Measurements of All-Particle Energy Spectrum and Mean Logarithmic Mass of Cosmic Rays from 0.3 to 30 PeV with LHAASO-KM2A.

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

Measurement of Ultra-High-Energy Diffuse Gamma-Ray Emission of the Galactic Plane from 10 TeV to 1 PeV with LHAASO-KM2A.

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10 TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60 TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

A tera-electron volt afterglow from a narrow jet in an extremely bright gamma-ray burst.

Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory (LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.

[Development and application syndromic surveillance and early warning system in border area in Yunnan Province].

Objective: To establish a dynamic syndromic surveillance system in the border areas of Yunnan Province based on information technology, evaluate its effectiveness and timeliness in the response to common communicable disease epidemics and improve the communicable disease prevention and control in border areas. Methods: Three border counties were selected for full coverage as study areas, and dynamic surveillance for 14 symptoms and 6 syndromes were conducted in medical institutions, the daily collection of information about students' school absence in primary schools and febrile illness in inbound people at border ports were conducted in these counties from January 2016 to February 2018 to establish an early warning system based on mobile phone and computer platform for a field experimental study. Results: With syndromes of rash, influenza-like illness and the numbers of primary school absence, the most common communicable disease events, such as hand foot and mouth disease, influenza and chickenpox, can be identified 1-5 days in advance by using EARS-3C and Kulldorff time-space scanning models with high sensitivity and specificity. The system is easy to use with strong security and feasibility. All the information and the warning alerts are released in the form of interactive charts and visual maps, which can facilitate the timely response. Conclusions: This system is highly effective and easy to operate in the detection of possible outbreaks of common communicable diseases in border areas in real time, so the timely and effective intervention can be conducted to reduce the risk of local and cross-border communicable disease outbreaks. It has practical application value.

[Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer].

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

[Validation of calculation method for dose distribution around radioactive iodine-125 particles based on AAPM TG43 report].

Objective: According to the formula provided by the TG43 report [AAPM TG43 (2004)] proposed by the American Association of Physicists in Medicine (AAPM) in 2004, we calculated the dose distribution around the radioactive iodine-125 particles, and verified the calculation accuracy of the radioactive iodine-125 particles treatment planning system. Methods: AAPM TG43 (2004) report provides two calculation methods when calculating the dose around a single radioactive source. The calculation method that does not consider the geometric structure of the radioactive source is called point source calculation method, and the calculation method that considers the geometric structure of the radioactive source is called line source calculation method. Assuming a single Amersham 6711 radioactive iodine-125 particle with an activity of 100 U, the following point doses were calculated according to the two calculation methods provided by AAPM TG43 (2004) report, at 0°, 90° directions, distances 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 and 6 cm; In the direction of 45°, the doses at 0.71, 1.41, 2.12, 2.83, 3.54, 4.24, 4.95, 5.66, 6.36, 7.07, 7.78 and 8.49 cm. On the clinically used brachytherapy planning system variseeds 8.0, the above two calculation methods are used to calculate the corresponding activity and the dose around the corresponding type of radioactive iodine-125 particles, and the function of capturing points to templates built in the planning system is used to accurately find the above corresponding point position, using a single measurement of the above corresponding point dose; and comparation of the results were performed to see if there is a statistical difference. Results: The AAPM TG43 report uses point source calculation method to calculate the dose of single Amersham 6711 radioactive iodine-125 particles with activity of 100 U at 0° and 90° directions. The points with the same distance and the same dose are 8 082.18, 1 870.08, 756.58, 381.47, 217.11, 131.91, 86.55, 58.32, 39.97, 27.42, 19.74, 14.13 Gy, respectively, at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 and 6 cm away from them. In the 45° direction, the doses at the distances of 0.71, 1.41, 2.12, 2.83, 3.54, 4.24, 4.95, 5.66, 6.36, 7.07, 7.78 and 8.49 cm are 3 957.37, 865.83, 329.99, 155.69, 84.10, 48.50, 28.49, 17.80, 11.37, 7.38, 4.98 and 3.39 Gy, respectively; For line source calculation method, radioactive particles are at the same distance as above. The doses at each point in the direction of 0° are 3 128.71, 755.44, 330.30, 180.53, 107.74, 68.56, 46.40, 32.22, 22.70, 16.00, 11.51, 8.24 Gy, respectively. The doses at each point in the direction of 90° are 8 306.46, 1 981.01, 802.74, 405.38, 230.60, 140.03, 91.83, 61.84, 42.36, 29.05, 20.91, 14.97 Gy; In the 45° direction, the dose at the corresponding distance as above is 4 020.78, 877.43, 333.49, 156.93, 84.69, 48.81, 28.65, 17.89, 11.42, 7.41, 4.99 and 3.40 Gy, respectively. The maximum dose difference (0.3%) between the two methods is 7.78 cm in the 45° direction, the maximum difference (-0.3%) between the two methods is 8.49 cm in the 45° direction, and the value of other sampling points is less than 0.3%. The closer the Amersham 6711 iodine-125 particles are to the source in the directions of 0°, 45°, and 90°, the faster the dose will drop, and the dose will drop gradually as the distance increases. Conclusion: The brachytherapy planning system variseeds 8.0 and the AAPM TG43 report calculate a maximum dose difference of 0.3%, which can accurately calculate the dose distribution around radioactive iodine-125 seeds, and provide a reliable tool for the clinical implementation of radioactive iodine-125 particles implantation for tumor treatment.

