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.

Diverse polarization angle swings from a repeating fast radio burst source.

Fast radio bursts (FRBs) are millisecond-duration radio transients1,2 of unknown origin. Two possible mechanisms that could generate extremely coherent emission from FRBs invoke neutron star magnetospheres3-5 or relativistic shocks far from the central energy source6-8. Detailed polarization observations may help us to understand the emission mechanism. However, the available FRB polarization data have been perplexing, because they show a host of polarimetric properties, including either a constant polarization angle during each burst for some repeaters9,10 or variable polarization angles in some other apparently one-off events11,12. Here we report observations of 15 bursts from FRB 180301 and find various polarization angle swings in seven of them. The diversity of the polarization angle features of these bursts is consistent with a magnetospheric origin of the radio emission, and disfavours the radiation models invoking relativistic shocks.

[Imaging risk factors for postoperative cerebral infarction in adults with ischemic Moyamoya disease].

Objective: To investigate the imaging factors associated with postoperative cerebral infarction in adult patients aged 18 and above with ischemic Moyamoya disease. Methods: The clinical data of adult patients who underwent surgeries for ischemic Moyamoya disease in the Department of Neurosurgery at Peking University International Hospital from October 2015 to October 2020 were retrospectively analyzed. Of the 239 patients, 120 were male and 119 were female, with ages ranging from 18 to 63 (41.7±10.3) years. A total of 239 patients(290 cases) underwent direct and indirect combined revascularization (CR).Gender, age, surgical side, preoperative transient ischemic attack (TIA), presence of old cerebral infarction, and imaging features were compared between the patients with (48 cases) and without (242 cases) cerebral infarction within 1 week after surgery. Multivariate logistic binary regression model was used to analyze the imaging risk factors of postoperative cerebral infarction. Results: Cerebral infarction occurred in 48 cases(16.5%) among the 290 CR group within 1 week after surgery. The proportion of patients with TIA, old cerebral infarction, ICA stenosis, A1 segment stenosis, M1 segment stenosis, abnormal posterior cerebral artery (PCA), and unstable compensation before CR in the cerebral infarction group was higher than that in the non-cerebral infarction group (P<0.05).Preoperative TIA (OR=4.514, 95%CI: 1.920-10.611), old cerebral infarction (OR=2.856,95%CI:1.176-6.936), A1 stenosis (OR=7.027,95%CI:1.877-26.308), M1 stenosis (OR=6.968,95%CI:2.162-22.459), abnormal PCA (OR=4.114,95%CI:1.330-12.728)and unstable compensation (OR=4.488,95%CI:1.194-16.865) were risk factors for cerebral infarction after CR surgery (all P<0.05). Conclusion: Among the imaging factors, TIA, old cerebral infarction, A1 stenosis, M1 stenosis, abnormal PCA and unstable compensation were risk factors for cerebral infarction in adult patients with ischemic Moyamoya disease treated by combined revascularization.

[Interpretation of Chinese guideline for the clinical management of patients with ruptured intracranial aneurysms (2024)].

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurological emergency with high mortality, and even patients receiving optimal medical care may develop long-term disability, which seriously affects their quality of life and increases the heavy medical burden on society and families. To provide comprehensive clinical management advice, the Society of Neurosurgery of the Chinese Medical Association, the Society of the Chinese Stroke Association of the National Medical Center for Neurological Diseases, and the National Clinical Research Center for Neurological Diseases jointly formulate "Chinese Guidelines for the Clinical Management of Patients With Ruptured Intracranial Aneurysms in 2024". The evidence sources are divided into the Chinese population and other populations, using a modular format to provide recommendations, summaries of relevant opinions, and future research directions on epidemiology, clinical imaging diagnosis, prognosis evaluation, treatment strategies and choices, anesthesia management, perioperative care, and recommendations for the management of aSAH in special populations. It provides practical clinical guidance and recommendations for doctors and related professionals.

[Lactate promotes HMGB1 phosphorylation and release via Akt signaling pathway in gastric cancer cells HGC-27].

