Objective To elucidate the molecular mechanism by which exosomes (Exo) derived from cancer-associated fibroblasts (CAF) carrying HOX transcript antisense intergenic RNA (lncRNA HOTAIR) promote the metastasis of esophageal squamous cell carcinoma (ESCC). Methods CAFs were collected from tumor tissues, and non-cancer associated fibroblasts (NFs) were obtained from adjacent normal tissues at least 5 cm away from the tumor. Exosomes (CAFs-Exo and NFs-Exo) were isolated from conditioned media collected from CAFs or NFs. CAFs-Exo and NFs-Exo were incubated with human ESCC cell line TE-1 for 24 hours, and CCK-8 was used to determine the cell proliferation ability. Scratch test and Transwell test were performed to determine the cell migration and invasion ability. TE-1 cells were divided into the following two groups: NC group and KD group. The NC group and KD group were transfected with control siRNAs or siRNAs targeting HOTAIR respectively. The effects of HOTAIR knock-down on cell proliferation, migration, invasion and glycolysis were determined. Results CAFs-Exo promoted the proliferation of TE-1 cells more significantly than NFs-Exo. Compared with NFs-Exo group, the migration and invasion ability of TE-1 cells treated with CAFs-Exo were improved significantly. In addition, CAFs-Exo treatment inhibited the expression of E-cadherin and enhanced the expression of N-cadherin. The expression of HOTAIR in CAFs was significantly higher than that in NFs. Compared with NFs-Exo, the expression level of HOTAIR in CAFs-Exo increased significantly. Compared with NC group, the proliferation, migration and invasion of TE-1 cells in KD group decreased significantly. Compared with NC group, hexokinase 2 (HK2), extracellular acidification rate (ECAR) and ATP/ADP ratio of TE-1 cells in KD group decreased significantly. Conclusion HOTAIR, an exosome derived from CAFs, may be involved in metastasis and EMT by regulating glycolysis in ESCC cells.
Humans ; RNA, Long Noncoding/metabolism* ; Esophageal Neoplasms/metabolism* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Esophageal Squamous Cell Carcinoma ; Exosomes/genetics* ; Neoplasm Metastasis ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic ; Glycolysis/genetics* ; Cancer-Associated Fibroblasts/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Cadherins/genetics*

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Traumatic sepsis is a life-threatening organ dysfunction syndrome caused by an uncontrolled host response to infection after trauma. It is characterized by complex pathogenesis,and rapid deterioration of clinical condition,and is often accompanied by septic shock and multiple organ dysfunction. The incidence and mortality of traumatic sepsis are high,and its treatment presents more difficult. The occurrence of traumatic sepsis is not only related to the traumatic type and severity,but also influenced by various factors such as the type of pathogenic microorganisms,the timing of infection,and the intensity of the immune response. As the key character in the progression of severe traumatic infection,the excessive inflammatory response and immune imbalance are important causes to constitute risk factors and biomarkers of traumatic sepsis. Previous studies on the prevention and treatment of traumatic sepsis paid more attention to early infection control,effective anti-infection treatment,fluid resuscitation,immune modulation and supportive treatment,especially for antibiotics use. However,the role of inflammatory response was ignored in the prognosis of traumatic patients. The immune system activation after trauma not only plays a crucial role in preventing and controlling infections but also closely relates to the systemic inflammatory response. Excessive or uncontrolled inflammatory response may exacerbate the situation of patients with traumatic sepsis,trigger multiple organ dysfunction syndrome (MODS),and even result in death. Current studies imply that the combined treatment of bacteria,their toxins,and inflammatory mediators may be a key measure for preventing and treating traumatic sepsis. This strategy emphasizes not only anti-infection therapy against pathogenic microorganisms but also immune modulation to suppress excessive inflammatory response and restore immune balance. The pattern of "combined treatment of bacteria,their toxins,and inflammation" is expected to reduce the incidence and mortality of traumatic sepsis by inhibiting excessive inflammatory response and enhancing immune capacity. This review describes the progress of the combined treatment of bacteria,their toxins,and inflammatory mediators in preventing and treatment for traumatic sepsis,from the perspectives of epidemiology,risk factors,biomarkers,pathogenesis,concept development,and application. It provides a new idea to study and research the key technologies for the prevention and treatment of severe traumatic complications.

Traumatic sepsis is a life-threatening organ dysfunction syndrome caused by an uncontrolled host response to infection after trauma. It is characterized by complex pathogenesis,and rapid deterioration of clinical condition,and is often accompanied by septic shock and multiple organ dysfunction. The incidence and mortality of traumatic sepsis are high,and its treatment presents more difficult. The occurrence of traumatic sepsis is not only related to the traumatic type and severity,but also influenced by various factors such as the type of pathogenic microorganisms,the timing of infection,and the intensity of the immune response. As the key character in the progression of severe traumatic infection,the excessive inflammatory response and immune imbalance are important causes to constitute risk factors and biomarkers of traumatic sepsis. Previous studies on the prevention and treatment of traumatic sepsis paid more attention to early infection control,effective anti-infection treatment,fluid resuscitation,immune modulation and supportive treatment,especially for antibiotics use. However,the role of inflammatory response was ignored in the prognosis of traumatic patients. The immune system activation after trauma not only plays a crucial role in preventing and controlling infections but also closely relates to the systemic inflammatory response. Excessive or uncontrolled inflammatory response may exacerbate the situation of patients with traumatic sepsis,trigger multiple organ dysfunction syndrome (MODS),and even result in death. Current studies imply that the combined treatment of bacteria,their toxins,and inflammatory mediators may be a key measure for preventing and treating traumatic sepsis. This strategy emphasizes not only anti-infection therapy against pathogenic microorganisms but also immune modulation to suppress excessive inflammatory response and restore immune balance. The pattern of "combined treatment of bacteria,their toxins,and inflammation" is expected to reduce the incidence and mortality of traumatic sepsis by inhibiting excessive inflammatory response and enhancing immune capacity. This review describes the progress of the combined treatment of bacteria,their toxins,and inflammatory mediators in preventing and treatment for traumatic sepsis,from the perspectives of epidemiology,risk factors,biomarkers,pathogenesis,concept development,and application. It provides a new idea to study and research the key technologies for the prevention and treatment of severe traumatic complications.

