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Xu Zhao,1,&ast; Jitao Zhang,1,&ast; Wenjuan Zhang,2 Ruping Dai,1 Junmei Xu,1 Zhijian Li,1 Lin Yang1 1Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Yang; Zhijian LiDepartment of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaFax +86 73185295970; Fax +86 73185295970Email linyang@csu.edu.cn; lizhijian@csu.edu.cnBackground: Bone morphogenetic protein-4 (BMP4) has been identified as an inflammation regulator in the diseases of arteries and other organs. However, the relationship between circulating BMP4 and perioperative inflammation remains unclear.Patients and Methods: Forty patients undergoing lobectomy were randomly allocated into the Control group (not receiving flurbiprofen) and the Flurb group (received 100mg flurbiprofen during surgery). Arterial blood was obtained before surgery (T1), at the end of surgery (T2), and 24 hours after surgery (T3) to test the plasma concentrations of BMP4, its antagonist Noggin, interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-10. The relationship between BMP4 and other variables and the effects of flurbiprofen on BMP4 changes were investigated.Results: A total of 35 patients were included. Circulating BMP4 was positively correlated with IL-1β (P< 0.01, r=0.575) and TNF-α (P< 0.01, r=0.491), negatively correlated with IL-10 (P< 0.01, r=− 0.675), but not correlated with Noggin. The plasma concentrations of BMP4, IL-1β, and TNF-α increased at T2 (P< 0.01, compared with T1) and decreased at T3 (P< 0.05, compared with T2). BMP4 concentrations at T3 were significantly higher than at T1 in the Control group (P< 0.05), while showing no significant difference in the Flurb group. However, in the Flurb group, the relative changes of BMP4 and IL-1β at T2 and T3 were significantly lower than those in the Control group.Conclusion: Circulating BMP4 was elevated during surgery and highly correlated with inflammation cytokines. The elevation of BMP4 and inflammatory cytokines could be alleviated by flurbiprofen, indicating that BMP4 may exert pro-inflammatory properties via cyclooxygenase-II signaling pathways.Keywords: bone morphogenetic protein-4, Noggin, inflammation, non-steroidal anti-inflammatory drugs, perioperative, cyclooxygenase-II

Rationale: Brain-derived neurotrophic factor precursor (proBDNF) is expressed in the central nervoussystem (CNS) and the immune system. However, the role of proBDNF in the pathogenesis of multiplesclerosis (MS) is unknown. Methods: Peripheral blood and post-mortem brain and spinal cord specimens were obtained from multiple sclerosis patients to analyze proBDNF expression in peripheral lymphocytes and infiltrating immune cells in the lesion site. The proBDNF expression profile was also examined in the experimental autoimmune encephalomyelitis (EAE) mouse model, and polyclonal and monoclonal anti-proBDNF antibodies were used to explore their therapeutic effect in EAE. Finally, the role of proBDNF in the inflammatory immune activity of peripheral blood mononuclear cells (PBMCs) was verified in vitro experiments. Results: High proBDNF expression was detected in the circulating lymphocytes and infiltrated inflammatory cells at the lesion sites of the brain and spinal cord in MS patients. In the EAE mouse model, proBDNF was upregulated in CNS and in circulating and splenic lymphocytes. Systemic but not intracranial administration of anti-proBDNF blocking antibodies attenuated clinical scores, limited demyelination, and inhibited proinflammatory cytokines in EAE mice. Immuno-stimulants treatment increased the proBDNF release and upregulated the expression of p75 neurotrophic receptors (p75NTR) in lymphocytes. The monoclonal antibody against proBDNF inhibited the inflammatory response of PBMCs upon stimulations. Conclusion: The findings suggest that proBDNF from immune cells promotes the immunopathogenesis of MS. Monoclonal Ab-proB may be a promising therapeutic agent for treating MS. Refereed/Peer-reviewed

Background BRAF V600E mutation represents a group of colorectal carcinoma with poor prognosis. Although treatment strategies have been recommended after clinical investigations, the progression-free survival is short and unsatisfying. Case presentation Here, we present the case of a 28-year-old male diagnosed with ascending colon adenocarcinoma with multiple liver metastases. Treatment with FOLFIRI plus cetuximab and vemurafenib achieved partial response, following which the patient received conversion surgery with clear resection margin. After disease recurrence, he received combination treatment of nivolumab and regorafenib. Until August 2020, the patient achieved a partial response with more than 12 months progression-free survival. Circulating tumor DNA (ctDNA) was monitored during the patient's treatment. His ctDNA fractions exhibited significant elevation two months before disease progression. As a comparison, the tumor markers were not elevated until the patient was confirmed PD through CT imaging. Conclusion This case exemplifies how liquid biopsy and ctDNA sequencing can aid in real-time molecular characterization of tumors.

AIM: To analyze changes in amplitude of low-frequency fluctuations (ALFFs) and default mode network (DMN) connectivity in the brain, using resting-state functional magnetic resonance imaging (rs-fMRI), in high myopia (HM) patients. METHODS: Eleven patients with HM (HM group) and 15 age- and sex-matched non-HM controls (non-HM group) were recruited. ALFFs were calculated and compared between HM group and non-HM group. Independent component analysis (ICA) was conducted to identify DMN, and comparisons between DMNs of two groups were performed. Region-of-interest (ROI)-based analysis was performed to explore functional connectivity (FC) between DMN regions. RESULTS: Significantly increased ALFFs in left inferior temporal gyrus (ITG), bilateral rectus gyrus (REC), bilateral middle temporal gyrus (MTG), left superior temporal gyrus (STG), and left angular gyrus (ANG) were detected in HM group compared with non-HM group (all P

Background Sepsis-associated encephalopathy (SAE) increases the mortality of septic patients, but its mechanism remains unclear. The present study aimed to investigate the roles of T lymphocytes, proBDNF, and their interaction in the pathogenesis of SAE. Methods Fear conditioning tests were conducted for cognitive assessment in the lipopolysaccharide (LPS, 5 mg kg−1)-induced septic mice. Meninges and peripheral blood were harvested for flow cytometry or qPCR. FTY720 and monoclonal anti-proBDNF antibody (McAb-proB) were used to investigate the effect of lymphocyte depletion and blocking proBDNF on the impaired cognitive functions in the septic mice. Results In the septic mice, cognitive function was impaired, the percentage of CD4+ T cells were decreased in the meninges (P = 0.0021) and circulation (P = 0.0222), and pro-inflammatory cytokines were upregulated, but the anti-inflammatory cytokines interleukin (IL)-4 (P < 0.0001) and IL-13 (P = 0.0350) were downregulated in the meninges. Lymphocyte depletion by intragastrically treated FTY720 (1 mg kg−1) for 1 week ameliorated LPS-induced learning deficit. In addition, proBDNF was increased in the meningeal (P = 0.0042) and peripheral (P = 0.0090) CD4+ T cells. Intraperitoneal injection of McAb-proB (100 μg) before LPS treatment significantly alleviated cognitive dysfunction, inhibited the downregulation of meningeal (P = 0.0264) and peripheral (P = 0.0080) CD4+ T cells, and normalized the gene expression of cytokines in the meninges. However, intra-cerebroventricular McAb-proB injection (1 μg) did not have such effect. Finally, exogenous proBDNF downregulated the percentage of CD4+ T cells in cultured splenocytes from septic mice (P = 0.0021). Conclusion Upregulated proBDNF in immune system promoted the pathogenesis of SAE through downregulating the circulating CD4+ T cells, limiting its infiltration into the meninges and perturbing the meningeal pro-/anti-inflammatory homeostasis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of synovial joints and often associated with chronic pain. Chronic joint inflammation is attributed to severe proliferation of synoviocytes and resident macrophages and infiltration of immune cells. These cells secrete pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and IL-17 to overcome actions of anti-inflammatory cytokines, thereby maintaining chronic inflammation and pain. The imbalance between pro-inflammatory cytokines (produced by M1 macrophages) and anti-inflammatory cytokines (produced by M2 macrophages) is a feature of RA progression, but the switch time of M1/M2 polarization and which receptor regulates the switch remain unsolved. Here we used an established RA mouse model to demonstrate that TNF-α expression was responsible for the initial acute stage of inflammation and pain (1-4 weeks), IL-17 expression the transition stage (4-12 weeks), and IL-6 expression the later maintenance stage (> 12 weeks). The switch time of M1/M2 polarization occurred at 4-8 weeks. We also identified a potential compound, anthra[2,1-c][1,2,5] thiadiazole-6,11-dione (NSC745885), that specifically inhibited T-cell death-associated gene 8 (TDAG8) function and expression. NSC745885 decreased joint inflammation and destruction and attenuated pain by reducing cytokine production and regulating the M1/M2 polarization switch. TDAG8 may participate in regulating the M1/M2 polarization and temporal expression of distinct cytokines to control RA progression.

