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.

Stringent Tests of Lorentz Invariance Violation from LHAASO Observations of GRB 221009A.

On 9 October 2022, the Large High Altitude Air Shower Observatory (LHAASO) reported the observation of the very early TeV afterglow of the brightest-of-all-time gamma-ray burst 221009A, recording the highest photon statistics in the TeV band ever obtained from a gamma-ray burst. We use this unique observation to place stringent constraints on the energy dependence of the speed of light in vacuum, a manifestation of Lorentz invariance violation (LIV) predicted by some quantum gravity (QG) theories. Our results show that the 95% confidence level lower limits on the QG energy scales are E_{QG,1}>10 times the Planck energy E_{Pl} for the linear LIV effect, and E_{QG,2}>6×10^{-8}E_{Pl} for the quadratic LIV effect. Our limits on the quadratic LIV case improve previous best bounds by factors of 5-7.

Constraints on Ultraheavy Dark Matter Properties from Dwarf Spheroidal Galaxies with LHAASO Observations.

In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.

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.

[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.

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.

[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.

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.

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.

Prognostic Role of Circulating Soluble uPAR in Various Cancers: a Systematic Review and Meta-Analysis.

BACKGROUND: Soluble uPAR (suPAR) is a soluble fraction of uPAR which is an important cell surface receptor. Recent evidence suggests that circulating suPAR levels are elevated in multiple malignancies and associated with prognosis of patients, although the results are not consistent. This study aimed to analyze the effect of suPAR on the prognosis in various carcinomas through a systematic review and meta-analysis. METHODS: Eligible studies were searched in PubMed and EMBASE. Data were extracted from studies investigating the relationship between circulating suPAR and survival in patients with cancers. A meta-analysis of the hazard ratio (HR) was then performed to evaluate the prognostic role of suPAR in various carcinomas. Pooled HRs of suPAR for overall survival (OS) were calculated to measure the effect of circulating suPAR level on prognosis. RESULTS: After the literature search and systematic review, 12 articles regarding suPAR (I - III + II - III) including 2878 patients were included in a meta-analysis, which indicated a significantly poor OS in patients with high expression levels of circulating suPAR in subgroups of colorectal cancer (CRC), ovarian cancer, breast cancer, and prostate cancer (total HR 1.63, 95% CI 1.46 - 1.81) , and this effect is most obvious in patients with CRC (HR 1.67, 95% CI 1.47 - 1.89). No evidence of heterogeneity and publication bias was present. CONCLUSIONS: Our results suggested that suPAR is a promising biomarker in the prediction of prognosis in patients with cancers. However, further studies are warranted to validate its clinical application and biological implication with tumor development.

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.

[Dosimetry verification of radioactive seed implantation with 3D printing template and CT guidance for paravertebral/retroperitoneal malignant tumor].

Objective: To compare the dose distributions of postoperative plans with preoperative plans for seeds implantations of paravertebral/retroperitoneal tumors assisted by 3D printing guide template and CT guidance, explore the effects of the technology for seeds implantations in dosimetry level and provide data support for the optimization and standardization in seeds implantation. Methods: Between December 2015 and July 2016, a total of 10 patients with paravertebral/retroperitoneal tumors (12 lesions) received 3D printing template assist radioactive seeds implantations in department of radiation oncology of Peking University Third Hospital, and included in the study. The diseases included cervical cancer, kidney cancer, abdominal stromal tumor, leiomyosarcoma of kidney, esophageal cancer and carcinoma of ureter. The prescribed doses was 110-150 Gy. All patients received preoperative planning design, individual template design and production, and the dose distribution of postoperative plan was compared with preoperative plan. Dose parameters including D(90), MPD, V(100), V(150,)conformal index(CI), EI of target volume and D(2cc) of organs at risk (spinal cord, aorta, kidney). Statistical software was SPSS 19.0 and statistical method was non-parameters Wilcoxon symbols test. Results: A total of 10 3D printing templates were designed and produced which were including 12 treatment areas.The mean D(90) of postoperative target area (GTV) was 131.1 (97.8-167.4 Gy) Gy. The actual seeds number of post operation increased by 3 to 12 in 5 cases (42.0%). The needle was well distributed. For postoperative plans, the mean D(90,)MPD, V(100,)V(150) was 131.1 Gy, 69.3 Gy, 90.2% and 65.2%, respectively, and which was 140.2 Gy, 65.6 Gy, 91.7% and 26.8%, respectively, in preoperative plans. This meant that the actual dose of target volume was slightly lower than preplanned dose, and the high dose area of target volume was larger than preplanned range, but there was no statistical difference in P value between the two groups except V(150)(P=0.004). The actual dose conformity of target volume was worse than preplanned (CI was 0.58 and 0.62, respectively) and the difference was statistically significant(P=0.019). The actual dose of external target volume was higher than preplanned (EI was 55% and 45.9%, respectively) and the difference had no significance. For organs at risk, the actual mean D(2cc) of spinal cord, aorta and kidney was 24.7, 54.4 and 29.7 Gy, respectively, which was higher than preplanned(20.6, 51.6 and 28.6 Gy, respectively), and there was no significant difference in two groups. Conclusions: Most parameters of postoperative validations for 3D printing template assisted seeds implantation in paravertebral/retroperitoneal are closed to the expectations of preoperative plans which means the improvement of accuracy in treatment.

