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Ling Duan,1 Wenhui Guo,1 Shuo Yin,1 Shoubo Yang,1 Jie Liu,2 Yunyun Duan,3 Gehong Dong,4 Wenbin Li,1 Feng Chen1 1Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 3Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 4Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of ChinaCorrespondence: Wenbin Li; Feng Chen, Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Nansihuan Road, Beijing, 100070, People’s Republic of China, Tel +86-10-59975034, Email liwenbin@ccmu.edu.cn; chenfeng406@sina.comPurpose: To investigate the prognostic significance of pan-immune-inflammation value (PIV) and PILE score (based on PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)) in patients with primary central nervous system lymphoma (PCNSL).Patients and Methods: A total of 109 patients were enrolled. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE score was incorporated based on PIV, LDH levels, and ECOG PS. The Kaplan–Meier curves and Cox hazards regression models were applied for survival analyses. The relationship between PIV, PILE, and therapeutic response was examined.Results: Baseline high PIV was significantly associated with worse overall survival (OS) in univariate (HR 3.990, 95% CI 1.778– 8.954, p < 0.001) and multivariate (HR 3.047, 95% CI 1.175– 7.897, p = 0.022) analyses. High PIV was also associated with worse progression-free survival (PFS) in univariate (HR 2.121, 95% CI 1.075– 4.186, p = 0.030) but not significant in multivariate analyses. PIV outperformed other systemic inflammation parameters. The patients in the high PILE group (PILE score 2– 3) had worse OS (p = 0.008) and PFS (p < 0.001) compared to the low PILE group (PILE score 0– 1). PILE was independently associated with therapeutic response to initial treatment (OR 0.17, 95% CI 0.05– 0.46; p < 0.001).Conclusion: High PIV and PILE were correlated with worse clinical outcomes in PCNSL patients, indicating that PIV and PILE might be a powerful predictor of prognosis and a potential predictive indicator for therapeutic response in PCNSL.Keywords: primary central nervous system lymphoma, pan-immune inflammation value, PILE score, prognosis

Yaxin Wei,1 Min Zhu,2 Yan Man,1 Hongyi Xiao,3 Guimin Dong,3 Xinyuan Shi,1 Fanceng Ji3 1School of Anesthesiology, Weifang Medical University, Weifang, 261053, People’s Republic of China; 2Department of Gynecology, Weifang People’s Hospital, Weifang, 261041, People’s Republic of China; 3Department of Anesthesiology, Weifang People’s Hospital, Weifang, 261041, People’s Republic of ChinaCorrespondence: Fanceng JiDepartment of Anesthesiology, Weifang People’s Hospital, No. 151 Guangwen Street, Kuiwen District, Weifang, 261041, People’s Republic of China, Tel +86-13563698838, Email jifanceng@163.comPurpose: To evaluate the effect of flumazenil antagonizing remimazolam on postoperative nausea and vomiting (PONV) after gynecologic day surgery.Patients and Methods: 141 cases of gynaecological daycase surgery patients in Weifang People’s Hospital were selected, randomized into group F (flumazenil group, 71 cases) and group C (control group, 70 cases). Dexamethasone 5 mg, flurbiprofen axetil 50 mg, and droperidol 1 mg were given intravenously before induction of anesthesia in both groups. Anesthesia induction: Remimazolam 0.25mg / kg was injected within 1 minute. After the patient fell asleep, mivacurium chloride 0.2mg / kg was injected for 30 seconds and alfentanil 20ug / kg was injected for 30 seconds. Anesthesia maintenance: Remimazolam 1mg/kg/h and alfentanil 40ug/kg/h were continuously pumped by micro pump. Stopping the injection of remimazolam and alfentanil at the end of the operation. Flumazenil 0.2 mg was given to antagonize remimazolam in group F after 1 minute. Group C was given an equal volume of saline. The incidence of PONV in the postoperative PACU and over a 24-hour period, patient awakening time, and general patient information were recorded.Results: The incidence of PONV in both groups within 24 hours was 50.70% in group F was significantly higher than 32.86% in group C. The difference was statistically significant (P < 0.05). The incidence of PONV in the PACU was 5.6% in group F and 8.6% in group C. The difference was not statistically significant (p > 0.05).Conclusion: Flumazenil antagonism of remimazolam increases the incidence of PONV within 24 hours in gynecologic day surgery patients and has no significant effect on the incidence of PONV in the PACU.Keywords: flumazenil, remimazolam, gynecologic day surgery, postoperative PONV

