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.

[Analysis of tumor regression after concurrent radiochemotherapy for locally advanced hypopharyngeal carcinoma].

Objective: To investigate the pathological characteristics of tumor regression and the expression level of chemoradiotherapy resistance-related molecular markers after preoperative concurrent radiochemotherapy in patients with locally advanced hypopharyngeal carcinoma. Methods: The clinical data of 44 patients with locally advanced hypopharyngeal carcinoma who underwent preoperative concurrent radiochemotherapy in the Department of Head and Neck Surgery of Shandong Otolaryngology Hospital from August 2016 to August 2020 were retrospectively analyzed. All patients received preoperative concurrent chemotherapy and radiotherapy. After radiochemotherapy, electronic laryngoscopy and imaging examination were performed to assess the tumor regression status. After 4 weeks, surgical resection was performed, and the specimens of the primary focus were processed as continuous pathological sections. After operation, HE staining and TdT-mediated dUTP nick-end labeling (TUNEL) method were used to detect the distribution characteristics and apoptosis of the remaining cancer focus, and immunohistochemistry was performed to determine the proliferation of the remaining cancer focus and the expression of radiation resistance-related molecular markers [signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1alpha (HIF-1α), sex determining region Y-box 2 (SOX2), and P53]. Results: A total of 44 patients were included, all of whom were male, with a mean age of (58.3±3.5) years. There were 40 cases of pyriform sinus carcinoma and 4 cases of posterior pharyngeal wall carcinoma. Twenty-nine cases were in stage T3 and 15 cases were in stage T4. There were 6 stage Ⅲ cases and 38 stage Ⅳ cases. According to the response evaluation criteria in solid tumors (RECIST), 13 patients achieved complete response (CR), 22 patients had partial response (PR), and 9 patients achieved stable disease (SD) after concurrent radiochemotherapy. The primary lesion resection methods included 19 cases of hypopharyngeal circumferential resection and 2 cases of total laryngectomy and partial hypopharyngeal resection. Twenty-three cases underwent supracricoid cartilage subtotal laryngectomy cricoid tongue fixation (CHP). Among 22 patients with PR, 10 had large PR (remission rate ≥70%) and 12 had small PR (remission rate <70%). The residual tumor was found in 30 patients (68.2%) after resection of all primary lesions by HE staining of pathological sections, of which 3 patients (3/13) with CR had residual cancer, all of which were focal residues. In large PR patients, residual cancer was detected in 6 cases (6/10), scattered in 4 cases, and focal residual in 2 cases, respectively. Large residual tumors were detected in small PR and SD patients. TUNEL method did not show any sign of apoptosis in 30 specimens with residual cancer focus, and the positive expression rate of Ki-67 was less than 10%. The expression of STAT3 (3.40±2.49 vs 5.23±3.02, t=-2.932, P=0.007) in 19 cases (63.3%) and HIF-1α (3.73±2.66 vs 6.97±3.05, t=-4.45, P<0.001) in 22 cases (73.3%) of residual cancer were significantly higher than those before radiochemotherapy. Other molecular markers showed no significant changes. All patients were followed up for 3 years. The 2-year survival rate was 59.3%, and the 3-year survival rate was 54.1%. Conclusions: Preoperative radiochemotherapy can make some patients with locally advanced hypopharyngeal carcinoma achieve complete or significant remission in clinical evaluation, but pathological detection still shows some residual cancer lesions with enhanced anti-apoptosis ability and decreased proliferation activity.

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.

[Clinical analysis of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma].

