BACKGROUND: Tissue engineering has a promising prospect in corneal transplantation. Scaffolds are always restricting the development of tissue-engineered cornea. OBJECTIVE: To analyze application of different seed cells and scaffolds, and to summarize the progress of tissue-engineered cornea in recent years.METHODS: First author searched literature from CNKI (2000/2010-10) and PubMed database (2000/2010-10). The key words are tissue engineering, corneal transplantation in Chinese or English. A total of 223 literatures were seized by computers, according to the inclusion criteria, papers concerning the advance, application and reconstruction of tissue-engineered cornea were analyzed. Finally, 33 papers were included for further analysis. The present study was to analyze the seed cells, scaffolds, organ building and clinical applications of tissue-engineered cornea and investigate the development direction in the future. RESULTS AND CONCLUSION: The results show that seed cells and scaffolds are the focus of the studies now. Corneal transplantation has a high success rate in organ transplantation since the immune privilege of eye and avascular cornea, and it will be able to be a tissue engineering organ that can be largely built, easy to transplant. Reconstruction of cornea has reached first base, but every kind of scaffold has certain drawbacks, so the next goal is to find an ideal scaffold material.

Objective:To investigate the effect and prognostic factors of rituximab-containing chemotherapy regimen in treatment of patients with mantle cell lymphoma (MCL).Methods:The clinical data of 56 patients aged ≤65 years in the First Affiliated Hospital of Soochow University from June 2007 to November 2018 were retrospectively analyzed. Rituximab-containing chemotherapy regimen was used, and the effects of clinical features, treatment regimen and biological indexes on overall survival (OS) and progression-free survival (PFS) were observed.Results:The median age of 56 patients was 57 years old, including 43 males and 13 females. Among these cases, 24 patients received R-CHOP chemotherapy regimen; 29 patients received cytarabine-containing chemotherapy regimen, including R-hyper CVAD/R-MA regimen used in 15 patients and R-CHOP alternating with R-DAHP regimen used in 14 patients; and 3 patients received other treatment regimens. Among 56 patients, 19 patients received autologous hematopoietic stem cell transplantation (ASCT) consolidation therapy. The median OS time was 74 months, 2-year OS rate was 83.8%, 3-year OS rate was 70.9%, 2-year PFS rate was 72.0% and 3-year PFS rate was 49.7%. International prognostic index (IPI) high-risk and receiving ASCT or not during the treatment were independent influencing factors of OS and PFS in MCL patients. The overall response rate (ORR) in cytarabine-containing regimen group was higher compared with that in R-CHOP regimen group (93.1% vs. 83.3%), and there was no statistically significant difference ( χ2=0.465, P=0.495). In addition, there were no significant differences between two groups in both OS ( χ2=0.291, P=0.590) and PFS ( χ2=0.912, P=0.339). ASCT consolidation prolonged the median OS time (72 months vs.124 months, χ2=3.973, P=0.040) and the median PFS time (34 months vs. 90 months, χ2=3.984, P=0.046) in MCL patients achieving remission after induction therapy. Among patients in simplified MCL IPI (sMIPI) score middle-high risk group, compared with those not receiving ASCT, patients receiving ASCT therapy could obtain better OS and PFS (OS: χ2=5.037, P=0.025; PFS: χ2=6.787, P=0.009); among patients of sMIPI score low risk, there were no statistically significant differences in OS and PFS between the group receiving ASCT and not (all P > 0.05). Conclusions:Cytarabine-containing chemotherapy regimen has no predicatively satisfactory value in improving the prognosis and survival for MCL patients. For MCL patients who have achieved remission after reduction therapy and those in sMIPI score middle-high risk group, ASCT consolidation therapy can improve the prognosis and can be taken as the first-line consolidation treatment in young patients.

Objective To explore the therapeutic effect of arterial PVA perfusion embolization in treating mid and advanced pulmonary carcinoma. Methods Thirty-one patients with pulmonary carcinoma in the mid or late stage diagnosed pathologically underwent selective angiographic studies of the bronchial arteries and intercostal arteries to provide information of the hypervascular feeding vessels, and then performed the perfusion with 5-FU? THP? DDP; followed by PVA grain embolization under fluoroscopic control. Results Abnormal tumor feeding vessels of pulmonary carcinoma were found deriving from bromehial arteries in 21 cases, and from intercostal arteries in 10. After arterial infusion of chemotherapy combined with embolization of PVA,alleviation of clinical symptoms was observed in all 31 cases(100%)without severe complication. The total effectiveness(CR plus PR) reached 80.6%(25/31). Conclusions Arterial embolization of PVA is safe, effective with less complication for treatment of mid or advanced pulmonary carcinoma.

