Objective:To compare the head magnetic resonance imaging (MRI) changes and the distribution of pathogens of purulent meningitis in premature and full term infants.Methods:This retrospective study assessed clinical data in 43 cases of neonatal purulent meningitis with positive blood or cerebrospinal fluid bacterial culture admitted to the Neonatal Ward of Shengjing Hospital of China Medical University from January 2012 to November 2019.According to the gestational age, those patients were divided into the premature infant group and the full term infant group.The general situation, head MRI and pathogen characteristics of both groups were compared.Results:The incidence of premature rupture of fetal membranes in the premature infant group was higher than that in the full term infant group [50.00%(13/26 cases) vs.5.88%(1/17 cases)], the rate of cesarean section in the premature infant group was higher than that in the term infant group [61.54%(16/26 cases) vs.23.53%(4/17 cases)], and there were significant difference between the 2 groups ( χ2=9.011 and 5.969, respectively, all P<0.05). There was no significant difference between 2 groups in age of onset [(9.8±7.0) d vs.(8.9±5.5) d], diagnosis[(13.0±7.1) d vs.(10.2±6.1) d] and examination [(16.1±7.9) d vs.(13.1±6.5) d] (all P>0.05). The top 3 pathogens were Klebsiella pneumonia ( K. pneumoniae) in 14 cases, Escherichia coli ( E. coli) in 11 cases and Streptococcus agalactiae (GBS) in 7 cases. K. pneumoniae was the most common pathogen in premature infants, and GBS was the most common pathogen in term infants.In the first MRI, white matter injury (WMI) was the most common disease (19 cases), the abnormal rate of MRI in the premature infant group was 65.38% (17/26 cases), the incidence of intracranial hemorrhage in the premature infant group was higher than that in the term infant group, the abnormal rate of MRI in the term infant group was 52.94% (9/17 cases), and the incidence of cerebral infarction in the term infant group was higher than that in the premature infant group.The MRI positive rates of meningitis caused by K. pneumoniae, E. coli and GBS were 57.14% (8/14 cases), 72.73% (8/11 cases) and 71.43% (5/7 cases), respectively.Infants with K. pneumoniae infections suffered from the main complications of WMI and intracranial hemorrhage.Infants infected with E. coli were prone to WMI in the early stage and hydrocephalus in the late stage.Infants with GBS were prone to WMI and cerebral infarction in the early stage and cerebromalacia in the late stage. Conclusions:There were some differences in the distribution of pathogenic bacteria and head MRI changes between premature infants and term infants, and head MRI of purulent meningitis caused by different pathogenic bacteria.A thorough understanding of the distribution of pathogens and the characteristics of head MRI in premature and full term infants contributed to the early diagnosis, treatment and prognosis of this disease.

Background::Mild traumatic brain injury (mTBI) is a common neurological trauma that can lead to cognitive impairment. The sirtuin-1 (SIRT-1)/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) pathway has been reported to have neuroprotective effects in rats with craniocerebral injury. We evaluated potential mechanisms underlying electroacupuncture-mediated recovery of cognitive function after mTBI, focusing on the SIRT-1/PGC-1α/mitochondrial pathway.Methods::We included forty 6-week-old male Sprague-Dawley rats in this study. Rats were randomly divided into four groups: controlled cortical impactor (CCI, n = 10), sham operation (sham, n = 10), electroacupuncture-treated CCI (CCI+EA, n = 10), and electroacupuncture-treated sham (sham+EA, n = 10) group. Randomization was performed by assigning a random number to each rat and using a random number table. The mTBI rat model was established using a controllable cortical impactor. Electroacupuncture therapy was performed on the back of rats, by inserting acupuncture needles to the specific acupoints and setting appropriate parameters for treatment. We evaluated spatial learning and memory functions with the Morris water maze test. We performed quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, adenosine triphosphate (ATP) determination, and mitochondrial respiratory chain complex I (MRCC I) determination on rat hippocampal tissue. We analyzed SIRT-1/PGC-1α expression levels and the results of mitochondrial function assays, and compared differences between groups using bilateral Student’s t-tests. Results::Compared with the sham group, SIRT-1/PGC-1α expression was downregulated in the hippocampus of CCI group ( P <0.01). Although this expression was upregulated following electroacupuncture, it did not reach the levels observed in the sham group ( P <0.05). Compared with the sham group, MRCC I and ATP levels in the CCI group were significantly reduced, and increased after electroacupuncture ( P <0.01). In the Morris water maze, electroacupuncture reduced the incubation period of rats and increased average speed and number of crossing platforms ( P <0.05). Conclusion::Electroacupuncture may improve cognitive function in the mTBI rat model by regulating the SIRT-1/PGC-1α/mitochondrial pathway.

