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.

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.

Multimodel habitats constructed by perfusion and/or diffusion MRI predict isocitrate dehydrogenase mutation status and prognosis in high-grade gliomas.

AIM: To determine whether tumour vascular and cellular heterogeneity of high-grade glioma (HGG) is predictive of isocitrate dehydrogenase (IDH) mutation status and overall survival (OS) by using tumour habitat-based analysis constructed by perfusion and/or diffusion magnetic resonance imaging (MRI). MATERIALS AND METHODS: Seventy-eight HGG patients that met the 2021 World Health Organization WHO Classification of Tumors of the Central Nervous System, 5th edition (WHO CNS5), were enrolled to predict IDH mutation status, of which 32 grade 4 patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter were enrolled for prognostic analysis. The deep-learning-based model nnU-Net and K-means clustering algorithm were applied to construct the Traditional Habitat, Vascular Habitat (VH), Cellular Density Habitat (DH), and their Combined Habitat (CH). Quantitative parameters were extracted and compared between IDH-mutant and IDH-wild-type patients, respectively, and the prediction potential was evaluated by receiver operating characteristic (ROC) curve analysis. OS was analysed using Kaplan-Meier survival analysis and the log-rank test. RESULTS: Compared with IDH-mutants, median relative cerebral blood volume (rCBVmedian) values in the whole enhancing tumour (WET), VH1, VH3, CH1-4 habitats were significantly increased in IDH-wild-type HGGs (all p<0.05). Additionally, the accuracy of rCBVmedian values in CH1 outperformed other habitats in identifying IDH mutation status (p<0.001) at a cut-off value of 4.83 with AUC of 0.815. Kaplan-Meier survival analysis highlighted significant differences in OS between the populations dichotomised by the median of rCBVmedian in WET, VH1, CH1-3 habitats (all p<0.05). CONCLUSIONS: The habitat imaging technique may improve the accuracy of predicting IDH mutation status and prognosis, and even provide a new direction for subsequent personalised precision treatment.

Surgical treatment of nasopharyngeal cancer - a consensus recommendation from two Chinese associations.

BACKGROUND: Surgical treatment is playing an increasingly important role in the management of nasopharyngeal carcinoma (NPC). This consensus focuses on the indications for optimal surgery, and surgical methods in the whole process of treatment for NPC to provide a useful reference to assist these difficult clinical decisions. METHODOLOGY: A thorough review of available literature on NPC and surgery was conducted by the Association for the prevention and treatment of nasopharyngeal carcinoma in China, international exchange and promotion Association for medicine and healthcare, and the Committee on nasopharyngeal cancer of Guangdong provincial anticancer association. A set of questions and a preliminary draft guideline was circulated to a panel of 1096 experienced specialists on this disease for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the experts in two authoritative medical science and technology academic groups in the prevention and treatment of NPC in China for review and reconsideration. RESULTS: The initial round of questions showed variations in clinical practice even among similar specialists, reflecting the lack of high-quality supporting data and resulting difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of surgery, including indications and surgical approaches. CONCLUSION: By standardizing the surgical indications and practice, we hope not only to improve the surgical outcomes, but also to highlight the key directions of future clinical research in the surgical management of NPC.

[Effect of dual fluorescence imaging in identifying central lymph nodes and parathyroid glands during thyroid cancer surgery].

