This study is to elucidate the metabolic pathway of 1,2-[bis (1,2-benzisoselenazolone-3 (2H)-ketone)]-ethane (BBSKE) in rats. Rats were administrated with a single dose of BBSKE 200 mg x kg(-1). The metabolites in rat urine, feces, bile and plasma were identified by LC-MSn analysis. The characterization of fragment ions from LC-MSn chromatography and mass spectrometry was applied to the investigation of structures of metabolites. Three phase I metabolites were detected in rat urine and feces. Two of them were also found in plasma and one existed in bile. These products were derived from oxidized, methylated and S-methylated BBSKE, separately. One phase II glucuronide of BBSKE was also found in bile. Therefore, it is possible that BBSKE was metabolized by oxidization, methylation and glucuronidation.
Administration, Oral ; Animals ; Antineoplastic Agents ; administration & dosage ; blood ; metabolism ; urine ; Bile ; metabolism ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; blood ; metabolism ; urine ; Chromatography, Liquid ; Feces ; chemistry ; Male ; Organoselenium Compounds ; administration & dosage ; blood ; metabolism ; urine ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization

OBJECTIVETo investigate the characteristics of New Delhi metallo-beta-lactamase-1 (NDM-1) gene of Klebsiella pneumoniae (K. pneumoniae) emerging in Hunan, and its relationship to antibiotic resistance.

METHODSThe clinical strain was isolated from a sputum sample of a child with severe pnemonia and toxic myocarditis who was admitted into a general hospital of Hunan Province. VITEK-2 compact instrument was used for bacterial identification and antibiotic susceptibility test. Modified Hodge test was used for the screening of carbapenemase. EDTA-synergy test and combination disk diffusion test were used for detection of metallo-β-lactamase (MBL). PCR was performed for amplification of NDM-1 genes and the positive products were sequenced and analyzed with BLAST. Conjugation was also performed to analyze mechanisms of antibiotic resistance. The results of antibiotic susceptibility tests were compared before and after conjugation.

RESULTSThe isolated strain was identified as K.pneumoniae. Modified Hodge test, EDTA-synergy test and combination disk diffusion test were all positive for the strain. The homology between gene sequence of PCR amplification products and NDM-1 gene FN396876.1 in the GenBank was 100%. Transconjugant DNA was used as template for the amplification of NDM-1 gene. The amplification products were sequenced and found to be the same as the NDM-1 gene amplification product of the donor strain. The MIC of transconjugant E.coli J53 (NDM-1) to all the β-lactams increased significantly compared with the recipient strain E.coli J53. The MIC of ertapenem and imipenem increased by more than 8 times, while the MIC of ceftazidime and ceftriaxone increased by more than 64 times.

CONCLUSIONSThis study first identified a strain of K. pneumoniae carrying NDM-1 in mainland China. NDM-1 gene can be transmitted among different strains and causes extensively drug-resistance to β-lactams.

Base Sequence ; China ; Drug Resistance, Bacterial ; Klebsiella pneumoniae ; drug effects ; enzymology ; genetics ; Molecular Sequence Data ; Polymerase Chain Reaction ; beta-Lactamases ; biosynthesis ; genetics

OBJECTIVETo investigate the histological components and solubility of the bile-cast, and to study the pathological course of bile cast formation.

METHODSHE staining, bilirubin staining (Gmelin reaction), Masson's staining, alcian blue staining and fibrin staining (weigert's) were performed on the formalin-fixed paraffin-embedded section of the bile cast. Ultrastructure was examined under the scanning electron microscope. Solubility test was also conducted using chymotrypsin, heparin, trypsin solution, HCl and NaOH solution to dissolve the bile-cast.

RESULTSThe major components of the bile-cast were bilirubin crystals and collagen fibers. Between the mass of collagen fibers there was certain blood vessel structure. Necrosis bile duct structure was not found in the cast. Under the scanning electron microscope, four kinds of crystal morphologies were viewed. There were some mucoid mass and necrosis defluvium epithelial cells in the bile cast. Solubility test showed that the bile cast could be partial dissolved in NaOH solution (pH = 12.5). No dissolution was found in HCl solution (pH = 5.0), chymotrypsin solution, heparin and trypsin solution.

