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Pingzhi Wang,1 Zhengtao Wang,1 Junyan Zhang,2 Caiqin Lan,1 Yani Zhao,1 Xiaoqing Chen,1 Yu Li,1 Qi Mei,3 Huijing Feng,3 Shuang Wei,4 Zhifeng Xue,4 Fang Gao,5 Xiaolei Liu,6,7 Ying Liang1 1Department of Rehabilitation Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Clinical Epidemiology and Evidence-Based Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 5Department of Prevention Care in HealthCare, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 6Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 7Yunnan Provincial Clinical Research Center for Neurological Diseases, Kunming, People’s Republic of ChinaCorrespondence: Ying Liang; Xiaolei Liu, Email Kfkliangying@126.com; ring@vip.163.comObjective: The aim of this study was to evaluate the impact of hyperbaric oxygen therapy (HBOT) on patients with SARS-CoV-2 infection and determine its efficacy and safety in reducing treatment failure events.Methods: A retrospective cohort study involving patients with COVID-19 was conducted. Inverse probability of treatment weighting (IPTW) was used to balance covariates between the HBOT and non-HBOT groups. The primary endpoint was the occurrence of a clinical treatment failure event, defined as all-cause mortality, abandonment of treatment, or transfer to the Intensive Care Unit due to worsening condition.Results: A total of 720 patients with COVID-19 were enrolled in the study, with 27 patients receiving HBOT and 693 patients not receiving HBOT. The occurrence of treatment failure was significantly lower in the HBOT group compared to the non-HBOT group, with no treatment failure events in the HBOT group versus 36 events in the non-HBOT group. The IPTW database analysis results showed that in comparison to the non-HBOT group, the hazard ratio (HR) for treatment failure in the HBOT group was less than 0.001 (95% CI: < 0.001 ~ < 0.001, p< 0.001). Lymphocyte count > 0.8× 109/L and HBOT was associated with a significantly lower risk of treatment failure. Glucocorticoid use was associated with a higher risk of treatment failure. The incidence of venous thrombosis events was significantly higher in the HBOT group compared to the non-HBOT group.Conclusion: This study revealed that adjunctive HBOT significantly reduces the risk of treatment failure in patients with COVID-19 and is associated with satisfactory safety. HBOT shows promise as a beneficial therapy for improving outcomes in COVID-19-infected patients.Keywords: hyperbaric oxygen therapy, COVID-19, retrospective cohort, inverse probability of treatment weighting, SARS-CoV-2 infection

Jiejie Zhu,1,2 Yumei Wu,1,2 Xiaoyuan Ge,1,2 Xinwen Chen,1,2 Qiao Mei1,2 1Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China; 2Key Laboratory of Digestive Diseases of Anhui Province, Hefei, People’s Republic of ChinaCorrespondence: Qiao Mei, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui Province, 230022, People’s Republic of China, Email meiqiao@hotmail.comBackground: Ulcerative colitis (UC) is a long-lasting idiopathic condition, but its precise mechanisms remain unclear. Meanwhile, evidence has demonstrated that ferroptosis seems to interlock with the progress of UC. This research sought to identify hub genes of UC related to ferroptosis.Methods: First, the relevant profiles for this article were obtained from GEO database. From the FerrDb, 479 genes linked to ferroptosis were retrieved. Using analysis of the difference and WGCNA on colonic samples from GSE73661, the remaining six hub genes linked to ferroptosis and UC were discovered. Through logistic regression analyses, the diagnostic model was constructed and was then evaluated by external validation using dataset GSE92415. Afterwards, the correlation between immune cell filtration in UC and hub genes was examined. Finally, a mice model of colitis was established, and the results were verified using qRT-PCR.Results: We acquired six hub genes linked to ferroptosis and UC. In order to create a diagnostic model for UC, we used logistic regression analysis to screen three of the six ferroptosis related genes (HIF1A, SLC7A11, and LPIN1). The ROC curve showed that the three hub genes had outstanding potential for disease diagnosis (AUC = 0.976), which was subsequently validated in samples from GSE92415 (AUC = 0.962) and blood samples from GSE3365 (AUC = 0.847) and GSE94648 (AUC = 0.769). These genes might be crucial for UC immunity based upon the results on the immune system. Furthermore, mouse samples examined using qRT-PCR also verified our findings.Conclusion: In conclusion, the findings have important implications for ferroptosis and UC, and these hub genes may also offer fresh perspectives on the aetiology and therapeutic approaches of UC.Keywords: ulcerative colitis, ferroptosis, hub genes, immune, bioinformatics analysis

