[Establish a whole-process comprehensive surveillance management mode for immune checkpoint inhibitor pneumonitis].

The application of immune checkpoint inhibitors (ICIs) has shown impressive anti-tumor efficacy across multiple malignant tumors, leading to the prolonged survival period of tumor patients. However, immune-related adverse events should not be ignored. Checkpoint inhibitor pneumonitis (CIP) is a pulmonary adverse event that can occur in malignant tumor patients after receiving ICIs treatment. The incidence of CIP has been reported to range from 2.7% to 20.0% in clinical trials and real-world research. Furthermore, some patients might suffer from serious or fatal CIP, and the prognosis of such patients will be poor. Early detection, diagnosis and treatment may improve the prognosis of these patients. The establishment of a whole-process CIP comprehensive surveillance management mode covering the health care system and patients during ICIs treatment might be helpful to improve the early diagnosis and treatment capacity of CIP, which is a key measure to improve the prognosis of these patients.

The PERCIVAL detector: first user experiments.

The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science.

Fizeau drag in graphene plasmonics.

Dragging of light by moving media was predicted by Fresnel1 and verified by Fizeau's celebrated experiments2 with flowing water. This momentous discovery is among the experimental cornerstones of Einstein's special relativity theory and is well understood3,4 in the context of relativistic kinematics. By contrast, experiments on dragging photons by an electron flow in solids are riddled with inconsistencies and have so far eluded agreement with the theory5-7. Here we report on the electron flow dragging surface plasmon polaritons8,9 (SPPs): hybrid quasiparticles of infrared photons and electrons in graphene. The drag is visualized directly through infrared nano-imaging of propagating plasmonic waves in the presence of a high-density current. The polaritons in graphene shorten their wavelength when propagating against the drifting carriers. Unlike the Fizeau effect for light, the SPP drag by electrical currents defies explanation by simple kinematics and is linked to the nonlinear electrodynamics of Dirac electrons in graphene. The observed plasmonic Fizeau drag enables breaking of time-reversal symmetry and reciprocity10 at infrared frequencies without resorting to magnetic fields11,12 or chiral optical pumping13,14. The Fizeau drag also provides a tool with which to study interactions and nonequilibrium effects in electron liquids.

Effect modification of the association between diurnal temperature range and hospitalisations for ischaemic stroke by temperature in Hefei, China.

OBJECTIVES: Diurnal temperature range (DTR) is an important indicator of global climate change. Many epidemiological studies have reported the associations between high DTR and human health. This study investigated the association between DTR and hospitalisations for ischaemic stroke in Hefei, China. STUDY DESIGN: This is an ecological study. METHODS: Data of daily hospital admissions for ischaemic stroke and meteorological variables from 1 January 2009 to 31 December 2017 were collected in Hefei, China. A generalised additive model combined with distributed lag non-linear model was used to quantify the effects of DTR on ischaemic stroke. The interactive effect between DTR and temperature was explored with a non-parametric bivariate response surface model. RESULTS: High DTR was associated with hospitalisations for ischaemic stroke. The adverse effect of extremely high DTR (99th percentile [17.1 °C]) occurred after 8 days (relative risk [RR] = 1.021, 95% confidence interval [CI] = 1.002, 1.041) and the maximum effect appeared after 12 days (RR = 1.029, 95% CI = 1.011, 1.046). The overall trend of the effect of DTR on ischaemic stroke was decreasing. In addition, there was a significant interactive effect of high DTR and low temperature on ischaemic stroke. CONCLUSIONS: This study suggests that the impact of high DTR should be considered when formulating targeted measures to prevent ischaemic stroke, especially for those days with high DTR and low mean temperature.

Ultrafast multi-cycle terahertz measurements of the electrical conductivity in strongly excited solids.