Exploring Lorentz Invariance Violation from Ultrahigh-Energy γ Rays Observed by LHAASO.

Recently, the LHAASO Collaboration published the detection of 12 ultrahigh-energy γ-ray sources above 100 TeV, with the highest energy photon reaching 1.4 PeV. The first detection of PeV γ rays from astrophysical sources may provide a very sensitive probe of the effect of the Lorentz invariance violation (LIV), which results in decay of high-energy γ rays in the superluminal scenario and hence a sharp cutoff of the energy spectrum. Two highest energy sources are studied in this work. No signature of the existence of the LIV is found in their energy spectra, and the lower limits on the LIV energy scale are derived. Our results show that the first-order LIV energy scale should be higher than about 10^{5} times the Planck scale M_{Pl} and that the second-order LIV scale is >10^{-3}M_{Pl}. Both limits improve by at least one order of magnitude the previous results.

Constraints on Heavy Decaying Dark Matter from 570 Days of LHAASO Observations.

The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9} GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.

Peta-electron volt gamma-ray emission from the Crab Nebula.

The Crab Nebula is a bright source of gamma rays powered by the Crab Pulsar's rotational energy through the formation and termination of a relativistic electron-positron wind. We report the detection of gamma rays from this source with energies from 5 × 10-4 to 1.1 peta-electron volts with a spectrum showing gradual steepening over three energy decades. The ultrahigh-energy photons imply the presence of a peta-electron volt electron accelerator (a pevatron) in the nebula, with an acceleration rate exceeding 15% of the theoretical limit. We constrain the pevatron's size between 0.025 and 0.1 parsecs and the magnetic field to ≈110 microgauss. The production rate of peta-electron volt electrons, 2.5 × 1036 ergs per second, constitutes 0.5% of the pulsar spin-down luminosity, although we cannot exclude a contribution of peta-electron volt protons to the production of the highest-energy gamma rays.

Curcumin improves experimentally induced colitis in mice by regulating follicular helper T cells and follicular regulatory T cells by inhibiting interleukin-21.