Objective To investigate correlation between the results of drug susceptibility and the extent of drug-resistances in Mycobacterium tuberculosis clinical isolates. Methods Liquid culture and MTT test were used. Twelve anti-TB drug MICs and drug susceptibility testing of the 163 MTB strains from random clinical isolates were detected, which including RFP, INH, SM, EBM, OFLX, LVFX, MOX, AMK,CPM, PTA, CLA and PAIN. Results There are 67% (42/62) Mycobacterium tuberculosis strains resistant to SM, 63% (51/81) Mycobacterium tuberculosis strains resistant to INH, 77% (50/65) Mycobacterium tuberculosis strains resistant to RFP, 41% ( 15/37 ) Mycobacterium tuberculosis strains resistant to AMK,41% (12/29) Mycobacterium tuberculosis strains resistant to CPM, 20% (12/60) Mycobacterium tuberculosis strains resistant to EMB and 43% (25/58) Mycobacterium tuberculosis strains resistant to OFLX which MICs were equal to or more than 16 μg/ml, 8 μg/ml, 8 μg/ml, 16 μg/ml and 4 μg/ml, 4 μg/ml and 8 μg/ml,respectively. There were significant differences in the MICs of OFLX, LVFX and MOX in OFLX resistant strains (2-128, 1-32 and 0.0625-1 μg/ml, respectively) by ANOVA ( F = 16.874, P ＜ 0.001 ). The MICs of SM, INH, RFP, EMB, OFLX, AMK and CPM in isolates resistant to six or seven drugs (0.5-128,2-64,0.25-128,1-32,1-64,0.5-128 and 1-128 μg/ml,respectively) were higher than those (0.25-128,0.0625-64,0.25-32,0.25-2,0.125-2,0.5-4 and 1-4 μg/ml,respectively) in isolates resistant to one or two drugs (F=20.066, 40.499, 47. 197, 70.373, 91.432, 41.840 and 21.547, respectively, P ＜0.05). The MICs of SM, INH, RFP and EMB in isolates resistant to four drugs (1-128,2-64,0.25-128 and 1-32 μg/ml,respectively ) were higher than those ( 0.25-128,0.0625-64, 0.25-64 and 0.25-2 μg/ml,respectively) in isolates resistant to one or two drugs (F = 26.242, 23.563, 31.541 and 64.469,respectively, P ＜0.05).The MICs of RFP in MDR isolates (2-64 μg/ml) were higher than those (0. 25 μg/ml) in other resistant isolate except M DR isolates (F = 5.613, P <0.05). Conclusions The study shows that there are associations between the results of routine drug susceptibility testing and the resistant extent of anti-TB drugs. This could help doctors select more effective anti-TB regimen for TB patients according to the correlations.

In order to evaluate the effect and mechanism of the mulberry leaf alkaloid, flavones, and polysaccharide intervention on diabetes, the overall metabolite profiling characteristics for the plasma of diabetic mouse was performed by using an ultra-performance liquid chromatography/electrospray-tandem mass spectrometry (UPLC-ESI-MS). The 8 potential biomarkers were found in diabetic mice plasma based on the data of MS/MS characteristics obtained from the UPLC-OrbitrapMS analysis, which mainly involved in sphingolipids, amino acid metabolic pathway. The principal component analysis showed that the normal group and model group were obviously distinguished and implied that metabolic disturbance was happened in diabetic mice plasma. The extracts of mulberry leaf flavonoids, polysaccharide, alkaloid had exhibited the effects of callback function for diabetic mice through regulating the amino acid metabolism and sphingolipid metabolism.

