In order to solve the problem of resistance of Pseudomonas aeruginosa to multiple antibiotics, it is an effective way to find inhibitors of P. aeruginosa efflux pump. In this study, 15 new ornithine peptidomimetic derivatives were designed and synthesized by changing the side chain structure of natural amino acids with PAβN, a dipeptide efflux pump inhibitor, and their synergic activity with aztreonam, a monocyclic β-lactam antibiotic, against P. aeruginosa was evaluated. Among them, the representative compound 12b not only enhanced the antibacterial activity of β-lactam antibiotics aztreonam, ceftazidime and meropenem, but also significantly enhanced the antibacterial action of macrolide antibiotics clarithromycin, showing a broad-spectrum synergic sensitization effect. In addition, compound 12b also has a good safety. Preliminary mechanisms suggest that 12b works by directly targeting the efflux transporter MexB. These results provide a new lead compound for the development of a new class of efflux pump inhibitors against P. aeruginosa.

Objective To investigate the effects of rigid gas permeable contact lens (RGPCL) wearing 3 years on ocular surface in keratoconus.Design Retrospective case series.Participants 73 patients with keratoconus.Methods From July 2001 to July 2004,73 patients (142 eyes) wearing RGPCL for more than 3 years were collected in Peking University Optometry & Ophthalmology Center.Be- fore and at 1 year,2 years and 3 years of RGPCL wearing,density and morphologic changes of corneal endothelium were examined with non-contact specular microscope.Eye axial length,central and peripheral thickness of cornea were measured with A-scan pachymeter. All eyes were examined with slit-lamp microscope periodically.Main Outcome Measures Corneal endothelial density and morphology, corneal thickness,eye axial length,ocular surface changes.Results Before and at 1 year,2 years and 3 years of RGPCL wearing,aver- age corneal endothelial density was 2901.92?445.20,2862.78?497.13,2854.71?526.80,3015.61?421.22 (cells/mm~2)without significant difference statistically (F=1.571,P=0.20).Morphologic changes were not significant during 3 years.Eye axial length was 25.15?1.50, 24.93?1.36,24.78?1.25,25.39?1.31 (mm) without significant difference statistically (F=2.218,P=0.10).Corneal central thickness was 489.09?59.64,484.02?60.80,496.61?59.74,487.44?54.25(?m)without significant difference statistically (F=0.991,P=0.40).Peripheral thickness changes were also not significant statistically during 3 years.69 eyes with mild conjunctival congestion,12 eyes with corneal fluorescence stain and 6 eyes with corneal epithelial rough were found with slit-lamp microscope during follow-up.Conclusions For the patients with keratoconus,long term of RGPCL wear will not lead to significant ocular changes or severe ocular complications.

Objective To measure the macular thickness of natural population in Changping district of Beijing by optical coherence tomography (OCT), and to analyze whether there is an increased thickness in diabetic patients.Methods In a cross-sectional population-based study, OCT was performed on 521 subjects (233 with normal glucose homeostasis, 174 with pre-diabetes and 114 with type 2 diabetes (T2D) according to 2011 Health Examination Survey of Changping.The subjects also received physical examination and laboratory measurements including fasting plasma glucose (FPG), oral glucose tolerance test (OGTT)-2 h plasma glucose and hemoglobin A1c (HbA1c).Results The results showed that central subfield thickness (CST) of the retina of men ((246±22) μm) was significantly greater than that of women ((235±26) μm) (P＜0.001).Meanwhile, no significant difference was found in the CST in subjects of different age, HbAlc and body mass index (BMI) (P＞0.05).Difference in thickness of different glucose groups was not seen in central subfield, inner subfields and outer subfields(P＞0.05).Conclusions Retina CST of men was significantly greater than that of women.No significant difference was found in the CST in subjects of different age, HbA1c and BMI.

