Ziquan Liu

Photodynamic antimicrobial chemotherapy with the novel amino acid-porphyrin conjugate 4I: In vitro and in vivo studies

Photodynamic antimicrobial chemotherapy (PACT), as a novel and effective therapeutic modality to eradicate drug resistant bacteria without provoking multidrug resistance, has attracted increasing attention. This study examined the antimicrobial efficacy of the novel cationic amino acid-porphyrin conjugate 4I with four lysine groups against two different clinical isolated strains (drug sensitive and multidrug resistant) of the Acinetobacter baumannii species and its toxicity on murine dermal fibroblasts in vitro, as well as the therapeutic effect of PACT on acute, potentially lethal multidrug resistant strain excisional wound infections in vivo. The PACT protocol exposed 4I to illumination, exhibiting high antimicrobial efficacy on two different strains due to a high yield of reactive oxygen species (ROS) and non-selectivity to microorganisms. The photoinactivation effects of 4I against two different strains were dose-dependent. At 3.9 μM and 7.8 μM, PACT induced 6 log units of inactivation of sensitive and multidrug resistant strains. In contrast, 4I alone and illumination alone treatments had no visibly antimicrobial effect. Moreover, cytotoxicity tests revealed the great safety of the photosensitizer 4I in mice. In the in vivo study, we found 4I-mediated PACT was not only able to kill bacteria but also accelerated wound recovery. Compared with non-treated mice, over 2.89 log reduction of multidrug resistant Acinetobacter baumannii strain was reached in PACT treat mice at 24 h post-treatment. These results imply that 4I-mediated PACT therapy is an effective and safe alternative to conventional antibiotic therapy and has clinical potential for superficial drug-resistant bacterial infections.

In Vivo Tracking of Systemically Administered Allogeneic Bone Marrow Mesenchymal Stem Cells in Normal Rats through Bioluminescence Imaging

Recently, mesenchymal stem cells (MSCs) are increasingly used as a panacea for multiple types of disease short of effective treatment. Dozens of clinical trials published demonstrated strikingly positive therapeutic effects of MSCs. However, as a specific agent, little research has focused on the dynamic distribution of MSCs after in vivo administration. In this study, we track systemically transplanted allogeneic bone marrow mesenchymal stem cells (BMSCs) in normal rats through bioluminescence imaging (BLI) in real time. Ex vivo organ imaging, immunohistochemistry (IHC), and RT-PCR were conducted to verify the histological distribution of BMSCs. Our results showed that BMSCs home to the dorsal skin apart from the lungs and kidneys after tail vein injection and could not be detected 14 days later. Allogeneic BMSCs mainly appeared not at the parenchymatous organs but at the subepidermal connective tissue and adipose tissue in healthy rats. There were no significant MSCs-related adverse effects except for transient decrease in neutrophils. These findings will provide experimental evidences for a better understanding of the biocharacteristics of BMSCs.

Dynamic Changes in Clinical Characteristics During an Outbreak of Human Adenovirus Serotype 55 in China.

OBJECTIVE To determine dynamic changes in clinical characteristics by examining an outbreak of adenovirus infection that occurred from December 20, 2012, to February 25, 2013, in Tianjin, China. METHODS Active surveillance for febrile respiratory illnesses was conducted, and medical records of patients were collected. Real-time quantitative polymerase chain reaction and sequencing were used for pathogen identification and viral genome study, respectively. Students t-test was used to compare the mean values of normally distributed continuous variables. Mann-Whitney U or Kruskal-Wallis tests were used if continuous variables were not normally distributed. Pearsons chi-square test or Fishers exact test was used to compare categorical variables. RESULTS The outbreak was sourced from the index case diagnosed as the common cold on December 20, 2012; a total of 856 cases were reported in the following 66 days. The pathogen was identified as human adenovirus (HAdV) 55. The symptoms manifested differently in severe and mild cases. Routine blood examinations, liver function indexes, and heart function indexes showed different dynamic patterns over time in hospitalized patients. CONCLUSIONS Clinical characteristics and laboratory examinations may reveal unique patterns over the course of HAdV-55 infection. (Disaster Med Public Health Preparedness. 2018;12:464-469).