To determine whether curcumin (Cur) can treat mice with experimentally-induced colitis by regulating follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr) by inhibiting interleukin (IL)-21. In this study, 40 male C57BL/6 mice were randomly grouped into four groups, i.e., normal, trinitrobenzene sulfonic acid (TNBS), TNBS + curcumin, and TNBS + anti-IL-21. Mice with experimental colitis were induced by 100 mg/kg TNBS. The mice in the TNBS + Cur group were treated with 100 mg/kg curcumin for seven days, and mice in the TNBS + anti-IL-21 group were treated with anti-IL-21 (150 µg/mouse) once per week, intraperitoneally, starting on the second day after establishing the experimental colitis model. On day eight, the therapeutic effect of curcumin was evaluated by colon mucosa damage index (CMDI), histological examination, and disease activity index (DAI). Furthermore, the number of CD4 + CXCR5 + PD-1 + Tfh and CD4 + CXCR5 + FoxP3 + Tfr cells were measured by flow cytometry. The mRNA and protein expression of IL-21, Bcl-6, FOXP3, ICOS, and PD-1 in colonic mucosa was detected by reverse transcription polymerase chain reaction and the Western blot technique. Compared with the TNBS group, the DAI, CMDI, histological score, the number of CD4 + CXCR5 + PD-1 + Tfh cells, the expression of IL-21, Bcl-6, ICOS, and PD-1 were significantly decreased in the TNBS + curcumin group and TNBS + anti-IL-21 group; body weight, number of CD4 + CXCR5 + FoxP3 + Tfr cells, and the expression of FoxP3 were observably elevated in the TNBS + curcumin group (all P < 0.05). Curcumin may have a potential therapeutic effect on mice with colitis treated experimentally through regulation of the balance of Tfh and Tfr cells via inhibiting the synthesis of IL-21.

Extended Very-High-Energy Gamma-Ray Emission Surrounding PSR J0622+3749 Observed by LHAASO-KM2A.

We report the discovery of an extended very-high-energy (VHE) gamma-ray source around the location of the middle-aged (207.8 kyr) pulsar PSR J0622+3749 with the Large High-Altitude Air Shower Observatory (LHAASO). The source is detected with a significance of 8.2σ for E>25 TeV assuming a Gaussian template. The best-fit location is (right ascension, declination) =(95.47°±0.11°,37.92°±0.09°), and the extension is 0.40°±0.07°. The energy spectrum can be described by a power-law spectrum with an index of -2.92±0.17_{stat}±0.02_{sys}. No clear extended multiwavelength counterpart of the LHAASO source has been found from the radio to sub-TeV bands. The LHAASO observations are consistent with the scenario that VHE electrons escaped from the pulsar, diffused in the interstellar medium, and scattered the interstellar radiation field. If interpreted as the pulsar halo scenario, the diffusion coefficient, inferred for electrons with median energies of ∼160 TeV, is consistent with those obtained from the extended halos around Geminga and Monogem and much smaller than that derived from cosmic ray secondaries. The LHAASO discovery of this source thus likely enriches the class of so-called pulsar halos and confirms that high-energy particles generally diffuse very slowly in the disturbed medium around pulsars.

Ultrahigh-energy photons up to 1.4 petaelectronvolts from 12 γ-ray Galactic sources.

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 1015 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays1. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane3-6, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.

[Value of joint prediction model based on the modified systemic inflammatory response syndrome score for predicting mortality risk of patients with large area burns at early stage after admission].