Chang Chen,1 Qian Mei,2 Qi Liu,3 Meichen Lu,4 Lu Hou,1 Xiaohong Liu,3 Xuezheng Gao,3 Limin Chen,3 Zhenhe Zhou,1– 4 Hongliang Zhou5 1Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi City, People’s Republic of China; 2School of Humanities and Management Science, Wannan Medical College, Wuhu City, People’s Republic of China; 3Grade 2021 Class 3, First Clinical Medical College of Jinzhou Medical University, Jinzhou City, People’s Republic of China; 4Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi City, People’s Republic of China; 5Department of Psychology, The Affiliated Hospital of Jiangnan University, Wuxi City, People’s Republic of ChinaCorrespondence: Zhenhe Zhou, Wuxi Mental Health Center, No. 156, Qianrong Road, Binhu District, Wuxi City, Jiangsu Province, People’s Republic of China, Tel +86-1-335-811-8986, Fax +86-510-83219366, Email zhouzh@njmu.edu.cn Hongliang Zhou, The Affiliated Hospital of Jiangnan University, No. 200, Huihe Road, Binhu District, Wuxi City, Jiangsu Province, People’s Republic of China, Tel +86-1-536-525-1126, Fax +86-510-85808820, Email Hongliangzh2022@hotmail.comPurpose: Schizophrenia patients show impaired conditional reasoning. This study was to investigate event-related potential (ERP) characteristics of the conditional reasoning in schizophrenia.Patients and methods: Participants included 24 schizophrenia patients and 30 normal controls (NCs), and the measurements of ERPs were conducted during the Wason selection task.Results: Results showed that NCs consistently outperformed schizophrenia patients in terms of accuracy. Among the different rule types of the task, the precautionary type experiment yielded the highest accuracy rates. In contrast, both the descriptive and abstract type experiments resulted in lower accuracy. The RTs of the abstract type experiment were the shortest among the four experiments. In the abstract type of the Wason selection task, the NCs exhibited higher amplitudes for both the N1 and P2 components compared to the schizophrenia patients. At the parietal lobe, the N2 amplitudes were higher for the social contract type of the task compared to the precautionary version. At the frontal lobe, the N2 amplitudes were highest for the abstract type of the task. In the abstract type, the N2 amplitude at the parietal lobe was higher than that at the central lobe. The NCs displayed lower amplitudes for both the P3 and slow wave compared to the schizophrenia patients. Differences were observed between the NC and schizophrenia groups in terms of the latencies for N1, P2, N2, P3 and slow wave components across different experiment types and regions of interest.Conclusion: In conclusion, the observed ERP patterns provide valuable insights into the neural mechanisms underlying the Wason selection task, highlighting the differences between NCs and patients with schizophrenia.Keywords: event-related potential, wason selection task, schizophrenia, conditional reasoning, neural mechanism

