[Efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage â ¡-â ¢ melanoma].

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.

Spontaneous Ferromagnetism Induced Topological Transition in EuB_{6}.

The interplay between various symmetries and electronic bands topology is one of the core issues for topological quantum materials. Spontaneous magnetism, which leads to the breaking of time-reversal symmetry, has been proven to be a powerful approach to trigger various exotic topological phases. In this Letter, utilizing the combination of angle-resolved photoemission spectroscopy, magneto-optical Kerr effect microscopy, and first-principles calculations, we present the direct evidence on the realization of the long-sought spontaneous ferromagnetism induced topological transition in soft ferromagnetic EuB_{6}. Explicitly, we reveal the topological transition is from Z_{2}=1 topological insulator in paramagnetic state to χ=1 magnetic topological semimetal in low temperature ferromagnetic state. Our results demonstrate that the simple band structure near the Fermi level and rich topological phases make EuB_{6} an ideal platform to study the topological phase physics.

[Combined application of field epidemiology and laboratory etiology analysis in the investigation of a foodborne disease outbreak in Xinjiang uygur Autonomous Region, 2016].

Objectives: To analyze the causes of a foodborne outbreak in rural areas of Xinjiang between April 2 and April 5 in 2016. Methods: Cases and the relevant background information were obtained by consulting outpatient records of local health centers and regional people's hospitals and interviewing doctors and residents. All samples were collected by the laboratory test through epidemiological and food hygiene investigations. The χ2 test (Fisher's exact probability method) was used to compare differences in incidence rates. Molecular typing, virulence genes and single nucleotide polymorphisms (SNPS) were analyzed by using Pulsed Field Gel Electrophoresis (PFGE) and Whole Genome Sequencing (WGS). Results: A total of 142 cases were found in this study, with incidence rate at 5.7‰ (142/24 979). Among all cases, the main symptoms were nausea (94%), vomiting (92%) and abdominal pain (67%), and the incubation period was about 2 h (1-7.5 h). There were 16 Staphylococcus aureus isolates identified and all of them could produce A+C+E mixed enterotoxin. PFGE showed 100% homology. WGS further revealed that there were 9 and 1 strains contained by Sequence Type 1 (ST1) and ST5405, respectively. All ST1 strains were in the same clade on the genome tree. Among these, 7 strains shared close proximity (74 SNPs) and 2 strains shared close relationships as well (127 SNPs). The S. aureus isolates that caused the outbreak were introduced by a mutant isolate from the milk supply station. Conclusions: This foodborne outbreak was mainly caused by Staphylococcus aureus contamination.

Geolocation Inference of Forensic Individual Origin by Soil Metagenomic Analysis.

ABSTRACT: Objective To preliminarily discuss the feasibility of geolocation inference of forensic individual origin by soil metagenomic analysis. Methods The 33 soil samples from Heilongjiang, Qinghai and Tibet were collected, total bacterial DNA in the samples were extracted, and universal primers were used to amplify the V3 and V4 hypervariable region of bacterial 16S rDNA. The region was sequenced by high-throughput sequencing （HTS） with the MiSeq sequencer. Bioinformatics analysis such as species composition and sample comparison was performed on sequencing data. The richness index and diversity index were calculated based on operational taxonomic unit （OTU） results. Results A total of 2 720 149 sequences were generated by sequencing. Those sequences were clustered into 114 848 OTUs. The Chao1 indexes of soil microorganisms in Heilongjiang, Qinghai, and Tibet were 797.45, 745.11 and 535.98, respectively, and Shannon indexes were 6.46, 6.36 and 6.25, respectively. The number of bacterial species and the community diversity in the soil from high to low were Heilongjiang > Qinghai > Tibet. The composition of soil bacteria in three provinces at various classification levels were obtained, the dominant genuses in Heilongjiang were Chthoniobacteraceae DA101 and an unannotated genus of Thermogemmatisporaceae; the dominant genuses in Qinghai were an unannotated genus of Cytophagaceae and an unannotated genus of Nocardioidaceae; the dominant genuses in Tibet were an unannotated genus of Comamonadaceae and Verrucomicrobiaceae Luteolibacter. The results of principal co-ordinates analysis demonstrated that, according to the weighted UniFrac analysis, the three principle components represented 56.36% of the total variable, and according to the unweighted UniFrac analysis, the three principle components represented 34.81% of the total variable. The samples from the same province could be clustered together, and the species and content of soil microorganisms from different provinces were significantly different. Conclusion Based on the metagenomic analysis method, soil samples from different regions can be effectively distinguished, which has potential application value in geolocation inference of forensic individual origin in the future.