[Effect of image fusion technology of radioactive particles implantation before and after the planning target and dosimetry].

Objective: To compare the post-implant target volumes and dosimetric evaluation with pre-plan, the gross tumor volume(GTV) by CT image fusion-based and the manual delineation of target volume in CT guided radioactive seeds implantation. Methods: A total of 10 patients treated under CT-guidance (125)I seed implantation during March 2016 to April 2016 were analyzed in Peking University Third Hospital.All patients underwent pre-operative CT simulation, pre-operative planning, implantation seeds, CT scanning after seed implantation and dosimetric evaluation of GTV.In every patient, post-implant target volumes were delineated by both two methods, and were divided into two groups. Group 1: image fusion pre-implantation simulation and post-operative CT image, then the contours of GTV were automatically performed by brachytherapy treatment planning system; Group 2: the contouring of the GTV on post-operative CT image were performed manually by three senior radiation oncologists independently. The average of three data was sets. Statistical analyses were performed using SPSS software, version 3.2.0. The paired t-test was used to compare the target volumes and D(90) parameters in two modality. Results: In Group 1, average volume of GTV in post-operation group was 12-167(73±56) cm(3). D(90) was 101-153 (142±19)Gy. In Group 2, they were 14-186(80±58)cm(3) and 96-146(122±16) Gy respectively. In both target volumes and D(90), there was no statistical difference between pre-operation and post-operation in Group 1.The D(90) was slightly lower than that of pre-plan group, but there was no statistical difference (P=0.142); in Group 2, between pre-operation and post-operation group, there was a significant statistical difference in the GTV (P=0.002). The difference of D(90) was similarly (P<0.01). Conclusion: The method of delineation of post-implant GTV through fusion pre-implantation simulation and post-operative CT scan images, the contours of GTV are automatically performed by brachytherapy treatment planning system appears to have improved more accuracy, reproducibility and convenience than manual delineation of target volume by maximum reduce the interference from artificial factor and metal artifacts. Further work and more cases are required in the future.

[Investigation of pregestational diabetes mellitus in 15 hospitals in Guangdong province].

