[Role of intercellular adhesion molecule-1 in adhesion and migration of mesenchymal stem cells in ankylosing spondylitis and its mechanisms].

Objective: To investigate the role and underlying mechanisms of intercellular adhesion molecule-1 (ICAM-1) in the adhesion and migration of mesenchymal stem cells (MSCs) in patients with ankylosing spondylitis (AS). Methods: Bone marrow and ligament tissues were collected during surgery from patients with AS and thoracolumbar fractures (as controls, HC) treated from October 2021 to October 2022 at Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital. MSCs were isolated and cultured from the bone marrow using the Ficoll separation method. Cell morphology was observed under high-resolution microscopy, and differences in the cytoskeletal features between AS-and HC-MSCs were analyzed through immunofluorescence staining. The expression of ICAM-1 was quantified in both groups using real-time quantitative polymerase chain reaction (RT-qPCR) and flow cytometry. Transwell migration assays and wound healing experiments were conducted to evaluate the differences in migration rates between the two groups of MSCs. Results: The interspinous ligament and bone marrow was acquired in AS (2 males and 1 female; 33, 37, 32 years old, respectively) and no-AS patients (2 males and 1 female; 35, 32, 38 years old, respectively). AS-MSCs exhibited broader cell morphology compared to HC-MSCs under bright field and fluorescence microscopy. Immunofluorescence staining of the interspinous ligament showed higher expression of ICAM-1 (68.38±3.42 vs 48.31±2.43) and CD105 (37.97±2.16 vs 23.36±2.06) in AS patients (both P<0.001). Western blot and RT-qPCR analysis revealed significantly stronger protein expression and transcription levels of ICAM-1 in AS-MSCs when compared to those in HC-MSCs (both P<0.001). Flow cytometry confirmed greater mean fluorescence intensity of ICAM-1 in AS-MSCs than in that in HC-MSCs (924.30±54.99 vs 636.47±40.03, P=0.002). Regarding cell adhesion efficiency, it showed no significant difference between AS-MSCs and HC-MSCs in the early stage of adhesion (0.5 h: 1 496±213 vs 1 205±163, P=0.133), but they were all significantly higher in AS-MSCs in the later stage (1 h: 2 894±172 vs 1 908±155, P=0.002; 2 h: 4 540±286 vs 3 334±188, P=0.004; 3 h: 5 212±281 vs 4 208±303, P=0.014). Finally, cell migration experiments demonstrated a stronger migration capability of AS-MSCs compared to HC-MSCs (5 449±172 vs 4 016±155, P<0.001), and the inhibition efficiency of A-205804 on the migration rate of AS-MSCs was stronger than that on HC-MSCs (2 145±239 vs 3 539±316, P=0.004). Conclusions: The aberrant expression of ICAM-1 markedly influences the adhesion and migration dynamics of MSCs. Elevated ICAM-1 levels in MSCs derives from patients with AS significantly enhance their migratory capabilities.

[Correlation analysis of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and central cervical lymph node metastasis of papillary thyroid microcarcinoma].

Objective: To investigate the correlation between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and central lymph node metastasis (CLNM) in patients with cN0 papillary thyroid microcarcinoma (PTMC). Methods: The clinicopathological data of PTMC patients confirmed by surgery and pathology in the 81st Military Hospital of People's Liberation Army from 2016 to 2019 were collected, and the relationship between preoperative NLR, PLR levels and postoperative PTMC CLNM were analyzed. Logistic regression analysis was used for multivariate analysis. Receiver operating characteristic (ROC) curve was used to determine the cutoff value of NLR and PLR. The interaction relative excess risk was used to analyze the relationship between NLR, PLR and CLNM. Results: Among 220 patients with cN0 stage PTMC, 92 were CLNM. The ROC curve showed that when the cutoff value of NLR was 2.5 and the cutoff value of PLR was 175, the highest Youden index was 0.318 and 0.264, respectively. NLR and PLR were both related to CLNM (P<0.05). The tumor long diameter, multifocality, NLR≥2.5 and PLR≥175 were independent impact factors of CLNM (P<0.05). The results of the interaction showed that the relative excess risk of the interaction was 5.531 (95%CI: 0.160, 10.901, P=0.016), the attribution ratio was 0.512 (95%CI: 0.230, 0.794, P=0.009), and the synergy index was 2.294 (95%CI: 1.492, 4.579, P=0.022), suggested that NLR and PLR had an interactive effect, and these two synergistically promoted CLNM. Conclusions: NLR and PLR are independent risk factors for cN0 stage PTMC CLNM. When NLR≥2.5 and PLR≥175, preventive central lymph node dissection should be routinely performed.