BACKGROUND A recent consensus statement in Europe has suggested that the fasting time for clear liquid in children can be shortened to 1 hour before a surgery. However, the study to show that 1-hour fasting time for clear fluids is safe in young children is still lacking. This study aimed to investigate the gastric emptying time for carbohydrate-rich drink and regular 5% glucose solution in children aged 3-7 years. METHODS After overnight fasting, individuals were randomly assigned to ingest 5 mL kg-1 of either carbohydrate-rich drink or 5% glucose solution. One week later, the same subjects were asked to ingest the other one. Ultrasonography was performed to examine the gastric contents. Gastric antral cross-sectional area was measured, and the gastric fluid volume was calculated before and after fluid ingestion within 120 minutes. The primary outcome was the gastric emptying time for both the clear fluids calculated using the antral cross-sectional area and logarithms of gastric fluid volume. The degrees of thirst and hunger of two drinks were evaluated using a visual analogue scale as the secondary outcomes. RESULTS Data from 16 individuals were analyzed. In the glucose solution group, the antral cross-sectional area and logarithms of gastric fluid volume returned to baseline at 30 minutes after ingestion. However, in the carbohydrate-rich drink group, the median [interquartile range; range] antral cross-sectional area (3.69 [2.64-5.15; 1.83-8.93] cm2 vs 2.41 [2.10-2.96; 1.81-4.37] cm2 , P

Context Our previous study found that Fengbaisan improved chronic obstructive pulmonary diseases (COPD). Objective To elucidate the mechanism of Fengbaisan in COPD. Materials and methods Rats in Model, FBS, FBS + DMSO and FBS + EX527 groups received cigarette smoke extract (CSE) inhalation and intratracheal instillation of lipopolysaccharide to establish COPD model. Normal group received room air and normal saline. The COPD rats were given Fengbaisan (1 mL/d) or combined with EX527 (5 mg/kg/2 d) by intraperitoneal injection. Human lung carcinoma (A549) cells were treated with 10% CSE, 10% serum-containing Fengbaisan or EX527. We observed lung percentage of forced expiratory volume in first 0.3 sec to forced vital capacity (FEV0.3/FVC), inspiratory resistance (RI) and lung dynamic compliance (Cdyn) of rats. The lung pathological changes, the number of inflammatory cells and neutrophils, inflammatory factor, apoptosis, gene and protein expression were examined. Results SIRT1 was downregulated in lung tissues of COPD rats and CSE-induced A549 cells. Fengbaisan enhanced FEV0.3/FVC (74.28%) and Cdyn (0.28 cm H2O/mL/s), and reduced RI (0.48 mL/cm H2O) of COPD rats. Moreover, Fengbaisan promoted SIRT1 expression, and repressed TIMP-1/MMP-9 expression. Fengbaisan enhanced apoptosis and the expression of GRP78, caspase-12 and caspase-3. The inflammatory factor levels, the number of inflammatory cells and neutrophils, and lung lesions were inhibited by Fengbaisan in COPD rats. The influence conferred by Fengbaisan was abolished by EX527. Discussion and conclusions Fengbaisan inhibits endoplasmic reticulum stress and inflammation reaction by up-regulating SIRT1 expression to improve COPD. Therefore, Fengbaisan may be an effective Chinese medicine for treating COPD.

STUDY OBJECTIVES: Despite the clinical and prognostic significance of obstructive sleep apnea (OSA) in chronic respiratory diseases (CRDs), there have been few studies about the possible predictors of OSA and the effect of OSA on quality of life in patients with CRDs. The objectives were to identify physiological and clinical parameters that predict the occurrence and severity of OSA and to investigate the effect of OSA on quality of life in patients with CRDs. METHODS: Seventy-three patients with chronic obstructive pulmonary disease (COPD) and 77 patients with fibrotic interstitial lung disease (ILD) underwent overnight polysomnography (PSG) and pulmonary function testing and completed clinical questionnaires. The oximetry tracing was interpreted blindly with respect to the PSG results. RESULTS: The prevalence of OSA was 44% and 62% in COPD and ILD, respectively. The COPD assessment test item scores related to sleep quality and daily vitality were worse among patients with OSA than among patients without OSA. The STOP-BANG questionnaire (cutoff point ≥ 3) and oxygen desaturation index from the oximetry recording (oxygen desaturation index (ODI) were associated with OSA in CRDs. The STOP-BANG questionnaire with a cutoff point ≥ 3 or 6 had the highest sensitivity and specificity, respectively, in detecting OSA in CRDs. ODI had the best accuracy in identifying OSA and was independently associated with the apnea-hypopnea index in CRDs. CONCLUSIONS: We found OSA to be common and associated with worse sleep quality and less daily vitality in patients with advanced CRDs. The STOP-BANG questionnaire with different cutoff points may help rule in or rule out OSA. Overnight oximetry can be used as a screening tool for OSA and can assist the clinical evaluation of OSA in patients with CRDs. CITATION: Zhang XL, Dai HP, Zhang H, Gao B, Zhang L, Han T, Wang C. Obstructive sleep apnea in patients with fibrotic interstitial lung disease and COPD. J Clin Sleep Med. 2019;15(12):1807–1815.