Objective: To investigate the effect of dual fluorescence imaging in identifying central lymph nodes and parathyroid glands during thyroid cancer surgery. Methods: This study was a cross-sectional study. Patients who underwent surgery for papillary thyroid cancer (PTC) at the Department of Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University between January 2022 and September 2023 were included. All patients underwent thyroid lobectomy or total resection, and central lymph node dissection was performed at the same time. During the operation, tracing injection of mitoxantrone hydrochloride and 785 nm and 660 nm dual fluorescence imaging technique were used to measure the fluorescence intensity (FI) of parathyroid glands, central lymph nodes and background. After correcting to obtain the standardized FI, the paired t-test was used to compare the standardized FI of the parathyroid glands and central lymph nodes, and the Spearman's rank correlation analysis was used to analyze the relationship between the standardized FI and various clinical indicators. Results: The study included 30 patients (8 males and 22 females), with a mean age of (41.8±10.4) years. A total of 76 parathyroid glands and 234 central lymph nodes were identified under dual fluorescence imaging, and the standardized FI of parathyroid glands was less than that of central lymph nodes (44.7±16.8 vs 99.5±28.4, P<0.001). The visualization rate, false rate and miscut rate of parathyroid glands under 785 nm wavelength excitation light were 98.7% (76/77), 0 (0/77) and 1.3% (1/77), respectively (one case with no visualization and miscutting parathyroid gland was the encapsulated type). The visualization rate of central lymph nodes under 660 nm wavelength excitation light was 98.7% (234/237). There was no significant correlation between FI and clinical indicators such as gender, age, height, weight, body mass index, preoperative thyroid stimulating hormone, thyroglobulin antibody, thyroid microsomal antibody, serum calcium, parathyroid hormone level and surgical procedure (all P>0.05). Conclusion: Dual fluorescence imaging of central lymph nodes and parathyroid glands can improve the ability to identify parathyroid gland while assisting central lymph node dissection.

[Study on the inhibitory and pro-apoptotic effects of different concentrations of total tanshinone alone and in combination with tyrosine kinase inhibitors on human myeloid leukemia cell lines].

Objective: To explore the effect and investigate the molecular mechanism of different concentrations of total tanshinones alone and in combination with tyrosine kinase inhibitors (TKIs) on the proliferation inhibition and apoptosis of human myeloid leukemia cell lines. Methods: K562 and Kasumi-1 cell lines were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences, and the TKIs-resistant strain K562/T315I cell line was constructed in Molecular Medicine Research Center, Beijing Lu Daopei Institute of Hematology. Logarithmic growth phase cells were taken and divided into intervention groups with total tanshinone of 0, 2.19, 4.38, 8.75, 17.50 and 35.00 µg/ml intervention groups, which were inoculated in 96-well plates at a density of 1×104 cells/well and exposed to the drug for 24 h, and a control group treated with dimethyl sulfoxide was also set up simultaneously. All experiments were repeated independently 3-5 times. The proliferative activity of the cells was assessed using the CCK-8 assay, the apoptotic rates were measured by flow cytometry, and the expression levels of apoptosis-regulating proteins Bcl-2 and Bax were analyzed by Western blotting. The cell lines treated and untreated with total tanshinone were subjected to transcriptome sequencing and gene set enrichment analysis to identify differentially expressed genes. Results: The half-inhibitory concentration (IC50) values of 8.75 µg/ml total tanshinone at 24 h for K562, K562/T315I and Kasumi-1 cells were (4.11±0.02), (4.95±0.04) and (3.98±0.01) µg/ml, respectively. When combined with 0.25 µmol/L imatinib, 8.75 µg/ml total tanshinone could enhance the induction of apoptosis effects on K562 and K562/T315I cell lines. After being treated with 4.38, 8.75, and 17.50 µg/ml of total tanshinone for 24 h, compared with the control group, total tanshinone upregulated the expression level of Bax protein, downregulated the expression level of Bcl-2 protein, and decreased the Bcl-2/Bax ratio (all P<0.05). Total tanshinone inhibited the proliferation-related signaling pathway and DNA damage repair pathway of myeloid leukemia cell lines, and activated the signaling pathway that induces apoptosis in leukemia cells. Conclusion: Different concentrations of total tanshinoneinhibites proliferation and promote apoptosis in K562, Kasumi-1 and TKIs-resistant K562/T315I cell lines, and further enhance the anti-leukemic effect when combined with TKIs.

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.