Yuxi He,1,&ast; Shike Geng,1,&ast; Qing Mei,1,&ast; Lei Zhang,1,&ast; Tianjun Yang,1 Chunyan Zhu,1 Xiaoqin Fan,1 Yinzhong Wang,1 Fei Tong,1 Yu Gao,1 Xiaowei Fang,1 Renren Bao,2 Ximei Sheng,3 Aijun Pan1– 3 1Department of Intensive Care Unit, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2Department of Intensive Care Unit, the Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Intensive Care Unit, the Training Center of Anhui Provincial Hospital, Wannan Medical College, Wuhu, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aijun Pan; Qing Mei, Department of Intensive Care Unit, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 17, Lu Jiang Road, Hefei, Anhui Province, People’s Republic of China, Tel +86-0551-62286175, Email aijunpan868@ustc.edu.cn; meiqing@ustc.edu.cnObjective: To evaluate the diagnostic value and clinical application of metagenomic next-generation sequencing (mNGS) for infections in critically ill patients.Methods: Comparison of diagnostic performance of mNGS and conventional microbiological testing for pathogens was analyzed in 234 patients. The differences between immunocompetent and immunocompromised individuals in mNGS-guided anti-infective treatment adjustment were also analyzed.Results: The sensitivity and specificity of mNGS for bacterial and fungal detection were 96.6% (95% confidence interval [CI], 93.5%– 99.6%) and 83.1% (95% CI, 75.2%– 91.1%), and 85.7% (95% CI, 71.9%– 99.5%) and 93.2% (95% CI, 89.7%– 96.7%), respectively. Overall, 152 viruses were detected by mNGS, but in which 28 viruses were considered causative agents. The proportion of mNGS-guided beneficial anti-infective therapy adjustments in the immunocompromised group was greater than in the immunocompetent group (48.5% vs 30.1%; P=0.008). In addition, mNGS-guided anti-infective regimens with peripheral blood and BALF specimens had the highest proportion (39.0%; 40.0%), but the proportion of patients not helpful due to peripheral blood mNGS was also as high as 22.0%.Conclusion: mNGS might be a promising technology to provide precision medicine for critically ill patients with infection.Keywords: next-generation sequencing, critically ill patients, community-acquired infection, hospital-acquired infection, immunosuppression

Qin Mei,1 Fengling Xing,2 Yue Yin,2 Chengda Yuan2 1Department of Dermatology, Dermatology Hospital of Fuzhou, Fuzhou, Fujian, People’s Republic of China; 2Department of Dermatology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Chengda Yuan, Department of Dermatology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, TiYuChang Road 453th, Hangzhou, 310007, People’s Republic of China, Tel +8613336116910, Fax +86-571-85827534, Email hztcmycd@qq.comAbstract: Porokeratosis ptychotropica (PPt) is a rare type of porokeratosis (PK) characterized by pruritic, reddish-brownish verrucous papules, and plaques usually around genital area or buttocks. Here, a case of a 70-year-old woman who was diagnosed as PPt was reported. The patient suffered from severe pruritic papules and plaques in the buttock region and pubis for 4 years. The skin lesions were giant, well-defined brown plaques with many satellite papules scattered around. Both clinical manifestations and histopathological features supported the diagnosis of PPt. In review of the identified mutation was found in patients with disseminated superficial actinic porokeratosis (DSAP) combined with PPt, while its unclear in PPt. To investigate the hypothesis that the variant reported in the present case report may played as an independent “likely pathogenic factor” of PPt. Consequently, a de novo missense pathogenic mutation in the MVK gene was identified in this case. Unexpectedly, it is a first report of a novel MVK mutation in sporadic PPt. This rare case suggested an isogenetic background between PPt and DSAP, which may help to explore the underlying pathogenesis of PPt.Keywords: PPt, MVK, genetic testing, missense mutations, mevalonate pathway