BACKGROUND Post-operative cognitive dysfunction (POCD) is a decline of cognitive status that commonly occurs after surgery in elderly patients. Whether DNA methylation is associated with the development of POCD remains unclear. METHODS Subjects (N = 124) older than 65 years-of-age undergoing hip replacement surgery were enrolled. A battery of neuropsychiatric tests was used to examine the perioperative cognitive function of the patients. Early POCD was analyzed using the reliable change index (RCI), and subjects were diagnosed with POCD if RCI

Background: Many patients with type A aortic dissection (AAD) show low lymphocyte counts pre-operatively. The present study investigated the prognostic values of lymphopenia and lymphocyte subsets for the postoperative major adverse events (MAEs) in AAD patients undergoing surgery, and explore mechanisms of lymphopenia.Methods: We retrospectively analyzed pre-operative lymphocyte counts in 295 AAD patients treated at two hospitals, and evaluated their correlation with MAEs. We prospectively recruited 40 AAD patients and 20 sex- and age-matched healthy donors (HDs), and evaluated lymphocyte subsets, apoptosis, and pyroptosis by flow cytometry.Results: Multivariable regression analysis of the retrospective cohort revealed pre-operative lymphopenia as a strong predictor of MAEs (odds ratio, 4.152; 95% CI, 2.434–7.081; p < 0.001). In the prospective cohort, lymphocyte depletion in the AAD group was mainly due to loss of CD4+ and CD8+ T cells as compared with HDs (CD4+ T cells: 346.7 ± 183.6 vs. 659.0 ± 214.6 cells/μl, p < 0.0001; CD8+ T cells: 219.5 ± 178.4 vs. 354.4 ± 121.8 cells/μl, p = 0.0036). The apoptosis rates of CD4+ and CD8+ T cells were significantly higher in AAD patients relative to HDs (both p < 0.0001). Furthermore, the pre-operative CD4+ T cells count at a cut-off value of 357.96 cells/μl was an effective and reliable predictor of MAEs (area under ROC curve = 0.817; 95% CI, 0.684-0.950; sensitivity, 74%; specificity, 81%; p < 0.005). Pre-operative lymphopenia, mainly due to CD4+ T cells exhaustion by apoptosis, correlates with poor prognosis in AAD patients undergoing surgery.Conclusion: Pre-operative lymphopenia in particular CD4+ T lymphopenia via apoptosis correlates with poor prognosis in AAD patients undergoing surgery.

Silicosis is a global occupational disease characterized by lung dysfunction, pulmonary inflammation, and fibrosis, for which there is a lack of effective drugs. Pirfenidone has been shown to exert anti-inflammatory and anti-fibrotic properties in the lung. However, whether and how pirfenidone is effective against silicosis remains unknown. Here, we evaluated the efficacy of pirfenidone in the treatment of early and advanced silicosis in an experimental mouse model and explored its potential pharmacological mechanisms. We found that pirfenidone alleviated silica-induced lung dysfunction, secretion of inflammatory cytokines (TNF-α, IL-1β, IL-6) and deposition of fibrotic proteins (collagen I and fibronectin) in both early and advanced silicosis models. Moreover, we observed that both 100 and 200 mg/kg pirfenidone can effectively treat early-stage silicosis, while 400 mg/kg was recommended for advanced silicosis. Mechanistically, antibody array and bioinformatic analysis showed that the pathways related to IL-17 secretion, including JAK-STAT pathway, Th17 differentiation, and IL-17 pathway, might be involved in the treatment of silicosis by pirfenidone. Further in vivo experiments confirmed that pirfenidone reduced the production of IL-17A induced by silica exposure via inhibiting STAT3 phosphorylation. Neutralizing IL-17A by anti-IL-17A antibody improved lung function and reduced pulmonary inflammation and fibrosis in silicosis animals. Collectively, our study has demonstrated that pirfenidone effectively ameliorated silica-induced lung dysfunction, pulmonary inflammation and fibrosis in mouse models by inhibiting the secretion of IL-17A.

Sepsis-associated encephalopathy (SAE) is a risk factor for cognitive and memory dysfunction; however, the mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) was reported to have a positive effect on cognition and emotion regulation, but the study of its precursor, proBDNF, has been limited. This study aimed to elucidate the effects and associated mechanisms of hippocampal proBDNF in a lipopolysaccharide (LPS)-induced SAE mouse model. In this study, we found that the mice exhibited cognitive dysfunction on day 7 after LPS injection. The expression of proBDNF and its receptor, p75NTR, was also increased in the hippocampus, while the levels of BDNF and its receptor, TrkB, were decreased. A co-localization study showed that proBDNF and p75NTR were mainly co-localized with neurons. Furthermore, LPS treatment reduced the expression of NeuN, Nissl bodies, GluR4, NR1, NR2A, and NR2B in the hippocampus of SAE mice. Furthermore, an intrahippocampal or intraperitoneal injection of anti-proBDNF antibody was able to ameliorate LPS-induced cognitive dysfunction and restore the expression of NeuN, Nissl bodies, GluR4, NR1, NR2A, NR2B, and PSD95. These results indicated that treatment with brain delivery by an intrahippocampal and systemic injection of mAb-proBDNF may represent a potential therapeutic strategy for treating patients with SAE.

A comparison between self-aligned process (using lift-off) and Ni-SALICIDE used in fabrication of ohmic contacts for SiC Power MOSFET is done. Both processes are demonstrated for 3.3 kV SiC VDMOS transistors fabricated on 100 mm substrates. It is shown that the Ni-SALICIDE process with first silicidation at 500 °C does not degrade the electrical properties of silicon dioxide; particularly, a degradation of the interlayer dielectric between source and gate is not evident. Additionally, this first silicidation is found to have a positive impact on the specific resistance of contacts formed on p-type SiC using NiAl2.6% as an ohmic metal.

To describe the ultrasound biomicroscopy (UBM) findings of extremely rare ciliary body lymphoma. This was a retrospective noncomparative case series study. Five patients (8 affected eyes) diagnosed with ciliary body lymphoma at Peking Union Medical College Hospital from 2008 to 2019 were included. The UBM findings, including the location, height, and acoustic features, were documented to assess the tumour characteristics. UBM in all 8 (100%) affected eyes revealed 360° ring-like, solid infiltration of the ciliary body with low and homogeneous internal reflectivity. The continuity of the tumours could be most vividly demonstrated by transverse sections. Ciliary body lymphoma tends to grow in a characteristic circumferential 360° pattern, and the name “ring lymphoma of the ciliary body” is proposed.

Sevoflurane exposure in neonates induces long-term impairment of learning and memory; however, its effect on cognition in the later developmental period and the underlying mechanisms remain unclear. In the present study, we showed that multiple sevoflurane exposures impaired fear memory at long retention delays in neonatal (postnatal day 7) and preadolescent mice (postnatal day 22), but not in mice at older ages. After the fear memory test, expression of phosphorylated extracellular signaling-regulated kinase (p-ERK) and c-fos were elevated in the bed nucleus of the stria terminalis (BNST) and central amygdala, but not in the hippocampus or prefrontal cortex. The upregulation of p-ERK was restricted to populations of γ-aminobutyric acid (GABAergic) neurons and was inhibited by multiple sevoflurane exposures. Intra-BNST injection of ERK inhibitor also impaired fear memory at long retention delays. In contrast, intra-BNST injection of ERK agonist attenuated impaired fear memory caused by repeated sevoflurane exposures. Injection of sevoflurane in the BNST but not the caudate putamen impaired the fear memory at long retention delays in preadolescent mice. Finally, chemogenetic activation of BNST GABAergic neurons by designer receptors exclusively activated by designer drug (DREADD) reversed the impaired fear memory at long retention delays by multiple sevoflurane exposures. These findings suggest that multiple sevoflurane exposures impaired fear memory at long retention delays in preadolescent mice by suppressing the ERK signaling in GABAergic neurons in the BNST.