CONCLUSIONSCollagen fibers work as framework in the bile cast with bilirubin crystal filling between the framework. The emergence of fibroblast and blood vessels indicated the formation of bile cast might be the course of exudation and organization due to bile duct epithelium damage. Bile cast could be partially dissolved in alkaline solution, but could not be dissolved in acid solution, or in chymotrypsin, heparin and trypsin solutions.

Bile Duct Diseases ; etiology ; pathology ; Bile Ducts ; ultrastructure ; Humans ; Immunohistochemistry ; Liver Transplantation ; adverse effects ; Microscopy ; Postoperative Complications ; Staining and Labeling

Cysticercosis is caused by the metacestode form of Taenia solium-Cysticercus cellulosae and it causes great economic losses and threatens the people's health. There are some problems on how to control cysticercosis, in order to resolve the key problem that the native antigen to diagnose and prevent cysticercosis is very limited and is not satisfied, Pichia pastoris Expression System was used to express recombinant P2 protein. The interested P2 gene was got by digesting the pGEM - P2 vector using restriction endonuclease, then it was inserted into the secretory pPIC9K Pichia pastoris expression vector and transformed into E. coli. Positive recombinant plasmids were selected sequenced and named pPIC9K-P2 and it was linearized by Sal I and Bgl II, then the linear DNA transfored into Pichia pastoris GS115 by electroporation. The recombinant expression vector pPIC9K - P2 integrated into GS115 via homologous recombination between the transforming DNA and regions of homology within the genome. The transformants were screened for multicopy recombinants using G418 and were distinguished for Mut phenotypes by MD and MM. Two different phenotypes were generated-HIS+ MUT+ (Methanol utilization plus) and HIS+ MUT(S) (Methanol utilization slow). PCR analysis of the multicopy recombinants indicated that the P2 gene was integrated within the genome of pichia Pastoris. The multicopy recombinants were named GS115/pPIC9K - P2HIS+ MUT+ and GS115/pPIC9K-P2HIS+ MUT(S), both HIS+ MUT+ and HIS+ MUT(S) were induced with methanol. The results of SDS-PAGE and Western blot demonstrated that the culture supernatant of the induced Pichia pastoris contained P2 protein which was accumulated up to 33 % of total proteins in the culture supernant and its molecular weight is 12.6kD. The results of the clinical study indicated that the expression P2 protein could be used to diagnose human cysticercosis and swine cysticercosis as diagnosis antigen.
Animals ; Blotting, Western ; Cysticercosis ; diagnosis ; metabolism ; Electrophoresis, Polyacrylamide Gel ; Genome, Fungal ; genetics ; Helminth Proteins ; genetics ; metabolism ; Humans ; Phosphoproteins ; genetics ; metabolism ; Pichia ; Polymerase Chain Reaction ; Recombinant Proteins ; genetics ; metabolism ; Swine ; Taenia ; metabolism

UNLABELLEDOBJECTIVE To verify the correlation between the points of eye acupuncture and zang-fu function so as to provide the theoretical evidence for the principle of point selection in eye acupuncture therapy.

METHODSSixty cases of cerebral infarction were treated with different points according to syndrome differentiation of Chinese medicine.

MAIN POINTSupper energizer area and lower energizer area. Supplementary points: liver area, kidney area and spleen area for hyperactivity of wind, phlegm and fire; liver area and spleen area for blockage of wind, phlegm and stasis; stomach area and large intestine area for excess fu syndrome due to phlegm heat; heart area and spleen area for qi deficiency and blood stasis; liver area and kidney area for yin deficiency and wind stirring. The single photon emission computed tomography (SPECT) was adopted to observe the changes in blood flow in local foci before and after treatment with eye acupuncture.

RESULTSAfter the treatment with eye acupuncture therapy, the intake ratio of region of interest (ROI) between the lesion area and corresponding area on the opposite side was 0.74 +/- 0.12 before eye acupuncture and was 0.91 +/- 0.08 after treatment, indicating significant statistical difference in comparison (P < 0.05). After eye acupuncture, cerebral blood flow increased apparently.