Jingbo Li,1,&ast; Kun Zhou,2,3,&ast; Meng Wu,3,&ast; Rongzheng Zhang,3 Xi Jin,3 Han Qiao,3 Jiaqi Li,3 Xinyang Cao,3 Shuyun Zhang,3 Guanglu Dong4 1Department of Anesthesiology Research Institute, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Department of Clinical Laboratory, Beidahuang Industry Group General Hospital, Harbin, People’s Republic of China; 3Scientific Research Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Tumor Radiotherapy, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanglu Dong, Department of Tumor Radiotherapy, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Tel +1 380 450 3001, Email DGL64@163.com Shuyun Zhang, Scientific Research Center, the Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Tel +1 321 450 1198, Email 13214501198@163.comPurpose: Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths, posing a significant threat to people in diverse regions. T-cell exhaustion (Tex) can hinder the efficacy of immunotherapy in patients with HCC, and the transcription factors that regulate Tex in HCC have not yet been fully elucidated.Patients and Methods: We used the single sample gene set enrichment analysis (ssGSEA) method to define the transcription factor pathway that regulates Tex and employed LASSO regression analysis to establish Tex related genes (TEXRS). To predict differences in immunotherapy efficacy between the two groups, we used the immunophenotype score and submap algorithm. RT-qPCR was used to detect the expression levels of the model genes in 21 pairs of HCC tissues. Finally, we assessed the cell communication strength and identified ligand receptors using the “CellChat” R package.Results: Nine Tex transcription factors were identified as regulators of the HCC immune microenvironment, with Tex scores affecting patient survival. Patients with a high Tex Risk Score (TEXRS) had significantly worse overall survival compared to patients with low TEXRS. After adjusting for confounding factors, TEXRS remained an independent prognostic factor. Importantly, TEXRS performed well in multiple independent external validation cohorts. Various algorithms have shown that patients in the low-TEXRS group might benefit more from immunotherapy. Finally, RT-qPCR analysis of 21 HCC samples showed that C7, CD5L, and SDS were significantly downregulated in HCC tissues, consistent with the bioinformatics analysis results.Conclusion: TEXRS proved to be a valuable predictor of immunotherapy and transcatheter arterial chemoembolization efficacy in patients with HCC. This holds promise for enhancing the prognosis and treatment outcomes of patients with HCC.Keywords: T-cell exhaustion, transcription factors, single-cell RNA sequencing, immune microenvironment, immunotherapy

Geng Dong,1 Tingting Ma,2 Zhe Xu,1 Min Zhang,1 Yidi Hu,1 Junmei Yang,1 Tiewei Li1 1Zhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Neurology, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, People’s Republic of ChinaCorrespondence: Tiewei Li, Email litieweind@163.comBackground: Previous studies have established an association between fibrinogen-to-albumin ratio (FAR) and cancer, cardiovascular disease, and coronavirus disease 2019. However, no studies have investigated the relationship between FAR and neonatal sepsis. This study aims to evaluate the association of fibrinogen-to-albumin ratio with the presence and severity of sepsis in neonates.Methods: A total of 1292 neonates with suspected sepsis were enrolled in this study. Clinical and laboratory data were collected from electronic medical records. Neonates with final diagnosis with sepsis were divided into the sepsis group, The remaining neonates were divided into the control group. Neonates with sepsis were further categorized into mild (n = 312) and severe (n = 425) groups based on the severity of their condition. FAR was determined by dividing the plasma fibrinogen concentration (g/L) by the serum albumin concentration (g/L). The statistical analyses were conducted using the SPSS 26.0 statistical software package, as deemed appropriate.Results: FAR levels were significantly higher in neonates with sepsis compared to the control group. Additionally, a significant gradual increase in FAR was observed in the control, mild sepsis, and severe sepsis groups (P < 0.001). Correlation analysis showed that FAR had a positive correlation with PCT, CRP, and the length of hospital stay. Multiple logistic regression analysis showed that FAR was independently associated with the presence and severity of neonatal sepsis. Specifically, FAR was identified as an independent risk factor for both the presence of sepsis (OR = 8.641, 95% CI 5.708– 13.080, P < 0.001) and severe sepsis (OR = 2.817, 95% CI 1.701– 4.666, P < 0.001).Conclusion: FAR is significantly increased in neonates with sepsis and had a correlation with the severity of sepsis. Increased FAR was an independent predictor for the presence and severity of neonatal sepsis.Keywords: fibrinogen-to-albumin ratio, neonatal sepsis, severe sepsis, predictor