Objective: To analyze the incidence and the related risk factors of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma, evaluate the accuracy of preoperative enhanced CT in judging retropharyngeal lymph node metastasis, and investigate the impact of retropharyngeal lymph node metastasis on the prognosis. Methods: Retrospective analyses were made on 398 patients with hypopharyngeal squamous cell carcinoma who underwent surgery as the primary therapy and accepted retropharyngeal lymph node exploration and clearance during surgery in Shandong Provincial ENT Hospital from January 2014 to December 2019. Multivariate logistic regression analysis was used to clarify the related risk factors of retropharyngeal lymph node metastasis. Multivariate Cox regression analysis was used to investigate the impact of retropharyngeal lymph node metastasis on prognosis. The retropharyngeal lymph nodes of 218 cases with available preoperative enhanced CT images were evaluated by two experienced radiologists and compared with postoperative pathological results. Results: Retropharyngeal lymph node metastasis were confirmed in 54 of 398 (13.6%) cases according to postoperative pathology. The sensitivity and specificity of preoperative enhanced CT in the diagnosis of retropharyngeal lymph node metastasis were 34.6% and 91.1%, respectively, and the overall accuracy was 84.4%. Multivariate logistic regression analysis showed that the site of the primary lesion and pathological N stage were independent risk factors for retropharyngeal lymph node metastasis in hypopharyngeal squamous cell carcinoma. Patients with primary lesion located in the posterior wall of hypopharynx (OR=4.83, 95% CI: 1.27-18.40), N2 stage (OR=6.30, 95% CI: 2.25-17.67), and N3 stage (OR=26.89, 95% CI: 5.76-125.58) were prone to retropharyngeal lymph node metastasis. The 5-year overall survival rate of the 398 patients was 50.4%, and the 5-year disease-free survival rate was 48.3%. Multivariate Cox regression analysis showed that T stage, N stage, retropharyngeal lymph node metastasis, and radiotherapy were independent influencing factors for overall survival (T stage: HR=1.28, 95% CI: 1.06-1.54; N stage: HR=1.26, 95% CI: 1.14-1.40; retropharyngeal lymph node metastasis: HR=2.13, 95% CI: 1.47-3.08; radiotherapy: HR=0.54, 95% CI: 0.38-0.76) and disease-free survival of patients with hypopharyngeal squamous cell carcinoma (T stage: HR=1.26, 95% CI: 1.06-1.51; N stage: HR=1.25, 95% CI: 1.13-1.37; retropharyngeal lymph node metastasis: HR=2.24, 95% CI: 1.56-3.21; radiotherapy: HR=0.55, 95% CI: 0.40-0.77). Conclusions: Metastasis of retropharyngeal lymph nodes in hypopharyngeal squamous cell carcinoma is not rare. Enhanced CT is of low accuracy and limited value in diagnosing retropharyngeal lymph node metastasis. Primary lesions located in the posterior wall of the hypopharyngx, N2 stage, and N3 stage are independent high-risk factors for retropharyngeal lymph node metastasis. The prognosis of hypopharyngeal cancer patients with retropharyngeal lymph node metastasis is worse, and active surgical exploration and clearance can effectively reduce the mortality caused by retropharyngeal lymph node metastasis.

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.

[Differential circRNA expression profiles in peripheral blood mononuclear cells among mild and severe influenza-associated pneumonia patients].