Dynamic Tracking Human Mesenchymal Stem Cells Tropism following Smoke Inhalation Injury in NOD/SCID Mice

Multiple preclinical evidences have supported the potential value of mesenchymal stem cells (MSCs) for treatment of acute lung injury (ALI). However, few studies focus on the dynamic tropism of MSCs in animals with acute lung injury. In this study, we track systemically transplanted human bone marrow-derived mesenchymal stem cells (hBMSCs) in NOD/SCID mice with smoke inhalation injury (SII) through bioluminescence imaging (BLI). The results showed that hBMSCs systemically delivered into healthy NOD/SCID mouse initially reside in the lungs and then partially translocate to the abdomen after 24 h. Compared with the uninjured control group treated with hBMSCs, higher numbers of hBMSCs were found in the lungs of the SII NOD/SCID mice. In both the uninjured and SII mice, the BLI signals in the lungs steadily decreased over time and disappeared by 5 days after treatment. hBMSCs significantly attenuated lung injury, elevated the levels of KGF, decreased the levels of TNF-α in BALF, and inhibited inflammatory cell infiltration in the mice with SII. In conclusion, our findings demonstrated that more systemically infused hBMSCs localized to the lungs in mice with SII. hBMSC xenografts repaired smoke inhalation-induced lung injury in mice. This repair was maybe due to the effect of anti-inflammatory and secreting KGF of hMSCs but not associated with the differentiation of the hBMSCs into alveolar epithelial cells.

Analysis of the Three-Tiered Treatment Model for Emergency Medical Rescue Services After the Lushan Earthquake.

OBJECTIVE To explore the 3-tiered treatment model for medical treatment after an earthquake. METHODS Based on the practices of the national emergency medical rescue services in the Lushan earthquake zone, the 3-tiered treatment classification approach was retrospectively reviewed. RESULTS Medical rescue teams assembled and reported quickly to the disaster areas after the earthquake. The number of injured people had reached 25,176 as of April 30; of these, 18,611 people were treated as outpatients, 6565 were hospitalized, and 977 were seriously or severely injured. CONCLUSIONS The 3-tiered treatment model was the main approach used by rescue services after the Lushan earthquake. Primary and secondary treatments were of the highest importance and formed the basis of the Lushan model of earthquake rescue and treatment. (Disaster Med Public Health Preparedness. 2018; 12: 301-304).

Disaster Medicine in China: Present and Future.

Disaster can strike people in any community at any time anywhere in the world. Disasters occur with high frequency, take on multiple forms, and exert wide influence, typically causing property damage, injuries, and death. As the worlds largest developing country, China incurs great costs when a disaster hits. After the Wenchuan earthquake in 2008, the Chinese government focused its attention on the construction of an emergency response system, the creation of disaster prevention and mitigation systems, and the development of a disaster medicine program. Here, we describe the current status of disaster medicine in China, focusing on the following four aspects: the Emergency Management System, Education & Training, Rescue Practices, and Research. We also discuss the future of disaster medicine in China. (Disaster Med Public Health Preparedness. 2018;12:157-165).

Intratracheal Instillation of Perfluorohexane Modulates the Pulmonary Immune Microenvironment by Attenuating Early Inflammatory Factors in Patients With Smoke Inhalation Injury: A Randomized Controlled Clinical Trial.

Smoke inhalation injury (SII) is associated with significant morbidity and mortality in burn patients, and effective treatments are lacking. Perfluorocarbons (PFCs) have a protective effect against acute lung injury. We aimed to assess the therapeutic effects of perfluorohexane on burn patients with SII. Patients with burns complicated by moderately severe SII were randomly divided into control (n = 11) and PFC groups (n = 12). The control group received conventional treatment (anti-infection, nutritional support, antishock measures, and supportive treatment). The PFC group received endotracheal perfluorohexane instillation in addition to conventional treatment. On admission and 3 days later, therapeutic effects were evaluated and inflammatory mediators in bronchoalveolar lavage fluid and plasma were analyzed. There was no significant difference between the control and PFC group on admission. After 3 days, perfluorohexane treatment significantly (P < .05) increased lung dynamic compliance, and reduced alveolar-arterial oxygen gradient, Acute Physiology and Chronic Health Evaluation II score, percentage of neutrophils, and levels of interleukin-6, interleukin-8, and tumor necrosis factor alpha in bronchoalveolar lavage fluid; there was no significant change in the control group before and after treatment. Intratracheal instillation of perfluorohexane modulates the pulmonary immune microenvironment and supplements current conventional treatments for burn patients with SII.

Analyses of the Disease Spectrum of Children After the Lushan Earthquake.