Performance of the BL03U beamline at SSRF.

The vacuum ultraviolet beamline BL03U with a photon energy range from 7 eV upwards has been constructed at the 3.5 GeV Shanghai Synchrotron Radiation Facility. Equipped with an APPLE-Knot undulator, this beamline is dedicated to angle-resolved photoemission spectroscopy. An energy-resolving power of higher than 4.6 × 104 has been achieved in the photon energy range 21.6-48 eV, which is almost the same as the theoretical estimation.

Photoemission Spectroscopic Evidence for the Dirac Nodal Line in the Monoclinic Semimetal SrAs_{3}.

Topological nodal-line semimetals with exotic quantum properties are characterized by symmetry-protected line-contact bulk band crossings in the momentum space. However, in most of identified topological nodal-line compounds, these topological nontrivial nodal lines are enclosed by complicated topological trivial states at the Fermi energy (E_{F}), which would perplex their identification and hinder further applications. Utilizing angle-resolved photoemission spectroscopy and first-principles calculations, we provide compelling evidence for the existence of Dirac nodal-line fermions in the monoclinic semimetal SrAs_{3}, which possesses a simple nodal loop in the vicinity of E_{F} without the distraction from complicated trivial Fermi surfaces. Our calculations revealed that two bands with opposite parities were inverted around Y near E_{F}, resulting in the single nodal loop at the Γ-Y-S plane with a negligible spin-orbit coupling effect. The band crossings were tracked experimentally and the complete nodal loop was identified quantitatively, which provide a critical experimental support for the existence of nodal-line fermions in the CaP_{3} family of materials. Hosting simple topological nontrivial bulk electronic states around E_{F} and without complication from the trivial states, SrAs_{3} is expected to be a potential platform for topological quantum state investigation and applications.

[The prognostic value of circulating microRNA-29b in left ventricular hypertrophy in patients with hypertension].

Objective: To analyze the relationship between the level of microRNA-29b in circulation and left ventricular hypertrophy in hypertensive patients. Methods: A total of 240 subjects from Henan Province People's Hospital from June 2015 to June 2018 were included in the present study. Among them, 160 were hospitalized patients, and were divided into two groups. Patients with simple hypertension and had no left ventricular hypertrophy (80 cases) were in the simple hypertension group (HBP-NLVH), and patients with hypertension combined with left ventricular hypertrophy (80 cases) were in the high blood pressure with left ventricular hypertrophy group (HBP-LVH). Normal control subjects (80 cases) were those with no hypertension and randomly selected from the medical center of Henan Province People's Hospital. Serum microRNA-29b expressions were detected by real time fluorescence quantitative PCR. The thickness of interventricular septum (IVSD) and left ventricular posterior wall thickness (LVPWD) were measured by echocardiography. Results: Compared with the normal control group (1.95±0.79), the relative expression of microRNA-29b in the patients both in the HBP-NLVH group (2.67±0.92) and the HBP-LVH group (5.12±1.23) was up-regulated, and the difference between normal control and patients was statistically significant (P<0.05). In patients, the microRNA-29b level in the HBP-LVH group was significantly higher than that in the HBP-NLVH group (P<0.05). The expression level of microRNA-29b was positively correlated with IVSD (r=0.71, P<0.05) and LVPWD (r=0.74, P<0.05), respectively. The sensitivity and specificity of serum microRNA-29b levels in the diagnosis of left ventricular hypertrophy in hypertension patients were 96.8% and 91.3%, respectively. Conclusion: Serum microRNA-29b level is elevated in hypertensive patients with left ventricular hypertrophy, and is positively correlated with left ventricular hypertrophy. The circulation microRNA-29b might be a useful biomarker with prognostic value in left ventricular hypertrophy in hypertension patients.

[The comparison of neurobehavioral changes and impaired locations between the mouse model of manganism and Parkinson's disease].