Guoqi Dong, Hui Li, Hui Gao, Yingqi Chen, Huayuan Yang School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Huayuan Yang, School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Email yhy4@shutcm.edu.cnBackground: Researchers have made significant progress in microglia associated with pain in recent years. However, more relevant bibliometric analyses are still needed on trends and directions in this field. The aim of this study is to provide a comprehensive perspective and to predict future directions of pain-related microglia research via bibliometric tools.Methods: English articles and reviews related with pain and microglia were extracted from the Web of Science core collection (WosCC) database between 2002 to 2022. Bibliometric tools such as VOSviewer, CiteSpace, and Bibliometrix R package were used to analyze publication characteristics, countries, authors, institutions, journals, research hotspots, and trend topics.Results: A total of 2761 articles were included in this analysis. Research on microglia associated with pain has increased significantly over the last two decades. China (n = 1020, 36.94%) and the United States (n = 751, 27.20%) contributed the most in terms of publications and citations, respectively. Kyushu University published the most articles in this field compared to other institutions, and Professor Inoue Kazuhide (n = 54) at this university made outstanding contributions in this field. Molecular Pain (n = 113) was the journal with the most publication, while Journal of Neuroscience had the highest number of citations. According to the authors keywords analysis, the research in this area can be summarized into 7 clusters such as “microglia activation pathways”, “pain treatment research”, “mental symptoms of chronic pain”, and so on.Conclusion: This study provides a comprehensive analysis of pain-related microglia research in the past two decades. We identified the countries, institutions, scholars, and journals with the highest number of publications and the most influence in the field, and the research trends identified in this paper may provide new insights for future research.Keywords: microglia, pain, bibliometrics, VOSviewer, CiteSpace

Guoping Dong,1,2 Fangying Fan,1,2 Yao He,3 Yanchun Luo,1 Jie Yu,1,2 Ping Liang1,2 1Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Chinese PLA Medical School, Beijing, 100853, People’s Republic of China; 3Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, People’s Republic of ChinaCorrespondence: Ping Liang; Jie Yu, Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China, Tel +86-10-66939530 ; +86-10-66937963, Email liangping301@126.com; jiemi301@163.comBackground: Extrahepatic metastasis in hepatocellular carcinoma (HCC) greatly limits the prognostic survival of HCC patients. Levels of preoperative peripheral lymphocyte subsets and cytokines in the serum for predicting extrahepatic spread of hepatocellular carcinoma are still not common in clinical practice. The aim of this study is to investigate the value and mechanisms of peripheral lymphocyte subsets and cytokines in predicting extrahepatic spread of HCC.Methods: We used a retrospective design to analyze data pertaining to a total of 380 patients with HCC who were examined for peripheral T-lymphocyte subsets before receiving microwave ablation. We performed Cox regression analysis to screen out independent risk factors and used pathology specimens from the patients and public databases of liver cancer to investigate the correlation between cytokines and intra-tumor immune cells.Results: The CD4low group had better metastasis-free 1-year, 3-year, and 5-year survival rates compared to the CD4high group (80% vs 69%, 67% vs 51%, and 57% vs 39%, respectively; HR 1.7 (1.2, 2.3), P = 0.0019). Similarly, the CD8high group had better metastasis-free 1-year, 3-year, and 5-year survival rates compared to the CD8low group (65% vs 78%, 46% vs 64%, and 34% vs 54%, respectively; HR 0.6 (0.4, 0.8), P < 0.001). Patients with the CD4high/CD8low phenotype had significantly worse metastasis-free survival times compared to other patients (HR 2.0 (1.5, 2.8), P < 0.001). Additionally, T lymphocyte-specific genes (CD4, CD8) were correlated with CCL5 expression, which was also positively correlated with the level of intra-tumoral infiltrating CD8 T cells and the prognosis of HCC patients.Conclusion: Both CD4+ and CD8+ T lymphocyte subsets were independent risk factors for extrahepatic metastasis in HCC. Serum CCL5 levels could indicate the infiltration level of intra-tumoral CD8+ T cells and the risk of extrahepatic metastasis in HCC patients, aiding in patient risk stratification for metastasis.Graphical Abstract: Keywords: cytokine CCL5, extrahepatic metastasis of hepatocellular carcinoma, peripheral lymphatic subset analysis, cytotoxic CD8+ T cells