Philadelphia chromosome-like B-lymphoblastic leukemia (Ph-like ALL) describes a group of genetically heterogeneous, Ph-negative entities with high relapse rates and poor prognoses. A Janus-kinase-2 (JAK2) rearrangement has been reported in approximately 7% of Ph-like ALL patients whose therapeutic responses to JAK inhibitors have been studied in clinical trials. Here, we report a novel STRBP-JAK2 fusion gene in a 21-year-old woman with Ph-like ALL. Although a normal karyotype was observed, a hitherto unreported JAK2 rearrangement was detected cytogenetically. STRBP-JAK2 fusion was identified by RNA sequencing and validated by Sanger sequencing. The Ph-like ALL proved refractory to traditional induction chemotherapy combined with ruxolitinib. The patient consented to infusion of autologous chimeric antigen receptor (CAR) T cells against both CD19 and CD22, which induced morphologic remission. Haplo-identical stem cell transplantation was then performed; however, she suffered relapse at just one month after transplantation. The patient subsequently received donor lymphocyte infusion after which she achieved and maintained a minimal residual disease negative remission. However, she succumbed to grade IV graft-versus-host disease 7 months post-transplant. In conclusion, this report describes a novel STRBP-JAK2 gene fusion in a Ph-like ALL patient with a very aggressive disease course, which proved resistant to chemotherapy combined with ruxolitinib but sensitive to immunotherapy. Our study suggests that CAR T-cell therapy may be a viable option for this type of leukemia.

Introduction: Previous studies showed that high density lipoprotein (HDL) can stimulate angiogenesis. However, the mechanisms by which HDL promotes angiogenesis remains unclear. Hypothesize: HDL may promote angiogenesis by regulating miRNAs expression. Methods: HDL was isolated from healthy subjects. Human umbilical vein endothelial cells (HUVECs) were cultured with vehicle or HDL (100 μg/ml), and the differential miRNAs expression were indentified by miRNA array and verified by qRT-PCR. HUVECs were treated with vehicle or HDL (100 μg/ml) with or without miRNAs mimic, endothelial cells proliferation, migration and tube formation were detected. The production of nitric oxide(NO) was measured. The expression and phosphorylation of endothelial nitric oxide synthase (eNOS) was determined. Results: The miRNAs profile of HDL-treated HUVECs is significantly different from control group. HDL significantly downregulated miR-24-3p expression. HDL significantly promoted HUVECs proliferation, migration and tube formation. HDL also significantly stimulated NO production and up-regulated the expression and phosphorylation of eNOS. However, HDL did not stimulated HUVECs proliferation, migration, tube formation and NO production as well as the expression and phosphorylation of eNOS after pretreated with miR-24-3p mimic. Conclusions: HDL can promote angiogenesis by suppressing miR-24-3p expression.

Background Since the outbreak of 2019 novel coronavirus (SARS‐CoV‐2) pneumonia, many patients with underlying disease, such as interstitial lung disease (ILD), were admitted to Tongji hospital in Wuhan, China. To date, no data have ever been reported to reflect the clinical features of Corona Virus Disease 2019 (COVID‐19) among these patients with pre‐existing ILD. Methods We analyzed the incidence and severity of COVID‐19 patients with ILD among 3201 COVID‐19 inpatients, and compared two independent cohorts of COVID‐19 patients with pre‐existing ILD (n=28) and non‐ILD COVID‐19 patients (n=130). Results Among those 3201 COVID‐19 inpatients, 28 of whom were COVID‐19 with ILD (0.88%). Fever was the predominant symptom both in COVID‐19 with ILD (81.54%) and non‐ILD COVID‐19 patients (72.22%). However, COVID‐19 patients with ILD were more likely to have cough, sputum, fatigue, dyspnea, and diarrhea. Very significantly higher number of neutrophils, monocytes, IL‐8, IL‐10, IL‐1β and D‐Dimer was characterized in COVID‐19 with ILD as compared to those of non‐ILD COVID‐19 patients. Furthermore, logistic regression models showed neutrophils counts, pro‐inflammatory cytokines (TNF‐α, IL6, IL1β, IL2R), and coagulation dysfunction biomarkers (D‐Dimer, PT, Fbg) were significantly associated with the poor clinical outcomes of COVID‐19. Conclusion ILD patients could be less vulnerable to SARS‐CoV‐2. However, ILD patients tend to severity condition after being infected with SARS‐CoV‐2. The prognosis of COVID‐19 patients with per‐existing ILD is significantly worse than that of non‐ILD patients. And more, aggravated inflammatory responses and coagulation dysfunction appear to be the critical mechanisms in the COVID‐19 patients with ILD. This article is protected by copyright. All rights reserved.

Objective s To investigate the effects of preoperative smoking and smoking cessation time on preoperative peripheral blood inflammatory indexes and postoperative hospitalization outcomes in male patients with lung cancer and surgery therapy.Methods We retrospectively enrolled 637 male patients who underwent curative-intent lung cancer resection between January 2014 and December 2016. Patients were classified as the current smokers, the never smokers, and the ex-smokers based on their smoking history, and the ex-smokers were allocated into five subgroups according to their smoking cessation times (CeT): CeT≤6 weeks, 6weeks 10years. The preoperative peripheral blood white blood cells (WBCs), albumin, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), intraoperative blood loss, 30-day mortality, in-hospital days, hospitalization costs, intensive care unit (ICU), admission days and placement time of closed thoracic drainage tube were compared among different groups.Results There were significant differences in WBC (F=5.275, P

To evaluate carotid stiffening in participants without conventional cardiovascular risk factors (CVRFs) by using ultrafast pulse wave velocity (ufPWV). The present study enrolled 517 participants without conventional CVRFs (CVRF-Free total population). Subjects in this population were defined as current non-smokers with untreated blood pressure

Background Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome is a rare paraneoplastic syndrome involving multisystem. Optic disc edema (ODE) is the most common ocular manifestation in patients with POEMS syndrome and serves as an independent prognostic factor. However, parameters previously used to estimate its severity were inconvenient and costly. This study was designed to bring forward a novel and practical parameter, optic disc edema area, to evaluate ODE in patients with this disease and applied it to assess effectiveness of lenalidomide combined with dexamethasone in respect of ODE. Results Forty-one treatment-naive patients with POEMS syndrome were enrolled in this single-center prospective study and treated with lenalidomide combined with dexamethasone. They received ocular examination to determine optic disc edema (ODE) area and other optic manifestations. Meanwhile, serum VEGF was measured before and after treatment. Among 41 enrolled patients, 38 received complete ocular examinations, and 25 of which had ODE at initial visit. Binocular mean ODE area of patients with ODE was significantly related to ODE grade (r = 0.620, p = 0.003) and peripapillary retinal thickness (r = 0.760, p p = 0.025) and positively correlated with binocular mean ODE area (r = 0.460, p = 0.036). After treatment, ODE area, along with serum VEGF, decreased markedly (p Conclusion ODE area was a reliable index to evaluate ODE severity and could precisely reflect ODE improvement through systemic treatment. Additionally, it was related to serum VEGF, a key factor in disease pathogenesis, suggesting its potential as an indicator of the overall severity of this disease. Trial registration Clinicaltrials, NCT01816620. Registered March 222,013.

