The crosstalk between SUMOylation and immune system in host-pathogen interactions.

Pathogens can not only cause infectious diseases, immune system diseases, and chronic diseases, but also serve as potential triggers or initiators for certain tumors. They directly or indirectly damage human health and are one of the leading causes of global deaths. Small ubiquitin-like modifier (SUMO) modification, a type of protein post-translational modification (PTM) that occurs when SUMO groups bond covalently to particular lysine residues on substrate proteins, plays a crucial role in both innate and adaptive immunologic responses, as well as pathogen-host immune system crosstalk. SUMOylation participates in the host's defense against pathogens by regulating immune responses, while numerically vast and taxonomically diverse pathogens have evolved to exploit the cellular SUMO modification system to break through innate defenses. Here, we describe the characteristics and multiple functions of SUMOylation as a pivotal PTM mechanism, the tactics employed by various pathogens to counteract the immune system through targeting host SUMOylation, and the character of the SUMOylation system in the fight between pathogens and the host immune system. We have also included a summary of the potential anti-pathogen SUMO enzyme inhibitors. This review serves as a reference for basic research and clinical practice in the diagnosis, prognosis, and treatment of pathogenic microorganism-caused disorders.

Application of single-arm objective performance criteria/performance goal in acupuncture-moxibustion clinical trials / 中国针灸

Due to various constraints, such as clinical implementation conditions and unique characteristics of acupuncture-moxibustion, some randomized controlled trials (RCTs) of acupuncture-moxibustion still suffer from relatively low quality and limited applicability. The single-arm objective performance criteria/performance goal can be considered as an ideal supplementary and alternative research approach to RCTs. In this paper, the feasibility of applying the single-arm objective performance criteria/performance goal in acupuncture-moxibustion clinical research is explored from the limitations of conducting acupuncture-moxibustion RCTs, the principles, the essential design considerations and key statistical steps. In addition, illustrative examples are provided. The objective is to offer insights into resolving practical difficulties in acupuncture-moxibustion clinical research.

Tubeimoside-I sensitizes temozolomide-resistant glioblastoma cells to chemotherapy by reducing MGMT expression and suppressing EGFR induced PI3K/Akt/mTOR/NF-κB-mediated signaling pathway.

BACKGROUND: Glioblastoma multiforme (GBM, World Health Organization [WHO] grade IV) is one of the malignant Central Nerve System (CNS) tumors with high incidence rate and poor prognosis. The use of alkylating agents, such as temozolomide (TMZ), has been the main method of cytotoxic therapy for glioma patients for decades. However, TMZ resistance may be one of the major reasons for treatment failure, so far. In searching for effective agents to reverse TMZ resistance, we found that Tubeimoside-I (TBMS1), a saponin from traditional Chinese medicine, Bolbostemma paniculatum (Maxim.) Franquet, showed activities of reversing TMZ resistance of GBM. However, the ability of TBMS1 enhancing the chemosensitivity of GBM has been rarely studied, and its underlying mechanisms remain unclear. PURPOSE: This study purposes to reveal the synergistic effects and mechanism of TBMS1 and TMZ against TMZ-resistant GBM cells. METHODS: CCK8 assay was used to investigate the anti-proliferative effects on grade IV glioblastoma human T98G and U118 MG cells. Cell proliferation was determined by EdU assay and clonogenic assay after TMZ plus TBMS1 treatment. Apoptosis was analyzed by flow cytometry. DNA damage and DNA Double Strand Break (DSB) were assessed by cleaved Poly (ADP-ribose) polymerase (PARP), γH2AX Foci Assay and Comet Assay, respectively. Expression of proteins associated with apoptosis and DNA repair enzymes were measured by Western blot analysis. The prognostic significance of key proteins of the epidermal growth factor receptor (EGFR) induced PI3K/Akt/mTOR/NF-κB signaling pathway was analyzed using GEPIA (http://gepia.cancer-pku.cn) and validated by Western blotting. RESULTS: Here we demonstrated that TBMS1 sensitized TMZ-resistant T98G and U118 MG glioblastoma cells to chemotherapy and exhibited promotion of apoptosis and inhibition on cell viability, proliferation and clone formation. Coefficient of drug in interaction (CDI) values showed a notable synergistic effect between TBMS1 and TMZ. Moreover, we observed that combination of TBMS1 and TMZ induced apoptosis was accompanied by robust DSB, γH2AX Foci formation and increasing cleaved PARP, as well as the heightened ratio of Bax/Bcl-2, cleavages of caspase-3 and caspase-9. In addition, the synergistic anti-glioma effect between TBMS1 and TMZ was intimately related to the reduction of MGMT expression in TMZ-resistant GBM cells. Moreover, it was also associated with attenuated expression of EGFR, p-PI3K-p85, p-Akt (Ser473), p-mTOR (Ser2481) and p-NF-κB p65(Ser536), which implying deactivation of the EGFR induced PI3K/Akt/mTOR/NF-κB signaling pathway. CONCLUSION: We first demonstrated that synergistic effects of TBMS1 and TMZ induced apoptosis in GBM cells through reducing MGMT expression and inhibiting the EGFR induced PI3K/Akt/mTOR/NF-κB signaling pathway. This study provides a rationale for combined application of TMZ and TBMS1 as a potential chemotherapeutic treatment for MGMT+ GBM patients.