[Clinical outcomes of different irradiation ranges in definitive intensity-modulated radiotherapy for esophageal cancer].

Objective: To explore the therapeutic efficacy and safety of elective nodal irradiation (ENI) and involved field irradiation (IFI) in intensity-modulated radiotherapy for esophageal cancer, screen the patients suitable to undergo ENI radiotherapy and provide evidences for individual treatment of esophageal cancer. Methods: A retrospective analysis was performed on the clinical data of 924 patients with esophageal cancer who received definitive intensity-modulated radiotherapy in our hospital from January 2006 to December 2015. Among them, 272 patients received ENI and the other 652 patients received IFI. The clinicopathologic characteristics of 272 cases in ENI group and 652 cases in IFI group, who were recruited according to the balance of propensity score matching method, were compared. The Kaplan-Meier method was used to calculate 1-year, 3-years and 5-years local-regional failure-free survival (LRFFS), progression-free survival (PFS) and overall survival (OS) rates. The univariate and multivariate analysis of prognostic factors were also determined by Cox proportional hazard model and Long-rank test. Results: The clinicopathologic characteristics of these two group were not significantly different (P>0.05). The median follow-up time was 85.9 months and the follow-up rate was 95.9%. The 1-year, 3-years, 5-years PFS rates of the ENI groups were 65.3%, 31.7%, 18.4%, respectively, higher than 54.0%, 20.9%, 12.7% of the IFI group (P=0.001). The 1-year, 3-years, 5-years OS rates of the ENI groups were 79.0%, 43.7%, 24.9%, respectively, higher than 75.0%, 31.8%, 17.2% of the IFI group (P=0.003). In multivariate analysis, the sex, tumor volume, N stage and radiation field were independent factors for PFS and OS (P<0.05). Subgroup analysis showed that patients with male, age≤66 year, cervical and upper-thoracic location, tumor length≤6 cm, T1-2 stage, N0-1 stage, Ⅰ-Ⅱ stage, tumor volume≤50 cm(3), dosage>60 Gy and≤2 cycles of chemotherapy in the ENI group had a better survival rate than those in the IFI group (P<0.05). The total failure rate, local-regional failure rate in ENI group were significantly lower than those of IFI group (P=0.001, P=0.004). The incidence of bone marrow depression≥ grade 2 and 3 in ENI group was higher than that of the IFI group (P<0.05). However, the incidences of radioactive esophagitis≥ grade 3, radioactive pneumonia and late adverse reactions were not significantly different between these two groups (P>0.05). Conclusion: Compared with IFI, ENI can significantly improve the long-term survival for young, early TN stage and cervical/upper-thoracic esophageal cancer patients underwent chemotherapy.

Global Disparities in Breast Cancer Genetics Testing, Counselling and Management.