Objective: To investigate the effect of manganese chloride (MnCl(2)) or 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) on the neurobehavioral and histopathology in C57BL/6 mice and provide evidence for the diagnosis, treatment and prevention of manganism. Methods: Adult male C57BL/6 mice were treated with MnCl(2) and MPTP respectively by intraperitoneal injection at the doses of 5, 10, 20mg Mn/kg and 30mg MPTP/kg. Controls were injected equivalent normal saline. All animals were administrated 5 times a week for 4 consecutive weeks and sacrificed after behavior tests on the fifth week. Balance ability, anxiety and depression level and cognitive function were tested respectively by vertical pole test, open field locomotion test and Morris swim task. The neuron pathological changes of striatum and substantia nigra were examined through HE-staining pathological section by using optical microscope. Results: Compared with the control group, the high dose of MnCl(2) reduced body weight obviously (P<0.01) . The results of vertical pole test showed that MnCl(2) and MPTP lengthened the pole-climbing time and turnaround time. Open field locomotion test showed that movement distance, stand-up time and central field time were decreased after the exposure of MnCl(2) or MPTP. In the Morris swim task, the escape latency time increased and the target quadrant activity time decreased significantly after the injection of MPTP as well as high-dose MnCl(2), comparing with controls (P<0.05) . Moreover, the escape latency time of high dose MnCl(2) prolonged prominently comparing with MPTP grou (P<0.05) . The results of histopathology showed that acidophilic changes elevated in MnCl(2) and MPTP group, comparing with controls. Furthermore, in striatum the oxyphil cells number increased in MnCl(2) high-dose group comparing with MPTP group (P<0.01) . On the contrary, there were more oxyphil cells in MPTP group comparing with MnCl(2) groups in substantia nigra (P<0.01) . Conclusion: Both manganese and MPTP can induce the impairment of dopaminergic neural system, but the symptons and injured location of manganism are inconsistent with PD models induced by MPTP.

Fungal Denitrification Activity in Vertical Flow Constructed Wetlands as Impacted by Plant Species Richness, Carbon, Nitrogen and pH Amendments.

To control potential fungal denitrification rate (PFDR) in vertical flow simulated wetlands (VFSW) microcosms, thirty VFSW microcosms were established and planted with three plant species richness levels (i.e. unplanted, monoculture, and four-species polyculture treatment), and effects of carbon, nitrogen and pH amendments on the PFDR were investigated using a room-incubating method. Among seven carbon compounds, sodium citrate, glycerol, glucose and sodium succinate were more effective in enhancing PFDRs. These enhanced effects were dependant on a given species richness level. Sodium nitrite mostly stimulated PFDRs to a greater extent than the other three nitrogen compound amendments at any richness level. Treatments with pH 5.6 or 8.4 had significantly greater PFDRs than the treatment with pH 2.8 in the three species richness levels. However, no effect of plant species richness on the PFDR was observed among any carbon, nitrogen and pH amendments. Current results suggest carbon, nitrogen and pH factors should be considered when mediating fungal denitrification in VFSW microcosms.

[Association between single nucleotide polymorphism of BARD1 gene and BRCA1 gene mutation in epithelial ovarian cancer].

Objective: To investigate the relationship between single nucleotide polymorphism (SNP) of BARD1 gene and BRCA1 gene in epithelial ovarian cancer (EOC). Methods: Nineteen EOC patients with BRCA1 gene mutation and 50 EOC cases without BRCA1 gene mutation between January 2016 and October 2016 were collected, and all EOC were diagnosed by pathological method. BARD1 gene variants were detected by next generation sequencing (NGS). The SNP of BARD1 gene was analyzed by Pearson linear correlation. Logistic regression analysis was used to research the clinicopathologic features and BRCA1 gene mutation associated with BARD1 gene SNP. Pearson's chi-square test was used to analyze the association between BARD1 gene Val507Met, Arg378Ser and Pro24Ser with different clinicopathologic features and BRCA1 gene mutation risk. Results: (1) Eight BARD1 gene variants were found in 69 ovarian cancer patients, in which Val507Met, Arg378Ser and Pro24Ser were common variants, and the rate of mutation were all 54% (37/69). (2) There was a significant linear correlation among Val507Met, Arg378Ser and Pro24Ser (all P<0.01). (3) Obvious differences were found in Val507Met, Arg378Ser and Pro24Ser of BARD1 gene between BRCA1(+) and BRCA1(-) (all P<0.05) . (4) No differences were found between BARD1 gene Val507Met, Arg378Ser and Pro24Ser and the clinicopathologic features (all P>0.05), while obvious differences were found in BRCA1 gene mutation compared to the controls group. The risk of BRCA1 mutation in Val507Met and Arg378Ser were more evident in subjects with negative family history, positive menopause history, negative tubal ligation, onset age (≤60 years old) and sensitivity to platinum-based chemotherapy in EOC (all P<0.05), while Pro24Ser was only more evident in positive menopause history of EOC (P<0.05). Conclusions: BARD1 Val507Met, Arg378Ser and Pro24Ser are the common genotypes, which are associated with BRCA1 mutation in EOC. The family history, menopause history, tubal ligation, onset age and sensitivity to platinum-based chemotherapy have effects on BARD1 SNP in the risk of BRCA1 gene mutation.