Measurement of oesophageal hiatus surface area by multiplanar reconstruction of MDCT: relationship with lower oesophageal sphincter pressure and acid reflux.

AIM: To evaluate the relationship between oesophageal hiatus surface area (OHSA) and gastro-oesophageal reflux disease (GERD). MATERIALS AND METHODS: Patients who underwent 24-h pH monitoring, oesophageal high-resolution manometry, and upper abdominal contrast-enhanced multidetector computed tomography (MDCT) during 2014-2021 were enrolled. Patients with a hiatus hernia (HH) on MDCT or who had a history of gastro-oesophageal surgery were excluded. Multiplanar reconstruction (MPR) of the MDCT image was used for the measurement of OHSA. Correlations of OHSA with acid exposure time (AET) and lower oesophageal sphincter (LOS) pressure of all patients were analysed. RESULTS: Seventy-eight patients were included in the study. OHSA was much less in the AET <4% group than in the AET >6% group (1.61 ± 0.42 versus 2.09 ± 0.55 cm2, p<0.001). Correlation analysis reveals that OHSA correlated positively with AET (correlation coefficient = 0.47, p<0.001). Receiver operating characteristic (ROC) curve analysis reveals that OHSA can significantly distinguish patients in different groups divided by AET (area under the ROC curve [AUC] = 0.76, 95% confidence interval [CI]: 0.63-0.90). OHSA was not related to LOS pressure (correlation coefficient = -0.268, p=0.051). There was no difference in OHSA between the low LOS pressure group and the normal LOS pressure group (1.84 ± 0.61 versus 1.74 ± 0.50 cm2, p=0.52). CONCLUSIONS: OHSA significantly correlated with AET but has no relationship with LOS pressure. It may be an independent risk factor of GERD.

Brusatol attenuated proliferation and invasion induced by KRAS in differentiated thyroid cancer through inhibiting Nrf2.

BACKGROUND: Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) can be developed from differentiated thyroid cancer, and this dedifferentiated transformation leads to poor prognosis and high mortality. The role of Nrf2 in the dedifferentiation of differentiated thyroid cancer (DTC) induced by KRAS remains unclear. METHODS AND MATERIALS: In this study, two DTC cell lines, BCPAP and WRO, were used to evaluate the function of Nrf2 in the dedifferentiation caused by wild-type KRAS (KRAS-WT) and G12V point mutation KRAS (KRAS-G12V). RESULTS: The overexpression of KRAS-WT and KRAS-G12V increased the proliferative and invasive ability of BCPAP and WRO cells. Aggressive morphology was observed in KRAS-WT and KRAS-G12V overexpressed WRO cells. These results suggested that overexpression of KRAS-WT or KRAS-G12V may induce dedifferentiation in DTC cells. The expression of Nrf2 was increased by KRAS-WT and KRAS-G12V in DTC cells. In addition, compared with normal thyroid tissues, the expression of Nrf2 protein was considerably higher in thyroid cancer tissues on immunohistochemistry (IHC) staining, and the increased expression of Nrf2 indicated a poor prognosis of thyroid cancer. These results indicated that Nrf2 is the KRAS downstream molecule in thyroid cancer. Functional studies showed that the Nrf2 inhibitor Brusatol counteracted the proliferative and invasive abilities induced by KRAS-WT and KRAS-G12V in BCPAP and WRO cells. In addition, the xenograft assay further confirmed that Brusatol inhibits tumor growth induced by KRAS-WT and KRAS-G12V. CONCLUSION: Collectively, this study suggests that Nrf2 could be a promising therapeutic target in KRAS-mediated dedifferentiation of thyroid cancer.

[Pre- and post-diagnosis body mass index in association with colorectal cancer death in a prospective cohort study].