Objective To assess the role of 68Ga-N,N′-bis(2-hydroxy-5-(carboxyethyl)benzyl) ethylenediamine-N,N′-diacetic acid(HBED-CC)-(Ahx)Lys-CO-Glu(PSMA-11) PET/CT on the detection of metastatic lesions from castration-resistant prostate cancer (CRPC).Methods Sixteen patients with CRPC who underwent 68Ga-PSMA-11 PET/CT between January 2015 and November 2015 were recruited in this study.Mean age of patients was (72±9) years.The PSA levels were 4-12 356 μg/L, Gleason score was 7-10.PET/CT was performed at 1 h postinjection of 68Ga-PSMA-11.Patient-based analysis and lesion-based analysis were performed.ROI analysis was used to calculate the tumor uptake (SUVmax).Final diagnosis was based on histopathology and results of other imaging examinations(99Tcm-MDP imaging, MRI).χ2 test was used to compare the diagnostic efficiencies of PET and CT.Results No adverse effects were observed in patients.68Ga-PSMA-11 PET/CT showed moderate physiologic uptake in salivary glands and proximal small intestine, with predominant tracer clearance by the kidneys.All patients were positive on 68Ga-PSMA-11 PET/CT.Bone metastasis was found in 16 patients, liver metastasis in 2 patients (5 lesions), and lymph node metastasis in 4 patients (26 lesions).The SUVmax of liver, lymph node and bone metastases were 15.06±2.77, 7.54±5.20, 19.01±16.96, respectively.The diagnostic sensitivity, specificity and accuracy on bone metastasis with 68Ga-PSMA-11 PET and CT were 96.30%(52/54) vs 61.11%(33/54), 3/3 vs 1/3, 96.49%(55/57) vs 59.65%(34/57).The sensitivities and accuracies of the two modalities were significantly different(χ2=19.943, 22.593, both P<0.01).Conclusions 68Ga-PSMA-11 PET/CT could precisely detect both primary and metastatic lesions of CRPC, suggesting that it is of great value for the clinical management and treatment.

The accumulation of various types of drug informatics data and computational approaches for drug repositioning can accelerate pharmaceutical research and development. How-ever, the integration of multi-dimensional drug data for precision repositioning remains a pressing challenge. Here, we propose a systematic framework named PIMD to predict drug therapeutic properties by integrating multi-dimensional data for drug repositioning. In PIMD, drug similarity networks (DSNs) based on chemical, pharmacological, and clinical data are fused into an integrated DSN (iDSN) composed of many clusters. Rather than simple fusion, PIMD offers a systematic way to annotate clusters. Unexpected drugs within clusters and drug pairs with a high iDSN similarity score are therefore identified to predict novel therapeutic uses. PIMD provides new insights into the universality, individuality, and complementarity of different drug properties by evaluating the con-tribution of each property data. To test the performance of PIMD, we use chemical, pharmacolog-ical, and clinical properties to generate an iDSN. Analyses of the contributions of each drug property indicate that this iDSN was driven by all data types and performs better than other DSNs. Within the top 20 recommended drug pairs, 7 drugs have been reported to be repurposed. The source code for PIMD is available at https://github.com/Sepstar/PIMD/.

OBJECTIVETo induce Mycobacterium tuberculosis (MTB) resistance with ofloxacin (Ofx) of stepwise increasing concentration in vitro, investigate stability to fluoroquinolone (FQs) antibiotic of MTB, and analyze the molecular mechanism and mutation specialty of drug resistance preliminarily.

METHODSMTB Standard strain H37RV and 24 clinical isolates susceptible to Ofx were selected and experimentally serially subcultured in liquid culture medium containing increasing concentration of Ofx and induced the drug resistance to Ofx. Variety of Minimal Inhibitory Concentrations (MICs) to FQs drugs were detected by microwell-MIC-test method. Mutations of quinolone resistance determining region (QRDR) of gyrA gene were sequenced and identified. Relationship of different mutation sites and drug resistant degree were analyzed. A total of 6 MTB clinical isolates resistant to Ofx and induced drug resistant isolates in vitro were serially subcultured in liquid culture medium without drug. Variety of drug resistant stability, including MIC and mutation of gyrA gene were detected.

RESULTSMIC values of 21 Ofx susceptible isolates after induction were eight times higher than before, which were induced to drug resistant strains successfully and also resistant to Lfx and Mfx. Hot mutations of QRDR of gyrA gene were detected by sequencing, except one strain. Mutation of codon 94 occurred in 60% (12/20) of the strains with mutations and corresponding value of 50% Minimal Inhibitory Concentrations(MIC50) was ≥ 8 µg/ml. In all, 4 of 6 MTB clinical isolates resistant to Ofx harbored mutation of codon 90 (67%) , but the corresponding value of MIC50 was 2 µg/ml. After 21 serially subcultured in liquid culture medium without drug, MIC values of 6 clinical isolates resistant to Ofx were not changed obviously and mutations were also not changed. After 11 times serially subcultured in culture medium without drug, MIC values of induced drug resistant strains were also not changed obviously, but new mutations were detected in QRDR of 3 isolates.

CONCLUSIONMTB strains resistant to three kinds of FQs antibiotic were obtained by induction in vitro with Ofx. Codons 88, 94 mutations of QRDR of gyrA gene were related to the high level FQs drug resistance of MTB. Drug resistant stability of MTB to FQs was strong, and it is difficult for MTB to resume susceptibility.