Objective: To investigate the predictive value of the joint prediction model based on the modified systemic inflammatory response syndrome (SIRS) score (hereinafter referred to as the joint prediction model) for the mortality risk of patients with large area burns within 24 hours after admission. Methods: The clinical data of 158 patients [111 males, 47 females, aged 40 (28, 50) years] admitted to the Department of Burn Surgery of the First Affiliated Hospital of Naval Medical University from January 2005 to January 2018, conforming to the study criteria, were analyzed retrospectively by the method of case-control study. The age, gender, total burn area, full-thickness burn area, injury cause, with or without inhalation injury, severity of inhalation injury, and tracheotomy condition of patients were recorded, and the modified SIRS score and the modified Baux score of patients were calculated. According to the final outcome, all patients were divided into survival group (n=123) and death group (n=35). The clinical data of patients between two groups, except for modified Baux score, were compared by chi-square test or Mann-Whitney U test to screen the death-related factors of patients. The indexes with statistically significant difference between the two groups were included in the multivariate logistic regression analysis to screen the independent risk factors related to the death of patients, and the prediction model was constructed by combining the modified SIRS score. The receiver's operating characteristic curves of the modified SIRS score, the modified Baux score, and the joint prediction model of 158 patients were drawn to analyze their ability to predict death of patients. The area under curve (AUC) of the receiver's operating characteristic and the sensitivity and specificity of optimal threshold were calculated, and the quality of AUC of the three prediction indexes was compared with Jonckheere-Terpstra test. Results: (1) There were statistically significant differences between the two groups in the modified SIRS score, age, total burn area, full-thickness burn area, severity of inhalation injury, with or without inhalation injury, and tracheotomy condition of patients (Z=-4.356, -3.568, -5.291, -6.052, -4.720, χ(2)=12.967, 19.692, P<0.01). (2) The modified SIRS score, age, full-thickness burn area were the independent risk factors for the death of patients with large area burn (odds ratio=2.699, 1.069, 1.029, 95% confidence interval=1.447-5.033, 1.029-1.109, 1.005-1.054, P<0.05). (3) The AUC of modified SIRS score, the joint prediction model, and the modified Baux score for predicting death of 158 patients within 24 hours after admission were 0.730, 0.879, and 0.895 respectively (95% confidence interval=0.653-0.797, 0.818-0.926, 0.836-0.938, P<0.01). The sensitivities of the three optimal threshold values to death prediction were 54.3%, 91.4%, and 82.9% respectively, while the specificities were 81.3%, 76.4%, and 84.6% respectively. The AUC quality of the joint prediction model was similar to that of the modified Baux score (95% confidence interval=-0.057-0.088, P>0.05), and both of them were significantly better than that of the modified SIRS score (95% confidence interval=0.072-0.259, 0.023-0.276, P<0.05 or P<0.01). Conclusions: Both the joint prediction model and the modified Baux score are considered to be good to predict the death rate of patients with large area burns at early stage after admission. However, the joint prediction model has better clinical practice value due to its advantage of simple scoring and easier access to data acquisition.

[3D printing non-coplanar template-assisted 125-iodine seed implantation for thorax movement tumor: individual template design method].

Objective: To compare the dosimetric data between preoperative plans and postoperative verification in computed tomography CT-guided and 3D printing template-assisted 125-iodine ((125)I) seed implantation for thorax movement tumor and to explore the feasibility and accuracy of the individualized template design method. Methods: A total of 35 patients, 20 males and 15 females with median age of 62 (17-87) years old, who registered from January 2016 to December 2017 applied with 3D printing guided template assisted radioactive seed implantations in Peking University Third Hospital were included in this study. (125)I seeds with a prescribed dose of 110-180 Gy were impanted. 3D printing templates were designed and produced for 35 cases. The dosimetric parameters: D(90), minimum peripheral dose (mPD), V(100), V(150), V(200), conformal index (CI), external index (EI), and homogeneity index (HI) were compared between pre-and post-plannings. Statistical method was two group of related non-parameters test. Results: The design and production of 35 cases' templates were in place well. Compared with the preoperative planning, the postoperative D(90), V(100), V(150), V(200), mPD, CI, EI and HI differences were 5.57%, 0.34%, 0.33%, -1.20%, 21%, 2.8%, -14.2%, 4.71%, -10.4%. All the included dosimetry parameters changed slightly after surgery compared with before surgery, but the difference was not statistically significant(all P>0.05). Conclusions: The dosimetric parameters of postoperative verification are consistent well with the preoperative planning and have good accuracy, the results could meet the clinical requirements.

[Comparison of preoperative planning of radioactive seed implantation for pelvic wall recurrent gynecological malignant tumors between 3D-printing non-coplanar template and 3D-printing coplanar template].