Objective: To evaluate the association between pre-and post-diagnosis body mass index (BMI) and risk of colorectal cancer (CRC) death. Methods: The cohort consisted of 3, 057 CRC patients from Shanghai who were diagnosed from Jan. 1, 2009 to Dec. 31, 2011 and aged from 20 to 74 years. The pre- and post-diagnosis BMI and clinical and lifestyle factors were collected at baseline. Death information was collected using record linkage with the Shanghai Cancer Registry and telephone confirmation during follow-up by the end of 2019. The Cox proportional regression model was used to estimate HR with 95% CI. Results: Analysis by multivariable Cox model showed no association between pre-diagnosis BMI and death risk in both male and female patients. Male patients with a post-diagnosis underweight BMI had an elevated risk of death compared to those in normal weight (HR=1.69, 95% CI: 1.21-2.37), especially in early stage cases. Overweight patients (HR=0.74, 95% CI: 0.61-0.89) and patients with obesity class Ⅰ (HR=0.63, 95% CI: 0.45-0.89)had better survival with decreased risks of death, especially in advanced stage cases. The decreased death risk in patients with obesity class Ⅱ was not significant (HR=0.57, 95% CI: 0.24-1.39). The P(trend) value for decreased risk of death with increased BMI in female patients was statistically significant (P<0.001), and the overweight and obesity class Ⅰ categories had better survival in advanced stage(HR(overweight)=0.62, 95% CI: 0.42-0.93; HR(obesity class Ⅰ)=0.39, 95% CI: 0.16-0.98). Both male and female patients with post-diagnosis BMI loss >2.0 kg/m(2) had an increased death risk when compared with those with stable BMI (change≤1.0 kg/m(2)) between pre- and post-diagnosis. BMI gain after diagnosis did not change death risk. Conclusions: Post-diagnosis BMI in the overweight or obesity class Ⅰ groups might be conducive to prolonging male CRC patients' survival, while underweight might result in poor prognosis. Keeping weight and avoiding excessive weight loss should be suggested for all CRC patients after diagnosis.

[Standardized and individualized treatment improves survival rate and quality of life for advanced thyroid cancer].

The overall prognosis of differentiated thyroid carcinoma is favorable, but some patients still progress to a locally advanced stage. At present, there are still some problems in the diagnosis and treatment of locally advanced thyroid cancer, which have not been completely clarified, and have caused some problems to the clinical treatment. This article provides a comprehensive analysis and elaboration on the selection of surgical methods for local advanced thyroid cancer, management of recurrent laryngeal nerve and trachea, timing selection of staging surgery, and targeted therapy, aiming at promoting standardized and individualized treatment for advanced thyroid cancer and improving the survival rate and quality of life.

[Performance verification and clinical application evaluation of D-dimer assay].