[Clinical significance and distribution of BRCA genes mutation in sporadic high grade serous ovarian cancer].

Objective: To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods: Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1) The BRCA genes were detected by next-generation sequencing (NGS) method. (2) The serum tumor markers included carcinoembryonic antigen (CEA), CA(125), CA(199), and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t-tests, Pearson's chi square test, Fisher's exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics (FIGO) stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM) . Results: (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA(199), and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found (P>0.05), but the level of CA(125) was much higher in BRCA mutation group than that in controls (t=-3.536, P=0.003). Further linear regression analysis found that there was a significant linear correlation between CA(125) and HE4 group (r=0.494, P<0.01), and the same correlation as CEA and CA(199) group (r=0.897, P<0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA(+) and BRCA(-) group (P>0.05), while significant differences were found in CA(125) and sensitivity to platinum-based chemotherapy between the patients with BRCA mutation and wild type (P<0.05). The multiple factors analysis showed that the high level of CA(125) was a independent risk factor of BRCA mutations in sporadic HGSOC (P=0.007). Conclusion: The combination of CA(125) with BRCA have great clinical significance, the mutation of BRCA gene could guild the clinical chemotherapy regiments.

[Oxidative stress and autophagy in SK-N-SH cells induced by manganese chloride or 1-methyl-4-phenylpyridinium: a comparative analysis].

Objective: To investigate the effect of manganese chloride (MnCl(2)) or 1-methyl-4-phenylpyridinium (MPP (+)) on oxidative stress and autophagy in human neuroblastomaSK-N-SH cells and the mechanism of the neurotoxicity of manganese. Methods: SK-N-SH cells were treated with MnCl(2) or MPP(+) at doses of 0.062 5, 0.125, 0.25, 0.5, 1.0, and 2.0 mmol/L for 24 hours, and MTT assay was used to measure cell viability. The cells weretreated with MnCl(2) or MPP(+) at doses of 0.125, 0.25, and 0.5 mmol/L for 24 hours, and flow cytometry was used to measure the content of reactive oxygen species (ROS) in cells, a laser scanning confocal microscope was used to observe autophagosome in cells, and Western blot was used to measure the expression of autophagy-related proteins P62 and LC3-II/LC3-I. Results: Compared with the control group, the 0.0625-2.0 mmol/L MnCl(2) and 0.125-2.0 mmol/L MPP (+) treatment groups had significant reductions in the viability of SK-N-SH cells, and the 0.25-2.0 mmol/L MnCl(2) treatment groups had significantly lower viability than the groups treated with the same doses of MPP(+) (all P<0.05) . Compared with the control group, the 0.125-0.25 mmol/L MnCl(2) and 0.125-0.5 mmol/L MPP(+) treatment groups had significant increases in the content of ROS, and the 0.25-0.5 mmol/L MPP(+) treatment groups had significantly higher content of ROS than the groups treated with the same doses of MnCl(2) (all P<0.05) . Compared with the control group, the 0.25-0.5 mmol/L MnCl(2) andMPP(+) treatment groups had significant increases in autophagy-related proteins LC3-II/LC3-I and significant reductions in P62 expression; the 0.125-0.5 mmol/L MPP(+) treatment groups had significantly higher LC3-II/LC3-I than the groups treated with the same doses of MnCl(2), and the 0.125 and 0.25 mmol/L MPP (+) treatment groups had significantly lower P62 expression than the groups treated with the same doses of MnCl(2) (all P<0.05) . Conclusion: Both MnCl(2) and MPP(+) can induce oxidative stress and autophagy in SK-N-SH cells, and MPP(+) has a significantly greater inductive effect on autophagy of SK-N-SH cells than MnCl(2).