Shuiying Tang,1 Bihong Xu,2 Huajin Pang,1 Lijun Xiao,1 Quelin Mei,1 Xiaofeng He1 1Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Interventional Radiology and Pathology, Nanfang Hospital, Department of Pathology, Southern Medical University, Guangzhou, 510515, People’s Republic of ChinaCorrespondence: Xiaofeng He, Email ozonetherapy@126.comBackground: Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. High-mobility group box 1 (HMGB1), a highly conserved chromosome protein, is considered as a potential therapeutic target and novel biomarker because of its regulation in the proliferation and metastasis of HCC. Ozone has been shown to be beneficial in the treatment of cancer. The objective of this study was to explore the effects and molecular mechanism of ozonated water on the proliferation, migration, and invasion of BEL7402 HCC cells.Materials and Methods: We assessed cell proliferation using a CCK-8 assay kit and flow cytometry; we performed wound healing and transwell assays to evaluate the effects of ozonated water treatment on cell invasion and migration. We determined reactive oxygen species (ROS) values by flow cytometry and used ELISAs to detect cytokines HMGB1, IL-6, and TNF-α. In addition, we assessed mRNA and protein cytokine expressions using RT-qPCR and Western blot.Results: Ozonated water decreased the viability of the HCC cells; the IC50 of ozonated water at 24 h was approximately 1.5 μg/mL. Compared with control groups, ozone treated cells revealed reduced mobility on wound healing assays and decreased invasion in transwell assays. HMGB1, IL-6, and TNF-α cytokines were found at lower levels in ozone treated cells than in control cells. Ozonated water-induced ROS accumulation. Likewise, the expressions of phosphorylated nuclear factor Kappa B (NF-κB), p65, NF-κB, P-STAT3, IL-6, JAK2, Slug, Twist, vimentin, MMP-2, MMP-9, and HMGB1 were decreased in the treated cells.Conclusion: Our findings suggest that ozonated water inhibits the proliferation, invasion, and metastasis of HCC cells via regulation of the HMGB1/NF-κB/STAT3 signaling pathway.Keywords: hepatocellular carcinoma, proliferation, migration, invasion, ozonated water

Tianjun Yang,1,2,&ast; Qing Mei,1,2,&ast; Xiaowei Fang,1,2 Shoujun Zhu,1,2 Yinzhong Wang,1,2 Wanli Li,1,2 Aijun Pan1,2 1Department of Intensive Care Unit, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui Province, 230001, People’s Republic of China; 2Department of Intensive Care Unit, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui Province, 230001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aijun Pan; Qing Mei, Department of Intensive Care Unit, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, No. 17, Lu Jiang Road, Hefei, Anhui Province, 230001, People’s Republic of China, Fax +86-551-62283114, Email aijunpan@fsyy.ustc.edu.cn; qingmei@fsyy.ustc.edu.cnBackground: Metagenomics next-generation sequencing (mNGS) is more efficient in identifying pathogens responsible for pneumonia. However, whether these patients ultimately benefit from this improvement remains unknown.Methods: In this retrospective, nested, case–control study, patients with severe hospital-acquired pneumonia (HAP) who had undergone mNGS of bronchoalveolar lavage fluid while in our intensive care unit from March 2017 to December 2020 (n = 33) were matched in a ratio of 1 to 2 (n = 66) by sex, age, comorbidities, immune status, Acute Physiology and Chronic Health Evaluation II score, severity of pulmonary infection, and use of extracorporeal life support with patients who had undergone conventional microbiological testing only. The primary outcome was 90-day mortality; secondary outcomes being length of intensive care unit stay, duration of mechanical ventilation support, 7-day and 28-day mortality, and efficacy of treatment of pulmonary infection.Results: In the CMT group, 17 patients (25.8%) had negative results, whereas only one (3.0%) had negative results in the mNGS group (P < 0.001). After receipt of microbiology results, antibiotics were altered in 23/33 patients (70.0%) in the mNGS group, but in only 29/66 (43.9%) in the CMT group (P = 0.016). Pulmonary infection-related findings improved in 20/33 patients (60.6%) in the mNGS group in the subsequent 7 days, but in only 25/66 (37.9%) in the CMT group (P = 0.032). However, the 28-day (33.3% vs 31.2%, P = 1.0) and 90-day (48.5% vs 45.5%, P = 0.78) mortality rates did not differ significantly between the two groups. These findings were supported by Cox-regression and Kaplan–Meier survival curve analyses.Conclusion: mNGS is helpful in the treatment of severe HAP but does not improve medium or long-term survival rates, especially in patients with severe comorbidities.Keywords: next generation sequencing, severe hospital-acquired pneumonia, bronchoalveolar lavage fluid, mortality, pathogenic microbes