Objective: To evaluate the clinical application performance of a domestic D-dimer assay reagent (ADX D-dimer). Methods: A total of 546 residual sodium citrate anticoagulated plasma samples (530 of which were used for comparability validation and 16 for sample preparation of other validation components) were selected after the completion of clinical testing at Peking Union Medical College Hospital from Jun 2022 to May 2023. According to the American Clinical Laboratory Standards Institute (CLSI) guidelines, national health industry standards and relevant references, the performance of ADX D-dimer used in Sysmex CS 5100 fully automated coagulation analyzer which included accuracy, precision, linear range, carryover rate, interference resistance capability and reference interval were validated and the agreement compared with two mainstream imported detection reagents (reagent A: Vidas D-dimer reagent; reagent B: Innovance D-dimer detection reagent) was evaluated. The clinical diagnostic efficacy of the ADX D-dimer was evaluated using the ELISA D-dimer (reagent A) test results as criteria. Results: The linear correlation coefficient of the 6-point calibrated absorbance and target value was 0.998, the bias of accuracy met the requirements (-2.8%-8.4%), and the coefficient of variation (CV) of within-run and between-day precision of the two levels were 1.0%-2.7% and 2.7%-4.1%, respectively, which were less than the requirements of the manufacturer's statement and the national health industry standard. The linear range within 0.33-9.69 mg/L FEU was verified and the carryover rate was 0. There was no significant interference with the assay results at bilirubin F≤0.22 g/L, bilirubin C≤0.22 g/L, hemoglobin≤5.5 g/L and celiac≤2 800 FTU. The manufacturer's reference interval≤0.5 mg/L FEU was verified suitable for this laboratory. For 358 samples without suspicious heterophilic antibody whose D-dimer levels range from 0.06 to143.63 mg/L FEU, the correlation between ADX D-dimer and another two assay was good, with r values being 0.968 and 0.975, respectively, the percentage of deviation and relative deviation beyond the 95% confidence interval was 3.4%-4.5% and 5.3%-7.0%. The correlation between ADX D-dimer and ELISA D-dimer was better than that of reagent B in the concentration range of 0.06-1.00 mg/L FEU (r=0.858, 0.134). For 172 samples with heterophilic antibody, the correlation between ADX D-dimer and ELISA D-dimer was still good(r=0.827), with the percentage of deviation and relative deviation being 6.4% (11/172). The diagnostic efficacy was evaluated using 530 samples, and the sensitivity, specificity, positive predictive value, negative predictive value of ADX D-dimer was 97.4%, 77.6%, 91.9%, 91.9%. The area under the curve was 0.976 (95%CI: 0.964-0.987, P<0.001). Conclusion: The ADX D-dimer reagent has superior assay and diagnostic performance, and can meet the needs of clinical laboratories.

[Application of near-infrared autofluorescence imaging-based convolution neural network in recognition of parathyroid gland].

Objective: To investigate the application value of near-infrared autofluorescence imaging-based convolution neural network (CNN) for automatic recognition of parathyroid gland. Methods: The data of 83 patients who underwent thyroid papillary cancer surgery in the Department of Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University from August 2020 to March 2022 were retrospectively analyzed, and a total of 725 autofluorescence images of parathyroid gland were collected during the surgery. Meanwhile, non-parathyroid fluorescence imaging videos in the operation area of 10 patients were also collected, and 928 non-parathyroid fluorescence images were captured from those videos. The fluorescence images of parathyroid and non-parathyroid glands were directly used as input features for deep learning to construct ResNet 34, VGGNet 16 and GoogleNet models for automatic parathyroid identification. The ability of different models to identify parathyroid glands was tested by indicators such as accuracy, specificity, sensitivity, precision, receiver operating characteristic curve and area under the curve (AUC). In addition, 30 fluorescence images of parathyroid and 35 fluorescence images of non-parathyroid glands in 13 patients with papillary thyroid cancer from March to May 2022 were collected to prospectively test the best performing CNN model. Results: Among the 83 patients, there were 25 males and 58 females, with the mean age of (46.7±12.4) years. In the binary classification (parathyroid gland and non-parathyroid gland), the ResNet 34 model performed the best in different CNN models, the accuracy, specificity, sensitivity and precision of the identification test set were 97.6%, 96.3%, 99.3% and 95.5%, and the AUC reached 0.978 (95%CI: 0.956-0.991). In the prospective test, the prediction accuracy of the ResNet 34 model reached 93.8%, and the AUC was 0.938 (95%CI: 0.853-0.984). Conclusion: The near-infrared autofluorescence imaging-based deep CNN has good application value in the automatic recognition of parathyroid gland, and can be used to assist the recognition and protection of parathyroid gland in thyroid cancer surgery.

[Preliminary analysis of neuroprotective effects of capillary fascia preservation recurrent laryngeal nerve anatomical method in right level â ¥ dissection].