Objective To explore the interaction between serum melatonin and the status of disease and probe the effect factor of serum melatonin change in asthmatic children.Methods Serum melatonin was measured in asthmatic children with 15 cases of mild persistent asthma,15 cases of moderate persistent asthma,15 cases of severe persistent asthma,15 cases of stable asthma and 15 cases of normal subjects by enzyme-linked immunosorbent assay(ELISA).Results The levels of serum melatonin in the 5 groups of mild persistent asthma,moderate presistent asthma,Severe Persistent asthma,Stable asthma,control subject were(22.76?5.16)ng/L,(16.79?3.35)ng/L,(11.54?1.45)ng/L,(22.06?3.36)ng/L,(28.72?4.32)ng/L,respectively.There were significant differences between any of them(Pa

Objective To evaluate the prognostic value of serial 18F-fluorodeexyglucose (FDG) PET/CT in patients with nasopharyngeal carcinoma (NPC).Methods Thirty-seven NPC patients who had 18F-FDG PET/CT scan before and after external beam intensity-modulated radiotherapy, were studied retrospectively.All patients were followed for five years.Correlation analysis between metabolic tumor volume (MTV)/uptake volume index (UVI) and survival was performed by Kaplan-Meier analysis, Log-rank test and multivariate Cox model.Results The 5-year overall survival (OS) and disease-free survival (DFS) rates were 70.3% (26/37) and 62.2% ( 23/37 ), respectively.Patients with a lower MTV (MTV＜30 cm3) had significantly higher 5-year OS ( 82.6% ( 19/23 ) ) and DFS (73.9% ( 17/23 )) rates than those with a higher MTV (OS:50.0% (7/14),x2 =5.28, P＜0.05; DFS:42.9% (6/14),x2 =4.84, P＜0.05).Patients with a lower UV1 (UVI＜150) had significantly higher 5-year OS( 87.5%( 21/24 )) and DFS (79.2% (19/24)) rates than those with a higher UVI (OS:38.5% (5/13),x2 =10.72, P＜0.01;DFS:30.8% (4/13), x2 =11.04, P＜0.01).Multivariate analysis showed that UVI and metabolic response (MR) were independent predictors of DFS.Conclusions Tumor volume parameters, UVI and MR, are independent prognostic factors for patients with NPC.Patients with a high UVI may benefit from more aggressive treatment.

Objective To assess the income status of primary care providers and to explore the determinants of income in a county of Dali. Methods In August 2016, the questionnaire was employed to collect the data of income status of 191 rural health workers and 217 village doctors in the county. Results Through the study, we found that the income of rural health workers in the county was 34, 000 (26, 000, 46,000) yuan with a satisfaction rate of 62.3% (95% CI 55.4%～69.2%) and no change (74.7%) was seen in the income among majorities after implementing the Zero Mark-up Policy for essential medicines. For the village doctors, the income was 20,000 (15,000, 24,000) yuan with a satisfaction rate of 40.6% (95% CI 34.0%～47.1%) and a fall of the income was found in more than half of the doctors after the implement of the policy. Conclusion Health care workers in towns are quite satisfied with their income whereas those in health stations of villages are not content, compared with the average income at the national level. We should increase government's investments on grass-root healthcare team, improve the incentive pay plans and promote the integrated management of health facilities in towns and villages.

OBJECTIVEInterleukin-12 receptor beta1 (IL-12 Rbeta1) deficiency is a rare primary immunodeficiency (PID) characterized by selective susceptibility to weakly virulent organisms, including Mycobacterium bovis, BCG, non-tuberculous environmental mycobacteria and non-typhoidal salmonellosis. The present study was conducted to identify the mutation type and to analyze clinical phenotype.

METHODSBased on the typical clinical manifestations and immunologic tests in this case, a varieties of PIDs were excluded and IL-12Rbeta1 deficiency was suspected. IL-12Rbeta1 chain expressed on Epstein-Barr virus-transformed lymphoblastoid B cell lines were detected by flow cytometric assay. The IL-12Rbeta1 gene sequences of the patient and her parents were analyzed by PCR-directed sequencing. The IL-12Rbeta1 gene sequences of the patient's younger brother also had been analyzed prenatally and after birth.

RESULTSAfter inoculating BCG, the patient suffered from multiple BCG infectious lymphadenitis. There was no detectable IL-12Rbeta1 on the Epstein-Barr virus-transformed lymphoblastoid B cell lines from the patient, while only mild expression on the cell line from her mother. Sequencing analysis by using sense and antisense primers separately, a novel IL-12Rbeta1 gene mutation was found in the patient which was homozygous single nucleotide substitution, a nonsense mutation with nucleotide substitution of C to T at position 853 (853C-->T) in exon 9 leading the glutamate at position 285 to the stop codon mutation (Q285X). The parents were carriers of the mutated IL-12Rbeta1 gene. But her younger brother has normal IL-12Rbeta1 gene.