Objective: To compare the difference of preoperative planning parameters between 3D-printing non-coplanar template (3D-PNCT) and 3D-printing coplanar template (3D-PCT) in the treatment of pelvic wall recurrent gynecological malignant tumor with radioactive seeds implantation, and to guide the clinical application. Methods: From January 2016 to March 2018, 33 patients with pelvic wall recurrent gynecological malignant tumor were treated with radioactive seeds implantation assisted by 3D-printing template and in Peking University Third Hospital. All patients underwent 3D-PNCT and 3D-PCT preoperative planning. The D(90) of target remained similar for the same patient. The parameters were compared with Wilcoxon test or Kruskal-Wallis test. Results: D(90) was similar between the two groups (P>0.05). The number of inserting needles through intestine and bone in 3D-PNCT group was less than that in 3D-PCT group (0 (0-13), 0 (0-25), Z=-2.941, P<0.05;0 (0-3), 0 (0-25), Z=-2.232, P<0.05). Conclusion: For patients with gynecological malignancies with pelvic recurrence, both of the two peroperative plans could achieve prescription dose, but 3D-PNCT is more safer.

Comparison of gefitinib and platinum-based chemotherapy and only platinum-based chemotherapy to treat lung adenocarcinoma.

To study the curative effects and safety for patients who adopt both gefitinib and platinum-based chemotherapy or only platinum-based chemotherapy in the treatment of lung adenocarcinoma, 80 EGFR mutation-positive lung adenocarcinoma patients in stage IIIB/IV were divided into two groups. Half of them received both gefitinib and standard chemotherapy (group A), and the others (group B) received only standard chemotherapy. Overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and the related toxicities of both groups were recorded in order to take certain nursing measures for a variety of toxicities. Next, statistical methods were used to analyze the curative effects and safety of the two treatments. The results showed that ORR, DCR and median progression-free (mPFS) survival of the two groups of patients showed no statistical difference (P >0.05). However, group A (18.56 months) had a longer median overall survival (mOS) than group B (14.87 months), which was of statistical significance (P less than 0.05). Nausea and loss of appetite were common mild adverse reactions, and anemia and leukocytopenia were moderate common adverse reactions. The difference between these two groups of patients regarding adverse reactions was not statistically significant (P>0.05). In conclusion, the two treatments have similar safety, but lung adenocarcinoma patients with drug resistance during stage IIIB/IV after using first-line gefitinib therapy have lower survival benefits than patients who take both gefitinib and platinum-based chemotherapy.

Differential expression profile of hepatic circular RNAs in chronic hepatitis B.

CircRNAs exert gene regulatory effects by sequestering target microRNAs (miRNAs) and play a vital role in the onset and development of disease. Until recently, little has been known about the expression, regulation and biological function of circRNAs in both health and chronic hepatitis B (CHB).To identify hepatic circRNAs associated with CHB, we performed RNA sequencing using liver biopsies from untreated CHB patients and controls. We then established a bioinformatics pipeline for identification of CHB-associated circRNAs and in silico analysis of the circRNA-miRNA-mRNA pathways. We used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to confirm these results. The profiles of hepatic circRNA expression were significantly different in CHB compared with controls, with a total of 99 dysregulated circRNAs identified to be correlated with CHB. Computational analysis of the circRNA-miRNA-mRNA pathways revealed a large number of miRNAs (665), which were putatively targeted by the differentially expressed hepatic circRNAs. Interestingly, four of the predicted CHB-related circRNA-miRNA-mRNA pathways were found to be involved in the pathogenesis of HBV infection and progression of HBV-associated liver disease. Among these pathways, regression analysis of gene expression revealed a strong positive correlation between hsa_circ_0000650 and TGFß2 and a negative correlation between hsa_circ_0000650 and miR-6873-3p, which hinted that hsa_circ_0000650 interacted with TGFß2 mediated by miR-6873-3p. This study firstly demonstrates that patients with CHB present different profiles of hepatic circRNAs and circRNA/miRNA interactions. Thus, circRNAs have promise as novel mechanisms underlying the pathogenesis and progression of CHB.