Hereditary breast cancers, mainly due to BRCA1 and BRCA2 mutations, account for only 5-10% of this disease. The threshold for genetic testing is a 10% likelihood of detecting a mutation, as determined by validated models such as BOADICEA and Manchester Scoring System. A 90-95% reduction in breast cancer risk can be achieved with bilateral risk-reducing mastectomy in unaffected BRCA mutation carriers. In patients with BRCA-associated breast cancer, there is a 40% risk of contralateral breast cancer and hence risk-reducing contralateral mastectomy is recommended, which can be performed simultaneously with surgery for unilateral breast cancer. Other options for risk management include surveillance by mammogram and breast magnetic resonance imaging, and chemoprevention with hormonal agents. With the advent of next-generation sequencing and development of multigene panel testing, the cost and time taken for genetic testing have reduced, making it possible for treatment-focused genetic testing. There are also drugs such as the PARP inhibitors that specifically target the BRCA mutation. Risk management multidisciplinary clinics are designed to quantify risk, and offer advice on preventative strategies. However, such services are only possible in high-income settings. In low-resource settings, the prohibitive cost of testing and the lack of genetic counsellors are major barriers to setting up a breast cancer genetics service. Family history is often not well documented because of the stigma associated with cancer. Breast cancer genetics services remain an unmet need in low- and middle-income countries, where the priority is to optimise access to quality treatment.

Ultra-narrow linewidth quantum dot coherent comb lasers with self-injection feedback locking.

We have used an external cavity self-injection feedback locking (SIFL) system to simultaneously reduce the optical linewidth of over 39 individual wavelength channels of an InAs/InP quantum dot (QD) coherent comb laser (CCL). Linewidth reduction from a few MHz to less than 200 kHz is observed. Measured phase noise spectra clearly indicate a significant decrease in phase noise in the frequency range above 2 kHz. The RF beating signal between two adjacent channels also shows a substantial reduction in 3-dB linewidth from 10 kHz to 300 Hz with the SIFL system, and a corresponding drop in baseline level (-27 dB to -50 dB).

High performance InAs/InP quantum dot 34.462-GHz C-band coherent comb laser module.

We have developed an InAs/InP quantum dot (QD) C-band coherent comb laser (CCL) module with actively stabilized absolute wavelength and power, and channel spacing of 34.462 GHz with ± 100 ppm accuracy. The total output power is up to 46 mW. The integrated average relative intensity noise (RIN) values of the lasing spectrum and a filtered single channel at 1540.19 nm were -165.6 dB/Hz and -130.3 dB/Hz respectively in the frequency range from 10 MHz to 10 GHz. The optical linewidth of the 45 filtered individual channels between 1531.77 nm to 1543.77 nm ranged from 850 kHz to 2.16 MHz. We have also analyzed the noise behaviors of each individual channel.

Influences of Patellofemoral Pain and Fatigue in Female Dancers during Ballet Jump-Landing.

This study investigated the influence of patellofemoral pain (PFP) and fatigue on lower-extremity joint biomechanics in female dancers during consecutive simple ground échappé. 3-dimensional joint mechanics were analyzed from the no-fatigue to fatigue conditions. 2-way mixed ANOVAs were used to compare the differences of the kinematic and kinetic variables between groups and conditions. Group main effects were seen in increased jump height (p=0.03), peak vertical ground reaction force (p=0.01), knee joint power absorption (p=0.04), and patellofemoral joint stress (PFJS, p=0.04) for PFP group. Fatigue main effects were found for decreased jump height (p<0.01), decreased ankle plantarflexion at initial foot-ground contact (p=0.01), and decreased ankle displacement (p<0.01). Hip external rotation impulse and hip joint stiffness increased (both p<0.01) while knee extension and external rotation moment, and ankle joint power absorption decreased (p<0.01, p=0.02, p<0.01, respectively) after fatigue. The peak PFJS also decreased after fatigue (p<0.01). Female ballet dancers with PFP sustained great ground impact and loads on the knee probably due to higher jump height compared to the controls. All dancers presented diminished knee joint loading for the protective mechanism and endurance of ankle joint musculature required for the dissipation of loads and displayed a distal-to-proximal dissipation strategy after fatigue.

Correlation between the genetic polymorphism of ORMDL3 gene and asthma risk: a meta-analysis.

