevent lung adenocarcinoma (LUAD) relapse by “nourishing yin and clearing heat”. In this study, the mechanism of YHT in LUAD recurrence was investigated.Methods: Firstly, the bioactive compounds and targets of YHT, as well as related targets of LUAD recurrence, were collected from public databases. The protein–protein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to find the pivotal compounds, hub genes, functional annotation and main pathways. Subsequently, RNA sequencing of recurrent tumor tissues from Lewis lung carcinoma mice treated with YHT was used to explore the main pathways. At the same time, pathways screened by network pharmacology and RNA sequencing analysis were considered the most important pathways. Finally, liquid chromatography mass spectrometry was used to validate the pivotal active ingredients. Molecular docking technology was performed to validate the binding association between the hub genes and the pivotal active ingredients. PCR and WB analysis were used to validate the main pathways.Results: There were 128 active compounds and 419 targets interacting with YHT and LUAD recurrence. Network analysis identified 4 pivotal compounds, 28 hub genes and 30 main pathways. Sphingolipid signaling pathway was the common main pathway in network pharmacology and RNA sequencing results. The hub gene related to the sphingolipid signaling pathway was S1PR5. Qualitative phytochemical analysis confirmed the presence of 3 pivotal compounds, namely stigmasterol, nootkatone and ergotamine. The molecular docking verified that the pivotal compounds could good affinity with S1PR5. The PCR and WB analysis verified YHT suppressed Lewis lung cancer cells proliferation and migration by inhibiting the sphingolipid signaling pathway.Conclusion: The potential mechanism and therapeutic effect of YHT against the recurrence of LUAD may be ascribed to inhibition of the sphingolipid signaling pathway.Graphical Abstract: Keywords: sphingolipid signaling pathway, traditional Chinese medicine, S1PR5, stigmasterol, nootkatone, ergotamine

Wu Yi,1 Tianxin Yang,2 Sisi Lin,1 Rui Hao,1 Jin Yu,1 Ying Wang,1,3 Xiangming Tong2,4 1Phase I Clinical Research Center, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 2Department of Hematology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 3Clinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of China; 4The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, People’s Republic of ChinaCorrespondence: Xiangming TongThe Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China, Tel +86-13758183497, Email tongxiangmin@163.comAbstract: Extranodal NK/T cell lymphoma (ENKL) is a rare subtype of lymphoma that shows a poor clinical outcome. The most common sites are the nasal cavity, nasopharynx, paranasal sinuses, tonsils and larynx. Because of P-glycoprotein expression on ENKL cells, ENKL is resistant to anthracycline-based chemotherapy. L-asparaginase-based chemotherapy with or without radiotherapy shows promising outcomes for advanced ENKL, but has limited efficacy in relapsed/refractory ENKL. immune-checkpoint inhibitors, histone deacetylase inhibitors, and monoclonal antibodies are being investigated. In this review, we summarize the new treatments for ENKL.Keywords: extranodal NK/T cell lymphoma, pathway, PD-1, immunotherapy

Guochao Mao, Yi Zheng, Shuai Lin, Li Ma, Zhangjian Zhou, Shuqun Zhang Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710000, People’s Republic of ChinaCorrespondence: Guochao MaoDepartment of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwu Road, Xi’an, Shaanxi, 710000, People’s Republic of ChinaTel +8615991381508Fax +8602987679512Email gchmao@163.comIntroduction: Breast cancer (BC) has become the malignant tumor with the highest incidence worldwide. As a critical components of epigenetic regulation complexes, chromobox (CBX) family members inhibit the transcription of target genes through chromatin modification, leading to the progression of various human diseases and cancers. So far, little is known about the role of different CBX members in BC, especially their association with immune cells.Methods: We conducted the analysis of differential expression of CBXs using Oncomine and GEPIA, prognostic value of CBXs using GEPIA and Kaplan-Meier, genetic interaction of CBXs using cBioPortal and GeneMANIA, and immune cell infiltration of CBXs in BC patients using TIMER.Results: The CBX2/3/4/8 expression levels were increased significantly, while the CBX6/7 expression levels were decreased. We found that CBX3 was significantly correlated with clinicopathological staging and short DFS in BC patients. High CBX3/5 expression was correlated with short OS in BC patients, while high expression of CBX4 was correlated with long OS in BC patients. In addition, the functions of CBXs family members mainly focus on methylated histone residue binding and chromatin organization. The CBXs expressions were closely related to the infiltration level of a variety of immune cells, including CD4/8+ T cells, B cells, neutrophils, macrophages and dendritic cells in BC cancers. The correlation between CBXs and immune cell infiltration was more common in Luminal BC than in Basal and Her-2 type.Conclusion: This study may provide a new understanding for selection of molecular typing, therapeutic and prognostic biomarkers of CBX family in BC.Keywords: comprehensive analysis, chromobox family members, breast cancer, prognosis, genetic interaction, immune infiltration

Shang Lin,1 Ya-ru Wei,2 Hong-xiang Yao3 1Department of Nuclear Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325002, People’s Republic of China; 2Department of Radiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325002, People’s Republic of China; 3Department of Interventional Radiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325002, People’s Republic of ChinaCorrespondence: Hong-xiang YaoDepartment of Interventional Radiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan Western Road, Wenzhou, 325002, Zhejiang, People’s Republic of ChinaEmail lsyhx2004@163.comBackground: Hundreds of studies have reported the application of iodine-131 (I-131) in thyroid carcinoma (THCA) in past years. However, the status of research in the field and other related topics have not been investigated. This study aimed to identify the cooperation of authors, countries, and institutions, as well as explore the hot topics and prospects regarding I-131 therapy in THCA based on previous studies.Methods: Publications from 2010 to 2020 were retrieved from Web of Science Core Collection according to research strategy. Bibliometric analyses were performed using VOSviewer 1.6.15 and CiteSpace 5.7.3 to evaluate and visualize the cooperation network, hot topic, and research frontier.Results: The number of publications showed a trend of fluctuation between 2010 and 2020. We identified 1387 publications related to I-131 therapy in THCA, which were published by 1628 institutions from 82 countries. The largest proportion of publications were emanated from the USA, and the majority of papers were published by Thyroid. Shanghai Jiao Tong University of China contributed the most papers. Although many authors participated in the research of this field, high-yield authors were few. Co-occurrence analysis classified keywords into five clusters, including assessment, efficacy measurement, monitoring, hormone regulation, and guidelines of I-131 therapy. The terms “bone marrow dosimetry and time” were among the latest hotspots. The research frontier topic in I-131 therapy focused on the “P53 and anti-Müllerian hormone”.Conclusion: The attention to I-131 therapy in THCA should be increased considerably. It was necessary to construct active co-operations between authors, countries, and institutions to promote the development of this field. Recent researches referred to the timing and dose assessment of I-131 therapy in THCA. Future studies likely focused on targeted therapy and adverse effects evaluation were worthy of research as well.Keywords: I-131, thyroid carcinoma, bibliometric analysis, hot spots, research trend