Objective of this study is to assess the efficacy and toxicity of ER121 in metastatic and triple negative breast cancer (TNBC, HER2+) cells and tumor models. The Herceptin-resistant breast cancer cell line JIMT-1 was used in an in vivo tumor model, and MMTV-erbB2 (Fo5) transgenic mice models were used to evaluate the efficacy and safety of ER121 as neoadjuvant. Methods: ER121 treatment focusing on experimental brain metastasis in TNBC, HER2+ model, was quantified by total flux employing the In Vivo Imaging System (IVIS). We also compared the brain tissue from the treated and the controls groups. Additionally, ER121 was evaluated in JIMT-1, a Herceptin-resistant breast cancer cell line, both in vitro and in vivo tumor model. We also administered ER121 orally in neoadjuvant model with the MMTV-erbB2 (Fo5) transgenic mice, the survival rates were compared with the control group. Tumor-free survival of multiple treated groups were analyzed by Kaplan-Meier analysis employing the log-rank test with the Bonferroni correction using R Statistical Software. Results: In this study, we present findings indicating that ER121 treatment significantly attenuated breast tumor growth using a TNBC, HER2+ model, focusing on experimental brain metastasis, as quantified by total flux employing IVIS. These observations were further corroborated by analysis of brain tissue from the treatment group compared to controls. Data is presented as Mean ± S.D. statistical significance was calculated using Student t test (*p <  0.05). Additionally, ER121 significantly inhibited JIMT-1, a Herceptin-resistant breast cancer cell line was used in vivo xenograft model. Additionally, we used a neoadjuvant model with the MMTV-erbB2 (Fo5) transgenics and the tumor-free survival rates exhibited a remarkable difference between the control and treated groups when ER121 was administered orally. We found statistically significant p values of 0.048 employing log-rank test with Bonferroni Correction for comparing ER121 high, ER121 Low, Herceptin and PBS groups. All analyses were performed using R Statistical Software. Conclusion: ER121 is a non-toxic small-molecule erbB kinase inhibitor and holds promise as an oral and systemic therapeutic agent for treating progressive erbB-driven tumors in therapeutic settings. Moreover, ER121 shows potential as a preventive therapy in neoadjuvant settings for erbB2-associated tumors and when administered systemically can dramatically limit erbB2 brain metastases in animal models. [ABSTRACT FROM AUTHOR]

Changbing Wang,1,2,* Yu Xia,1,3,* Shaochuan Huo,4,5,* Diwen Shou,3 Qing Mei,3 Wenjuan Tang,3 Yinghua Li,1 Hongsheng Liu,6 Yongjian Zhou,3 Bing Zhu1 1Central Laboratory, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510120, People’s Republic of China; 2State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510230, People’s Republic of China; 3Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, People’s Republic of China; 4Department of Orthopedics, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen 518048, People’s Republic of China; 5Shenzhen Research Institute of Guangzhou University of Chinese Medicine, Shenzhen 518048, People’s Republic of China; 6Department of Radiology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bing ZhuCentral Laboratory, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510120, People’s Republic of ChinaTel +86 2081322725Email zhubing2017@hotmail.comYongjian ZhouDepartment of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, People’s Republic of ChinaTel +86 2081045106Email eyzhouyongjian@scut.edu.cnBackground: Delivery of therapeutic small interfering RNA (siRNA) via functionalized nanoparticles holds great promise for cancer therapy. However, developing a safe and efficient delivery carrier of siRNA is a challenging issue.Methods: RGDfC peptide was used to modify the surface of selenium nanoparticles (SeNPs) to synthesize a biocompatible siRNA delivery vehicle (R-SeNPs), and MEF2D-siRNA was loaded onto R-SeNPs to prepare a functionalized selenium nanoparticle R-Se@MEF2D-siRNA. The chemical properties of R-SeNPs were characterized, and the anticancer efficacy as well as related mechanisms of R-Se@MEF2D-siRNA were further explored.Results: R-Se@MEF2D-siRNA was significantly taken up by SKOV3 cells and could enter SKOV3 cells mainly in the clathrin-associated endocytosis way. The result of in vitro siRNA release demonstrated that R-Se@MEF2D-siRNA could release MEF2D-siRNA quicker in a microenvironment simulating a lysosomal environment in tumor cells compared to a normal physiological environment. The results of qRT-PCR assay proved that R-Se@MEF2D-siRNA could effectively silence the expression of the MEF2D gene in SKOV3 cells. R-Se@MEF2D-siRNA remarkably suppressed the proliferation of SKOV3 cells and further triggered its apoptosis. In addition, R-Se@MEF2D-siRNA had the capability to disrupt mitochondrial membrane potential (MMP) in SKOV3 cells and resulted in the overproduction of reactive oxygen species (ROS), indicating that mitochondrial dysfunction and ROS generation played an important role in the apoptosis of SKOV3 cells induced by R-Se@MEF2D-siRNA. In vivo, R-Se@MEF2D-siRNA also exhibited excellent antitumor activity mainly through decreasing tumor cells proliferation and triggering their apoptosis in tumor-bearing nude mice.Conclusion: R-Se@MEF2D-siRNA provides an alternative strategy for ovarian cancer treatment in the clinic.Keywords: ovarian cancer, siRNA delivery, gene therapy, tumor targeting, MEF2D