Objective: To investigate the molecular mechanism of how lactate induces high mobility group box 1 (HMGB1) release. Methods: Gastric cancer HGC-27 cells were divided into the control group and the lactate group (The cells were treated with lactate for 6 h). The level of HMGB1 in the cell culture medium was detected by enzyme-linked immunosorbent assay (ELISA), the localization of HMGB1 was detected using laser confocal microscopy, and the nuclear translocation of HMGB1 was detected using the nucleoplasmic separation assay. The phosphorylation and acetylation levels of HMGB1 were determined by co-immunoprecipitation, and Western blot was used to measure the phosphorylation of Akt and protein kinase C (PKC). HGC-27 cells were first treated with lactate and LY294002, the inhibitor of Akt, and then the phosphorylation of HMGB1 and Akt was analyzed by co-immunoprecipitation and Western blot, respectively. The localization of HMGB1 in cells was detected by laser confocal microscopy. EdU and Transwell assays were used to detect the proliferation and migration abilities of HGC-27 cells, respectively. HGC-27 cells were then injected into the BALB/C null mice for subcutaneous tumor implantation. Mice in the lactate group were intraperitoneally injected with lactate (0.2 g/kg/2 d), while those in the control group were intraperitoneally injected with an equal amount of PBS for 20 consecutive days. ELISA was used to detect the HMGB1 levels in the blood samples taken from the medial canthus vein of the mice, while co-immunoprecipitation and Western blot were used to detect the phosphorylation of HMGB1 and Akt in tumor tissue proteins, respectively. Results: The release levels of HMGB1 in the lactate group were (2 995.00±660.91) pg/ml and (696.33±22.03) pg/ml, after lactate treatment for 6 h and 12 h, respectively, both higher than those in the control group (485.00±105.83) pg/ml (P<0.001 and P=0.028, respectively). After lactate treatment for 6 h, the relative expression of HMGB1 protein in the cytoplasm of HGC-27 cells was 1.13±0.09, higher than that of the control group (0.83±0.07, P=0.001), while the relative expression of HMGB1 in the nucleus was 0.79±0.06, lower than that of the control group (1.07±0.06, P=0.007). The phosphorylation level of HMGB1 reached 1.41±0.09, which was higher than that of the control group (0.97±0.10, P=0.031). The phosphorylation level of Akt was 11.16±0.06, higher than that of the control group (0.91±0.022, P=0.002). The phosphorylation level and nuclear translocation of HMGB1 induced by lactate decreased obviously after Akt inhibition; the proliferation and migration abilities induced by lactate were also obviously inhibited after Akt inhibition. In vivo, the HMGB1 level in the peripheral blood was (1 280.70±389.66) pg/ml in the lactate group, which was obviously higher than that in the control group (595.11±44.75) pg/ml (P=0.008), and the phosphorylation levels of HMGB1 and Akt in tumor tissues in the lactate group were obviously enhanced compared with the control group. Conclusion: Lactate induces HMGB1 release through enhancing HMGB1 phosphorylation via the Akt signaling pathway.

[Clinical application of a classification based on crucial curvature of coronal imbalance in degenerative lumbar scoliosis].