While increasing scientific evidence suggests that the ORMDL3 rs7216389 polymorphism may contribute to a higher susceptibility to asthma, many of the current studies have yielded inconclusive results. This meta-analysis aimed to assess the association between the ORMDL3 rs7216389 polymorphism and the risk of asthma. An extensive literature search for relevant studies was conducted in PubMed, Embase, the Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure, and Google Scholar. This meta-analysis was performed using the STATA 12.0 software. Crude odds ratios (OR) and their 95% confidence intervals (CI) were calculated. Thirteen studies were included with a total of 14,851 subjects, comprised of 6739 patients with asthma and 8112 healthy controls. Our meta-analysis results revealed that the ORMDL3 rs7216389 polymorphism may be associated with an increased risk of asthma (allele model: OR = 1.39, 95%CI = 1.27-1.52, P < 0.001; dominant model: OR = 1.46, 95%CI = 1.31-1.62, P < 0.001; recessive model: OR = 1.57, 95%CI = 1.37-1.81, P < 0.001; homozygous model: OR = 1.58, 95%CI = 1.32-1.90, P < 0.001; heterozygous model: OR = 1.54, 95%CI = 1.30-1.82, P < 0.001). We also found significant associations in our subgroup analyses based on ethnicity and type of asthma. However, in our subgroup analysis based on sources of controls, an association was found in the population-based case-control subgroup but not in the hospital-based case-control subgroup. This meta-analysis indicates that ORMDL3 rs7216389 may contribute to increasing susceptibility to asthma.

Comparison of efficacy between uncovered and covered self-expanding metallic stents in malignant large bowel obstruction: a systematic review and meta-analysis.

AIM: Insertion of a self-expandable metallic stent (SEMS) can rapidly relieve colorectal obstruction. This study aimed to compare the efficacy between uncovered and covered SEMSs in the treatment of malignant colorectal obstruction. METHOD: A systematic search in Medline, Embase, the Cochrane controlled trials register and bibliographies of retrieved articles was performed. Randomized controlled trials and other comparative studies comparing uncovered and covered SEMSs for treatment of malignant colorectal obstruction were selected for this systematic review and meta-analysis. The main outcome measures were technical success, clinical success, tumour ingrowth, tumour overgrowth, early migration (≤ 7 days), late migration (> 7 days), overall complications and the duration of stent patency. RESULTS: Compared with covered SEMSs, uncovered SEMSs were associated with a lower late migration rate (relative risk 0.25; 95% CI 0.08, 0.80; P = 0.02), a higher tumour ingrowth rate (relative risk 5.99; 95% CI 2.23, 16.10; P = 0.0004) and a prolonged stent patency (weighted mean difference 15.34 days; 95% CI 4.31, 26.37; P = 0.006). There was no significant difference in technical success, clinical success, tumour overgrowth, early migration, perforation or overall complications between the two groups. CONCLUSION: Tumour ingrowth occurred more frequently in the uncovered SEMS group, while late migration was more common in the covered SEMS group.

Spatial and temporal gene expression of Fn-type II and cysteine-rich secretory proteins in the reproductive tracts and ejaculated sperm of Chinese Meishan pigs.

Fibronectin type II and cysteine-rich secretory proteins have been well studied in the murine and human. The present study evaluated CRISP1, CRISP2, CRISP3 and Fn-type II (ELSPBP1 and pB1) gene expression patterns in ejaculated sperm and reproductive tracts of Chinese Meishan pigs from birth to day 150 of age. In ejaculated sperm, except for ELSPBP1, all others genes studied were detectable. In sexually mature boars and gilts, CRISP1 gene was expressed strongly in whole epididymides, moderate in prostate and weak in seminal vesicle. CRISP2 gene represented extensive distribution along reproductive tracts with highest abundance in testis. CRISP3 gene was expressed highly in prostate and bulbourethral gland, but weakly in testis. ELSPBP1 gene was expressed with highest abundance in cauda epididymides, moderate in corpus epididymides and weak in seminal vesicle and prostate. pB1 mRNA expression was also abundant along reproductive tracts. During the sexual development of boars after birth, these genes showed different expression patterns. CRISP1 and CRISP3 gene expression was high on day 1 and maintained until day 150, while CRISP2 expression was detectable on day 60 with high abundance and maintained until day 90 and dropped on day 150. ELSPBP1 showed low expression at birth and increased significantly on day 30 (p < 0.05) and then kept static until day 150. pB1 gene displayed moderate expression from birth to day 30 and increased significantly on day 60 (p < 0.05) and maintained at high level until day 150. Collectively, CRISP and Fn-type II genes were expressed extensively along genital tracts, and most of them showed mRNA signal in ejaculated sperm. The expression of CRISP1 and CRISP3 genes in Meishan boar was not age-dependent, while CRISP2 and pB1 gene expression was parallel with sexual development. Their unique gene expression patterns may shed light on the mechanism for the high prolificacy of Meishan pigs.