Malignant tumor has become an urgent threat to global public healthcare. Because of the heterogeneity of tumor, single therapy presents great limitations while synergistic therapy is arousing much attention, which shows desperate need of intelligent carrier for co-delivery. A core‒shell dual metal-organic frameworks (MOFs) system was delicately designed in this study, which not only possessed the unique properties of both materials, but also provided two individual specific functional zones for co-drug delivery. Photosensitizer indocyanine green (ICG) and chemotherapeutic agent doxorubicin (DOX) were stepwisely encapsulated into the nanopores of MIL-88 core and ZIF-8 shell to construct a synergistic photothermal/photodynamic/chemotherapy nanoplatform. Except for efficient drug delivery, the MIL-88 could be functioned as a nanomotor to convert the excessive hydrogen peroxide at tumor microenvironment into adequate oxygen for photodynamic therapy. The DOX release from MIL-88-ICG@ZIF-8-DOX nanoparticles was triggered at tumor acidic microenvironment and further accelerated by near-infrared (NIR) light irradiation. The

Pulmonary drug delivery has attracted increasing attention in biomedicine, and porous particles can effectively enhance the aerosolization performance and bioavailability of drugs. However, the existing methods for preparing porous particles using porogens have several drawbacks, such as the inhomogeneous and uncontrollable pores, drug leakage, and high risk of fragmentation. In this study, a series of cyclodextrin-based metal-organic framework (CD-MOF) particles containing homogenous nanopores were delicately engineered without porogens. Compared with commercial inhalation carrier, CD-MOF showed excellent aerosolization performance because of the homogenous nanoporous structure. The great biocompatibility of CD-MOF in pulmonary delivery was also confirmed by a series of experiments, including cytotoxicity assay, hemolysis ratio test, lung function evaluation,

Nicotinamide phosphoribosyl transferase (NAMPT) is considered as a promising target for cancer therapy given its critical engagement in cancer metabolism and inflammation. However, therapeutic benefit of NAMPT enzymatic inhibitors appears very limited, likely due to the failure to intervene non-enzymatic functions of NAMPT. Herein, we show that NAMPT dampens antitumor immunity by promoting the expansion of tumor infiltrating myeloid derived suppressive cells (MDSCs) via a mechanism independent of its enzymatic activity. Using proteolysis-targeting chimera (PROTAC) technology, PROTAC A7 is identified as a potent and selective degrader of NAMPT, which degrades intracellular NAMPT (iNAMPT) via the ubiquitin-proteasome system, and in turn decreases the secretion of extracellular NAMPT (eNAMPT), the major player of the non-enzymatic activity of NAMPT. In vivo, PROTAC A7 efficiently degrades NAMPT, inhibits tumor infiltrating MDSCs, and boosts antitumor efficacy. Of note, the anticancer activity of PROTAC A7 is superior to NAMPT enzymatic inhibitors that fail to achieve the same impact on MDSCs. Together, our findings uncover the new role of enzymatically-independent function of NAMPT in remodeling the immunosuppressive tumor microenvironment, and reports the first NAMPT PROTAC A7 that is able to block the pro-tumor function of both iNAMPT and eNAMPT, pointing out a new direction for the development of NAMPT-targeted therapies.