Yali Yu,1,&ast; Shaohua Wang,2,&ast; Guixiang Dong,1 Yanli Niu3 1Department of Clinical Laboratory, Zhengzhou Orthopaedics Hospital, Zhengzhou, People’s Republic of China; 2Department of Joint Surgery, Zhengzhou Orthopaedics Hospital, Zhengzhou, People’s Republic of China; 3Laboratory of Cell Signal Transduction, School of Basic Medical Sciences, Henan University, Kaifeng, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanli Niu, Laboratory of Cell Signal Transduction, School of Basic Medical Sciences, Henan University, Kaifeng, People’s Republic of China, Email nyl0925@vip.henu.edu.cnPurpose: The purpose of this study was to evaluate the ability of metagenomic next-generation sequencing (mNGS) diagnosing prosthetic joint infection (PJI) using tissue from hip/knee rapidly and precisely, especially in patients who had received antibiotic treatment within the preceding two weeks.Methods: From May 2020 to March 2022, 52 cases with suspected PJI were enrolled. mNGS was performed on surgical tissue samples. The sensitivity and specificity of mNGS in diagnosis was evaluated using culture in conjunction with MSIS criteria. This study also looked at how antibiotic use affected culture and mNGS efficacy.Results: According to MSIS criteria, 31 of the 44 cases had PJI, and 13 were classified in the aseptic loosening group. Sensitivity, specificity, positive/negative predictive value (PPV/NPV), positive/negative likelihood ratio (PLR/NLR), and area under the curve (AUC) of mNGS assay were 80.6% (71.9– 91.8%), 84.6 (73.7– 97.9%), 92.6 (84.2– 98.7%), 64.7 (58.6– 74.7%), 5.241 (4.081– 6.693), 0.229 (0.108– 0.482) and 0.826 (0.786– 0.967), respectively, with MSIS as a reference. When MSIS was used as a reference, the results of culture assay were 45.2% (40.8– 51.5%), 100 (100.0– 100.0%), 100 (100.0– 100.0%), 43.3 (39.1– 49.5%), +∞, 0.548 (0.396– 0.617) and 0.726 (0.621– 0.864), respectively. The AUC values for mNGS and culture were 0.826 and 0.731, respectively, and the differences were insignificant. mNGS demonstrated higher sensitivity than culture in PJI subjects who had previously received antibiotic treatment within 2 weeks (69.5% vs 23.1%, P = 0.03).Conclusion: In our series, mNGS yield a higher sensitivity for diagnosis and pathogen detection of PJI compared to microbiological culture. Additionally, mNGS is less affected by prior antibiotic exposure.Keywords: prosthetic joint infection, metagenomic next⁃generation sequencing MSIS criteria, antibiotic treatment

Xiaojuan Li, Tiewei Li, Geng Dong, Yulei Wei, Zhe Xu, Junmei Yang Zhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, People’s Republic of ChinaCorrespondence: Tiewei Li, Email litieweind@63.comPurpose: Previous studies have demonstrated that interleukin-18 (IL-18) levels were elevated in adult patients with sepsis. However, its role in neonatal sepsis remains unknown. The current research was conducted to assess the clinical value of serum IL-18 level as a candidate biomarker in neonatal sepsis diagnosis and prediction of mortality.Patients and Methods: From July 2022 to September 2022, we prospectively enrolled 91 septic neonates and 31 non-sepsis neonates in the intensive care unit of neonates at Henan Children’s Hospital in Zhengzhou, China. Neonatal peripheral blood serum was collected at admission and levels of serum IL-18 were assessed. Employing multivariate logistic regression analysis, the evaluation of the potential of IL-18 as an independent biomarker for sepsis was executed. Furthermore, employing the receiver operating characteristic (ROC) curve analysis, the diagnostic value of IL-18 in sepsis and the ability of IL-18 in predicting the mortality of neonatal sepsis was measured. The statistical package SPSS 24.0 was employed to conduct all statistical analyses.Results: Serum IL-18 levels in neonates in the sepsis group were elevated compared to the control group, reaching the highest levels in the non-survival sepsis group (P < 0.001). Correlation analysis exhibited a positive relationship between IL-18 levels and age, body temperature, respiratory rate, and C-reactive protein levels. IL-18 was identified as an independent biomarker in identifying sepsis (OR = 4.747, 95% CI 1.493– 15.092, P = 0.008) by multiple logistic regression. ROC curve analysis exhibited that IL-18 was good in identifying neonatal sepsis (area under curve (AUC) = 0.77, 95% CI = 0.68– 0.85, P < 0.001) and predicting neonatal mortality (AUC = 0.80, 95% CI = 0.63– 0.96, P = 0.003).Conclusion: IL-18 was a potential biomarker for identifying neonatal sepsis and neonatal mortality prediction.Keywords: interleukin-18, neonatal sepsis, mortality

