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.

[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.

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

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

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

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

[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.

[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.

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.

[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.

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.

[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.

[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.

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.

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

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

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

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

[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.

[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.

[Influence of directed restrictive fluid management strategy on patients with serious burns complicated by severe inhalation injury].

Objective: To explore the influence of directed restrictive fluid management strategy (RFMS) on patients with serious burns complicated by severe inhalation injury. Methods: Sixteen patients with serious burns complicated by severe inhalation injury hospitalized in our department from December 2014 to December 2017, meeting the inclusion criteria and treated with RFMS, were enrolled in directed treatment group. Thirty-four patients with serious burns complicated by severe inhalation injury hospitalized in our department from December 2012 to December 2017, meeting the inclusion criteria and without RFMS, were enrolled in routine treatment group. Medical records of patients in 2 groups were retrospectively analyzed. Within post injury day 2, mean arterial pressure (MAP), central venous pressure (CVP), extravascular lung water index (ELWI), global end-diastolic volume index, and pulmonary vascular permeability index of patients in directed treatment group were monitored by pulse contour cardiac output monitoring technology, while MAP and CVP of patients in routine treatment group were monitored by routine method. On post injury day 3 to 7, patients in 2 groups were treated with routine fluid supplement therapy of our Department to maintain hemodynamic stability, and patients in directed treatment group were treated according to RFMS directed with goal of ELWI≤7 mL·kg(-1)·m(-2). On post injury day 3 to 7, total fluid intake, total fluid output, and total fluid difference between fluid intake and output within 24 h, value of blood lactic acid, and oxygenation index of patients in 2 groups were recorded. Occurrence of acute respiratory distress syndrome (ARDS) on post injury day 3 to 7 and 8 to 28, mechanical ventilation time within post injury day 28, and occurrence of death of patients in 2 groups were counted. Data were processed with chi-square test, t test, and analysis of variance for repeated measurement. Results: The total fluid intakes within 24 h of patients in directed treatment group were close to those in routine treatment group on post injury day 3, 4, 5, 6, 7 (t=-0.835, -1.618, -2.463, -1.244, -2.552, P>0.05). The total fluid outputs and total fluid differences between fluid intake and output within 24 h of patients in 2 groups on post injury day 3 were close (t=0.931, -2.274, P>0.05). The total fluid outputs within 24 h of patients in directed treatment group were significantly higher than those in routine treatment group on post injury day 4, 5, 6, 7 (t=2.645, 2.352, 1.847, 1.152, P<0.05). The total fluid differences between fluid intake and output within 24 h of patients in directed treatment group were (2 928±768), (2 028±1 001), (2 186±815), and (2 071±963) mL, significantly lower than (4 455±960), (3 434±819), (3 233±1 022), and (3 453±829) mL in routine treatment group (t=-4.331, -3.882, -3.211, -4.024, P<0.05). The values of blood lactic acid of patients in directed treatment group and routine treatment group on post injury day 3, 4, 5, 6, 7 were close (t=0.847, 1.221, 0.994, 1.873, 1.948, P>0.05). The oxygenation indexes of patients in directed treatment group on post injury day 3 and 4 were (298±78) and (324±85) mmHg (1 mmHg=0.133 kPa ), which were close to (270±110) and (291±90) mmHg in routine treatment group (t=-1.574, 2.011, P>0.05). The oxygenation indexes of patients in directed treatment group on post injury day 5, 6, 7 were (372±88), (369±65), and (377±39) mmHg, significantly higher than (302±103), (313±89), and (336±78) mmHg in routine treatment group (t=3.657, 3.223, 2.441, P<0.05). On post injury day 3, 4, 5, 6, 7, patients with ARDS in directed treatment group were less than those in routine treatment group, but with no significantly statistical difference between the 2 groups (χ(2)=0.105, P>0.05). On post injury day 8 to 28, patients with ARDS in directed treatment group were significantly less than those in routine treatment group (χ(2)=0.827, P<0.05). The mechanical ventilation time within post injury day 28 of patients in directed treatment group was apparently shorter than that in routine treatment group (t=-2.895, P<0.05). Death of patients in directed treatment group within post injury day 28 was less than that in routine treatment group, but with no significantly statistical difference between the 2 groups (χ(2)=0.002, P>0.05). Conclusions: Under the circumstance of hemodynamics stability, RFMS directed with goal of ELWI≤7 mL·kg(-1)·m(-2) on post injury day 3 to 7 is an useful strategy, which can reduce occurrence rate of ADRS and shorten mechanical ventilation time of patients with serious burns complicated by severe inhalation injury at late stage of burns.

[The oncologic and functional outcomes of supracricoid partial laryngectomy for the treatment of laryngeal cancer].