Objective: To investigate the application and effect of capillary fascia preservation between the recurrent laryngeal nerve (RLN) and common carotid artery (fascia preservation method) in nerve protection when dissecting right level Ⅵ lymph nodes for patients with papillary thyroid carcinoma. Methods: A retrospective cohort study enrolling 195 patients with papillary thyroid carcinoma undergoing right level Ⅵ lymph node dissection in Beijing Tongren Hospital from March 2021 to August 2022 was carried out. The RLN was dissected by fascia preservation method in study group and by routine method in control group. The intraoperative electrical signal amplitude of the RLN, the number of dissected lymph nodes, and the postoperative complications were recorded and analyzed. Results: A total of 195 patients (study group: 94 cases, control group: 101 cases) were collected. There were 71 males and 124 females, with the median age of 32 (39, 51) years. In the study group, the total number of right level Ⅵ lymph nodes was significantly larger than the number of right Ⅵa level lymph nodes [8 (6, 11) vs 6 (4, 8), P<0.001]. There were no significant differences between the two groups in the number of level Ⅵa or level Ⅵb lymph nodes [Ⅵa: 6 (4, 8) vs 5 (3, 7), P=0.373; Ⅵb: 3 (1, 4) vs 2 (1, 4), P=0.337] and metastasis rate [Ⅵa: 51.1% (48/94) vs 52.5% (53/101), P=0.844; Ⅵb: 12.8% (12/94) vs 15.8% (16/101), P=0.541]. The ratio of electromyography (EMG) amplitude R2 in lower level Ⅵ and entry into larynx (grouped as>90%, 50%~90%,<50%) in the study group was significantly higher than that in the control group (P<0.001). No significant differences were detected between the two groups in temporary RLN paralysis [1.1% (1/94) vs 2.0% (2/101), P=1.000]. Conclusions: Fascia preservation method can decrease the stimulus and traction to RLN and preserve the capillary network serving RLN. It can thoroughly dissect lymph nodes and decrease the injury of RLN.

[Study on formulation and revision of standard limits for inhalable particulate matter (PM10) and fine particulate matter (PM2.5) in "Standards for indoor air quality（GB/T 18883-2022）" in China].

The pollution and health effects of indoor inhalable particulate matter (PM10) and fine particulate matter (PM2.5) are increasingly receiving public attention. The"Standards for indoor air quality (GB/T 18883-2022)"has revised the standard limit for PM10 and added the standard limit for PM2.5. This study analyzed and interpreted the relevant technical contents of the revision of the standard limits for two indicators, including the exposure status, health effects, and the basis for the determination of the limit value. It also proposed prospects for the future development and revision of standard limits for indoor particulate matters.

[A panel study on the effect of atmospheric PM2.5 exposure on the gut microbiome in healthy elderly people aged 60-69 years old].

Objective: To analyze the short-term effect of individual atmospheric PM2.5 exposure on the diversity, enterotype, and community structure of gut microbiome in healthy elderly people in Jinan, Shandong province. Methods: The present panel study recruited 76 healthy elderly people aged 60-69 years old in Dianliu Street, Lixia District, Jinan, Shandong Province, and followed them up five times from September 2018 to January 2019. The relevant information was collected by questionnaire, physical examination, precise monitoring of individual PM2.5 exposure, fecal sample collection and gut microbiome 16S rDNA sequencing. The Dirichlet multinomial mixtures (DMM) model was used to analyze the enterotype. Linear mixed effect model and generalized linear mixed effect model were used to analyze the effect of PM2.5 exposure on gut microbiome α diversity indices (Shannon, Simpson, Chao1, and ACE indices), enterotype and abundance of core species. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 352 person-visits. The age of 76 subjects was (65.0±2.8) years old with BMI (25.0±2.4) kg/m2. There were 38 males accounting for 50% of the subjects. People with an educational level of primary school or below accounted for 10.5% of the 76 subjects, and those with secondary school and junior college or above accounting for 71.1% and 18.4%. The individual PM2.5 exposure concentration of 76 subjects during the study period was (58.7±53.7) µg/m3. DMM model showed that the subjects could be divided into four enterotypes, which were mainly driven by Bacteroides, Faecalibacterium, Lachnospiraceae, Prevotellaceae, and Ruminococcaceae. Linear mixed effects model showed that different lag periods of PM2.5 exposure were significantly associated with a lower gut α diversity index (FDR<0.05 after correction). Further analysis showed that PM2.5 exposure was significantly associated with changes in the abundances of Firmicutes (Megamonas, Blautia, Streptococcus, etc.) and Bacteroidetes (Alistipes) (FDR<0.05 after correction). Conclusion: Short-term PM2.5 exposure is significantly associated with a decrease in gut microbiome diversity and changes in the abundance of several species of Firmicutes and Bacteroidetes in the elderly. It is necessary to further explore the underlying mechanisms between PM2.5 exposure and the gut microbiome, so as to provide a scientific basis for promoting the intestinal health of the elderly.