CONCLUSIONThe point selection according to syndrome differentiation in eye acupuncture therapy may increase local brain blood flow in the patients with cerebral infarction and improve the state of brain ischemia so that the correlation can be proved between the points of eye acupuncture and zang-fu function.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Brain ; diagnostic imaging ; Cerebral Infarction ; diagnostic imaging ; physiopathology ; therapy ; Cerebrovascular Circulation ; Eye ; Female ; Humans ; Male ; Middle Aged ; Tomography, Emission-Computed, Single-Photon

OBJECTIVE Corona-virus disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2 virus. The variant of corona-virus first identified in India, known as Delta, has become the dominant strain in China. Unfortunately, more conta-gious and unknown variants are coming, leading to a number of close contacts under quarantine. Chinese medicine (TCM) has been recommended to prevention and treatment due to the satisfactory therapeutic effects. However, the effect of TCM to decrease positive rate in close contacts remains unknown. METHODS We conducted an retrospective cohort study in Yangzhou, China to assess the effect of Chinese medicine on decreasing positive rate in close contacts under quarantine. The primary observation outcome was positive rate of Nucleic Acid Amplification Tests (NAATs). The secondary observation outcome was a composite of viral load of positive NAATs, severity levels of confirmed cases (asymptomatic, mild, moderate, or severe), daily body temperature, and levels of close contact (primary or secondary). RESULTS A total of 1286 subjects were collected, of which 1016 (79.00％) in TCM group and 270 (21.00％) in control group with 55 participants tested positive. The incidence of the primary outcome, positive rate of NAATs was significantly lower in the Chinese medicine group than in the control group, occurring in male and age≥60 years subjects. Multi-varia-ble logistic regression (excluding NO viral load) indicated that the risk of testing positive was reduced by 0.547 times in TCM groupcompared to control group. CT value of TCM group was higher than that of control group in all subjects and female subjects, and the re-sult showed statistically significant difference. CONCLUSIONS In our study involving close contacts under quarantine, Chinese medicine resulted in lower positive rate of NAATs and viral load than control.

BACKGROUNDKlebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bacteria, which cause serious disease outbreaks worldwide, was rarely detected in Xiangya Hospital, prior to an outbreak that occurred from August 4, 2014, to March 17, 2015. The aim of this study was to analyze the epidemiology and molecular characteristics of the K. pneumoniae strains isolated during the outbreak.

METHODSNonduplicate carbapenem-resistant K. pneumoniae isolates were screened for blaKPC-2and multiple other resistance determinants using polymerase chain reaction. Subsequent studies included pulsed-field gel electrophoresis (PFGE), multilocus sequence typing, analysis of plasmids, and genetic organization of blaKPC-2locus.

RESULTSSeventeen blaKPC-2-positive K. pneumoniae were identified. A wide range of resistant determinants was detected. Most isolates (88.2%) coharbored blaKPC-2and rmtB in addition to other resistance genes, including blaSHV-1, blaTEM-1, and aac(3)-IIa. The blaKPC-2and rmtB genes were located on the conjugative IncFIB-type plasmid. Genetic organization of blaKPC-2locusin most strains was consistent with that of the plasmid pKP048. Four types (A1, A2, A3, and B) were detected by PFGE, and Type A1, an ST11, was the predominant PFGE type. A novel K. pneumoniae sequence type (ST1883) related to ST11 was discovered.

CONCLUSIONSThese isolates in our study appeared to be clonal and ST11 K. pneumoniae was the predominant clone attributed to the outbreak. Coharbing of blaKPC-2and rmtB, which were located on a transferable plasmid, in clinical K. pneumoniae isolates may lead to the emergence of a new pattern of drug resistance.