Strong correlation between flux pinning and epitaxial strain in the GdBa2Cu3O7-x /La0.7Sr0.3MnO3 nanocrystalline heterostructure.

The effect of magnetic flux pinning is investigated in GdBa2Cu3O7 (GdBCO) thin films with two different types of ferromagnetic La0.7Sr0.3MnO3 (LSMO) buffers (nanoparticles and a layer) deposited on an STO substrate. Magnetization analyses reveal the presence of multiple flux pinning mechanisms responsible for the improvement in the critical current density of GdBCO films. While core pinning becomes a dominant pinning mechanism in GdBCO films with LSMO nanoparticles, a hybrid effect of magnetic-volume and core-point pinning is observed in GdBCO films with LSMO layers. Examinations of local structures for both LSMO and GdBCO using extended X-ray absorption fine structure spectroscopy (EXAFS) exhibit a close relation between the parameters in the pinning force scaling and the length ratio of the Mn-O bond to the Cu-O bond. This result implies that the origin of core pinning is probably attributed to epitaxial strain induced by lattice mismatch between LSMO and GdBCO. Therefore, an appropriate strain state of LSMO is required for an effective operation of magnetic pinning.

Terahertz two-photon quantum well infrared photodetector.

A two-photon detector based on intersubband transitions in GaAs/AlGaAs quantum wells operating in the Terahertz regime below the Reststrahlenband is reported. Resonantly enhanced optical nonlinearities enables sensitive quadratic detection at pJ pulse energies. We demonstrate its use in a quadratic autocorrelator for far-infrared picosecond pulses at around 7 THz.

Mode-locked pulses from mid-infrared quantum cascade lasers.

In this study, we report the unequivocal demonstration of midinfrared mode-locked pulses from quantum cascade lasers. The train of short pulses was generated by actively modulating the current and hence the gain of an edge-emitting quantum cascade laser (QCL). Pulses with duration of about 3 ps at full-width-at-half-maxima and energy of 0.5 pJ were characterized using a second-order interferometric autocorrelation technique based on a nonlinear quantum well infrared photodetector. The mode-locking dynamics in the QCLs was modeled based on the Maxwell-Bloch equations in an open two-level system. Our model reproduces the overall shape of the measured autocorrelation traces and predicts that the short pulses are accompanied by substantial wings as a result of strong spatial hole burning. The range of parameters where short mode-locked pulses can be formed is found.

Protective effects of melatonin on mitochondrial biogenesis and mitochondrial structure and function in the HEK293-APPswe cell model of Alzheimer's disease.

OBJECTIVE: The effects and mechanisms of melatonin on Alzheimer's disease (AD) are still not researched thoroughly. 20E2 cells (HEK293-APPswe cells) are a cellular model of AD. The modulation effects of melatonin on the structure and function of mitochondria in 20E2 cells need to be studied. MATERIALS AND METHODS: The Alzheimer's disease (AD) cell model was assessed for cell viability, expression levels of mitochondrial biogenesis factors (peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC-1α], nuclear respiratory factor 1 [NRF1], nuclear respiratory factor 2 [NRF2], mitochondrial transcription factor A [TFAM]), mitochondrial membrane potential, Na+-K+-adenosine triphosphatase (ATPase) and cytochrome C oxidase activity, adenosine triphosphate (ATP) level, mitochondrial DNA/nuclear DNA (mtDNA/nDNA) ratio, and mitochondrial structure with and without melatonin. RESULTS: Melatonin improved 20E2 cell viability, expression of mitochondrial biogenesis factors (PGC-1α, NRF1, NRF2, TFAM), mitochondrial membrane potential, Na+-K+-ATPase, and cytochrome C oxidase activity, ATP level, mtDNA/nDNA ratio, mitochondrial structure, and decreased amyloidogenic amyloid precursor protein processing. CONCLUSIONS: Mitochondrial biogenesis disorder is associated with the pathogenesis of AD through PGC-1α-NRF-TFAM pathway, and melatonin improves the mitochondrial structure and function by enhancing mitochondrial biogenesis and decreasing amyloidogenic APP processing in Alzheimer's disease.