Key insights in materials at extreme temperatures and pressures can be gained by accurate measurements that determine the electrical conductivity. Free-electron laser pulses can ionize and excite matter out of equilibrium on femtosecond time scales, modifying the electronic and ionic structures and enhancing electronic scattering properties. The transient evolution of the conductivity manifests the energy coupling from high temperature electrons to low temperature ions. Here we combine accelerator-based, high-brightness multi-cycle terahertz radiation with a single-shot electro-optic sampling technique to probe the evolution of DC electrical conductivity using terahertz transmission measurements on sub-picosecond time scales with a multi-undulator free electron laser. Our results allow the direct determination of the electron-electron and electron-ion scattering frequencies that are the major contributors of the electrical resistivity.

Effects of wet atmospheric nitrogen deposition on epiphytic lichens in the subtropical forests of Central China: Evaluation of the lichen food supply and quality of two endangered primates.

Over the last few decades, the threat posed to biodiversity and ecosystem function by atmospheric nitrogen (N) deposition has been increasingly recognized. The disturbed nutrient balance and species composition of plants induced by higher N deposition can impact the biodiversity of the organisms that consume the plants. In this research, we implemented several experiments to estimate the effects of increased N deposition on the growth, survival, and nutrients of the dominant epiphytic lichens in the subtropical mountains in Central China to assess the lichen food amount and nutritional quality for two endangered primates endemic to China. Our results indicated that the thallus growth and propagule survival of the lichens were significantly decreased when nitrogen addition changed from 6.25 to 50.0 kg N·ha-1·y-1; it was also shown that lichen biomass could be decreased by 11.2%-70.2% when the deposition addition exceeded 6.25 kg N·ha-1·y-1. Further, our study revealed that increased nitrogen deposition also reduced the nutritional quality of the lichens via reducing the soluble protein and soluble sugar levels and increasing the fiber content, which would substantially affect the diet selection of the plants consumers in the region, particularly the populations of the two lichen-eating endangered primate species, Rhinopithecus roxellana and R. bieti. Our experimental study suggested that the nitrogen pollution derived from anthropogenic activities could cause cascading effects for the whole forest ecosystem of Central China; thus, more studies about nitrogen deposition in this region are required.

XUV-driven plasma switch for THz: new spatio-temporal overlap tool for XUV-THz pump-probe experiments at FELs.

A simple and robust tool for spatio-temporal overlap of THz and XUV pulses in in-vacuum pump-probe experiments is presented. The technique exploits ultrafast changes of the optical properties in semiconductors (i.e. silicon) driven by ultrashort XUV pulses that are probed by THz pulses. This work demonstrates that this tool can be used for a large range of XUV fluences that are significantly lower than when probing by visible and near-infrared pulses. This tool is mainly targeted at emerging X-ray free-electron laser facilities, but can be utilized also at table-top high-harmonics sources.

Electronic decay of core-excited HCl molecules probed by THz streaking.

The ultrafast electronic decay of HCl molecules in the time domain after resonant core excitation was measured. Here, a Cl-2p core electron was promoted to the antibonding σ* orbital initiating molecular dissociation, and simultaneously, the electronic excitation relaxes via an Auger decay. For HCl, both processes compete on similar ultrashort femtosecond time scales. In order to measure the lifetime of the core hole excitation, we collinearly superimposed 40 fs soft x-ray pulses with intense terahertz (THz) radiation from the free-electron laser in Hamburg (FLASH). Electrons emitted from the molecules are accelerated (streaked) by the THz electric field where the resulting momentum change depends on the field's phase at the instant of ionization. Evaluation of a time-shift between the delay-dependent streaking spectra of photo- and Auger electrons yields a decay constant of (11 ± 2) fs for LMM Auger electrons. For further validation, the method was also applied to the MNN Auger decay of krypton. Reproduction of the value already published in the literature confirms that a temporal resolution much below the duration of the exciting x-ray pulses can be reached.

Evolution and characterisation of the AhRAF4 NB-ARC gene family induced by Aspergillus flavus inoculation and abiotic stresses in peanut.