Dongbo Liu,1 Dingkun Wang,2 Cheng Wu,1 Linli Zhang,1 Qi Mei,1 Guangyuan Hu,1 Guoxian Long,1 Wei Sun11Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People’s Republic of China; 2Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People’s Republic of ChinaBackground: Multiple studies have assessed the prognostic significance of serum lactate dehydrogenase (LDH) in patients with breast cancer, but their results remain controversial. This study aimed to evaluate the prognostic value of LDH in breast cancer by meta-analysis.Methods: Electronic searches for relevant articles were conducted in PubMed, Embase and Web of Science databases. The HR and their 95% CI were used to assess the prognostic value of serum LDH. Stata Statistical Software 12.0 was applied for statistical analysis.Results: A total of 11 studies involving 6,102 patients were subjected to final analysis. Our results showed that higher serum LDH had significant effect on poor overall survival (HR, 1.88; 95% CI, 1.68–2.11) and progression-free survival (HR, 1.98; 95% CI, 1.46–2.68). Moreover, the results of subgroup analyses were consistent with that of overall outcomes. No significant heterogeneity and publication bias were found in this study.Conclusion: Serum LDH could act as a prognostic factor for patients with breast cancer. Future data are needed to validate and update our results.Keywords: breast cancer, lactate dehydrogenase, prognosis, biomarker, meta-analysis

Quanjing Mei,1,* Peipei Luo,1,* Yi Zuo,1 Jidong Li,1 Qin Zou,1 Yubao Li,1 Dianming Jiang,2 Yaning Wang3 1Research Center for Nano Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu, People’s Republic of China; 2Center of Bone and Trauma, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, People’s Republic of China *These authors contributed equally to this work Purpose: Mycobacterium tuberculosis is a serious public health problem affecting hundreds of millions of elderly people worldwide, which is difficult to be treated by traditional methods because of the peculiarity of skeletal system and liver damage caused by high-dose administration. In this research, a porous drug release system has been attempted to encapsulate rifampicin (RIF) into poly (ε-caprolactone) (PCL) microspheres to improve the efficacy and benefit of anti-tuberculosis drug in skeletal system. Materials and methods: The microspheres prepared by two different methods, oil-in-oil (o/o) emulsion solvent evaporation method and oil-in-water (o/w) method, were characterized in terms of morphology, size, encapsulation efficiency, drug distribution, degradation, and crystallinity. Results: The microspheres exhibited a porous structure with evenly drug distribution prepared by o/o emulsion solvent evaporation method, and their diameter ranged from 50.54 to 57.34 μm. The encapsulation efficiency was up to 61.86% when drug-loading content was only 1.51%, and showed a little decrease with the drug-loading content increasing. In vitro release studies revealed that the drug release from porous microspheres was controlled by non-Fickian diffusion, and almost 80% of the RIF were completely released after 10 days. The results of RIF-loaded microspheres on the antibacterial activity against Staphylococcus aureus proved that the porous microspheres had strong antibacterial ability. In addition, the polymer crystallinity had prominent influence on the degradation rate of microspheres regardless of the morphology.Conclusion: It was an efficient way to entrap slightly water-soluble drug like RIF into PCL by o/o emulsion solvent evaporation method with uniform drug distribution. The RIF-loaded porous PCL microspheres showed the combination of good antimicrobial properties and excellent cytocompatibility, and it could generate gentle environment by PCL slow degradation.Keywords: rifampicin-loaded porous microspheres, poly (ε-caprolactone), oil-in-oil solvent evaporation method, encapsulation efficiency, antibacterial ability