Repair of triplex-directed DNA alkylation by nucleotide excision repair.

Triplex-forming oligonucleotides (TFOs) are being investigated as highly specific DNA binding agents to inhibit the expression of clinically relevant genes. So far, they have been shown to inhibit transcription from the HER-2/neu gene in vitro, whereas their use in vivo has been studied to a limited extent. This study uses a TFO-chlorambucil (chl) conjugate capable of forming site-specific covalent guanine adducts within the HER-2/neu promoter. We demonstrate that nucleotide excision repair (NER) represents a mechanism of cellular resistance to TFO-directed DNA alkylation. In vitro repair assays demonstrate that triplex-directed chl-guanine adducts are substrates for repair by NER competent cell extracts but not XP12BE cell extracts deficient in NER. The degree of repair is estimated by a ligation-mediated polymerase chain reaction with a pre-formed triplex in a plasmid transfected into repair competent cells, indicating that approximately 25% of the guanine adducts are removed after 24 h. These data indicate that guanine adducts from TFO-directed alkylation are a substrate for NER and that DNA repair is a significant barrier to the intracellular persistence of target gene binding by TFOs.

Expression and preliminary characterization of recombinant human tissue kallikrein in egg white of laying hens.

Human tissue kallikrein (hK1) plays an important role in regulation of blood pressure, electrolyte and glucose transport, and renal function. To evaluate the feasibility of expression of recombinant human tissue kallikrein (rhK1) in the egg whites of laying hens, human tissue kallikrein gene (hKLK1) cDNA was subcloned into the chicken oviduct-specific expression vector (pOV3), and the resultant recombinant vector pOV3K was injected into laying hens via wing vein after mixing with polyethyleneimine. Following injection twice with the recombinant vector, the enzymatic activity at a maximal level of 59 U/mL was detected in the egg whites, which lasted for more than 7 d. The expression level of rhK1 in the egg whites in the 3-mg group was relatively higher than that in the 2-mg group, but the significant differences were identified on d 7 and 8 (P < 0.05). Ten days after the primary injection, the hens were reinjected with the same dose of the vector, and even higher enzymatic activity was detected in their egg whites. Two different breeds of hen were tested with no difference in expression level found (P > 0.05). Western blot analysis of the egg whites from vector-injected hens showed the rhK1 was recognized by a polyclonal antibody specific for hK1 with molecular weights of 37 and 43 kDa, which probably corresponded to the mature and preenzyme, respectively. Biochemical studies showed that the recombinant enzyme had a similar thermostability, optimal pH, hypotensive effect, and sensitivity to different ions to the natural enzymes in human and porcine tissues. These data indicate that the chicken oviduct-specific transient expression system can produce relatively high level and authentic recombinant enzyme with a potential for further development for therapeutic use.

Gold nanoflowers with tunable sheet-like petals: facile synthesis, SERS performances and cell imaging.

So far only a few approaches have been reported for the successful synthesis of 3D flower-like hierarchical gold nanostructures. In this paper, a facile, seedless and one-pot approach to synthesize a new class of flower-shaped gold nanoparticles with sheet-like petals has been proposed by reduction of HAuCl4 with ascorbic acid in (1-hexadecyl)trimethylammonium chloride solution, in the presence of silver nitrate (AgNO3). The growth of petals can be controlled and tuned by adjusting the amount of silver nitrate in the growth solution, and the reaction progress and evolution of the petals were monitored by time-course measurements via UV-vis-NIR spectroscopy and SEM to observe the growth mechanisms of nanoparticles. Besides, their optical properties, especially SERS performances, were also studied. These SERS-active gold nanoparticles were further utilized in the design of bright SERS tags for selectively in vitro imaging cancer cells. The results indicate that these Au NFs can be used as good SERS substrates or to design sensitive SERS sensors.