To compare the efficacy and safety profile of S-1-based versus non-S-1-based chemotherapy as first-line treatment in mCRC. Relevant randomized controlled trials (RCTs) were obtained from PubMed, Embase, and Ovid databases and the Cochrane library from database set up in May 2018. The RCTs of S-1-based monotherapy or combination therapy as first-line treatment were selected. The impact of S-1-based chemotherapy on progression-free survival (PFS) and overall survival (OS) was assessed by pooling data via RevMan 5.3. Meta-analysis of 10 RCTs showed that S-1-based chemotherapy significantly improved PFS (HR 0.90, 95% CI 0.84–0.97, P = 0.006). In subgroup analysis, there was a statistically significant increase in PFS when S-1-based chemotherapy was compared with 5-FU-based (HR 0.92, 95% CI 0.84–1.00, P = 0.04) or capecitabine-based chemotherapy (HR 0.85, 95% CI 0.73–0.99, P = 0.04). The meta-analysis of OS (HR 0.95, 95% CI 0.86–1.05, P = 0.36), overall response rate (ORR) (HR 0.99, 95% CI 0.84–1.17, P = 0.90), and disease control rate (DCR) (HR 1.61, 95% CI 0.87–3.00, P = 0.13) showed no statistical significance between S-1-based and non-S-1-based chemotherapy. The statistically significant differences in the meta-analysis indicated less incidence of graded 3–4 leucopenia (OR = 0.30, 95% CI 0.13–0.71, P = 0.006) and hand–foot syndrome (HFS) (OR = 0.24, 95% CI 0.10–0.58, P = 0.001) in the S-1-based chemotherapy, and there was no statistically significant difference for other adverse events. S-1-based chemotherapy in mono or combined therapy was an attractive alternative to standard first-line regimen for patients of mCRC.

Background: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is associated with high rates of treatment failure and poor outcome. Activation of ABL/Src family kinases is found in ~10% of Ph-like ALL, which can be therapeutically targeted by tyrosine kinase inhibitors. LYN is a member of the ABL/Src-tyrosine kinase family. Somatic LYN rearrangements are found in 5 cases of hematopoietic malignancies so far, although none of them were treated with tyrosine kinase inhibitors. Case presentation: A 6-year-old boy with relapsed B-ALL had no response to reinduction chemotherapy. He was then treated with the ABL1 tyrosine kinase inhibitor dasatinib and achieved complete remission within 2 weeks. Haploidentical allogenic stem cell transplantation (allo-HSCT) was subsequently performed and maintenance therapy with dasatinib initiated 8 weeks post-transplantation. He has been in minimal residual disease negative remission for 10 months after allo-HSCT. Result: His bone marrow karyotype showed a balanced translocation between chromosomes 8 and 17, leading to a NCOR1-LYN fusion gene confirmed with sequencing. Conclusion: Although LYN overexpression is described in many AML and B-ALL patients, intragenic LYN rearrangement is a rare event. For the first time, we present evidence that dasatinib is effective in treating a pediatric B-ALL with NCOR-LYN fusion.

Background Hydrogen peroxide has been widely used in Orthopaedics including Orthopaedic oncology, trauma and joint surgeries. However, we encountered an oxygen embolism and myoglobinuria after hydrogen peroxide was used to irrigate a septic hip arthroscopically. Case presentation A 61-year-old male patient with right hip septic arthritis underwent an arthroscopic hip washout and debridement. During the operation, the surgeon used 100 ml of 3% hydrogen peroxide to irrigate the joint cavity. Two minutes after irrigation, there was a transient decrease in oxygen saturation, heart rate and blood pressure, with significant subcutaneous emphysema around the wound. Concentrated urine was drained out 8 h after operation which resolved the following day. Post-operatively, the patient was managed in the intensive care unit for a pulmonary embolism and discharged without further complications. Conclusion Medical staff should be aware of the risk of oxygen embolism and be extremely careful when using hydrogen peroxide in patient care. Oxygen embolism following hydrogen peroxide use is rare, however, once encountered, it may bring serious consequences. Therefore, the use of hydrogen peroxide in closed spaces or arthroscopic procedures should be discontinued.

Background: Allergic bronchopulmonary mycosis (ABPM) is a complex pulmonary disorder caused by a hyperimmune response to the endobronchial growth of certain fungi. This study aims to aid physicians in better understanding the need for earlier recognition of ABPM. Methods: Patients with a confirmed diagnosis of ABPM after evaluation were analyzed retrospectively. Clinical features, previous diagnoses and potential diagnostic errors, laboratory findings were reviewed and compiled. Results: Fifty-seven patients were diagnosed with ABPM in which 22 were misdiagnosed. Eosinophilia was observed in 11 patients and an elevated total serum Ig E level greater than 1,000 kU/L was detected in 25 of the 57 patients. All of the patients were tested for specific Ig E in which positive to different fungi. The two most common abnormalities found on chest high-resolution computed tomography (HRCT) exams were central bronchiectasis and mucus plugs. A mild to moderate obstructive pattern of lung function was observed in 32 cases. By bronchofiberscopic observation, bronchial lumen was seen to have significant inflammation in 12 patients. After 3 weeks of treatment, a decreased serum total Ig E value was observed. Conclusions: This study highlights the importance of increasing awareness and understanding of non- Aspergillus-ABPM among physicians and draws attention to the need for establishing more elaborate diagnostic criteria for non-Aspergillus-ABPM, which is a rare kind of disease.

Background: Sleep disturbance is one of the major non-motor symptoms which cause the disability of Parkinson’s disease (PD) patients. Cystatin C (CysC) is a more sensitive biomarker than serum creatinine or estimated glomerular filtration rate. Previous studies have reported altered CysC levels in neurodegenerative disorders and sleep disorders. This study aimed to explore the correlations of serum CysC levels and objective sleep disturbances in early PD. Methods: We recruited 106 early PD patients and 146 age- and sex-matched controls. All participants underwent clinical investigation and video-polysomnography. Sleep parameters and serum levels of CysC were measured. Then, we investigated the relationships between CysC and clinical variables and objective sleep disturbances in early PD patients. Results: The mean serum level of CysC was significantly higher in patients with early PD (1.03 ± 0.19 mg/L) compared to controls (0.96 ± 0.15 mg/L, P = 0.009). There were significantly positive correlations between serum CysC levels and age (r = 0.334, P < 0.001), gender (r = 0.264, P = 0.013), and creatinine levels (r = 0.302, P = 0.018) in early PD patients. Increased serum CysC levels in early PD patients were significantly associated with higher apnea and hypopnea index (AHI) (r = 0.231, P = 0.017), especially hypopnea index (r = 0.333, P < 0.001). In early PD patients, elevated serum CysC levels were positively correlated with oxygen desaturation index (r = 0.223, P = 0.021), percentage of time spent at oxygen saturation (SaO2)

To achieve efficient polymer solar cells (PSCs), it is important to increase the optical absorption coefficient and charge mobility of photovoltaic materials for obtaining a high short-circuit current density (Jsc) and fill factor (FF) in the devices without sacrificing the open-circuit voltage (Voc). Herein, we designed and synthesized two novel narrow bandgap n-type organic semiconductor (n-OS) acceptors named POIT-M and MOIT-M by modifying the side-chains of IT-M from para-hexylphenyl to para-hexyloxylphenyl and then to meta-hexyloxylphenyl. Due to the synergistic effects of introducing oxygen atoms and varying substitution positions on the phenyl side-chains, MOIT-M shows a significantly improved absorption coefficient, stronger intermolecular π–π stacking interaction, increased crystallinity and higher electron mobility in comparison with IT-M and POIT-M, which helps to gain higher Jsc and FF in PSCs. These special features combined with the complementary absorption of the MOIT-M acceptor and wide bandgap polymer PTZ1 donor resulted in a high power conversion efficiency (PCE) of 11.6% with a Voc of 0.96 V, a Jsc of 17.5 mA cm−2 and a FF of 68.8% for the PSCs processed with simple thermal annealing at 120 °C for 10 min, which is one of the highest PCEs reported for additive-free PSCs and significantly higher than those of the PSCs based on PTZ1:IT-M (9.1%) or PTZ1:POIT-M (9.7%). Our results indicate that side-chain engineering is an effective way to further improve the photovoltaic performance of n-OS acceptors in PSCs.