&NA; An earthquake with a magnitude of 7.0 struck Lushan in Sichuan Province in China on April 20, 2013. Uniformed pediatricians visited the area where the epicenter was located to provide emergency relief care for children 10 days after the earthquake. Objectives The aims of the study were to analyze the features of the disease spectrum of children in Baoxing at early time after Lushan earthquake and to provide basis information, which will be useful for the arrangement of the medical resources of pediatrics in the medical relief after Lushan earthquake in similar situation in the future. Methods A total of 220 case files were classified and analyzed. These files provided information regarding pediatric patients whose conditions were diagnosed and treated in the mobile hospital established by the Affiliated Hospital of Logistical University of Chinese Peoples Armed Police Forces in Baoxing from April 20, 2013 to April 30, 2013. The demographic data of all these patients were collected and the disease spectrum was analyzed. Results Childrens ages differed. A total of 59 patients were neonates, infants, and toddlers (27%); 111 were school-aged children (50%) and 50 were adolescents (23%). Common diseases and injuries include respiratory tract infection, dermatosis, and trauma, which were observed 10 days after the earthquake. Trauma was mainly accidental injury. The morbidity rate of infectious diseases was low. Conclusions Pediatricians have an important role in the early treatment and subsequent control of infectious diseases during earthquakes.

Role of CD46 Polymorphisms in the Occurrence of Disease in Young Chinese Men With Human Adenovirus Type 55 Infection.

OBJECTIVE Human adenovirus type 55 (HAdV-55) has recently caused multiple outbreaks. This study examined polymorphisms in CD46 to determine their involvement in HAdV-55 infection. METHODS A total of 214 study subjects infected with HAdV-55 were included in our study. The study subjects were divided into those with silent infections (n=91), minor infections (n=85), and severe infections (n=38). Ten single nucleotide polymorphisms (SNPs) from CD46 were examined. RESULTS Compared with the AA genotype, the TT genotype at rs2724385 (CD46, A/T) was associated with a protective effect against disease occurrence, with an odds ratio (95% confidence interval) of 0.20 (0.04-0.97) (P=0.038). There were no significant differences between the patients with minor and severe infection and those who had silent HAdV-55 infection in the other CD46 SNPs. We next compared the polymorphisms of these genes according to disease severity in HAdV-55-infected patients with clinical symptoms. The results showed that there were no significant differences between minor infections and severe infections. CONCLUSIONS Our results suggested that the CD46 SNP at rs2724385 is associated with the occurrence of disease in HAdV-55-infected patients. A much larger number of samples is required to understand the role of CD46 polymorphisms in the occurrence and progression of infection by HAdV-55. (Disaster Med Public Health Preparedness. 2018;12:427-430).

Expression profile of microRNAs in bronchoalveolar lavage fluid of rats as predictors for smoke inhalation injury

Smoke inhalation injury (SII) is an independent risk factor for morbidity and mortality in patients with severe burns, however, the underlying mechanisms of SII are still not fully understood. In our study, we established an advanced rat model of SII based on the previous work, and explored the dynamic changes of pathophysiology and inflammatory factors during 28days post SII. We also measured the different expressions of miRNAs in bronchoalveolar lavage fluid (BALF) between SII and normal control rats by miRNA microarray. At 1day after smoke inhalation, the histopathological results exhibited inflammatory exudates in the lung tissue with significant edema. As time went on, the lung injuries gradually appeared at alveolar septum thickening and alveolar collapse, which suggested that it further induced damage to lung parenchyma by smoke inhalation. Particularly, the collagen deposition indicating pulmonary fibrosis happened at 28days post-injury. Plasma IL-6 and TNF-a were significantly increased after 1day of smoke inhalation. Plasma IL-10, BALF TNF-α and IL-10 were significantly increased after 2days of smoke inhalation. By extending the observation time, the levels of plasma IL-6, BALF TNF-a and IL-10 appeared a second peak again after 14days of injury. Compared with the normal control group, there were 23 upregulated miRNAs and 2 downregulated miRNAs in BALF of SII group at 1day post-injury. RT-qPCR validation assay confirmed that the changes of miR-34c-5p, miR-92b-3p, miR-205, miR-34b-3p, miR-92a-3p, let-7b-5p, let-7c-5p in BALF were consistent with the conclusion of the miRNA microarray. In summary, we showed the dynamic changes of pathologic changes and inflammatory factors in rats with SII, and a subset of seven miRNAs changed in BALF after SII which may be used for diagnosis and potential therapeutic targets.