Objective: To explore the difference in the expression profile of circular RNA in peripheral blood mononuclear cells between patients with mild and severe influenza pneumonia. Methods: From December 2018 to March 2019, 10 inpatients with mild and 10 inpatients with severe influenza pneumonia admitted to the Department of Infection and Clinical Microbiology of Beijing Chaoyang Hospital were included. Clariom™ D gene chip was used to explore the circRNA expression profiles of peripheral blood mononuclear cells (PBMC) isolated from the patients. The absolute value of the fold change (FC value)>2 and P<0.05 were used as the criteria to screen the differentially expressed circRNA, and the gene ontology (GO) enrichment analysis and the Kyoto Encyclopedia of Gene and Genome database (Kyoto Encyclopedia of Genes and Genomes, KEGG) signal pathway enrichment analysis were also performed. Results: The age of mild patients [M (P25, P75)] was 62.0 (34.5, 69.8) years old, including 4 males; the age of severe patients [M (P25, P75)] was 50.0 (37.0, 60.0) years old, all were males. A total of 137 differentially expressed circRNAs in PBMCs of mild and severe patients were screened. The numbers of up-regulated and down-regulated circRNAs in mild patients were 101 and 36, respectively. Among them, hsa_circ_0091073 (FC value=160.898, P<0.05) was the most significantly up-regulated circRNA and hsa_circ_0092219 (FC value =-17.630, P<0.05) was the most significantly down-regulated circRNA. GO enrichment analysis showed that a total of 111 secondary GO items were significantly associated with related differential expression of circRNA (P<0.05). The GO terms associated with upregulated circRNAs included DNA-templated transcription, regulation of DNA-templated transcription, regulation of transcription from RNA polymerase Ⅱ promoter, etc.; The GO terms associated with downregulated circRNAs included neutrophil degranulation, killing of cells of other organism, defense response to fungus, etc. KEGG signaling pathway analysis showed that there were 37 metabolic pathways related to differentially expressed circRNAs (P<0.05). Signaling pathways related to up-regulated circRNAs included nuclear factor-κB (NF-κB) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, tumor necrosis factor (TNF) signaling pathway, etc. Signaling pathways related to down-regulation of circRNAs included cancer transcription disorders, folate carbon pool, and other types of O-glycan biosynthesis. Conclusion: The expression of circRNA in PBMC of mild and severe influenza pneumonia patients is significantly different, and it may play a role in the pathogenic mechanism of influenza pneumonia through multiple signal pathways.

[Study on the cut-off values of urinary microalbumin, transferrin and α1-microglobulin during pregnancy in pre-eclampsia with proteinuria].

Objective: To study the cut-off values of urinary microalbumin (mAlb), transferrin (TRF) and α1-microglobulin (α1-MG) during pregnancy in pre-eclampsia (PE) with proteinuria. Methods: A total of 210 pregnant women were enrolled in Renji Hospital from January 2016 to December 2019, including 92 (43.8%) cases of PE pregnant women and 118 (56.2%) cases of normal pregnant women. According to the diagnostic test evaluation method, the positive predictive values, negative predictive values and accuracy of non-pregnant cut-off values of urinary mAlb, TRF and α1-MG for the quantitative determination of 24-hour proteinuria were analyzed. The receiver operating characteristic (ROC) curve was applied to determine the optimal cut-point values of urinary mAlb, TRF and α1-MG during pregnancy. Results: (1) The diagnostic study of non-pregnant adults urinary mAlb, TRF and α1-MG cut-off values for the determination of 24-hour proteinuria value: when urinary mAlb was 30.0 mg/L, TRF was 2.5 mg/L, α1-MG was 12.5 mg/L as the cut-off value, the positive predictive values of the corresponding 24-hour proteinuria value≥ 300 mg were 88.1% (89/101), 88.2% (90/102) and 78.9% (75/95), its negative predictive values were 97.2% (106/109), 98.1% (106/108) and 85.2% (98/115), its diagnostic accuracy were 92.9% (195/210), 93.3% (196/210) and 82.4% (173/210), respectively. As the 24-hour proteinuria value≥ 300 mg was the golden standard, there were significant differences between the diagnostic method of the non-pregnant cut-off value of urinary mAlb, TRF and the golden standard (P<0.05). There was no significant difference between the diagnostic method of the non-pregnant cut-off value of urinary α1-MG and the golden standard (P>0.05). (2) Research on the ROC curve and the optimal cut-point value of urinary mAlb, TRF and α1-MG value: as the 24-hour proteinuria value≥ 300 mg as the criterion, the ROC curve of urinary mAlb, TRF and α1-MG were 0.992, 0.984 and 0.907, respectively. The optimal cut-point values of urinary mAlb, TRF and α1-MG were 86.5 mg/L (Youden index=0.927), 5.5 mg/L (Youden index=0.923), and 15.4 mg/L (Youden index=0.687). (3) The diagnostic study of the optimal cut-point value of urinary mAlb, TRF and α1-MG for the determination of 24-hour proteinuria value: according to the ROC results, when urinary mAlb was 86.5 mg/L, urinary TRF was 5.5 mg/L, and urinary α1-MG was 15.4 mg/L as the cut-off value, the positive predictive values of the corresponding 24-hour proteinuria value≥300 mg were 98.9% (86/87), 95.7% (88/92), 87.7% (71/81), and its negative predictive values were 95.1% (117/123), 96.6% (114/118), 83.7% (108/129), and its accuracy were 96.7% (203/210), 96.2% (202/210), 85.2% (179/210). As the 24-hour proteinuria value≥ 300 mg was the golden standard, there was no significant difference between the diagnostic method of the best cut-off values of urinary mAlb, TRF, α1-MG and the golden standard (P>0.05). Conclusion: It is recommended to define the cut-off values of mAlb, TRF and α1-MG as 86.5 mg/L, 5.5 mg/L and 15.4 mg/L, respectively, during pregnancy.