An ultrasensitive SERS sensor for simultaneous detection of multiple cancer-related miRNAs.

Simultaneous detection of multiple trace cancer associated serum miRNA biomarkers is considered as a feasible method for early cancer screening and diagnosis. In the present work, an ultrasensitive SERS sensor was prepared based on an Ag nanorod array SERS substrate by assembling special hairpin-shaped molecular beacons (MBs) for the detection of multiple lung cancer-related miRNA biomarkers. The portable SERS sensor exhibits excellent performance for the qualitative and quantitative detection of miRNAs, with advantages of ultra-sensitivity, good specificity, uniformity, reproducibility and stability, as well as remarkable reusability. By monitoring the SERS signal quenching of the MBs in the presence of target miRNA biomarkers, three lung cancer related-miRNAs (miRNA-21, miRNA-486, and miRNA-375) in buffer and human serum were simultaneously assayed using the SERS sensor array, and the limits of detection of the three miRNAs in human serum are 393 aM, 176 aM, and 144 aM, respectively. The reliable results demonstrate that the proposed SERS sensor array can be a promising candidate with great potential for the screening and clinical diagnosis of cancer in the early stage.

Long-term outcomes of HLA-haploidentical stem cell transplantation based on an FBCA conditioning regimen compared with those of HLA-identical sibling stem cell transplantation for haematologic malignancies.

A comparison was conducted of 213 patients with haematologic malignancies who underwent HLA-identical sibling (n=108) or HLA-haploidentical (n=105) haematopoietic cell transplantation (haplo-HCT) at our centre. The conditioning regimen included fludarabine, busulphan, cyclophosphamide and antilymphocyte globulin (ATG) (FBCA). The total dose of ATG differed between identical and haploidentical groups (3.75 mg/kg versus 12.5 mg/kg). The cumulative incidences of grade II-IV acute GvHD in the identical and haploidentical groups were 20.4% and 21.9% (P=0.73), and 2-year cumulative incidences of chronic GvHD were 36.4% and 24.1% (P=0.17), respectively. The 3-year probabilities of non-relapse mortality for identical and haploidentical groups were 20.5% and 34.9% (P=0.048), and for relapse were 22.2% and 21.0% (P=0.85), respectively. The 3-year overall survivals in the identical and haploidentical groups were 62.6% and 52.6% (P=0.054), whereas the 3-year disease-free survivals were 54.7% and 43.1% (P=0.14), respectively. In the multivariate analysis, patients in the high-risk group exhibited reduced survival, and the higher dose of mononuclear or CD34+ cells resulted in an increase in the likelihood of survival. In conclusion, haplo-HCT based on an FBCA conditioning regimen could achieve nearly comparable outcomes to HLA-identical sibling HCT.

Functional expression of a recombinant copper/zinc superoxide dismutase of filarial nematode, Brugia malayi.

A gene encoding a copper/zinc superoxide dismutase (Cu/ Zn-SOD) of a filarial nematode, Brugia malayi, has been isolated and the biochemical properties of a functionally expressed recombinant enzyme were investigated. The cloned complementary DNA contained a single open reading frame of 477 bp encoding 158 amino acids (aa), which conserved metal-binding residues as well as residues specific for Cu/Zn-SODs. Comparison of the deduced aa sequence of the enzyme with that of other helminthes species, including filarial worms, exhibited high degree of similarities (49-98%). Recombinant enzyme of 32 kDa had an isoelectric point of 6.6 and was shown to consist of 2 subunits linked by interchain disulfide bonds. Enzyme activity of the recombinant protein was inhibited by potassium cyanide and hydrogen peroxide but not by sodium azide. It showed a wide range of pH optima, i.e., 7.0-11.0 and was highly resistant to heat inactivation.