Antitubercular Agents ; pharmacology ; DNA Gyrase ; genetics ; Drug Resistance, Bacterial ; genetics ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis ; drug effects ; genetics ; isolation & purification ; Ofloxacin ; pharmacology

OBJECTIVETo obtain the C7C peptide ligands of Mycobacterium tuberculosis by affinity screening based on the phage-displayed random C7C peptide library, and preliminarily identify the binding capacity of the peptide to Mycobacterium.

METHODSInactive Mycobacterium tuberculosis reference strain H37Rv was used as the target molecule to screen the Ph. D.-C7C peptide library, and Mycobacterium bovis, BCG was used for reverse screening. After 4 rounds of affinity screening, single phages eluted by H37Rv and BCG were selected for DNA sequencing. ELISA was used to detect the binding affinities of different single phage clones. The cyclic peptides displayed by the phage clones showing the highest appetency were synthesized in vitro with fluorescent markers. Fluorescence microscopy and flow cytometer was used to detect the binding affinities of synthesized cyclic peptides, comparing with linear binding peptides obtained before.

RESULTSAfter 4 rounds of biopanning, phages that could bind with target molecules were remarkable enriched. 16 common sequences were obtained by sequencing analysis of single phages. With ELISA, phage SB1, SB5, SB8 and SB26 all showed higher affinity with H37Rv and BCG, the ratio to negative control of which were ≥ 2.1, but could not bind to the 3 nonmycobacteria, which were identified as the positive clones. Based on the results of flow cytometer detection, the affinities to H37Rv of 4 cyclic peptides SB1, SB5, SB24, SB26 were (73.2 ± 6.3)%, (63.2 ± 5.3)%, (32.9 ± 3.1)%, (89.4 ± 7.0)%, and to BCG were (65.6 ± 6.1)%, (48.6 ± 4.5)%, (10.3 ± 1.8)%, (86.6 ± 7.9)%, separately, which were all higher than H8 ((4.0 ± 1.0)%, (5.5 ± 1.2)%) . From the results of fluorescence microscopy observation, all of the fluorescent labeled cyclic peptides SB1, SB5, SB24, SB26 could bind to H37Rv and showed higher fluorescence intensities, which also had certain affinities to other 18 mycobacteria, but the fluorescence intensities were lower than H37Rv, and didn't bind to 3 non-mycobacteria.

CONCLUSIONBased on the replacement of linear 7 peptide library with C7C peptide library, new ligands of Mycobacterium tuberculosis were achieved successfully, which showed significantly higher binding affinities to mycobacteria.

Base Sequence ; Enzyme-Linked Immunosorbent Assay ; Ligands ; Mycobacterium tuberculosis ; Peptide Library ; Peptides

Objective:To investigate the association between oxygen desaturation rate and blood pressure (BP) among severe obstructive sleep apnea syndrome (OSAS) and the possible mechanism.Methods:Patients with snoring were enrolled from the Department of Sleep Medicine Center, the Affiliated Huaian No.1 People′s Hospital of Nanjing Medical University form March 2018 to January 2019 and underwent polysomnography (PSG). Noninvasive BP and Heart rate variability were full-night monitored continuously and synchronized with PSG. Based on the PSG results and exclusion criteria, a total of 86 severe OSAS patients were enrolled in this study and divided into two groups according to the ambulatory BP measurements: hypertensive group ( n=44) and normotensive group ( n=42). Oxygen desaturation rate was expressed as the change in the percentage of pulse oxyhemoglobin saturation (SpO 2) per second during desaturation events after the obstructive apnea events occurred. The PSG parameters were compared between the two group and the multiple regression analyses were used to explore the association between oxygen desaturation rate and BP and its possible mechanism. Results:The apnea-hyperpnoea index (AHI) and respiratory event-related arousals (RERAs) were significantly higher in hypertensive group than those in normotensive group [(69.8±18.2) vs. (56.5±13.9) event/h; (40.5±17.4) vs. (30.2±14.6) event/h, both P<0.01]. In addition, hypoxia exposure conditions in the hypertensive group were more severe than those in the normotensive group, especially oxygen desaturation rate [(0.45±0.14)%/s vs. (0.33±0.10)%/s, P<0.001]. After adjusting for age, sex, neck circumference, waist circumference, smoking, drinking, the regression analyses showed that only the oxygen desaturation rate was significantly associated with both awake and asleep BP in OSAS patients ( β=0.473, 0.478, both P<0.01) and the correlation analyses suggested that the oxygen desaturation rate was related to the both awake and asleep sympathetic-parasympathetic imbalance ( r=0.367, 0.337, both P<0.01). Conclusion:Oxygen desaturation rate is closely related to BP levels in patients with severe OSAS, and the underlying mechanism is associated with the increased sympathetic activity.