[Analysis of maternal deaths with cardiovascular diseases in Shanghai obstetric heart disease intensive care unit within twenty-six years].

Objective: To analyze risk factors, cardiovascular complications, time of death, gestational age of delivery and offspring outcomes in the maternal deaths with cardiovascular diseases (CVD). Methods: Totally 4 112 cases of pregnant women with CVD in Shanghai obstetric heart disease intensive care unit within 26 years (from January 1993 to December 2018) were collected, and 20 maternal deaths within these cases were analyzed retrospectively. Results: (1) Among the 20 deaths, structural heart diseases accounted for 90% (18/20), pregnancy induced heart diseases was 10% (2/20) while there was no dysfunctional heart disease. The mortality of pregnant women with CVD was 0.486% (20/4 112). (2) The following risk factors were common in these women, getting pregnant without counselling (95%, 19/20) , New York Heart Association classⅢ or Ⅳcardiac function (70%, 14/20), complicated with pulmonary hypertension (75%, 15/20) and prior heart events (60%, 12/20). And 85% (17/20) deaths occurred in puerperium, 15% (3/20) occurred before labor,while no death occurred during labor. And 65% (13/20) deaths died due to heart failure, 20% (4/20) deaths were due to pulmonary hypertension crisis, 5% (1/20) died on sudden cardiac arrest, rupture of aortic dissection and sudden death, respectively. Conclusions: Women with CVD should get pregnant after strict evaluation. Pulmonary hypertension is one of the most severe contraindications to pregnancy, especially in patients with moderate to severe pulmonary hypertension. The puerperium period is a critical period that threatens the safety of these patients. Since heart failure is the most common cause of death, it is necessary to prevent and treat heart failure and to monitor heart function dynamically, especially in those with structural abnormal heart diseases. Moreover, it is also of importance to standardize antenatal care and to identify the severity of heart diseases in time.

Unifying miscellaneous performance criteria for a prototype supercapacitor via Co(OH)2 active material and current collector interactions.

The use of transition metal oxides and hydroxides in supercapacitors can yield high specific capacity electrodes. However, the effect of interaction between active material and current collector has remained unexplored. Here the behaviour of electrodeposited hexagonal cobalt hydroxide nanosheets on a variety of substrates was investigated, and the resulting valence bonding, morphological evolutions and phase transformations examined. It is shown that the electrochemical activity of the face centred cubic (FCC) Ni substrate dramatically decreases cyclability, the FCC Cu substrate also demonstrates decreased performance, and hexagonal carbon nanofibre (CNF) and Ti substrates exhibit far more stability. The miscellaneous roles of valence bonding, redox reactions and crystal structure mismatch between active material and current collector are examined, and their consequences discussed. Using the resulting insights into performance criteria, it was possible to select a suitable substrate for the fabrication of an asymmetric supercapacitor. The high performance and stability of the device demonstrates the usefulness of this approach, and the utility of applying these insights to energy storage devices.