Characterizing the correlations between local phase fractions of gas-liquid two-phase flow with wire-mesh sensor.

Understanding of flow patterns and their transitions is significant to uncover the flow mechanics of two-phase flow. The local phase distribution and its fluctuations contain rich information regarding the flow structures. A wire-mesh sensor (WMS) was used to study the local phase fluctuations of horizontal gas-liquid two-phase flow, which was verified through comparing the reconstructed three-dimensional flow structure with photographs taken during the experiments. Each crossing point of the WMS is treated as a node, so the measurement on each node is the phase fraction in this local area. An undirected and unweighted flow pattern network was established based on connections that are formed by cross-correlating the time series of each node under different flow patterns. The structure of the flow pattern network reveals the relationship of the phase fluctuations at each node during flow pattern transition, which is then quantified by introducing the topological index of the complex network. The proposed analysis method using the WMS not only provides three-dimensional visualizations of the gas-liquid two-phase flow, but is also a thorough analysis for the structure of flow patterns and the characteristics of flow pattern transition. This article is part of the themed issue 'Supersensing through industrial process tomography'.

A proposal for a new scoring system to predict difficult ventilation through a supraglottic airway.

BACKGROUND: The aim of this study was to propose and validate a new clinical score to predict difficult ventilation through a supraglottic airway device. METHODS: The score was proposed from our previously reported derivation data, and we prospectively validated the score in 5532 patients from November 2013 to April 2014. Predictive accuracy of the score was compared by the area under the receiver operating characteristic (ROC) curve (AUC). We assigned point values to each of the identified four risk factors: male, age >45 yr, short thyromental distance, and limited neck movement, their sum composing the score. The score ranged between 0 and 7 points. The optimal predictive level of the score was determined using ROC curve analysis. RESULTS: The AUC of the score was 0.75 (95% CI 0.66 to 0.84) in the validation data set, and was similar to that in the derivation data set (0.80; 95% CI 0.75 to 0.86). In derivation and validation data sets, the incidence of low risk categories (scores 0-3) was 0.42% vs 0.32% and of high risk categories (scores 4-7) was 3% vs 1.7% respectively. A score 4 or greater is associated with a six to seven fold increased risk of difficult ventilation through a supraglottic airway device. CONCLUSIONS: The new score for prediction of difficult ventilation through a supraglottic airway device is easy to perform and reliable, and could help anaesthetists plan for difficult airway management.

Skin characteristics: normative data for elasticity, erythema, melanin, and thickness at 16 different anatomical locations.

BACKGROUND: The clinical use of non-invasive instrumentation to evaluate skin characteristics for diagnostic purposes and to evaluate treatment outcomes has become more prevalent. The purpose of this study was to generate normative data for skin elasticity, erythema (vascularity), melanin (pigmentation), and thickness across a broad age range at a wide variety of anatomical locations using the Cutometer(®) (6 mm probe), Mexameter(®) , and high-frequency ultrasound in a healthy adult sample. METHODS: We measured skin characteristics of 241 healthy participants who were stratified according to age and gender. Sixteen different anatomical locations were measured using the Cutometer(®) for maximum skin deformation, gross elasticity, and biological elasticity, the Mexameter(®) for erythema and melanin, and high-frequency ultrasound for skin thickness. Standardized measurement procedures were applied for all participants. RESULTS: The means and standard deviations for each measured skin characteristic for females and males across five different age groups (20-29, 30-39, 40-49, 50-59, 60-69, and 70-85 years old) are presented. As previously described, there were variations in skin characteristics across age groups, anatomical locations, and between females and males highlighting the need to use site specific, age and gender matched data when comparing skin characteristics. CONCLUSION: The reported data provides normative data stratified by anatomical location, age, and gender that can be used by clinicians and researchers to objectively determine whether patients' skin characteristics vary significantly from healthy subjects.

Roles of oxidative DNA damage of bone marrow hematopoietic cells in steroid-induced avascular necrosis of femoral head.

