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.

A multicentre, randomized, double-blind, placebo-controlled trial of topical oestradiol gel for endometrial regeneration after induced abortion.

STUDY QUESTION: Is topical oestradiol gel effective in promoting endometrial regeneration after a surgical abortion? SUMMARY ANSWER: Topical oestradiol gel is effective in promoting endometrial regeneration after a surgical abortion with few side-effects. WHAT IS KNOWN ALREADY: Oestrogen is effective in promoting endometrial regeneration. Transdermal oestrogen has been widely used in clinical practice for endometrial regeneration after induced abortion, but high-level evidence is limited. STUDY DESIGN, SIZE, DURATION: We conducted a multicentre, superiority, randomized, double-blind, placebo-controlled trial. Between 9 March 2022 and 21 February 2023, 200 women were assigned in a 1:1 ratio to receive either oestradiol gel (treatment) and or oestradiol gel simulant (control) for 28 days. The participants were scheduled to have their endometrial thickness (mm) measured by ultrasonographic scan at 21-23 days post-abortion. The trial was blinded for participants, investigators, medical staff, and statistical analysts until final unblinding. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were women undergoing induced abortion within 10 weeks of gestation. A total of 200 participants were enrolled, with 100 in each group. Eighty-eight (88%) in the treatment group and 82 (82%) in the control group completed the study as per the protocol and were included in the per-protocol set (PPS). The intent-to-treat (ITT) analysis included all participants randomized to the study groups and used inverse probability weighting to account for loss to follow-up. MAIN RESULTS AND THE ROLE OF CHANCE: The ITT analysis showed revealed significantly greater endometrial thickness in the treatment group (mean 8.1 ± 2.5 mm) compared to the control group (mean 6.9 ± 2.1 mm) 21-23 days postabortion (mean difference 1.2 mm, 95% CI 0.7 to 1.9; P < 0.001). The median time to menstrual return was shorter in the treatment group (34 days, inter-quartile range [IQR] 30-38) than in the control group (35 days, IQR 32-42), with a difference of -1 day (95% CI -2.3 to -0.9; P = 0.036). No differences were observed in the timing or volume of bleeding in the first post-abortion cycle. The PPS analysis mirrored the ITT findings. Adverse events were minimal (6% versus 8%), and the blood profile, liver, kidney and coagulation test results were comparable between groups (all P > 0.05). LIMITATIONS, REASONS FOR CAUTION: Loss to follow-up was 11% in the treatment group and 15% of controls, with no significant difference (P > 0.05). Inconsistencies in the timing of the ultrasonographic scans may have affected the accuracy of endometrial thickness measurements. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that topical oestrogen supplementation immediately after abortion within the first 10 weeks of gestation improves endometrial regeneration and growth, thereby potentially increasing the chances of a successful subsequent pregnancy. Clinical application of these findings may improve endometrial health management practices and provide a perspective on fertility treatment and women's reproductive health. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a grant (FW-HKKT2021111501900) from Jianmin Pharmaceutical Group Co., Ltd (JMPG), Wuhan, Hubei, China. Both the oestradiol gel and the simulant were provided by JMPG. The funding source had no role in the study. X.Y.L. reports JMPG grant funding paid to their institutions. All other authors declare no competing interests. TRIAL REGISTRATION NUMBER: CHiCTR2100053565. TRIAL REGISTRATION DATE: 24 November 2021. DATE OF FIRST PATIENT'S ENROLMENT: 9 March 2022.

[Association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40-89 in selected areas of China].

Objective: To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China. Methods: The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function. Results: The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M (Q1, Q3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) µg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95%CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion: Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

[Curative effect of percutaneous microwave ablation therapy on hepatocellular carcinoma survival: a 15-year real-world study].

Objective: To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma. Methods: 2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival. Results: A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P < 0.001, especially for liver cancer 3.1~5.0 cm (P < 0.001). Conclusion: Microwave ablation therapy is a safe and effective method for BCLC stage 0-B, with significantly enhanced technical efficacy and survival rate over time.

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.

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.

[Incidence of unintended pregnancy within 2 years after delivery and its influencing factors in China].

Objective: To investigate the present situation of unintended pregnancy within two years postpartum and its influencing factors in China. Methods: Participants who delivered a live birth at 60 hospitals in 15 provinces in the eastern, central and western regions of China during July 2015 to June 2016 were interviewed by using structured questionnaire. Information on occurrence of unintended pregnancy within 2 years after delivery, postpartum contraceptive use, sexual resumption, breastfeeding, and women's socio-demographic characteristics, and so on, were collected. Life-table analysis, cluster log-rank tests and a 2-level Cox regression model were used for data analysis. Results: A total of 18 045 postpartum women were investigated. The cumulative 1- and 2-year unintended pregnancy rates after delivery were 5.3% (95%CI: 4.5%－6.1%) and 13.1% (95%CI: 11.3%－14.8%), respectively. Cox regression model analysis showed that the risk of unintended pregnancy within 2 years postpartum were increased in younger women, ethnic minorities, women with abortion history, and those who had a vaginal delivery with short lactation time and late postpartum contraceptive initiation (all P<0.01). The risk of postpartum unintended pregnancy was not associated with geographic regions and hospitals where women gave a birth (all P>0.05). Conclusions: In China, the risk of unintended pregnancy within 2 years after delivery is relatively high. Service institutions and service providers should improve the quality of postpartum family planning services, promote the use of high effect contraceptive methods, and educate women to use a method at the time of their sexual resumption or even before.