[Factors influencing bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt].

Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.

[Recompensation of complications in patients with hepatitis B virus-related decompensated cirrhosis treated with entecavir antiviral therapy].

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.

[Safety and efficacy of toric intraocular lens implantation for more than 5 years].

Objective: To evaluate the clinical safety and efficacy of toric intraocular lens (IOL) implantation for more than 5 years. Methods: This study was a prospective cohort study in which subjects were continuously observed over a two-year period (May 2014 to May 2016) in nine hospitals. The study randomly assigned subjects to two groups using a central dynamic randomization system: the study group, which received Proming® IQ toric IOL implants, and the control group, which received AcrySof® IQ toric IOL implants. The subjects completed a one-year follow-up, during which various measures were taken and evaluated, including visual acuity, IOL rotation, postoperative complications, intraocular pressure, and subjective evaluation (preoperatively and at 1 day, 6 months, 1 year, and 5 years post-surgery). The main statistical analysis methods include the Mann-Whitney U test, independent sample t-test, Wilcoxon signed rank test, paired sample t-test, chi-square test, and Fisher's exact test. Results: A total of 45 eyes (26 in the study group and 19 in the control group) completed the five-year continuous observation period. The mean age of the subjects was (72.07±10.67) years and the mean interval from surgery to the last visit was (5.39±0.47) years. After five years, there were no significant differences in uncorrected distance visual acuity (0.20±0.26 vs. 0.16±0.13, t=0.17,P=0.752), best corrected distance visual acuity[0.00(0.00, 0.20) vs. 0.05±0.10, U=188.00, P=0.880], uncorrected near visual acuity[0.50 (0.20, 0.60) vs. 0.42±0.20, t=0.35, P=0.857], and best corrected near visual acuity (0.13±0.16 vs. 0.17±0.23, U=161.00, P=0.884) between the two groups. However, all measures improved significantly from baseline levels in both groups (all P<0.05). Five years after surgery, no matter objective refraction [(-0.67±0.85) D vs. (-0.73±1.08)D] or subjective refraction[-0.50 (-1.00, 0.00)D vs. (0.69±0.87)D], the degree of cylindrical degree is significantly lower than preoperative corneal astigmatism [(1.27±0.49) D vs. (1.34±0.82) D, all P<0.001]. In addition, there were no significant differences in intraocular pressure, subjective evaluation of visual adverse symptoms, distance vision spectacle independence, or overall satisfaction evaluation between the two groups (all P>0.05). The IOL rotation was 3.0°(1.0°, 6.0°) in the study group and 4.0°(2.0°, 6.0°)in the control group (U=185.50,P=0.574), indicating no significant difference between the groups in terms of rotational stability. Five years after surgery, there were 7 cases of posterior capsular opacification in the study group and 4 cases in the control group. There were no cases of IOL glistening in the study group, but 5 cases (26.32%) were observed in the control group. Conclusions: The long-term effects of Proming® toric IOL implantation in correcting cataracts with regular corneal astigmatism are clear after five years, with few complications and stable results.

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.