Objective: To evaluate the oncologic and functional outcomes of laryngeal squamous cell carcinomas treated by supracricoid laryngectomy. Methods: The clinical data of 134 patients with laryngeal cancer who underwent supracricoid laryngectomy with cricohyoidoepiglottopexy (CHEP) or cricohyoidopexy (CHP) between July 2005 and April 2014 at Shandong Provincial ENT Hospital were retrospectively reviewed. Ninety-one patients including 31 cases of stage Ⅰ, 36 of stage Ⅱ, 18 of stage Ⅲ and 6 of stage Ⅳ underwent CHEP and 43 patients underwent CHP. Two patients received CHEP due to recurrence after open surgery and laser surgery. Three patients received CHP due to the recurrence of disease after open surgery and postradiotherapy persistence of disease. The Kaplan-Meier method was used to calculate the 3-year and 5-year survival rates. The Chi-square test was used to compare the survival rates between different surgical procedures. Results: All 91 patients who underwent CHEP had successful removals of PEG tubes, and 88 (96.7%) of them had tracheostomy tube decannulation. Among 43 patients with CHP, 42(97.6%) cases removal of PEG tubes(97.6%), including and 40(93.0%) cases with tracheostomy tube decannulation. There was one patient with local recurrence in all cases. In CHEP group, 3-year local control rate was 98.2%; 3-year and 5-year overall survival rate were 94.5% and 93.9%, respectively. In CHP group, 3-year local control rate was 97.6%; 3-year and 5-year overall survival rates were 86.0% and 83.3%, respectively. Pharyngeal fistula appeared in 2 cases of CHEP group and 4 cases of CHP group, and all of them were cured by conservative treatment. Conclusion: Supracricoid laryngectomy shows excellent oncologic and functional results for treatment of laryngeal cancer while maintaining laryngeal functions, especially in terms of local control rate and tracheostomy tube decannulation.

[Establishment and development of Department of Burns and Plastic Surgery of the Affiliated Hospital of Nankai University (Tianjin No.4 Hospital)].

Tianjin No.4 Hospital is a general hospital featured in burns, and the Department of Burns and Plastic Surgery has six secondary clinical departments with 110 hospital beds. After hard working by several generations, the department has successively developed into a key discipline in Tianjin and Tianjin Burn Emergency Center. Tianjin Burn Research Institute was established in 1992, and then the department became master's granting unit of Tianjin Medical University. In scientific research aspect, many researches have been completed and obtained important results, such as the mechanism and effect of integrated traditional Chinese and Western medicine in prevention and treatment of intestinal failure, early diagnosis and local treatment with fiberoptic bronchoscope, energy metabolism regularity of burn patients, and the development of irradiated biological dressings. In clinic aspect, tens of thousands of complex wounds and chronic refractory wounds were repaired by various kinds of flaps and advanced methods, and the cure rate of patients with large burn area reached 94.1%. In 2016, Tianjin No.4 Hospital became the Affiliated Hospital of Nankai University. Hereafter, a number of research intentions have collaborated between the department and the State Key Laboratory of Academy of Life Sciences of Nankai University. In the future, our department will focus on improving the treatment level of patients with large burn area, carrying out researches on comprehensive anti-shock in the early stage, inhalation injury treatment, infection treatment, comprehensive treatment of multiple organ failure, wound repair, scar treatment, rehabilitation, and the clinical application.

[Treatment and prognosis of 264 patients with hypopharyngeal carcinoma].

Objective: To investigate the key factors influencing the prognosis of hypopharyngeal carcinoma and the therapeutic methods improving the efficacy of treatments for hypopharyngeal carcinoma. Methods: Two hundred and sixty-four cases of hypopharyngeal squamous cell carcinoma treated from May 2010 to May 2015 were analyzed retrospectively. There were 211 cases of pyriform sinus carcinoma, 37 cases of posterior pharyngeal wall carcinoma, and 16 cases of postcricoid carcinoma. According to UICC 2002 criteria, 2 cases were for stage Ⅰ, 14 for stage Ⅱ, 32 for stage Ⅲ and 216 for stage Ⅳ. Postoperative circumferential defects existed in 112 (42.4%) cases, and 86 of them were reconstructed with free jejunum transplantation. Among all cases, 54 patients (20.5%) had the preservation of laryngeal functions after surgery and 210 patients (79.5%) with total laryngectomy; 238 cases (90.2%) underwent bilateral cervical lymph node dissection and 203 patients received posterior pharyngeal lymph node exploration and dissection, with positive metastases for posterior pharyngeal lymph nodes in 36 cases (17.7%). Eight cases with cervical lymph node metastasis extensively involving the soft tissue, prevertebral fascia or encases carotid artery received preoperative radiotherapy of 50 Gy. After surgery 13 patients received concurrent radiotherapy and chemotherapy, 337 underwent adjuvant radiotherapy with a dose of 50-60 Gy each, and 14 patients did not receive radiotherapy or did not completed their radiotherapy programs. SPSS 13.0 saftware was used to analyze the data. Results: All patients were followed up for more than 2 years. With Kaplan-Meier method, the 2-, 3- and 5-years survival rates were 69.6%, 62.8% and 51.3%, respectively. There were significant differences in 3-year survival rates between T1-2 group (75.5%) and T3-4 group (59.2%) (χ(2)=4.282 P=0.039), N0 group (81.6%) and N+ group (58.2%) (χ(2)=6.802 P=0.009), laryngeal functions preserved (81.8%) and unpreserved group (58.9%) (χ(2)=5.314 P=0.021). Multivariate Logistic regression analysis showed that cervical lymph node metastasis was an independent prognostic factor (P=0.027). The success rate of free jejunum transplantation was 98.8%. Local recurrence, cervical lymph node recurrence, second primary cancer, and distant metastasis accounted respectively for 11.2%, 18.8%, 12.5% and 45.0% of death cases. Conclusions: The prognosis-associated factors for hypopharyngeal carcinoma should be taken into account, including the evaluation of the carcinogenesis of the mucosal area, early screening of premalignant lesion or second primary cancer in the esophagus and dissection of the posterior pharyngeal lymph nodes, which will help to improve the local control rate and recent survival rate in patients with hypopharyngeal cancer.