Tiewei Li,1,&ast; Xiaojuan Li,1,&ast; Xinrui Liu,1 Zhiwei Zhu,1 Min Zhang,1 Zhe Xu,1 Yulei Wei,1 Yichuang Feng,1 Xiaoliang Qiao,2 Junmei Yang,1 Geng Dong1 1Zhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, People’s Republic of China; 2Center of Laboratory Medicine, Women & Infants Hospital of Zhengzhou, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junmei Yang; Geng Dong, Email yangjunmei7683@163.com; donggeng90@126.comPurpose: Previous studies have demonstrated that procalcitonin and albumin have a close correlation with sepsis. However, the role of procalcitonin (PCT) to albumin (ALB) ratio (PAR) in sepsis was still unclear, especially in neonates. Thus, this study aimed to investigate the association between PAR and neonatal sepsis.Patients and Methods: A total of 1,196 neonates with suspected sepsis were included in this study. Neonates were divided into control group and sepsis group, according to whether they were diagnosed with sepsis. Neonates with sepsis were further divided into mild sepsis and severe sepsis group according to the severity of sepsis. PAR was calculated as serum PCT (ng/mL)/ALB (mg/mL). All statistical analyses were performed using the statistical package SPSS 24.0, as appropriate.Results: Compared with the control group, neonates with sepsis had a higher PAR. PAR also showed a significant gradual increase in the control, mild sepsis, and severe sepsis groups (P< 0.001). Correlation analysis showed that there was a strong positive correlation between PAR and hsCRP, neonatal sequential organ failure assessment score (nSOFA), and prolonged length of hospital stay (P< 0.001). On multiple logistic regression, higher PAR was independently associated with the presence and severity of neonatal sepsis. According to the receiver operating characteristic curve analysis, a PAR ≥ 0.065 had 64% sensitivity and 72% specificity in predicting the presence of neonatal sepsis (area under curve (AUC)=0.72, 95% CI=0.69– 0.75, P< 0.001) and a PAR≥ 0.070 had 69% sensitivity and 63% specificity in predicting the presence of severe sepsis (AUC=0.71, 95% CI=0.68– 0.74, P< 0.001).Conclusion: PAR is significantly higher in neonates with sepsis and correlated with the severity of the disease. Increased PAR is an independent predictor useful for identifying the presence and severity of neonatal sepsis.Keywords: procalcitonin-to-albumin ratio, neonatal sepsis, severe sepsis, predictor

Tiewei Li,1,&ast; Minglu Qi,2,&ast; Geng Dong,1 Xiaojuan Li,1 Zhe Xu,1 Yulei Wei,1 Yichuang Feng,1 Chong Ren,1 Yaguo Wang,3 Junmei Yang1 1Zhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Emergency Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Institute of Biophysics, Chinese Academy of Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tiewei Li; Junmei Yang Email litieweind@63.com; yangjunmei7683@163.comPurpose: The prognostic nutritional index (PNI) is a common indicator of nutritional and inflammatory status and is associated with various diseases such as cancer, cardiovascular diseases and infectious diseases. However, to date, no study has concentrated on the role of PNI in assessing and predicting the presence and severity of neonatal sepsis. Therefore, the present study aimed to explore the association of the PNI with the presence and severity of neonatal sepsis.Materials and Methods: A total of 1196 neonates with suspected sepsis were enrolled in this study and their complete clinical and laboratory data were collected. PNI was calculated as serum albumin (g/L) + 5 × total lymphocyte count (109/L). Multivariate logistic regression analysis was performed to identify the risk factors for the presence and severity of neonatal sepsis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of PNI. All statistical analyses were performed using the statistical package SPSS 24.0.Results: PNI was lower in neonates with sepsis and decreased significantly with the severity of sepsis. The correlation analysis demonstrated that the PNI was negatively correlated with the levels of the inflammatory marker procalcitonin (PCT) and C-reactive protein (CRP), and the length of hospital stay. Multivariate logistic regression analysis revealed that the PNI was independently and inversely associated with the presence and severity of neonatal sepsis. The area under the ROC curve of the PNI was 0.64 (95% confidence interval (CI): 0.61– 0.67, P < 0.001) for severe sepsis and 0.69 (95% CI: 0.60– 0.78, P < 0.001) for septic shock. In addition, our data revealed that PNI was also independently correlated with the length of hospital stay.Conclusion: PNI is an independent predictor for the presence and severity of neonatal sepsis.Keywords: neonatal sepsis, predictor, prognostic nutritional index, severity