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Humans ; Pyrazinamide/therapeutic use* ; Isoniazid/therapeutic use* ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/microbiology* ; Mycobacterium tuberculosis/genetics* ; Tuberculosis/drug therapy* ; Rifampin/therapeutic use* ; Mutation ; Drug Resistance, Multiple, Bacterial/genetics*

Oral and maxillofacial space infections (OMSI) are common diseases of the facial region involving fascial spaces. Recently, OMSI shows trends of multi drug-resistance, severe symptoms, and increased mortality. OMSI treatment principles need to be updated to improve the cure rate. Based on the clinical experiences of Chinese experts and with the incorporation of international counterparts′ expertise, the principles of preoperative checklist, interpretation of examination results, empirical medication principles, surgical treatment principles, postoperative drainage principles, prevention strategies of wisdom teeth pericoronitis-related OMSI, blood glucose management, physiotherapy principles, Ludwig′s angina treatment and perioperative care were systematically summarized and an expert consensus on the diagnosis and treatment of OMSI was reached. The consensus aims to provide criteria for the diagnosis and treatment of OMSI in China so as to improve the level of OMSI treatment.

Antiviral therapy is important for COVID-19. Currently, the anti-2019-nCoV drugs in clinical trials include broad-spectrum antiviral drugs (alpha interferon and ribavirin), hemagglutinin inhibitors (arbidol), human immunodeficiency virus protease inhibitors (lopinavir/ritonavir and darunavir/cobicistat), nucleoside analogues (favipiravir and remdesivir) and antimalarial drug (chloroquine); while liver damage may occur in some patients with the medication. This article reviews the research on liver damage associated with anti-2019-nCoV drugs, aiming at promoting the safe and effective antiviral therapy for COVID-19 patients.

The most important treatment of anti 2019 novel coronavirus is antiviral and supportive treatment. Currently, the anti novel coronavirus drugs in clinical trials include broad-spectrum antiviral drugs (Alpha interferon and Ribavirin), hemagglutinin inhibitors (Arbidol), human immunodeficiency virus protease inhibitors (Lopinavir/Ritonavir and Darunavir/Cobicistat), nucleoside analogues (Favipiravir and Remdesivir) and antimalarial drug (chloroquine), however, some patients suffered from liver damage during the actual usage. This article reviews the research on liver damage associated with anti novel coronavirus drugs, aiming at promoting the rational, safe and effective use of anti novel coronavirus drugs.

BACKGROUND:Three-dimensional (3D) printing technology has been successful y used in the field of joint replacement, fracture fixation and spinal implant, but the potential of 3D printing technology in the field of surgery for ossification of posterior longitudinal ligament of cervical spine remains to be discussed. OBJECTIVE:To determine the application value of a 3D printing model in the selection of anterior and posterior surgical decompression for cervical ossification of the posterior longitudinal ligament. METHODS:A retrospective analysis was carried out involving 15 patients with ossification of the posterior longitudinal ligament col ected by computed tomography (CT) and printed by a 3D model pre-operatively between October 2014 and October 2015 in Affiliated Hospital of Xuzhou Medical University. There were isolated type (n=2), segmental type (n=6), continuous type (n=4), and combined type (n=3). The application value of a 3D printer model in patients with ossification of the posterior longitudinal ligament was evaluated by Japanese Orthopedic Association scores, Visual Analog Scale scores, symptoms, and imaging data 1 month pre-operatively, 1 month post-operatively, and at the final fol ow-up. RESULTS AND CONCLUSION:(1) Al 15 patients underwent successful treatment of cervical spine decompression surgery and were fol owed up for 4-16 months. The post-operative symptoms were relieved more significantly than the pre-operative symptoms. Using the posterior approach for cervical spinal surgery, 1 patient had incision fat necrosis and healed after negative pressure drainage. (2) Japanese Orthopedic Association scores 1 month pre-operatively, 1 month post-operatively, and at the final fol ow-up were 9.0±1.6, 11.7±1.8, and 15.5±1.4, respectively;the differences were statistical y significant (P<0.05). Visual Analog Scale scores 1 month pre-operatively, 1 month post-operatively, and at the final fol ow-up were 6.7±2.5, 2.13±1.4, and 1.4±0.5, respectively;the difference was statistical y significant (P<0.05). (3) The imaging results at fol ow-up showed that the anterior interbodies were fused, and the pivot of the posterior operation was healed wel without a re-closing phenomenon. (4) A 3D printer model was shown to be beneficial in observing the characteristics of cervical ossification of the posterior longitudinal ligament, performing the pre-operative evaluation, and simulating the surgical procedure. There was value for the choice of operative approach.