Prediction of cause-specific disability-adjusted life years in China from 2018 through 2021: a systematic analysis.

OBJECTIVE: We aimed to predict population composition, mortality, sociodemographic index (SDI), and cause-specific disability-adjusted life year (DALY) rate in China from 2018 through 2021. STUDY DESIGN: Using the time series method autoregressive integrated moving average (ARIMA) models on all available data, mainly Statistics Year Report by the Global Burden of Disease Study 2017, we predicted populations, deaths, DALYs attributable to disease conditions, and injuries (causes) for China from 2018 through 2021 at levels 0, 1, 2, and 3. METHODS: The time series method ARIMA models was used on history data. RESULTS: The predicted total population and SDI in China are increasing from 2018 through 2021. The under-5 mortality is decreasing; from 10.24% to 0.65% in the period 1990-2021. The all-cause DALY rate decreases. The top causes of DALY rate are non-communicable diseases (level 1), cardiovascular diseases (level 2), and stroke (level 3). For the leading 22 level 2 causes in 2018, the trend of ranking in 2021 is as follows: unchanged, 15; increasing, 4; and decreasing, 3. For the leading 169 level 3 causes in 2018, the trend of ranking in 2021 is: as follows: unchanged, 49; increasing, 63; and decreasing 57. CONCLUSIONS: Cause-specific and time-dependent health policy should be steered to reduce the major burden focuses and to improve population health.

[Preliminary clinical observations of the effect of posterior continuous curvilinear capsulorhexis with intraocular lens optic capture in the treatment of pediatric cataract].

Objective: To observe the preliminary clinical effect of intraocular lens optic capture through posterior continuous curvilinear capsulorhexis in the treatment of pediatric cataract. Methods: It was a retrospective case series study. Forty-three eyes of 28 children underwent posterior continuous curvilinear capsulorhexis with posterior chamber intraocular lens optic capture to treat cataract from June 2017 to October 2018 in Qingdao Eye Hospital. Postoperative best corrected visual acuity, diopters, intraocular pressure, the position of intraocular lens, and postoperative complications were assessed. The distribution of preoperative and postoperative best corrected visual acuity was analyzed by Fisher's exact probability test. Results: Twenty-eight patients were 14 females and 14 males aged from 2 years old to 12 years old [mean age, (7±4) years]. All intraocular lenses were successfully captured in the posterior capsule. Patients were followed-up for 6.0 to 12.0 months (mean, 8.4 months). Except 2 eyes from one uncooperative child, the distribution of preoperative and postoperative best corrected visual acuity (<0.1, 0.1-<0.3, 0.3-<0.5, ≥0.5) had a significant difference (17, 17, 4, 3 eyes vs. 4, 4, 5, 28 eyes, P<0.01). At the last postoperative follow-up visit, the mean spherical equivalent was (0.21±0.74) D. Transient intraocular hypertension occurred in 3 eyes at 1 week after surgery and was controlled with stopping the use of corticosteroid eyedrops. No visual axis opacification or intraocular lens decentration or tilt was observed during the follow-up period. No other complications such as iris synechia, secondary glaucoma, retinal detachment, and cystoid macular edema were observed. Conclusions: Posterior continuous curvilinear capsulorhexis with intraocular lens optic capture is a safe and effective technique to treat pediatric cataract. It has a significant effect on the prevention of visual axis opacification after cataract surgery in children. (Chin J Ophthalmol, 2020, 56: 343-348).

Role of MnSOD in propofol protection of human umbilical vein endothelial cells injured by heat stress.

PURPOSE: Heat stress stimulation can cause various injuries in human umbilical vein endothelial cells (HUVEC), including apoptotic cell death and an increase in cell permeability. Propofol (PPF), a commonly used anesthetic, is known to have an important role in antioxidation as well as organ protection. Therefore, our aim is to evaluate the protective effects of PPF on heat stress (HS)-induced oxidative stress injury and its possible mechanism of action. METHODS: For HS + PPF, cells were treated with propofol followed by 2 h heat stress at 43 °C and then 4 h incubation under normal conditions. For propofol treatment, HUVEC were cultured in serum-free Dulbecco's modified Eagle medium supplemented with 0, 10, 25, or 50 µM propofol for 6 h under normal conditions. RESULTS: During the study, we found that, in HS-induced cellular damage, the protective effect of propofol was related closely with its antioxidation properties. We further revealed that heat stress significantly reduced the level of manganese superoxide demutase (MnSOD) and Cu/Zn SOD, but that propofol could inhibit the reduction of MnSOD only. Transfection of HUVEC with MnSOD small interfering RNA (siRNA) markedly decreased the expression of MnSOD, and the protective effect of propofol in the MnSOD siRNA clones was significantly reduced. CONCLUSION: Propofol protected the heat stress-injured cells, at least partly, through upregulating MnSOD expression, effectively reducing the direct or indirect cell damage caused by oxidative stress.