Aflatoxin contamination in peanut is a serious food safety issue to human health around the world. Finding disease resistance genes is a key strategy for genetic improvement in breeding to deal with this issue. We identified an Aspergillus flavus-induced NBS-LRR gene, AhRAF4, using a microarray-based approach. By comparison of 23 sequences from three species using phytogenetics, protein secondary structure and three-dimensional structural analyses, AhRAF4 was revealed to be derived from Arachis duranensis by recombination, and has newly evolved into a family of several members, characterised by duplications and point mutations. However, the members of the family descended from A. ipaensis were lost following tetraploidisation. AhRAF4 was slightly up-regulated by low temperature, drought, salicylic acid and ethylene, but down-regulated by methyl jasmonate. The distinct responses upon As. flavus inoculation and the differential reactions between resistant and susceptible varieties indicate that AhRAF4 might play a role in defence responses. Temporal and spatial expression and the phenotype of transformed protoplasts suggest that AhRAF4 may also be associated with pericarp development. Because tetraploid cultivated peanuts are vulnerable to many pathogens, an exploration of R-genes may provide an effective method for genetic improvement of peanut cultivars.

Calhm2 governs astrocytic ATP releasing in the development of depression-like behaviors.

Extracellular ATP is a widespread cell-to-cell signaling molecule in the brain, where it functions as a neuromodulator by activating glia and neurons. Although ATP exerts multiple effects on synaptic plasticity and neuro-glia interactions, as well as in mood disorders, the source and regulation of ATP release remain to be elaborated. Here, we define Calhm2 as an ATP-releasing channel protein based on in vitro and in vivo models. Conventional knockout and conditional astrocyte knockout of Calhm2 both lead to significantly reduced ATP concentrations, loss of hippocampal spine number, neural dysfunction and depression-like behaviors in mice, which can be significantly rescued by ATP replenishment. Our findings identify Calhm2 as a critical ATP-releasing channel that modulates neural activity and as a potential risk factor of depression.

Differential prevalence and correlates of whole blood Epstein-Barr virus DNA between HIV-positive and HIV-negative men who have sex with men in Shanghai, China.

This cross-sectional study aimed to examine and compare prevalence and correlates of whole blood Epstein-Barr virus (EBV) DNA between HIV-positive and HIV-negative men who have sex with men (MSM). Five hundred and four HIV-positive MSM and 504 age-matched HIV-negative MSM were recruited from an HIV counseling and testing clinic in Shanghai, China from November 2014 to November 2015 and were administered with a face-to-face questionnaire interview. Whole blood EBV DNA was tested by nested polymerase chain reaction assays on EBNA-1, EBNA-2, and LMP-1 genes. The prevalence of whole blood EBV DNA was 56·0% (95% CI 51·7-60·3%) among HIV-positive MSM and 26·0% (95% CI 22·4-30·0%) among HIV-negative MSM. Whole blood EBV DNA positivity was significantly associated with HIV infection (adjusted odds ratio (aOR) 3·43, 95% CI 2·58-4·57) and frequent intake of pickled, smoked, or salty food (aOR 1·71, 95% CI 1·02-2·86) in the whole sample, and with <200 cells/µl CD4 cell counts (aOR 1·79, 95% CI 1·05-3·05) and pickled, smoked, or salty food intake (aOR 3·14, 95% CI 1·39-7·08) in HIV-positive group. HIV-infected MSM are at higher risk of active EBV replication than HIV-uninfected MSM, underscoring needs of surveillance and research on EBV-related carcinogenesis in this population.

[The situation and associated factors of satisfaction with follow-up management of HIV/AIDS cases conducted by Community Health Service Center in Hongkou district of Shanghai].