MiR-494-3p Upregulation Exacerbates Cerebral Ischemia Injury by Targeting Bhlhe40

Purpose@#Cerebral ischemia is related to insufficient blood supply and is characterized by abnormal reactive oxygen species (ROS) production and cell apoptosis. Previous studies have revealed a key role for basic helix-loop-helix family member e40 (Bhlhe40) in oxidative stress and cell apoptosis. This study aimed to investigate the roles of miR-494-3p in cerebral ischemia/reperfusion (I/R) injury. @*Materials and Methods@#A mouse middle cerebral artery occlusion (MCAO/R) model was established to mimic cerebral ischemia in vivo. Brain infarct area was assessed using triphenyl tetrazolium chloride staining. Oxygen-glucose deprivation/reoxygenation (OGD/R) operation was adopted to mimic neuronal injury in vitro. Cell apoptosis was analyzed by flow cytometry. The relationship between miR-494-3p and Bhlhe40 was validated by luciferase reporter and RNA immunoprecipitation assays. @*Results@#Bhlhe40 expression was downregulated both in MCAO/R animal models and OGD/R-induced SH-SY5Y cells. Bhlhe40 overexpression inhibited cell apoptosis and reduced ROS production in SH-SY5Y cells after OGD/R treatment. MiR-494-3p was verified to bind to Bhlhe40 and negatively regulate Bhlhe40 expression. Additionally, cell apoptosis and ROS production in OGD/ R-treated SH-SY5Y cells were accelerated by miR-494-3p overexpression. Rescue experiments suggested that Bhlhe40 could reverse the effects of miR-494-3p overexpression on ROS production and cell apoptosis. @*Conclusion@#MiR-494-3p exacerbates brain injury and neuronal injury by regulating Bhlhe40 after I/R.

Tumor Associated Macrophages, as the Dominant Immune Cells, Are an Indispensable Target for Immunologically Cold Tumor-Glioma Therapy?

Tumor microenvironment (TME) is the cornerstone of the occurrence, development, invasion and diffusion of the malignant central nerve system (CNS) tumor, glioma. As the largest number of inflammatory cells in glioma TME, tumor associated macrophages (TAMs) and their secreted factors are indispensable to the progression of glioma, which is a well-known immunologically "cold" tumor, including the growth of tumor cells, invasion, migration, angiogenesis, cancer immunosuppression and metabolism. TAMs intimately interface with the treatment failure and poor prognosis of glioma patients, and their density increases with increasing glioma grade. Recently, great progress has been made in TAM-targeting for anti-tumor therapy. According to TAMs' function in tumorigenesis and progression, the major anti-tumor treatment strategies targeting TAMs are to hinder macrophage recruitment in TME, reduce TAMs viability or remodel TAMs phenotype from M2 to M1. Different approaches offer unique and effective anti-tumor effect by regulating the phagocytosis, polarization and pro-tumor behaviors of macrophages in the therapy of glioma. The present review summarizes the significant characteristics and related mechanisms of TAMs and addresses the related research progress on targeting TAMs in glioma.

Diagnostic value of dynamic-extended focused assessment with sonography for trauma in patients with multiple trauma / 中华危重病急救医学