Objective: To investigate the morbidity, diagnostic profile and perinatal outcome of pregestational diabetes mellitus (PGDM) in 15 hospitals in Guangdong province. Methods: A total of 41 338 women delivered in the 15 hospitals during the 6 months, 195 women with PGDM (PGDM group) and 195 women with normal glucose test result (control group) were recruited from these tertiary hospitals in Guangdong province from January 2016 to June 2016. The morbidity and diagnostic profile of PGDM were analyzed. The complications during pregnancy and perinatal outcomes were compared between the two groups. In the PGDM group, pregnancy outcomes were analyzed in women who used insulin treatment (n=91) and women who did not (n=104). Results: (1) The incidence of PGDM was 0.472%(195/41 338). Diabetes mellitus were diagnosed in 59 women (30.3%, 59/195) before pregnancy, and 136 women (69.7%,136/195) were diagnosed as PGDM after conceptions. Forty-six women (33.8%) were diagnosed by fasting glucose and glycohemoglobin (HbA1c) screening. (2) The maternal age, pre-pregnancy body mass index (BMI) , prenatal BMI, percentage of family history of diabetes, incidence of macrosomia, concentration of low density lipoprotein were significantly higher in PGDM group than those in control group (all P<0.05). Women in PGDM group had significantly higher HbA1c concentration ((6.3±1.3)% vs (5.2±0.4)%) , fasting glucose [(6.3±2.3) vs (4.8±1.1) mmol/L], oral glucose tolerance test (OGTT) -1 h glucose ((12.6±2.9) vs (7.1±1.3) mmol/L) and OGTT-2 h glucose [(12.0±3.0) vs (6.4±1.0) mmol/L] than those in control group (P<0.01). (3) The morbidity of preterm births was significantly higher (11.3% vs 1.0%, P<0.01), and the gestational age at delivery in PGDM group was significantly smaller [(37.6±2.3) vs (39.2±1.2) weeks, P<0.01]. Cesarean delivery rate in the PGDM group (70.8% vs 29.7%) was significantly higher than the control group (P<0.01). There was significantly difference between PGDM group and control in the neonatal male/female ratio (98/97 vs 111/84, P=0.033). The neonatal birth weight in PGDM group was significantly higher ((3 159±700) vs (3 451±423) g, P<0.01) . And the incidence of neonatal hypoglycemia in the PGDM group was higher than the control group (7.7% vs 2.6%, P=0.036). (4) In the PGDM group, women who were treated with insulin had a smaller gestational age at delivery [(36.9±2.9) vs (37.9±2.5) weeks, P<0.01], and the neonates had a higher neonatal ICU (NICU) admission rate (24.2% vs 9.6%, P<0.01). Conclusions: The morbidity of PGDM in the 15 hospitals in Guangdong province is 0.472%. The majority of PGDM was diagnosed during pregnancy; HbA1c and fasting glucose are reliable parameters for PGDM screening. Women with PGDM have obvious family history of diabetes and repeated pregnancy may accelerate the process of diabetes mellitus. Women with PGDM have higher risk for preterm delivery and neonatal hypoglycemia. Unsatisfied glucose control followed by insulin treatment may increase the need for NICU admission.

[Association of HLA-DQ and IFNL4 polymorphisms with hepatitis B virus infection and clearance].

Objective: To confirmed the polymorphisms of HLA-DQ and IFNL4 were associated with HBV infection and clearance in a Chinese population. Methods: The Sequenom MassARRAY MALDI-TOF system was used to genotype the HLA-DQrs9275319 and IFNL4rs368234815, rs12971396, rs12979860, and rs8099917. A binary logistic regression test was conducted to estimate the relative risk of these SNPs with HBV infection and clearance. Haploview4.2 software and PHASE software (v2.0.2) were employed to analyze linkage disequilibrium (LD) and haplotype frequencies. The MDR program was applied to analyze interactions between SNP and SNP.Statistical analysis was performed using SPSS 19.0 and P-values were corrected by Bonferroni's corrections. Results: A total of 1,069 subjects were recruited and divided into three groups: 238 healthy controls(HC), 397 with HBV-related chronic liver disease (CLD), 434 with spontaneous clearance (SC). The rs9275319TT was most frequently identified among all groups(86.2% in the CLD group, 77.6% in the SC group, and 75.9% in the HC group).Carriage of the rs9275319 C allele was a protective factor for chronic HBV infection (the allele model: P = 0.000 3, OR,0.514; 95% CI, 0.359-0.738) and clearance (the allele model: P = 0.002, OR, 1.659; 95% CI, 1.197-2.300). HLA-DQ rs9275319 showed a significant association with HBV infection (allele model, OR, 0.514; 95% CI, 0.359-0.738, adjusted P = 0.000 3) and spontaneous clearance (allele model, OR, 1.659; 95% CI, 1.197-2.300, adjusted P = 0.002). However, there was no association between IFNL4 polymorphism and HBV infection((allele model: P = 0.082 for rs368234815; P = 0.063 for rs12971396; P = 0.517 for rs12979860; P =0.695 for rs8099917) or spontaneous clearance ((allele model: P = 0.358 for rs368234815; P = 0.105 for rs12971396; P = 0.640 for rs12979860; P = 0.640 for rs8099917;all P > 0.05). The multifactor dimensionality reduction (MDR) test showed there was a three-way interaction (rs12971396, rs12979860, and rs9275319) between IFNL4 and HLA-DQ polymorphisms for HBV infection (permutation P = 0.009 for the best factor model) and clearance (permutation P = 0.014 for the best factor model). Conclusion: The SNP-SNP interaction between HLA-DQ and IFNL4 is associated with the regulation of HBV infection and natural clearance.