In summary, this article briefly reviews the evidence that three separate autonomic inputs to the islet are capable of stimulating glucagon secretion and that each is activated during IIH. We have reviewed our evidence that these autonomic inputs mediate the glucagon response to IIH, both in non-diabetic animals and humans. Finally, we outline our new preliminary data suggesting an eSIN in an autoimmune animal model of T1DM. We conclude that the glucagon response to IIH is autonomically mediated in non-diabetic animals and humans. We further suggest that at least one of these autonomic inputs, the sympathetic innervation of the islet, is diminished in autoimmune T1DM. These data raise the novel possibility that an autonomic defect contributes to the loss of the glucagon response to IIH in T1DM.

Regulatory T cells (Tregs) are a subpopulation of T cells that are specialized in suppressing immune responses. Here we show that the arginine methyl transferase protein PRMT5 can complex with FOXP3 transcription factors in Tregs. Mice with conditional knock out (cKO) of PRMT5 expression in Tregs develop severe scurfy-like autoimmunity. In these PRMT5 cKO mice, the spleen has reduced numbers of Tregs, but normal numbers of Tregs are found in the peripheral lymph nodes. These peripheral Tregs that lack PRMT5, however, display a limited suppressive function. Mass spectrometric analysis showed that FOXP3 can be di-methylated at positions R27, R51, and R146. A point mutation of Arginine (R) 51 to Lysine (K) led to defective suppressive functions in human CD4 T cells. Pharmacological inhibition of PRMT5 by DS-437 also reduced human Treg functions and inhibited the methylation of FOXP3. In addition, DS-437 significantly enhanced the anti-tumor effects of anti-erbB2/neu monoclonal antibody targeted therapy in Balb/c mice bearing CT26Her2 tumors by inhibiting Treg function and induction of tumor immunity. Controlling PRMT5 activity is a promising strategy for cancer therapy in situations where host immunity against tumors is attenuated in a FOXP3 dependent manner.

Despite substantial clinical progress with targeted therapies, current antibody-based approaches have limited efficacy at controlling HER2/neu-positive breast cancers, especially in the absence of chemotherapies. Previously, we showed that the combination of IFNγ and anti-HER2/neu antibody synergistically reduces tumor growth in an in vivo implanted mammary tumor model. Here, we report a recombinant approach to produce an anti-HER2/neu scFv and IFNγ fusion protein using an engineered effector domain (EED) scaffold. The new molecule induces in vitro apoptosis in an IFNγ receptor-dependent manner. At a very low dose in the in vivo xenografted tumor models, the new EED-IFNγ fusion protein demonstrates superior activity over the anti-HER2/neu antibody and is even active on tumors that are resistant to anti-HER2/neu antibody therapy. Examination of tumor infiltrated macrophages and lymphocytes reveals that the fusion protein can induce changes in tumor microenvironment to support immune reactivity against tumors. Our studies have defined a targeted immunotherapy approach for the treatment of cancers.