Dan Wu,1 Guirong Dong2 1Shanghai Academy of Traditional Chinese Medicine, Shanghai, 200120, People’s Republic of China; 2Department of Acupuncture, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 20000, People’s Republic of ChinaCorrespondence: Guirong Dong Tel +86-18930132113Email dongguirong2000@126.comAim: Male, 68 years old, suffering from prurigo nodularis for 7 months, and did not show any significant improvement after oral and topical medications. After 4 months of acupuncture treatment, the NRS for itch scores decreased from 9 to 1; the NRS for sleep scores increased from 5 to 9; HADS decreased from 14 to 2; DLQI decreased from 9 to 5; IGA decreased from 4 to 3. After a 2-month follow-up, the patient was stable in all aspects without new rash.Conclusion: Acupuncture is a feasible method for the treatment of prurigo nodularis.Keywords: prurigo nodularis, acupuncture, acupoints

Tiewei Li,1,&ast; Xiaojuan Li,1,&ast; Yulei Wei,1 Geng Dong,1 Jianwei Yang,1 Junmei Yang,1 Panpan Fang,1 Minglu Qi2 1Zhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, People’s Republic of China; 2General Hospital of Taiyuan Steel (Group) Co., Ltd., Taiyuan, 030000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Panpan FangZhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, 33M Waihuan East Road, Longhu, Zhengzhou, 450018, People’s Republic of ChinaTel +8637185515779Email fang_panpan@163.comMinglu QiGeneral Hospital of Taiyuan Steel (Group) Co., Ltd., No. 7, South 2nd Lane, Yingxin Street, Jiancaoping District, Taiyuan City, 030008, People’s Republic of ChinaTel +863512139774Email feiyuxiaotian109@163.comPurpose: Previous studies have reported that C-reactive protein-to-albumin ratio (CAR) was a risk factor for sepsis in adults. However, little is known regarding the role of CAR in neonates with sepsis. The aim of this study was to explore the relationship between CAR and neonatal sepsis.Patients and Methods: In this research, from January 2016 to February 2020, a total of 1076 neonates were enrolled at Henan Children’s Hospital in China. Complete clinical and laboratory data were collected. To identify the potential independent risk factor for neonatal sepsis, multivariate logistic regression analysis was performed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy of CAR in identifying neonatal sepsis.Results: CAR levels were higher in neonates with sepsis and showed a gradual increase among the control group, mild sepsis group and severe sepsis group. The prevalence of neonates with overall sepsis, mild sepsis and severe sepsis increased significantly from CAR tertile 1 to tertile 3. Multiple logistic regression analysis showed that CAR was an independent risk factor for the presence of sepsis (OR = 10.144, 95% CI 4.151– 24.790, P < 0.001) and severe sepsis (OR = 1.876, 95% CI 1.562– 2.253, P < 0.001). ROC curve analysis showed that CAR had a well discriminatory power in predicting sepsis (area under curve (AUC) = 0.74, 95% CI, 0.71– 0.77, P < 0.001) and severe sepsis (AUC = 0.70, 95% CI, 0.67– 0.74, P < 0.001).Conclusion: CAR was an independent predictor for the presence and severity of neonatal sepsis.Keywords: C-reactive protein-to-albumin ratio, neonatal sepsis, risk factor, severe sepsis