Objective: To analyze satisfaction with follow-up management of HIV/AIDS cases conducted by Community Health Service Center (CHS) and related factors in Hongkou district, Shanghai. Methods: Out of 302 HIV/AIDS cases followed up by CHS in Hongkou district from 2012 to 2016, 263 HIV/AIDS cases were recruited to participate in a cross-sectional study assessed by self-designed questionnaire-based interview during October 1, 2016 and October 20, 2016, with efficiency of 87.1%. Information of basic characteristics including sociodemographic, routes of infection, CD4(+)T cell counts, diagnose of AIDS and status of receiving ART were collected, as well as satisfaction with follow-up management conducted by CHS including service professionalism, service attitude, service environment, referral service, privacy protection, health education, psychological support, and care and assistance. Factors related to satisfaction were analyzed using multiple binary logistic regression. Results: Among 263 HIV/AIDS cases, the average age was 42.0±13.5, 93.2% (245 cases) were male and the proportion of overall satisfaction was 72.2% (190 cases). Out of 8 items of satisfaction, service attitude and health education got the highest score with a total number of 235 (89.4%) answering "very satisfied" or "satisfied" , while care and assistance got the lowest score with a total number of 69 (26.2%) answering "dissatisfied" or "very dissatisfied" . Compared to HIV/AIDS local residents and followed up by CHS <12 months, those who were non-local residents and followed up by CHS ≥12 months were more likely to be satisfied, the OR (95%CI) were 2.66 (1.30-5.44) and 2.52 (1.01-6.29), respectively. Compared to HIV/AIDS ≤30 years old and receiving ART, those who were 31-50 years or >50 years old and not receiving ART were less likely to be satisfied, the OR (95%CI) were 0.36 (0.15-0.89), 0.32 (0.10-0.97) and 0.11 (0.01-0.90), respectively. Conclusion: Satisfaction with follow-up management conducted by CHS in Hongkou district is relatively high. Age, residence, status of receiving ART and cumulative time of following up by CHS are significantly associated with satisfaction, suggesting that CHS should improve their professional abilities during follow-up management, as well as be more targeted and focus on different aspects.

Uncertainty quantification and design-of-experiment in absorption-based aqueous film parameter measurements using Bayesian inference.

Diode laser-based multi-wavelength near-infrared (NIR) absorption in aqueous films is a promising diagnostic for making temporally resolved, simultaneous measurements of film thickness, temperature, and concentration of a solute. Our previous work in aqueous urea solutions aimed at determining simultaneously two of these system parameters, while the third one must be fixed or specified by additional measurements. The current work presents a simultaneous NIR absorption-based multi-parameter measurement of thickness, temperature, and solute concentration coupled with the Bayesian methodology that is used to infer probability densities for the obtained data. The Bayesian analysis is based on a temperature- and concentration-dependent spectral database generated with a Fourier transform infrared spectrometer in the range 5500-8000 cm-1 for water with variable temperature and urea concentration. The concept was first validated with measurements using a calibration cell. Probability densities in the measured parameters were quantified using a Markov chain Monte Carlo algorithm, which were used to derive credibility intervals. As a practical demonstration, the temporal variation of film thickness, urea concentration, and liquid temperature were recorded during evaporation of a liquid film deposited on a transparent heated quartz plate.

Pharmacogenomic Advances in the Prediction and Prevention of Cutaneous Idiosyncratic Drug Reactions.

Cutaneous idiosyncratic drug reactions (CIDRs) are usually unpredictable, ranging from mild maculopapular exanthema (MPE) to severe cutaneous adverse drug reactions (SCARs) such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Increasing evidence suggests that HLA alleles are strongly associated with drug-induced-CIDRs. The pathomechanisms for CIDRs include genetic polymorphisms affecting complex immune-specific HLA/drug antigen/T-cell receptor interactions and drug metabolism. Pharmacogenomic tests to prevent CIDRs have been widely implemented in clinical practice in recent years.

Prevalence and severity by age and other clinical correlates of haemophilic arthropathy of the elbow, knee and ankle among Taiwanese patients with haemophilia.