Purpose: To evaluate the performance of the xTAG liquid chip technology (xTAG-LCT) for etiological diagnosis of acute retinal necrosis (ARN).Methods: Fifteen vitreous and 3 aqueous samples from 18 ARN patients were analyzed by xTAG-LCT and multiplex PCR (mPCR)/quantitative PCR (qPCR).Results: xTAG-LCT revealed positive results in 17 of the 18 samples: 10 for Varicella Zoster Virus (VZV) alone; 5 for VZV and Epstein-Barr virus (EBV); 1 for herpes simplex viruses type 1 (HSV-1) and EBV; 1 for VZV, HSV-1 and EBV. While mPCR revealed the same results as xTAG-LCT for VZV and HSV-1 in all samples, only 2 of the 7 samples positive for EBV on xTAG-LCT were confirmed by qPCR. None of the 28 control vitreous samples from 8 non-ARN patients and 10 pair of cadaveric eyes was positive for any of the tested viruses.Conclusions: xTAG-LCT could be a useful alternative for etiological diagnosis of ARN.

Background Blood purification is an emerging approach to dampening the cytokine storm. This study aims to assess the efficacy of HA330 resin-directed hemoadsorption (HA) on endotoxin-induced porcine acute respiratory distress syndrome (ARDS) model. Methods Twenty-four Chinese domestic pigs were allocated into saline group receiving intravenous infusion of saline (N = 6) and endotoxin group receiving intravenous infusion of LPS (N = 18). When ALI model was initially diagnosed, six pigs in the LPS and saline group were killed for BALF and histopathological analysis. The remaining 12 pigs in LPS group received 3-h HA (N = 6) or HA-sham (N = 6) treatment, respectively. Following another 5-h observation, animals were killed. Variables on hemodynamics, blood gases and lung mechanics were recorded at a series of time points. Differentially expressed cytokines and proteins were determined by ELISA and proteomics. Results HA treatment significantly improved injured oxygenation induced by LPS. HA also partially improved the barrier permeability and reduced lung edema and inflammation/injury induced by LPS infusion. Proteomic analysis showed the differentially expressed proteins between HA- and HA-sham-treated groups mostly belonged to the categories of acute inflammation/immune response, and proteolysis. Conclusions Hemoadsorption improved ARDS possibly by blunting the cytokine storm and by restoring homeostasis of the disordered proteome milieu in the exudative phase. Electronic supplementary material The online version of this article (doi:10.1186/s13613-017-0287-0) contains supplementary material, which is available to authorized users.

Neurofilament light (NFL) is a putative biomarker of neurodegeneration. This study evaluates the correlative association of NFL with Alzheimer's disease (AD) indices. Relevant studies were identified after a literature search in electronic databases and study selection was based on pre-determined eligibility criteria. Correlation coefficients between NFL levels and important AD indices reported by individual studies were pooled as z-scores. Meta-regression analyses were performed to evaluate the relationships between important covariates. Data from 38 studies (age 68.3 years [95% confidence interval (CI): 65.7, 70.9]; 54 % [95% CI: 50, 57] females) were used. Meta-analyses of correlation coefficients reported by the included studies showed that NFL levels in blood and cerebrospinal fluid (CSF) correlated well (r = 0.59 [95% CI: 0.45, 0.71]; p < 0.0001). NFL levels correlated with MMSE score (r = −0.345 [95% CI: −0.43, −0.25]; p = 0.0001), and age (r = 0.485 [95% CI: 0.35, 0.61]; p = 0.00001). CSF NFL levels correlated with total tau (t-tau; r = 0.39 [95% CI: 0.27, 0.50]; p = 0.0001), phosphorylated tau (p-tau; r = 0.34 [95% CI: 0.19, 0.47]; p = 0.00001), and neurogranin (r = 0.25 [95% CI: 0.12, 0.37]; p = 0.001) but not with beta amyloid (Aβ) (r = 0.00 [95%CI: −0.13, 0.12]; p = 0.937). In meta-regression, MMSE scores were associated inversely with blood NFL (metaregression coefficient (MC) −0.236 [95% CI:−0.40, −0.072; p = 0.008), and age (MC) −0.235 [−0.36, −0.11]; p = 0.001) and positively with CSF Aβ-42 (MC 0.017 [0.010, 0.023]; p = 0.00001). NFL has good correlations with t-tau, and p-tau in CSF and CSF NFL levels correlates well with blood NFL levels. These results show that NFL can be a useful biomarker for improving diagnosis and predicting prognosis in AD patients especially if age weighted.

To investigate the clinical features and spectral-domain optical coherence tomography (SD-OCT) findings of retinal astrocytic hamartoma (RAH) in Chinese patients with tuberous sclerosis complex (TSC). The medical records of 91 consecutive patients with established TSC diagnosis were retrospectively reviewed. Fundus findings regarding RAH documented by fundus photography and SD-OCT at presentation were collected and analyzed. RAHs were seen in 69 of the 91 patients (75.8%); 50.7% of these patients showed bilateral retinal involvement. Type 1 RAH was found the most common type with a prevalence of 94.2%, while type 2 and type 3 RAH with 7.2% and 18.8% respectively. A significant correlation between age and RAH types was shown by Fisher’s exact test (p

Background The autoimmune disease rheumatoid arthritis (RA) affects approximately 1% of the global population. RA is characterized with chronic joint inflammation and often associated with chronic pain. The imbalance of pro-inflammatory and anti-inflammatory macrophages is a feature of RA progression. Glial cells affecting neuronal sensitivity at both peripheral and central levels may also be important for RA progression and associated pain. Genetic variants in the T cell death-associated gene 8 (TDAG8) locus are found to associate with spondyloarthritis. TDAG8 was also found involved in RA disease progression and associated hyperalgesia in the RA mouse model. However, its modulation in RA remains unclear. Methods To address this question, we intra-articularly injected complete Freund’s adjuvant (CFA) into TDAG8+/+, TDAG8−/− or wild-type mice, followed by pain behavioral tests. Joints and dorsal root ganglia were taken, sectioned, and stained with antibodies to observe the number of immune cells, macrophages, and satellite glial cells (SGCs). For compound treatments, compounds were intraperitoneally or orally administered weekly for 9 consecutive weeks after CFA injection. Results We demonstrated that TDAG8 deletion slightly reduced RA pain in the early phase but dramatically attenuated RA progression and pain in the chronic phase (> 7 weeks). TDAG8 deletion inhibited an increase in SGC number and inhibition of SGC function attenuated chronic phase of RA pain, so TDAG8 could regulate SGC number to control chronic pain. TDAG8 deletion also reduced M1 pro-inflammatory macrophage number at 12 weeks, contributing to the attenuation of chronic RA pain. Such results were further confirmed by using salicylanilide derivatives, CCL-2d or LCC-09, to suppress TDAG8 expression and function. Conclusions This study demonstrates that TDAG8 deletion reduced SGC and M1 macrophage number to relieve RA disease severity and associated chronic pain. M1 macrophages are critical for the development and maintenance of RA disease and pain, but glial activation is also required for the chronic phase of RA pain.