An animal model of steroid-induced avascular necrosis of femoral head (SANFH) was established to investigate the role of oxidative DNA damage of bone marrow hematopoietic cells in SANFH. Forty-five-month-old Japanese white rabbits (male or female, 2.5 ± 0.5 kg) were randomly divided into groups A (methylprednisolone + Escherichia coli endotoxin), B (methylprednisolone alone), C (E. coli endotoxin alone), and D (blank control). The animals were sacrificed two and four weeks after administration of the last dose (N = 5 each group and each time). Left and right femoral heads were fixed and decalcified. Empty lacunae were counted by hematoxylin and eosin staining and oxidative DNA damage of bone marrow hematopoietic cells was detected by immunohistochemistry. At week 2, the rate of oxidative DNA damage in bone marrow hematopoietic cells was significantly higher in group A than in groups B, C, and D (P < 0.01), while there was no significant difference between groups B, C, and D. At week 4, the rate of oxidative DNA damage in bone marrow hematopoietic cells was significantly higher in group A than in groups B, C, and D (P < 0.01), while there was no significant difference among groups B, C, and D. Thus, oxidative DNA damage of bone marrow hematopoietic cells appears to play an important role in SANFH.

Roles of osteocyte apoptosis in steroid-induced avascular necrosis of the femoral head.

An animal model of steroid-induced avascular necrosis of the femoral head (SANFH) was established to investigate the roles of osteocyte apoptosis in this process. Forty five-month-old male and female Japanese white rabbits were randomly divided into groups A (hormone + endotoxin), B (hormone alone), C (endotoxin alone), and D (blank control). Animals were sacrificed two and four weeks following the final treatment (N = 5 for each group at each time point). Bilateral femoral heads were fixed and decalcified, and empty lacunae were counted by hematoxylin staining. At weeks 2 and 4, the empty lacunae percentage was significantly higher in group A than that in groups B, C, or D (P < 0.01), while no significant difference was observed between these latter three. At week 2, all osteocyte apoptosis indexes were within normal ranges in all the groups, which therefore did not significantly differ in this respect (P > 0.05). However, at week 4, the apoptotic index was significantly higher in group A than that in groups B, C, or D (P < 0.01), comparisons between which revealed no such differences. Moreover, a positive correlation was observed between the percentage of empty lacunae and the apoptotic index at week 4 in group A (r = 0.893). We conclude that osteocyte apoptosis plays an important role in SANFH.

Expression and regulation of osteopontin in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Osteopontin (OPN) has been proposed to be associated with airway inflammation including asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). This study sought to evaluate the expression and regulation of the OPN in CRSwNP patients. METHODS: Nasal polyp (NP) tissues and normal tissues were collected from 30 CRSwNP patients and 16 control subjects. The expression and regulation of OPN, as well eosinophil (EOS) accumulation and activation, were examined in nasal tissues using DNA microarray, immunohistochemical (IHC), immunofluorescent (IF) staining and qPCR analysis. Moreover, the regulation of OPN in nasal epithelial cells and its effects on migration and activation of EOS were evaluated in vitro using flow cytometry, ELISA, qPCR and Western blot, etc. RESULTS: DNA microarray analysis identified OPN as one of the 19 upregulated genes in polyp tissues. The mean number of OPN(+) cells in polyp tissues was found to be significantly increased compared with the normal controls (P < 0.01), and OPN(+) cells in polyp tissues significantly correlated with tissue eosinophilia [major basic protein (MBP)(+) cells; r = 0.51, P < 0.01]. Accordingly, the mRNA and protein levels of OPN in NP tissues were significantly higher than those in normal controls (P < 0.01). Poly I:C, flagellin and TLR-9 agonist CpG ODN, as well as TNF-α, IFN-γ, IL-6, IL-17A and TGF-ß, significantly increased OPN mRNA expression in cultured PECs and NECs (P < 0.05). Recombinant human OPN significantly promoted the migration of EOS, as well as enhanced EOS cationic protein (ECP) production, in an in vitro dispersed NP cells (DNPCs) culture system (P < 0.05). CONCLUSIONS: OPN promotes eosinophilic nasal inflammation in CRSwNP patients, which may represent a promising therapeutic target.

Communication: Tracking molecular structure deformation and relaxation in real time.

The CH3I structural deformation induced by strong laser fields is revealed by time- and frequency-resolved ro-vibrational spectra. The experimental results show that the CH3I molecule undergoes ultrafast structural deformation of CH3 "umbrella-closing" induced by the strong fs laser field (more than 10(11) W/cm(2)) and followed by a structural relaxation of "umbrella-opening" within an exponential decay time scale of ∼620 fs. This study provides a first glimpse of the immense potential of the time- and frequency-resolved vibrational spectra in studying molecular deformation dynamics.