INTRODUCTION & AIMS: Haemophilic arthropathy (HA) is a major complication in patients with haemophilia (PWH), but the study of age-specific prevalence and severity of HA is very limited in Asian countries. MATERIALS & METHODS: This study retrospectively reviewed 146 severe- and moderate-type Taiwanese PWH aged 4-73 years, with roentgenograms of elbows, knees and ankles and calculated Pettersson scores. RESULTS: The prevalence of HA, mean number of HAs per patient and mean Pettersson scores of all the joints were 42.8%, 1.3 and 1.9 points in PWH aged 4-10 years; 64.3%, 1.4 and 4.1 points in PWH aged 11-19 years; 97.1%, 2.9 and 15.6 points in PWH aged 20-29 years; 93.1%, 4.4 and 33.1 points in PWH aged 30-39 years; 100%, 5.1 and 46.1 points in PWH aged 40-49 years and 100%, 5 and 49.6 points in PWH aged ≥50 years, respectively. There was a high prevalence of HA for PWH aged ≥20 years. Among PWH aged <20 years, prevalence of HA was low and mild ankle arthropathy was the most common. Besides, in the four age groups aged <40 years, the prevalence of ankle arthropathy was the highest, followed by elbow arthropathy and then knee arthropathy. CONCLUSIONS: Although severe arthropathy of the six major joints was rare in PWH aged <30 years, it increased rapidly in PWH after 30 years. Analysis of clinical correlates suggested that age, severity of haemophilia, absence of prophylaxis and presence of HCV infection correlated positively with Pettersson scores.

[The influence on the peeling off time of the tunica albuginea after 4-8℃ cool water was applied to children's low temperature plasma-assisted tonsillectomy].

Objective:The aim of this study is to discuss the influence on the peeling off time of the tunica albuginea after 4-8℃ cool water was applied to children 's low temperature plasmaassisted tonsillectomy.Method:One hundred and seventeen benign hypertrophy of tonsil patients were recruited,the 56 cases of them were served as experimental group,who were treated with plasma tonsillectomy using 4-8℃ normal saline as medium,while the 61 cases were served as control group,who were treated with plasma tonsillectomy using 22-25℃ normal saline as medium.Then,we analyzed the peeling off time of the tunica albuginea between experimental and control group.Result:The difference of formation time between experimental group and control group was not statistically significant(P >0.05).The average peeling off time of the tunica albuginea was (11.32±2.51) days in experimental group,while time was(15.03±4.12) days in control group.There was a statistical difference between them.Conclusion:The use of 4-8℃ cold water in children's low temperature plasma-assisted tonsillectomy can reduce the peeling off time of the tunica albuginea,and it indicate that the ice water medium can reduce the heat injury caused by the plasma operation.

Lack of association between the hOGG1 gene Ser326Cys polymorphism and gastric cancer risk: evidence from a case-control study and a meta-analysis.

The association between the human 8-oxoguanine glycosylase 1 (hOGG1) gene Ser326Cys polymorphism (rs1052133) and gastric cancer has been widely evaluated, yet a definitive answer to whether this association exists is lacking. We first conducted a case-control study to assess this association in a large Han Chinese population, and then performed a meta-analysis to further address this issue. This case-control study involved 448 patients clinically diagnosed with gastric cancer and 372 cancer-free control individuals from China. Genotyping was conducted using the polymerase chain reaction-ligase detection reaction method. Meta-analysis was performed by the STATA software. Data and study quality were assessed in duplicate. Our case-control association study indicated that there were no significant differences in the genotype and allele distributions of the Ser326Cys polymorphism between gastric cancer patients and controls (P = 0.8026 for genotype, and P = 0.5857 for allele), consistent with the results of the subsequent meta-analysis involving 2745 patients and 4588 controls under both allelic [odds ratio (OR) = 1.02; 95% confidence interval (CI) = 0.91-1.14; P = 0.739] and dominant (OR = 0.97; 95%CI = 0.78-1.21; P = 0.803) models. Further subgroup analyses by ethnicity, source of controls, and sample size also did not detect any positive associations in this meta-analysis. Overall, our study in the Han Chinese population, along with the meta-analysis, failed to confirm the association of the hOGG1 gene Ser326Cys polymorphism with gastric cancer risk, even across different ethnic populations.

Arctigenin suppresses transforming growth factor-ß1-induced expression of monocyte chemoattractant protein-1 and the subsequent epithelial-mesenchymal transition through reactive oxygen species-dependent ERK/NF-κB signaling pathway in renal tubular epithelial cells.