Depression and anxiety are two affective disorders that greatly threaten the mental health of a large population worldwide. Previous studies have shown that brain-derived neurotrophic factor precursor (proBDNF) is involved in the development of depression. However, it is still elusive whether proBDNF is involved in anxiety, and if so, which brain regions of proBDNF regulate these two affective disorders. The present study aims to investigate the role of proBDNF in the hippocampus in the development of depression and anxiety. Rat models of an anxiety-like phenotype and depression-like phenotype were established by complete Freund's adjuvant intra-plantar injection and chronic restraint stress, respectively. Both rat models developed anxiety-like behaviors as determined by the open field test and elevated plus maze test. However, only rats with depression-like phenotype displayed the lower sucrose consumption in the sucrose preference test and a longer immobility time in the forced swimming test. Sholl analysis showed that the dendritic arborization of granule cells in the hippocampus was decreased in rats with depression-like phenotype but was not changed in rats with anxiety-like phenotype. In addition, synaptophysin was downregulated in the rats with depression-like phenotype but upregulated in the rats with anxiety-like phenotype. In both models, proBDNF was greatly increased in the hippocampus. Intra-hippocampal injection anti-proBDNF antibody greatly ameliorated the anxiety-like and depressive behaviors in the rats. These findings suggest that despite some behavioral and morphological differences between depression and anxiety, hippocampal proBDNF is a common mediator to regulate these two mental disorders. Refereed/Peer-reviewed

In the process of digital printing, due to the change of the performance of the printer, the targeted color space of the traditional printer and the color gamut differences of the output devices, the actual printing colors may deviate from the allowable range of the target color. Therefore, in order to solve this problem, this paper proposes a method of using local nine-item polynomial to set up the mapping relation to modify the color, and realizes the color correction of digital printing by modifying the specific file. The method can control the chromatic aberration to the lowest, more accord with the color correction, and make the digital printing color approximate to the target color in the gamut space of the whole digital printing press.

Purpose: To explore the impact of coronavirus disease 2019 (COVID-19) on the prognosis of patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), and share the experience in managing them during pandemics. Method: This is a retrospective study of nAMD and PCV patients treated at Peking Union Medical College Hospital from 31 December 2019 to 1 August 2020. Baseline demographic and clinical characteristics, best corrected visual acuity (BCVA), optical coherence tomography (OCT) features, duration of delayed treatment and number of anti-vascular endothelial growth factor (VEGF) injections were analyzed. Results: A total of 130 nAMD patients (155 eyes) and 76 PCV patients (89 eyes) were identified. Compared to the conditions before COVID-19, the BCVA of delayed cases decreased significantly, and the proportion of patients presenting with sub-macular scar was significantly greater in the delayed treatment group ( p Conclusions: The delayed cases due to the pandemic suffered compromised visual function and a higher rate of sub-macular scar formation, while the visual function of non-delayed cases remained stable with favorable anatomical outcomes, suggesting the importance of regular follow-up for nAMD and PCV patients. Besides, effective measures of hospitals during pandemics are crucial to provide timely treatment for chronic disease.

Breast cancer is one of the major threats to female health, and its incidence is rapidly increasing in many countries. Currently, breast cancer is treated with surgery, followed by chemotherapy or radiation therapy, or both. However, a substantial proportion of breast cancer patients might have a risk for local relapse that leads to recurrence of their disease and/or metastatic breast cancer. Therefore searching for new and potential strategies for breast cancer treatment remains necessary. Immunotherapy is an attractive and promising approach that can exploit the ability of the immune system to identify and destroy tumors and thus prevent recurrence and metastatic lesions. The most promising and attractive approach of immunotherapeutic research in cancer is the blockade of immune checkpoints. In this review, we discuss the potential of certain inhibitors of immune checkpoints, such as antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1) and lymphocyte activation gene-3 (LAG-3), in breast cancer therapeutics. Immune checkpoint inhibitors may represent future standards of care for breast cancer as monotherapy or combined with standard therapies.

Thermochromic films have been deposited by magnetron sputtering technique on different substrates. The crystallinity and surface morphology of the films have been characterized. Characterization result shows that the films are of perovskite structure. Composition analysis is performed and the result indicated that the element composition of the film can be close to its stoichiometric ratio. Temperature-dependent reflectivity and emissivity are studied. Reflectivity spectra show a downward trend with increasing temperature. Emissivity of the film is large at high temperature and it decreases sharply upon cooling. The emissivity increment at 123–373 K can approach 0.43 at 1.4 Pa sputtering pressure environment, which is attractive for thermal control application in spacecraft.

Objective: Acute respiratory distress syndrome (ARDS) is an acute and lethal clinical syndrome that is characterized by hypoxemic respiratory failure and diffuse alveolar inflammatory damage. This review aimed to search and discuss the mass spectrometry (MS)-based proteomic studies on different subsets of ARDS patients. Data Sources: Original research articles were collected from the PubMed database published in English up to December 2015. Study Selection: The literature search was done using the term “(acute lung injury OR acute respiratory distress syndrome) AND (proteomics OR proteome OR mass spectrum OR differential in-gel electrophoresis OR two-dimensional polyacrylamide gel electrophoresis)”. Related original research articles were included and were carefully analyzed. Results: Eight original proteomic researches on ARDS patients were found. The common proteomic modalities were two-dimensional (2D) high-performance liquid chromatography-based electronic spray ion-MS/MS and 2D-polyacrylamide gel electrophoresis/differential in-gel electrophoresis-based matrix-assisted laser desorption ionization-time of flight/MS. They compared the proteome between ARDS patients and normal controls and analyzed the dynamic changes of proteome at different ARDS stages or severity. The disturbed proteome in ARDS patients includes plasma acute-phase proteins, inflammatory/immune-associated proteins, and coagulation proteins. Conclusions: Although several previous studies have provided some useful information about the lung proteome in ARDS patients and gained several interesting disease-associated biomarkers, clinical proteomic studies in ARDS patients are still in the initial stage. An increased cooperation is still needed to establish a global and faithful database containing disease-specific proteome from the largest ARDS subsets.

Aims The aim of this paper is to observe the change of aqueous humor levels of placenta growth factor (PlGF) and vascular endothelial growth factor (VEGF) in proliferative diabetic retinopathy (PDR) patients before and one week after intravitreal conbercept injection. Methods A prospective case series study was conducted in 24 active PDR patients (24 eyes). All the patients had received 0.5 mg of intravitreal conbercept followed by vitrectomy one week later. The aqueous humor was collected before conbercept injection and at the beginning of vitrectomy. Results Before conbercept injection, the aqueous humor median levels of VEGF-A, VEGF-B and PlGF were 457.0 p g / m L ( I Q R f r o m 392.9 t o 860.6 p g / m L ) , 43.6 p g / m L ( I Q R f r o m 33.6 t o 81.6 p g / m L ) , 37.5 p g / m L ( I Q R f r o m 25.0 t o 53.6 p g / m L ) , respectively. One week after conbercept injection, the aqueous humor levels of VEGF-A, VEGF-B and PiGF decreased significantly. The aqueous humor VEGF-A levels in PDR patients with fibrovascular membranes were lower than those without them. There was positive correlation between aqueous humor VEGF-B and PiGF levels (P = 0.007). No significant correlation was found between VEGF-A and PiGF levels. No ocular and systemic adverse events were observed. Conclusions The aqueous humor levels of PlGF was correlated with VEGF-B, and levels of VEGF-A, VEGF-B, and PlGF decreased after intravitreal conbercept injection in active PDR patients.