Qixing Mao,1–4,* Louqian Zhang,1–3,* Yi Zhang,1,* Gaochao Dong,1,3 Yao Yang,4 Wenjie Xia,1–4 Bing Chen,1–3 Weidong Ma,1–3 Jianzhong Hu,4 Feng Jiang,1,3 Lin Xu1,3 1Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China; 2The Fourth Clinical College of Nanjing Medical University, Nanjing, China; 3Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China; 4Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA *These authors contributed equally to this work Background: A substantial increase in the number of non-smoking lung adenocarcinoma (LAC) patients has been drawing extensive attention in the past decade. However, effective biomarkers, which could guide the precise treatment, are still limited for identifying high-risk patients. Here, we provide a network-based signature to predict the survival of non-smoking LAC.Materials and methods: Gene expression profiles were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus. Significant gene co-expression networks and hub genes were identified by Weighted Gene Co-expression Network Analysis. Potential mechanisms and pathways of co-expression networks were analyzed by Gene Ontology. The predictive signature was constructed by penalized Cox regression analysis and tested in two independent datasets.Results: Two distinct co-expression modules were significantly correlated with the non-smoking status across 4 Gene Expression Omnibus datasets. Gene Ontology revealed that nuclear division and cell cycle pathways were main mechanisms of the blue module and that genes in the turquoise module were involved in lymphocyte activation and cell adhesion pathways. Seventeen genes were selected from hub genes at an optimal lambda value and built the prognostic signature. The prognostic signature distinguished the survival of non-smoking LAC (training: hazard ratio [HR]=3.696, 95% CI: 2.025–6.748, P

Wenjie Xia,1,2,* Anpeng Wang,1,2,* Meng Jin,3,* Qixing Mao,1,2 Wenying Xia,4 Gaochao Dong,1 Bing Chen,1,2 Weidong Ma,1,2 Lin Xu,1 Feng Jiang1 1Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, 2Department of Oncology, Fourth Clinical College of Nanjing Medical University, Nanjing, 3Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 4Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Non-small cell lung cancer (NSCLC) prognosis and risk of lymph node positivity (LN+) are reference points for reasonable treatments. The aim of the current study was to investigate the effect of age on LN+ and NSCLC death. Data from the Surveillance, Epidemiology, and End Results (SEER) registry were used to identify 82,253 patients with NSCLC diagnosed between 1988 and 2008. All the patients underwent standard lung cancer surgery with lymph node examination. Demographic and clinicopathological parameters were extracted and compared among each age group. Impact of age on LN+ and NSCLC death was evaluated by the Cochran–Armitage trend test and logistic univariate and multivariate analyses for all T stages. Overall, 22,711 (27.60%) patients of the entirety had lymph node metastasis and 28,968 (35.22%) patients died of NSCLC within 5 years. With the increase in age, LN+ rates decreased regardless of T stages (P

Julio Pascual,1 Titte R Srinivas,2 Steven Chadban,3 Franco Citterio,4 Federico Oppenheimer,5 Helio Tedesco,6 Mitchell L Henry,7 Christophe Legendre,8 Yoshihiko Watarai,9 Claudia Sommerer,10 Po-Chang Lee,11 J Mark Hexham,12 Gaohong Dong,12 Peter Bernhardt,13 Flavio Vincenti14 1Nephrology Department, Hospital del Mar, Barcelona, Spain; 2Division of Nephrology, Medical University of South Carolina, Mt Pleasant, SC, USA; 3Department of Transplantation, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; 4Centro Trapianti d'Organo Istituto di Clinica Chirurgica, Università Cattolica del Sacro Cuore, Policlinico Universitario A Gemelli, Rome, Italy; 5Renal Transplant Unit, Hospital Clínic de Barcelona, Barcelona, Spain; 6Nephrology Division, Hospital do Rim, UNIFESP, São Paulo, Brazil; 7The Comprehensive Transplant Center, The Ohio State University, Wexner Medical Center, Columbus, OH, USA; 8Service de Transplantation Adultes, Université Paris Descartes and Hôpital Necker, Paris, France; 9Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya City, Aich, Japan; 10Medizinische Klinik, Sektion Nephrologie, Universitätsklinikum Heidelberg, Heidelberg, Germany; 11Medical College, National Cheng Kung University, Tainan City, Taiwan; 12Biometrics and Statistical Science, Novartis Pharmaceuticals, East Hanover, NJ, USA; 13Research and Development, Novartis Pharma AG, Basel, Switzerland; 14Kidney Transplant Service, University of California San Francisco, San Francisco, CA, USA Abstract: Two well defined, modifiable risk factors for kidney allograft failure are acute rejection and poor graft function at one year post-transplant. Regulatory bodies and expert panels in the USA and Europe have recognized that both acute rejection and one-year graft function should be assessed when evaluating immunosuppressive regimens. TRANSFORM (Clinicaltrials.gov NCT01950819) is one of the first trials to adopt this approach and the first that applies a novel combined clinically meaningful endpoint to take the first step towards changing the paradigm for immunosuppression in kidney transplant patients. Everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy is a strategy designed to reduce the risk of chronic nephrotoxicity and other dose-dependent complications associated with CNI therapy. In TRANSFORM, de novo kidney transplant patients are randomized to everolimus with reduced-exposure CNI, or mycophenolic acid with standard-exposure CNI, both with induction therapy and maintenance steroids. The primary endpoint is a composite of treated biopsy-proven acute rejection or estimated glomerular filtration rate ,50 mL/min/1.73 m2 at month 12 post-transplant, which is expected to be sensitive both to the effects of acute and chronic allograft rejection and nephrotoxic side effects of immunosuppressive therapies. The construct of this endpoint allows the integration of a continuous outcome (graft function) with a logistic outcome (rejection). The trial uses a randomized, multicenter, open-label, two-arm design. After completion of a 2-year core study, patients enter a further 3-year prospective observational study. By capturing follow-up to 5 years, TRANSFORM will provide substantial data on the incidence of graft loss, graft dysfunction, cancer, cardiovascular events, and other patient-relevant outcomes. TRANSFORM will determine whether de novo CNI reduction with an everolimus-based regimen achieves short-term outcomes compared with standard CNI. As the largest clinical trial undertaken to date in kidney transplantation, recruiting more than 2,000 patients, and with extended follow-up to 5 years, TRANSFORM will provide critical data required to help maximize long-term outcomes. Keywords: mTOR inhibitor, calcineurin inhibitor, reduced exposure