Isolation and phylogenetic analysis of porcine deltacoronavirus from pigs with diarrhoea in Hebei province, China.

Porcine deltacoronavirus (PDCoV) is a recently identified coronavirus in the genus Deltacoronavirus that can cause enteric disease with clinical signs including diarrhoea, vomiting, dehydration and mortality in neonatal piglets. Although evidence of the prevalence of PDCoV in China is accumulating, little published information about Chinese PDCoV isolates is available. In this study, we investigated the presence of PDCoV in 49 faecal/intestinal samples from piglets with diarrhoea on different farms in Hebei province. Five samples (10.2%) were positive for PDCoV, but no coinfection of PDCoV with other enteropathogens was observed. A PDCoV strain named HB-BD was successfully isolated from the intestinal contents of a diarrhoeic piglet and serially propagated in swine testicular (ST) cells for >40 passages. The complete genome of the HB-BD strain was sequenced and analysed. Genomic analysis showed that the HB-BD strain had a closer relationship with Chinese strains than those from other countries and was grouped within the Chinese PDCoV cluster. The results of this study will be valuable for further research of PDCoV genetic evolution and development of effective diagnostic reagents, assays and potential vaccines against newly emerged PDCoV strains.

Facilitating the measurement of circulatory hydrogen sulfide with fluorescence probe-coated microplates.

OBJECTIVE: The hydrogen sulfide (H2S) role in pathogenesis of various diseases were wildly addressed in recent decade. The circulatory (plasma or serum) and biological fluid H2S measurement is still an enormous issues due to the technical limitation. This paper aimed to develop a novel measurement method based on fluorescence probe. METHODS: Firstly, 20 µL ethanol was used to dissolve 100 pmol fluorescence probe, then added in a 96-well plate. An equal volume of ethanol was also added to the blank well of the plate. The plate was placed in a dark room for about 1 h until the fluorescence probe was evenly coated in the 96-well microplate and dried. The plate was frozen at -20 °C for later use. Secondly, the plasma or serum sample was added with saturated ammonium sulfate buffer (pH 7.8) and then centrifuged to remove the proteins. The equal volume supernatant liquid was added to the probe-coated well and the probe-uncoated well. The plate was incubated in a dark environment at 37 °C for 2 h. Finally, after incubation, the fluorescence density was acquired at ΛEx/ΛEm 340/445 nm in a microplate reader. The differences of the fluorescence density values between the probe-coated well and probe-uncoated well were counted and H2S concentration of plasma/serum was calculated by standard curve with NaHS. RESULTS: The method had high sensitivity (from 0.3 to 100 µmol/L) and specificity for measuring H2S as compared with other biologically relevant reactive sulfur species and sulfur-containing amino acid. Serum H2S concentrations were assayed in 188 health volunteers using this method [(12.1±3.5) µmol/L, 95%CI: 4.6-19.8 µmol/L], and the frequency distribution showed a normal tendency(one-sample Kolmogorov-Smirnov test, P>0.1). The serum H2S concentrations in 30 hypertension patients were decreased compared with 22 age- and gender-matched health individuals (paired-samples t test, t=9.937, P<0.001). There were no differences of H2S concentration in serum [(19.66±2.32) µmol/L] or plasma [(18.67±2.07) µmol/L], between the samples acquired from artery [(19.34±0.51) µmol/L] or vein [(18.99±0.50) µmol/L] of male Wistar rats (repeated measurement of ANOVA, P=0.38). One week frozen samples did not affect the detection. The values of the repeated measurement did not differ (two-way ANOVA, P>0.05). CONCLUSION: The present method is easily performed with high sensitivity, specificity and repeatability for circulatory H2S. It is also quick and may apply for large samples.