Ginsenoside Rh2 promotes nonamyloidgenic cleavage of amyloid precursor protein via a cholesterol-dependent pathway.

Ginsenoside Rh2 (Rh2) is a ginseng derivative used in Chinese traditional medicine. We investigated whether Rh2 can help prevent Alzheimer's disease symptoms and examined underlying mechanisms. We injected Rh2 into tg2576 Alzheimer's disease model mice and looked for behavioral improvement and senile plaque reduction in brain slices. We measured amyloid precursor protein (APP) metabolism species changes, amyloid beta40 and 42 levels and ß, γ secretase activity in primary hippocampal neurons. By living cell staining, we detected surface and endocytosed APP. We also measured cholesterol and lipid rafts in primary neurons. Rh2 treatment significantly improved learning and memory performance at 14 months of age; it also reduced brain senile plaques at this age. Based on in vitro experiments, we found that Rh2 treatment increased soluble APPα (sAPPα) levels, increased CTFα/ß ratios, and reduced amyloid beta 40 and 42 concentrations. Surface APP levels dramatically increased. Based on living cell staining, we found that Rh2 inhibited APP endocytosis. Based on lipid removal and reload experiments, we found that Rh2 can modulate APP by reducing cholesterol and lipid raft levels. We concluded that Rh2 improves learning and memory function in Alzheimer's disease model mice, and that this improvement is accomplished by reducing amyloid beta secretion and APP endocytosis, which in turn is achieved by reducing cholesterol and lipid raft concentrations.

Distinctive stages and strain variations of A. baumannii biofilm development under shear flow.

OBJECTIVE: To examine and characterise the process of Acinetocbacter baumannii biofilm development under shear flow. METHOD: Using an automated flow-cell system with microfluidic channels connected to an imaging system, I 0 clinical wound isolates of A. baumannii were examined for their ability to form biofilms under shear flow, on the glass surface of the flow through device. Flow biofilm development by this organism was observed to comprise four stages: attachment, microcolony formation, maturation with three dimensional structures, and dispersion. RESULTS: A. baumannii adheres readily to glass surfaces and quickly forms biofilm. Significant variations were observed among these I 0 clinical strains in their ability to attach and form flow biofilms. CONCLUSION: These specific characteristics in biofilm formation may contribute to this organism's ability to disseminate within health-care environments.

[Efficacy of surgical comprehensive therapy for 456 cases of hypopharyngeal carcinoma].