Minerals are ubiquitous in the natural environment and have close contact with microorganisms. In various scenarios, microorganisms that harbor extracellular electron transfer (EET) capabilities have evolved a series of beneficial strategies through the mutual exchange of electrons with extracellular minerals to enhance survival and metabolism. These electron exchange interactions are highly relevant to the cycling of elements in the epigeosphere and have a profound significance in bioelectrochemical engineering applications. In this review, we summarize recent advances related to the effects of different minerals that facilitate the EET process and discuss the underlying mechanisms and outlooks for future applications. The promotional effects of minerals arise from their redox-active ability, electrical conductivity and photocatalytic capability. In mineral-promoted EET processes, various responses have concurrently arisen in microorganisms, such as stretching of electrically conductive pili (e-pili), upregulated expression of outer-membrane cytochromes (Cyts) and production of specific enzymes, and secretion of extracellular polymeric substances (EPSs). This review synthesizes the understanding of electron exchange mechanisms between microorganisms and minerals and highlights potential applications in development of renewable energy production and pollutant remediation, which are topics of particular significance to future exploitation of biotechnology.

Semiconducting minerals are ubiquitous in soil and their association with microbes often affects the environment. In this study, the impacts of zinc sulfide (ZnS, used as a model compound for semiconducting sphalerite) on As/Fe mobility of flooded tailing soils under dark and intermittent illumination conditions were elucidated for the first time. Microbial reductive dissolution of As(V) and Fe(III) was more pronounced under intermittent illumination than under dark conditions. In ZnS-amended soils, release of As(III) and Fe(II) was 1.3 and 1.7 times higher, respectively, under intermittent illumination than the highest concentrations released from soils amended with acetate alone under dark conditions (12741.1 ± 714.3 μg/L and 37.9 ± 2.3 mg/L, respectively). However, under dark conditions in ZnS-amended soil, the release of As(III) and Fe(II) was 0.8 and 0.7 times that of the highest concentrations released from soils amended with acetate under dark conditions, respectively. Treatment with ZnS potentially decreased the abundance of several metal-reducing bacteria (e.g., Bacillus, Geobacter, Clostridium, and Desulfitobacterium), which resulted in lower As/Fe reduction than for the acetate alone treatment under dark conditions. However, under intermittent illumination, the excited mineral photoholes were scavenged by humic/fulvic acids, and photoelectrons were synchronously separated and participated in the microbial electron chain. The fortification provided by the photoelectrons subsequently boosted As/Fe reduction, even though there was a lower abundance of metal-reducing bacteria. Hence, this study provides an in-depth understanding of the impacts of semiconducting minerals on the fates of metal pollutants, microbial diversity, and the bioavailability of dissolved organic matter in flooded soils.