CONCLUSIONThe novel IL-12Rbeta1 gene mutation is responsible for BCG infection in this case and genetic analysis is useful in carrier detection and prenatal diagnosis is feasible when the mother had a baby with identified IL-12Rbeta1 gene mutation before.

BCG Vaccine ; adverse effects ; Base Sequence ; Exons ; Female ; Humans ; Infant ; Molecular Sequence Data ; Mutation ; Mycobacterium bovis ; Phenotype ; Receptors, Interleukin-12 ; deficiency ; genetics ; Severe Combined Immunodeficiency ; complications ; genetics ; Tuberculosis ; complications

The essence of endogenous turbidity in Chinese medicine (CM) is different from cream, fat, phlegm, retention, damp, toxicity, and stasis. Along with the development of modern scientific technologies and biology, researches on the essence of endogenous turbidity should keep pace with the time. Its material bases should be defined and new connotation endowed at the microscopic level. The essence of turbidity lies in abnormal functions of zang-fu organs. Sugar, fat, protein, and other nutrient substances cannot be properly decomposed, but into semi-finished products or intermediate metabolites. They are inactive and cannot participate in normal material syntheses and decomposition. They cannot be transformed to energy metabolism, but also cannot be synthesized as executive functioning of active proteins. If they cannot be degraded by autophagy-lysosome or ubiquitin-prosome into glucose, fatty acids, amino acids, and other basic nutrients to be used again, they will accumulate inside the human body and become endogenous turbidity. Therefore, endogenous turbidity is different from final metabolites such as urea, carbon dioxide, etc., which can transform vital qi. How to improve the function of zang-fu organs, enhance its degradation by autophagy-lysosome or ubiquitin-prosome is of great significance in normal operating of zang-fu organs and preventing the emergence and progress of related diseases.
Autophagy ; Humans ; Medicine, Chinese Traditional ; Proteasome Endopeptidase Complex

To explore the possible linkage between telomerase and acute leukemia, we detected telomerase activity expressed in 3 leukemia cell lines, 22 acute leukemia bone marrow and 6 normal bone marrow with PCR ELISA assay. Results showed that telomerase activities of three leukemia cell lines were positive with the average (1.57 +/- 0.056) U, normal bone marrow samples average was (0.085 +/- 0.081) U, telomerase value from 22 acute leukemia patients was (0.512 +/- 0.294) U. Telomerase activity is higher expressed in acute leukemia than normal samples and decreased significantly after chemotherapy (P < 0.01). The results suggested that telomerase activity was related to some malignant diseases and might be used as a marker for tumor diagnosis and therapy.

OBJECTIVETo verify the clinical efficacy of heat-sensitive moxibustion in treatment of knee osteoarthritis (KOA).

METHODSSixty cases of KOA were randomly divided into a heat-sensitive moxibustion group and a conventional moxibustion group, 30 cases in each one. Dubi (ST 35), Yanglingquan (GB 34), Zusanli (ST 36) and Heding (EX-LE 2) on the affected side were selected in two groups. In heat-sensitive moxibustion group, the techniques of circling moxibustion, sparrow-pecking moxibustion, moving moxibustion and mild moxibustion were applied. In conventional moxibustion group, the mild moxibustion was used, 2 to 3 cm far from the skin of the acupoints selected. Lysholm scale for the assessment of knee joint function was adopted to evaluate the efficacy. The scores of joint pain, morning stiffness, joint swelling and walking ability were compared before and after treatment in two groups.

RESULTSThe scores of joint pain, morning stiffness, joint swelling and walking ability after treatment were all apparently improved as compared with those before treatment in either group (all P < 0.05). The improvement in the above-mentioned indices in heat-sensitive moxibustion group was much more apparent as compared with that in conventional moxibustion group (all P < 0.01). The effective rate was 90.0% (27/30) in heat-sensitive moxibustion group and was 73.3% (22/30) in conventional moxibustion group. The effective rate in heat-sensitive moxibustion group was obviously superior to that in conventional moxibustion group (P < 0.01).

CONCLUSIONThe efficacy of heat-sensitive moxibustion is superior to that of conventional moxibustion in the treatment of KOA. This therapy can more significantly improve the symptoms and physical signs of the patients with KOA.

Acupuncture Points ; Aged ; Female ; Humans ; Locomotion ; Male ; Middle Aged ; Moxibustion ; Osteoarthritis, Knee ; physiopathology ; therapy ; Treatment Outcome