Ki20227 aggravates apoptosis, inflammatory response, and oxidative stress after focal cerebral ischemia injury.

The survival of microglia depends on the colony-stimulating factor-1 receptor (CSF1R) signaling pathway under physiological conditions. Ki20227 is a highly selective CSF1R inhibitor that has been shown to change the morphology of microglia. However, the effects of Ki20227 on the progression of ischemic stroke are unclear. In this study, male C57BL/6 mouse models of focal cerebral ischemic injury were established through the occlusion of the middle cerebral artery and then administered 3 mg/g Ki20227 for 3 successive days. The results revealed that the number of ionized calcium-binding adaptor molecule 1/bromodeoxyuridine double positive cells in the infarct tissue was reduced, the degree of edema was increased, neurological deficits were aggravated, infarct volume was increased, and the number of peri-infarct Nissl bodies was reduced. The number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells in the peri-infarct tissue was increased. The expression levels of Bax and Cleaved caspase-3 were up-regulated. Bcl-2 expression was downregulated. The expression levels of inflammatory factors and oxidative stress-associated factors were increased. These findings suggested that Ki20227 blocked microglial proliferation and aggravated the pathological progression of ischemia/reperfusion injury in a transient middle cerebral artery occlusion model. This study was approved by the Animal Ethics Committee of Lanzhou University Second Hospital (approval No. D2020-68) on March 6, 2020.

Bilateral Dysplastic Gangliocytoma with Concurrent Polyostotic Fibrous Dysplasia: A Case Report and Literature Review.

BACKGROUND: Dysplastic gangliocytoma is a sporadic cerebellar benign tumor with the characteristics of hamartoma and true tumor, also known as Lhermitte-Duclos disease (LDD). Bone fibrous dysplasia (FD) is a slowly progressive self-limited benign bone tissue disease. Cowden syndrome, an autosomal dominant genetic disorder caused by germline mutations in the PTEN gene, is considered to be closely related to dysplastic gangliocytoma. McCune-Albright syndrome is a disease characterized by café-au-lait skin macules, polyostotic FD, and precocious puberty. The etiologic mechanism of both conditions is not yet clear. We report a rare case of bilateral dysplastic gangliocytoma with concurrent polyostotic FD. CASE DESCRIPTION: We describe a 16-year-old boy with both LDD and FD. He presented for medical examination with headache and poor eyesight. Magnetic resonance imaging revealed proliferation of the skull and abnormal signals in the cerebellum, and supratentorial hydrocephalus. Subtotal resection of the cerebellar tumor was performed, and the diagnosis of LDD and FD was confirmed by histopathology. No other abnormal changes were found in systemic medical examination and no PTEN gene mutation was found in the genetic analysis; therefore, the diagnoses of Cowden syndrome and McCune-Albright syndrome were excluded. CONCLUSIONS: LDD and FD are 2 rare diseases, and the simultaneous occurrence of the 2 conditions has not been reported before, to our knowledge. Our report challenges the etiology of the 2 diseases and the relationship between them, hoping to provide a reference for the study of the 2 diseases.

[Comparison study on polymerase chain reaction (PCR) and standard culture technique in detecting mycobacterium tuberculosis to diagnose of joint tuberculosis].

OBJECTIVE: To study the role of PCR technique in detection of mycobacterium tuberculosis in the samples from joint tuberculosis, and to evaluate the clinical value of PCR in diagnosis of joint tuberculosis. METHODS: From June 1993 to August 2001, PCR was used to detect DNA of mycobacterium tuberculosis, and the standard culture was applied to detect mycobacterium tuberculosis. Mycobacterium tuberculosis were respectively blindly by the two techniques in the samples obtained from 95 patients with joint tuberculosis (55 males and 40 females, the age ranging from 2 to 75 years, with an average of 34 years). The positive rate of mycobacterium tuberculosis detection was calculated. RESULTS: In the detection of mycobacterium tuberculosis, positive rate was 82% (78/95) in PCR technique, and 16% (15/95) in standard culture technique. There were statistical differences between the two groups (chi2=67, P<0.001). The whole process of PCR amplification was automatic and could be finished within several hours, and the detecting time was considerably shorter. CONCLUSION: PCR technique is a rapid, simple, sensitive and specific method for detection of mycobacterium tuberculosis in the samples of joint tuberculosis, showing more marked advantages than the standard culture technique. It is valuable in the early rapid diagnosis and differential diagnosis of joint tuberculosis.

[Study on the genetic structure and transmission mechanism of a plasmid-mediated AmpC beta-lactamase].

OBJECTIVE: To clone the gene of plasmid-mediated AmpC beta-lactamase from the plasmid of multiple-drug resistance Klebsiella pneumoniae producing plasmid-mediated AmpC beta-lactamase and demonstrate its mechanism of transmission. METHODS: Plasmids of the transconjugant were extracted and digested with restriction endonuclease HindIII. Taq DNA polymerase was applied to fill the recessed 3' termini, and a single deoxyadenosine was added to the 3' termimi of fragments. Then these fragments were ligated with pGEM-T Easy vector. E. coli DH5alpha containing recombinant plasmid was selected on MacConkey agar plates containing ampicillin and cefoxitin. Insert fragments were sequenced by primer walking. MIC determinations and isoelectric focusing electrophoresis (IFE) were utilized to analyze recombinant. RESULTS: The recombinant plasmid pT948 containing a 5.2-kb insert was obtained. The inserted fragment contained a bla(DHA-1) and a regulatory gene ampR. The insertion sequence (IS26), qacEDelta1 and sulI genes of the I type integron were obtained near the bla(DHA-1) gene. Recombinant expressed a beta-lactamase with pI of 7.7. MIC determinations showed that recombinant was resistant to cefoxitin and the resistance to ceftazidime could be induced by the cefoxitin. CONCLUSION: The plasmid-mediated ampC gene cloned was identified as bla(DHA-1). IS26 observed on the flanks of the bla(DHA-1) maybe relate to the translocation of bla(DHA-1) gene region from the chromosome to plasmid.

Nosocomial spread of multi-resistant Klebsiella pneumoniae containing a plasmid encoding multiple beta-lactamases.

Six Klebsiella pneumoniae isolates that exhibited resistance to a wide spectrum of antibiotics were recovered from the intensive care units in the First Affiliated Hospital, Zhejiang University, Hangzhou, China. All isolates contained two plasmids of approximately 95 kb and 200 kb. The 95 kb plasmid was shown to be transferable by conjugation experiments. Isoelectric focusing patterns of the beta-lactamases extracted from the six transconjugants were identical, displaying five pI bands: 5.4, 7.75, 8.0, 8.2 and 8.4. The band corresponding to a pI of 7.75 could be inhibited by cloxacillin but not clavulanic acid, while the other bands could be inhibited by clavulanic acid but not cloxacillin. The 95 kb plasmid was digested with HindIII and a recombinant plasmid pT948 was obtained. The insert was found to contain blaDHA-1, regulatory gene ampR and an insertion element (IS26), which was downstream of blaDHA-1. PCR and DNA sequencing results confirmed that the 95 kb plasmid encoded at least four beta-lactamase genes: blaTEM-1, blaSHV-12), blaCTX-M-3 and blaDHA-1. Epidemiological typing by PFGE of the six clinical isolates of K. pneumoniae demonstrated identical genotypic patterns. In conclusion, all results indicated that the six multi-drug resistant clinical isolates of K. pneumoniae most probably originated from one clone and caused a localized epidemic in the intensive care units.