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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

Psychedelics hold promise as alternate treatments for neuropsychiatric disorders. However, the neural mechanisms by which they drive adaptive behavioral effects remain unclear. We isolated the specific neurons modulated by a psychedelic to determine their role in driving behavior. Using a light- and calcium-dependent activity integrator, we genetically tagged psychedelic-responsive neurons in the medial prefrontal cortex (mPFC) of mice. Single-nucleus RNA sequencing revealed that the psychedelic drove network-level activation of multiple cell types beyond just those expressing 5-hydroxytryptamine 2A receptors. We labeled psychedelic-responsive mPFC neurons with an excitatory channelrhodopsin to enable their targeted manipulation. We found that reactivation of these cells recapitulated the anxiolytic effects of the psychedelic without driving its hallucinogenic-like effects. These findings reveal essential insight into the cell-type-specific mechanisms underlying psychedelic-induced behavioral states. [ABSTRACT FROM AUTHOR]