Objective: To retrospectively analyse the efficacy of surgerical comprehensive treatment for hypopharyngeal cancer. Methods: Four hundred and fifty-six cases of hypopharyngeal squamous cell carcinoma treated from Jan 2014 to Dec 2019 were analyzed retrospectively, including 432 males and 24 females, aged 37-82 years old. There were 328 cases of pyriform sinus carcinoma, 88 cases of posterior pharyngeal wall carcinoma, and 40 cases of postcricoid carcinoma. According to American Joint Committe on Cancer(AJCC) 2018 criteria, 420 cases were of stage Ⅲ or Ⅳ; 325 cases were of T3 or T4 stage. Treatment methods included surgery alone in 84 cases, preoperative planned radiotherapy plus surgery in 49 cases, surgery plus adjuvant radiotherapy or concurrent chemoradiotherapy in 314 cases, and inductive chemotherapy plus surgery and adjuvant radiotherapy in 9 cases. The primary tumor resection methods included transoral laser surgery in 5 cases, partial laryngopharyngectomy in 74 cases, of them 48 cases (64.9%) presented with supracricoid hemilaryngopharyngectomy, total laryngectomy with patial pharyngectomy in 90 cases, total laryngopharyngectomy or with cervical esophagectomy in 226 cases, and total laryngopharyngectomy with total esophagectomy in 61 cases. Among 456 cases, 226 cases received reconstruction surgery with free jejunum transplantation, 61 cases with gastric pull-up, and 32 cases with pectoralis myocutaneous flaps. All patients underwent retropharyngeal lymph node dissection, and high-definition gastroscopy was performed during admission and follow-up. SPSS 24.0 software was used to analyze the data. Results: The 3-year and 5-year overall survival rates were respectively 59.8%, and 49.5%. The 3-year and 5-year disease specific survival rates were respectively 69.0% and 58.8%. Total metastasis rate of retropharyngeal lymph nodes was 12.7%. A total of 132 patients (28.9%) suffered from simultaneous and metachronous multiple primary carcinoma of the hypopharynx. Multivariate Logistic regression analysis showed that T3-4 disease, cervical lymph node metastasis, retropharyngeal lymph node metastasis and postoperative adjuvant radiotherapy were independent factors affecting the prognosis of patients (all P<0.05). As of April 30, 2022, a total of 221 patients died during follow-up, of 109 (49.3%) with distant metastases, which were the main cause of death. Conclusions: The efficacy of comprehensive treatment for hypopharyngeal cancer can be improved by accurate preoperative evaluation, improved surgical resection, active retropharyngeal lymph node dissection and full process intervention of the second primary cancer.

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

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

[Introduction of a tool to assess Risk of Bias in Non-randomized Studies-of Environmental Exposure (ROBINS-E)].

This paper summaries the Risk of Bias in Non-randomized Studies-of Environmental Exposure (ROBINS-E), a tool for evaluating risk of bias about non-randomized studies of exposures (NRSE), and introduces the application of ROBINS-E in a published NRSE. According to the characteristics of NRSE, evaluation fields and signaling questions were designed in ROBINS-E to provide essential information about risk of bias for NRSE included in systematic reviews and GRADE. ROBINS-E is the tool in assessment of risk of bias in observational studies and quasi-randomized studies. Although the tool has been used in practice to some extent, but it still needs further improvement. Attention should be paid to its update and progress.

[The effect of cervical lymph node metastasis density on prognosis of hypopharyngeal carcinoma].

Objective: To investigate the relationship between the cervical lymph node density (LND) and the prognosis of hypopharyngeal carcinoma. Methods: The clinical and pathological data of 241 patients with hypopharyngeal carcinoma who underwent surgery in Shandong Provincial ENT Hospital from January 2014 to December 2017 were retrospectively analyzed, including 229 males and 12 females, aged 37-81 years. The LND was calculated, i.e. the ratio of the number of lymph nodes with metastasis to the total number of lymph nodes removed. The patients were divided into low LND group and high LND group based on the cutoff value of LND determined by receiver operating characteristic curve (ROC curve). The univariate and multivariate analyses of the disease-free survival (DFS) and the overall survival (OS) were performed in two groups. Results: With the cutoff value of 0.068, 165 patients were in the low LND group (<0.068) and 76 patients in the high LND group (≥0.068). T stage, N stage, maximum lymph node diameter, extracellular invasion of lymph node, and postpharyngeal lymph node metastasis were associated with LND (statistical values were -3.15, -6.82, 23.37, 20.44, and 30.18, respectively, all P values were<0.05). The univariate analysis showed that age, T stage, N stage, maximum diameter of cervical lymph nodes, extracapsular invasion, retropharyngeal lymph node metastasis and LND were the main factors affecting the patients' DFS (χ2=9.31, 7.30, 20.09, 15.30, 9.04, 19.44, 50.27, all P values<0.05) and OS (χ2 were 5.02, 12.94, 18.28, 15.91, 7.95, 16.88, 49.45, all P values<0.05). Multivariate analysis showed that patients with age≤60 years old and LND≥0.068 had reduced DFS [HR values were 0.61 (95%CI 0.43-0.88) and 2.23 (95%CI 1.44-3.45), both P values<0.05]; patients with advanced T stage and LND≥0.068 had reduced OS [HR values were 1.73 (95%CI 1.02-2.93) and 2.39 (95%CI 1.51-3.80), both P values<0.05]. Conclusion: LND is a prognostic factor for patients with hypopharyngeal carcinoma after surgery, with worse prognosis in patients with LND≥0.068.