This study reports the short-term efficacy and safety of intravitreal conbercept injections for neovascularization at the disc (NVD) in patients with proliferative diabetic retinopathy (PDR). Conbercept is a recombinant fusion protein with a high affinity for all isoforms of vascular endothelial growth factor (VEGF)-A, placental growth factor and VEGF-B. A prospective case series study was conducted in 15 patients (15 eyes). Patients had complete ocular examinations and received a 0.5 mg intravitreal conbercept injection followed by supplemental pan-retinal photocoagulation (PRP). Optical coherence tomography angiography (OCTA) was performed before and after treatment. Before treatment, the mean NVD area was 1.05 ± 0.33 mm2, and it decreased to 0.56 ± 0.17 mm2 after an interval of 7.5 d (p = 0.000). One eye required vitrectomy during follow-up. Recurrent NVD was observed in 2 eyes, which resolved after repeated injections. The remaining 12 eyes were stable over a mean follow-up period of 8.3 months. The mean area of the NVD in 14 patients without vitrectomy was 0.22 ± 0.11 mm2 (p = 0.000) at the last visit. Intravitreal conbercept injections combined with intensive PRP are an effective and safe treatment for PDR with NVD. Quantitative information on NVD can be obtained with OCTA, which may be clinically useful in evaluating the therapeutic effect.

Ping Dai, Jing Li, Xiao-Ping Ma, Jian Huang, Juan-Juan Meng, Ping Gong Department of Oncology, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, People’s Republic of China Background: The study of cyclooxygenase-2 (COX-2) inhibitors is now mired in controversy. We performed a meta-analysis to assess the efficacy and safety profile of COX-2 inhibitors in patients with advanced non-small-cell lung cancer (NSCLC).Patients and methods: A literature search of PubMed, EMBASE, the Cochrane Central databases, and ClinicalTrials.gov, up until March 26, 2017, identified relevant randomized controlled trials. Data analysis was performed using Stata 12.0.Results: Six eligible trials (1,794 patients) were selected from the 407 studies that were identified initially. A significant difference, favoring COX-2 inhibitors plus chemotherapy over chemotherapy alone, was observed in the overall response rate (relative risk [RR] =1.25, 95% confidence interval [CI]: 1.06–1.48). Further, we conducted two subgroup analyses according to the type of COX-2 inhibitors (celecoxib, rofecoxib, or apricoxib) and treatment line (first or second chemotherapy). The first-line treatment includes: NP (changchun red bean + cisplatin or carboplatin), GP (double fluorine cytidine + cisplatin or carboplatin), or TP (paclitaxel + cisplatin or carboplatin, docetaxel + cisplatin or carboplatin). The second-line treatment includes two internationally recognized compounds, one is docetaxel and the other is the pemetrexed, both of which are individually selected. In subgroup analysis, significantly increased overall response rate (ORR) results were found for rofecoxib plus chemotherapy (RR =1.56, 95% CI: 1.08–2.25) and COX-2 inhibitor given with first-line chemotherapy (RR =1.27, 95% CI: 1.07–1.50). However, there was no difference between COX-2 inhibitors plus chemotherapy and chemotherapy alone in overall survival (hazard ratio [HR] =1.04, 95% CI: 0.91–1.18), progression-free survival (HR =0.97, 95% CI: 0.86–1.10), and 1-year survival rate (RR =1.03, 95% CI: 0.89–1.20). Toxicity did not differ significantly between COX-2 inhibitors plus chemotherapy and chemotherapy alone with the exception of leukopenia (RR =1.21, 95% CI: 1.03–1.42), thrombocytopenia (RR =1.32, 95% CI: 1.04–1.67), and cardiovascular events (RR =2.39, 95% CI: 1.06–5.42). The results of the Egger’s test indicated no significant difference in primary outcomes.Conclusion: COX-2 inhibitors improved ORR of advanced NSCLC with chemotherapy, but had no effect on survival indices. Moreover, COX-2 inhibitors may lead to higher rates of hematologic toxicities and cardiovascular events. Keywords: cyclooxygenase-2 inhibitors, non-small-cell lung cancer, chemotherapy, overall survival, meta-analysis&nbsp

// Li-Ping Dai 1, 2, 3, * , Ji-Tian Li 3, * , Xiao Wang 1, 2, 3 and Jian-Ying Zhang 1, 2, 3 1 The First Affiliated Hospital & Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450052, China 2 Henan Key Laboratory for Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan 450052, China 3 Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968, USA * These authors contributed equally to this work Correspondence to: Jian-Ying Zhang, email: jzhang@utep.edu Li-Ping Dai, email: lpdai@zzu.edu.cn Keywords: hepatocellular carcinoma (HCC); autoantibody; MDM2; p53 Received: July 13, 2017 Accepted: October 30, 2017 Published: January 02, 2018 ABSTRACT Purpose : The human homologue of the mouse double minute 2 (MDM2) is a transcriptional target and negative regulator of p53. This study aims to investigate the immune response of MDM2 and p53 in hepatocellular carcinoma (HCC). Materials and Methods : The autoantibodies were examined by immunoassay in individual sera from 160 HCC patients and 89 normal controls, as well as 76 sequential serum samples from an independent group of 16 HCC patients. The receiver operating characteristic (ROC) analysis was conducted for autoantibody for the distinguishing of HCC from controls. Results : Anti-MDM2 and anti-p53 autoantibodies could distinguish HCC patients from normal individuals in derivation set with area under curve (AUC) of 0.752 and 0.844, as well as in validation set with AUC of 0.658 and 0.703, respectively. The frequencies of anti-MDM2 (30.3%) and anti-p53 (32.9%) autoantibodies were significantly higher in HCC patients than that in normal individuals (10.1%). When anti-MDM2 and anti-p53 autoantibodies combined together, the positive frequency in HCC patients increased to 44.7% which was still significantly higher than that in normal individuals (18.0%). By using longitudinal preclinical samples, 62.5% of patients were observed with anti-MDM2 or anti-p53 autoantibody positive one year prior to diagnosis of HCC. Serum level of autoantibodies against these two TAAs were positively associated with each other ( r = 0.500, P < 0.001). Conclusions : MDM2 and p53 are autoantigens that elicit autoimmune responses in HCC and can be the potential biomarkers for the early detection or predictor of HCC.

Rheumatoid arthritis (RA), characterized by chronic inflammation of synovial joints, is often associated with ongoing pain and increased pain sensitivity. Chronic pain that comes with RA turns independent, essentially becoming its own disease. It could partly explain that a significant number (50%) of RA patients fail to respond to current RA therapies that focus mainly on suppression of joint inflammation. The acute phase of pain seems to associate with joint inflammation in early RA. In established RA, the chronic phase of pain could be linked to inflammatory components of neuron-immune interactions and noninflammatory components. Accumulating evidence suggests that the initial inflammation and autoimmunity in RA (preclinical RA) begin outside of the joint and may originate at mucosal sites and alterations in the composition of microbiota located at mucosal sites could be essential for mucosal inflammation, triggering joint inflammation. Fibroblast-like synoviocytes in the inflamed joint respond to cytokines to release acidic components, lowering pH in synovial fluid. Extracellular proton binds to proton-sensing ion channels, and G-protein-coupled receptors in joint nociceptive fibers may contribute to sensory transduction and release of neurotransmitters, leading to pain and hyperalgesia. Activation of peripheral sensory neurons or nociceptors further modulates inflammation, resulting in neuroinflammation or neurogenic inflammation. Peripheral and central nerves work with non-neuronal cells (such as immune cells, glial cells) in concert to contribute to the chronic phase of RA-associated pain. This review will discuss actions of proton-sensing receptors on neurons or non-neuronal cells that modulate RA pathology and associated chronic pain, and it will be beneficial for the development of future therapeutic treatments.