Anti-Bacterial Agents ; pharmacology ; Bacterial Proteins ; metabolism ; China ; Electrophoresis, Gel, Pulsed-Field ; Hospitals, Teaching ; Klebsiella Infections ; etiology ; Klebsiella pneumoniae ; drug effects ; metabolism ; Methyltransferases ; metabolism ; Microbial Sensitivity Tests ; Multilocus Sequence Typing ; beta-Lactamases ; metabolism

Neonatal seizures are the most common clinical manifestations of critically ill neonates and often suggest serious diseases and complicated etiologies. The precise diagnosis of this disease can optimize the use of anti-seizure medication, reduce hospital costs, and improve the long-term neurodevelopmental outcomes. Currently, a few artificial intelligence-assisted diagnosis and treatment systems have been developed for neonatal seizures, but there is still a lack of high-level evidence for the diagnosis and treatment value in the real world. Based on an artificial intelligence-assisted diagnosis and treatment systems that has been developed for neonatal seizures, this study plans to recruit 370 neonates at a high risk of seizures from 6 neonatal intensive care units (NICUs) in China, in order to evaluate the effect of the system on the diagnosis, treatment, and prognosis of neonatal seizures in neonates with different gestational ages in the NICU. In this study, a diagnostic study protocol is used to evaluate the diagnostic value of the system, and a randomized parallel-controlled trial is designed to evaluate the effect of the system on the treatment and prognosis of neonates at a high risk of seizures. This multicenter prospective study will provide high-level evidence for the clinical application of artificial intelligence-assisted diagnosis and treatment systems for neonatal seizures in the real world.
Artificial Intelligence ; Electroencephalography/methods* ; Epilepsy/diagnosis* ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases/diagnosis* ; Intensive Care Units, Neonatal ; Multicenter Studies as Topic ; Prospective Studies ; Randomized Controlled Trials as Topic ; Seizures/drug therapy*

Objective To study the single nucleotide polymorphisms (SNPs)that predict a patient's risk of grade 2-3 paclitaxel-induced peripheral sensory neuropathy (PSN) in Chinese Han populations.Methods Totally 216 patients received paclitaxel in Peking Union Medical College Hospital from May 2014 to December 2016 were enrolled.DNA was isolated from peripheral blood.Genotyping for eight candidate SNPs was performed on Sequenom-MassARRARYiPLEX platform.Patients were followed up and PSN was assessed by trained physicians according to National Cancer Institute-Common Terminology Criteria for Adverse Events v4.03.Results A total of 209 patients entered the final analysis.Among the candidate SNPs,only rs4141404:A>C(LIMK2) was significantly associated with grade 2/3 PSN (OR:4.32,95%CI:2.37-7.89,P<0.0001).In multivariate logistic regression analysis,both rs4141404:A>C(LIMK2) and history of receiving platinum compound (OR:2.70,95%CI:1.32-5.51,P=0.007) were associated with grade 2/3 PSN.Conclusion rs4141404:A>C(LIMK2) may be the markers of risk of grade 2/3 PSN.

Dendrobium officinale Kimura et Migo (D. officinale) is a famous traditional Chinese medicine (TCM). A mixture of D. officinale and American ginseng has been shown to enhance cell-mediated immunity, humoral immunity, and monocyte/macrophage functions in mice. Here, the effects of a D. officinale and American ginseng mixture on the structure of gut microbial community in dogs were examined using high-throughput 16S rRNA gene amplicon sequencing. The data revealed that while the mixture did not change the diversity of gut microbial community significantly, differences among individuals were significantly reduced. Furthermore, the mixture-responsive operational taxonomic units (OTUs) exhibited a phase-dependent expression pattern. Fifty-five OTUs were found to exhibit a mixture-induced expression pattern, among which one third were short-chain fatty acid (SCFA)-producing genera and the others were probiotic genera included Lactobacillus spp., Sutterella, Alistipes, Anaerovorax, Bilophila, Coprococcus, Gordonibacter, Oscillibacter, among others. By contrast, 36% of the OTUs exhibiting a mixture-repressed expression pattern were disease-associated microorganisms, and six genera, namely Actinomyces, Escherichia/Shigella, Fusobacterium, Slackia, Streptococcus and Solobacterium, were associated with cancer. In addition, five genera were closely associated with diabetes, namely Collinsella, Rothia, Howardella, Slackia and Intestinibacter. Our results indicate that this D. officinale and American ginseng mixture may be used as a prebiotic agent to enhance SCFA-producing genera and prevent gut dysbiosis.