Objective To investigate the diagnostic value of dynamic-extended focused assessment with sonography for trauma (D-EFAST) in patients with multiple trauma in intensive care unit (ICU). Methods A prospective clinical study was conducted. Eighty patients with multiple trauma admitted to ICU of Anhui Provincial Hospital from September 1st, 2014 to December 31st, 2016 were enrolled. Extended focused assessment with sonography for trauma (E-FAST) check was conducted at first, for those who had positive findings diagnosis was confirmed by immediately CT examination or surgical exploration. If it was negative, the patients received E-FAST every morning for 7 days (defined as D-EFAST), for those with positive findings, immediately CT or surgery was performed to clarify the diagnosis. The final clinical diagnosis was used as the "gold standard" to calculate the diagnostic accordance rate of EFAST and D-EFAST examination technique for pneumothorax, pleural effusion, spleen injury, kidney damage, liver damage, gastrointestinal injury, pericardial effusion, bladder rupture, and pancreatic injury, as well as their sensitivity, specificity, positive predictive value, negative predictive value, accuracy rate, and missed diagnosis rate, and the difference between EFAST and D-EFAST was compared. Results There were 4 patients excluded because of death and abandoning treatment, and finally 76 patients were included in the study. The total sensitivity of E-FAST examination technique for pneumothorax, pleural effusion, spleen injury, liver damage, gastrointestinal injury, pericardial effusion, and bladder rupture was 75.9% (66/87), and the specificity was 98.3% (587/597), the positive predictive value was 86.8% (66/76), and the negative predictive value was 96.5% (587/608), the accuracy rate was 95.5% (653/684), and the rate of missed diagnosis was 24.1% (21/87). The most of the delayed injury in patients with multiple trauma occurred at 2-7 days after injury with incidence of 4.8% (33/684). The diagnostic sensitivity of D-EFAST for delayed injury was 98.3% (118/120), the specificity was 99.8% (563/564), the positive predictive value was 99.2% (118/119), the negative predictive value was 99.6% (563/565), the diagnostic accuracy rate was 99.6% (681/684), and rate of missed diagnosis was 1.7% (2/120). When the final clinical diagnosis was set as the "gold standard", D-EFAST technology for the detection rate was 98.3% (118/120) for patients with multiple trauma on organ injury while the detection rate of E-FAST was 75.9% (66/87), with statistical significant difference (P < 0.01), indicating that D-EFAST was better than E-FAST in check of multiple trauma patients with organ injury. Conclusion Although the E-FAST technology can quickly diagnose the multiple trauma patients and win the rescue time for critical patients, multiple trauma patients injured after 2-7 days prone to delayed damage and are difficult to detect, and D-EFAST can be used to find delayed damage earlier, and reduce the misdiagnosis rate of multiple trauma patients.

Clinicopathological analysis of Paget's disease of the scrotum and penis / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the clinical pathological characteristics, diagnosis and differential diagnosis of Paget's disease of the scrotum and penis.</p><p><b>METHODS</b>Thirteen cases of Paget's disease of the scrotum and penis were analyzed by light microscopy, alcian-blue (AB)/periodic-acid-Schiff (PAS) and immunohistochemical staining.</p><p><b>RESULTS</b>Paget's disease of the scrotum and penis mainly affected old individuals aged 55-84 (mean 71) years. Macroscopically, typical presentations of Paget's disease of the scrotum and penis were eczematoid lesions. Microscopically, Paget cells were distributed singly or in groups (as strands, nests or glandular patterns) within the epidermis. Paget cells were typically stained for AB/PAS, positive for CK7, CEA and EMA, and negative for CK5/6, S-100 and P63. The positive rates of GCDFP-15 and CK20 expressions were 76.92% (10/13)and 53.85% (7/13) respectively.</p><p><b>CONCLUSION</b>Paget's disease of the scrotum and penis is a low-malignancy cutaneous tumor with typical clinical and pathological features. Pathologic diagnosis is based on immunohistochemical findings.</p>

Treatment of the patients with the diseases stomatology,otorhinolaryngology and ophthalmology in peacekeeping level Ⅱ hospital / 医学研究生学报

Objective:To evaluate the clinical experience and working method of the department of stomatology,otorhinolarynogology and ophthalmology during the peacekeeping period in Liberia.Methods:Five hundred twenty five patients with stomatological,otorhinolaryngological or ophthalmological diseases during the peacekeeping period were reviewed.Results:The patients with stomatogical disease(455),NEN disease(38) and eye disease(32) were treated by a stomatological without mistake during 7 months. Conclusion:Stomatological doctors should be versatile to accomplish their peacekeeping mission.

The Effects of Asiaticoside on the Growth of Melanoma B16 Cells / 中华皮肤科杂志

Objective To study the effects of asiaticoside on the growth of melanoma B16 cell cultures in vitro. Methods Melanoma B16 cells were subcultured and the inhibition of cellular growth was investigated. The morphology of the cells was observed after inhibition. The induction of apoptosis by asiaticoside was determined by flow cytometry. Results It was found that asiaticoside could significantly inhibit the growth of B16 cell cultures in vitro in a dose-dependent manner. The annexin-v positive cells were increased, along with that cells intaking R123 marked mitochondria were decreased, and PI positive cells increased, which indicated that cellular apoptosis was induced. Conclusion Asiaticoside plays an inhibitory role in the growth of melanoma B16 cells.