Transforming growth factor-ß1 (TGF-ß1) induces expression of the proinflammatory and profibrotic cytokine monocyte chemoattractant protein-1 (MCP-1) in tubular epithelial cells (TECs) and thereby contributes to the tubular epithelial-mesenchymal transition (EMT), which in turn leads to the progression of tubulointerstitial inflammation into tubulointerstitial fibrosis. Exactly how TGF-ß1 causes MCP-1 overexpression and subsequent EMT is not well understood. Using human tubular epithelial cultures, we found that TGF-ß1 upregulated the expression of reduced nicotinamide adenine dinucleotide phosphate oxidases 2 and 4 and their regulatory subunits, inducing the production of reactive oxygen species. These reactive species activated a signaling pathway mediated by extracellular signal-regulated kinase (ERK1/2) and nuclear factor-κB (NF-κB), which upregulated expression of MCP-1. Incubating cultures with TGF-ß1 was sufficient to induce hallmarks of EMT, such as downregulation of epithelial marker proteins (E-cadherin and zonula occludens-1), induction of mesenchymal marker proteins (α-smooth muscle actin, fibronectin, and vimentin), and elevated cell migration and invasion in an EMT-like manner. Overexpressing MCP-1 in cells exposed to TGF-ß1 exacerbated these EMT-like changes. Pretreating cells with the antioxidant and anti-inflammatory compound arctigenin (ATG) protected them against these TGF-ß1-induced EMT-like changes; the compound worked by inhibiting the ROS/ERK1/2/NF-κB pathway to decrease MCP-1 upregulation. These findings suggest ATG as a new therapeutic candidate to inhibit or even reverse tubular EMT-like changes during progression to tubulointerstitial fibrosis, and they provide the first clues to how ATG may work.

Role of misalignment-induced angular chirp in the electro-optic detection of THz waves.

A general description of electro-optic detection including non-collinear phase matching and finite transverse beam profiles is presented. It is shown theoretically and experimentally that non-collinear phase matching in ZnTe (and similar materials) produces an angular chirp in the χ(2)-generated optical signal. Due to this, in non-collinear THz and probe arrangements such as single-shot THz measurements or through accidental misalignment, measurement of an undistorted THz signal is critically dependent on having sufficient angular acceptance in the optical probe path. The associated spatial walk-off can also preclude the phase retardation approximation used in THz-TDS. The rate of misalignment-induced chirping in commonly used ZnTe and GaP schemes is tabulated, allowing ready analysis of a detection system.

Norisoboldine attenuates inflammatory pain via the adenosine A1 receptor.

BACKGROUND: Norisoboldine (NOR) is a benzylisoquinoline alkaloid isolated from Radix Linderae, a traditional Chinese medicine. Our previous studies have demonstrated that it produces anti-inflammatory and anti-rheumatoid arthritis effects. METHODS: The present study was undertaken to explore the analgesic effects of NOR and its potential mechanism in the formalin test and the acetic acid writhing test. RESULTS: Oral administration of NOR dose dependently attenuated the formalin-induced pain responses in the second phase, and reduced formalin-induced paw oedema. It also diminished acetic acid-induced writhing responses but had no effect on acute thermal pain in the hotplate test. The mechanistic studies suggested that the adenosine system, but not the opioid receptor system, is involved in NOR-induced antinociception. Naloxone, a non-selective opioid receptor antagonist, had no effect on NOR-induced analgesic action. However, caffeine (a non-selective adenosine receptor antagonist) completely reversed the analgesic effect of NOR in formalin-induced nociceptive responses in the second phase, and 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX, a selective adenosine A1 receptor antagonist) completely inhibited NOR-induced analgesia in both formalin-induced nociceptive responses and acetic acid-induced writhing responses. In addition, NOR reduced formalin-induced activation of extracellular signal-regulated kinase and calcium/calmodulin-dependent protein kinase II in the spinal cord, which is also blocked by DPCPX. Furthermore, NOR decreased forskolin-evoked cyclic adenosine monophosphate levels in mouse spinal cord neuronal cultures through the adenosine A1 receptor. CONCLUSION: Our data demonstrate that NOR produces the analgesic effect in inflammatory pain by a mechanism related to the adenosine system.