[Effects of regional citrate anticoagulation in continuous veno-venous hemofiltration of severe burn patients].

Objective: To investigate the effects of regional citrate anticoagulation in continuous veno-venous hemofiltration (CVVH) of severe burn patients. Methods: A retrospective non-randomized controlled study was conducted. From January 2017 to August 2020, sixty-eight severe burn patients who met the inclusion criteria were treated with CVVH in Affiliated Hospital of Nankai University. According to the different methods of blood anticoagulation in CVVH treatment, patients were divided into citrate group (n=40) and heparin group (n=28). In the citrate group, 32 males and 8 females were (40±18) years old with total burn area of (62±14)% total body surface area (TBSA); in the heparin group, 22 males and 6 females were (38±16) years old with total burn area of (57±20)%TBSA. Creatinine level, C-reactive protein (CRP) value, and urea nitrogen level in serum of patients were recorded at 0 (immediately), 48, and 96 h after CVVH treatment in 2 groups, urea clearance index was calculated based on urea nitrogen level at 0, 48, and 96 h after CVVH treatment in 2 groups, platelet count (PLT), prothrombin time (PT), and activated partial thromboplastin time (APTT) in total coagulation of patients were recorded. The frequency of forced hemofiltration termination caused by adverse reactions such as severe hypocalcemia, aggravated wound bleeding, and new bleeding on non-wound surface of patients was recorded within 96 h of CVVH treatment. The duration of daily CVVH use from the beginning to the end was recorded. Data were statistically analyzed with chi-square test, analysis of variance for repeated measurement, independent samples t test, and Bonferroni correction. Results: There were no significant differences in urea nitrogen level, creatinine level, and CRP value in serum of patients between 2 groups at 0 h after treatment (P>0.05). At 48 and 96 h after treatment, urea nitrogen level, creatinine level, and CRP value in serum of patients in citrate group were significantly lower than those in heparin group (t=3.366, -2.315, 2.942, -2.657, 2.011, -2.441, P<0.05), and urea clearance index of patients in citrate group was significantly higher than that in heparin group (t=1.017, 2.233, P<0.05). There were no statistically significant differences in PLT, PT, and APTT of patients between 2 groups at 0 h after treatment (P>0.05). At 48 and 96 h, PLT of patients in citrate group was significantly higher than that in heparin group (t=-3.417, -4.143, P<0.05 or P<0.01), PT of patients in citrate group was significantly shorter than that in heparin group (t=2.760, -3.655, P<0.01), APTT of patients in citrate group was significantly shorter than that in heparin group (t=3.719, 5.146, P<0.05 or P<0.01). Within 96 h of treatment, there was 1 case of hypocalcemia and 1 case of aggravated wound bleeding resulting in forced hemofiltration termination in citrate group, but there was no new bleeding on non-wound surface; in heparin group, there was no hypocalcemia, but 7 cases of aggravated wound bleeding and 2 cases of new bleeding on non-wound surface (both at the tracheotomy site) resulting in forced hemofiltration termination. The use time of blood purification filter of patients in citrate group was (11.7±4.8) h, obviously longer than (6.6±2.5) h in heparin group (t=3.310, P<0.01). Conclusions: The use of regional citrate anticoagulation in CVVH treatment of severe burn patients has the advantages including little effect on coagulation function and high safety, can effectively prolong the use time of filter and improve the therapeutic effect, but this conclusion still needs to be further verified in clinical application.

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

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