Objective: To present efficacy of clinical application of a classification based on crucial curvature of coronal imbalance in degenerative lumbar scoliosis (DLS). Methods: A case series study. Clinical data of 61 cases (8 males, 53 females) who underwent posterior correction surgery for DLS from January 2019 to January 2021 were retrospectively analyzed. The mean age was (71.7±6.2) years (ranged 60-82 years). According to the direction of C7 plumb line (C7PL) deviated from central sacral vertical line (CSVL) and orientation of L4 coronal tilt, the author determined which one was the crucial curve. If C7PL deviated from CSVL in the same direction as concave side of the thoracolumbar curve and L4 coronally tilts opposite direction of C7PL deviates from CSVL, then the crucial curve was thoracolumbar curve (type 1). On the contrary, if C7PL deviated from CSVL in the same direction as concave side of the lumbosacral curve and L4 coronally tilts consist with direction of C7PL deviates from CSVL, then the crucial curve was lumbosacral curve (type 2). According to absolute value of coronal balance distance (|CBD|), each type of patients was divided into two groups, respectively, namely coronal balance (CB) (|CBD|≤3 cm) and coronal imbalance (CIB) (|CBD|>3 cm). Changes of Cobb angles of thoracolumbar curve and lumbosacral curve and CBD were recorded and analyzed. Results: The rate of preoperative CIB was 55.7% (34/61) in all the patients. Of the patients, 23 cases were classified as type 1 and 38 cases as type 2. The rate of preoperative CIB was 34.8% (8/23) in type 1 patients and 68.4% (26/38) in type 2. The rate of postoperative CIB was 27.9% (17/61) in all the patients, with 13.0% (3/23) in type 1 and 36.8% (14/38) in type 2. The |CBD| of CB group in type 1 patients decreased from (2.6±1.4) cm before the operation to (1.5±1.0) cm after (P=0.015); and the correction rate of thoracolumbar curve (68.8%±18.4%) was significantly higher than that of lumbosacral curve (34.5%±23.9%) (P=0.005). The |CBD| of CB group in type 2 patients decreased from (2.6±3.0) cm before the operation to (1.6±1.2) cm after (P=0.027); the correction rate of lumbosacral curve (71.3%±18.6%) was higher than that of thoracolumbar curve (57.3%±21.1%), but the difference was not statistically significant (P=0.546). There was no significant difference in |CBD| of CIB group in type 2 patients before and after the operation (P=0.222); the correction rate of lumbosacral curve (38.3%±14.8%) was significantly lower than that of thoracolumbar curve (53.6%±16.0%) (P=0.001). There was a correlation between the change of CBD (3.8±1.5) cm and the difference in correction rate between thoracolumbar and lumbosacral curve (32.3%±19.6%) in CB group in type 1 patients after surgery (r=0.904, P<0.001). There was a correlation between the change of CBD (1.9±2.2) cm and the difference in correction rate between lumbosacral and thoracolumbar curve (14.0%±26.2%) in CB group in type 2 patients after surgery (r=0.960, P<0.001). Conclusion: Clinical application of a classification based on crucial curvature of coronal imbalance in DLS is satisfactory, and its combination with matching correction can effectively prevent the occurrence of coronal imbalance after spinal correction surgery.

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.

[A decade of pecision neurosurgery: the informative and systematic upgrading of brain glioma surgery].

Precision neurosurgery concept as well as the establishment of it's technical platform, have played essential roles in promoting the modern surgical management of brain gliomas in China.In the past decade,the multidisciplinary integration of medical sciences and technology innovations has significantly promoted the clinical implementation of new imaging and novel navigation technology.With active clinical translational research and practice,precision neurosurgery has developed from "startup prologue" (simple anatomical navigation) to "precision neurosurgery 1.0" (intraoperative MRI with multimodal neuronavigation),followed by "precision neurosurgery 2.0" (informative and systematic upgrading).In the past decade,Chinese researchers have made significant and remarkable achievements in precision neurosurgery through continuous efforts and innovation.In the future,state-of-art technologies such as artificial intelligence on deep learning and machine learning,multimodal real-time navigation,intraoperative optical imaging,and targeted molecular imaging technology will promote the development of precision neurosurgery in a coordinated manner, leading to the advent of "precision neurosurgery 3.0".

[Implement of mixed reality navigation based on multimodal imaging in the resection of intracranial eloquent lesions].

Objective: To examine the clinical feasibility of mixed reality navigation (MRN) technology based on multimodal imaging for the resection of intracranial eloquent lesions. Methods: Fifteen patients with intracranial eloquent lesions admitted to the Department of Neurosurgery, the First Medical Center, People's Liberation Army General Hospital from September 2020 to September 2021 were retrospectively enrolled. There were 7 males and 8 females, aged (50±16) years (range: 16 to 70 years). Postoperative pathological diagnosis included meningioma (n=7), metastatic carcinoma (n=3), cavernous hemangioma, glioma, ependymoma, aneurysmal changes and lymphoma (n=1, respectively). The open-source software was used to perform the three-dimensional visualization of preoperative images, and the self-developed MRN system was used to perform the fusion and interaction of multimodal images, so as to formulate the surgical plan and avoid damaging the eloquent white matter fiber tracts. Traditional navigation, intraoperative ultrasound and fluorescein sodium angiography were used to determine the extent of lesion resection. The intraoperative conditions of MRN-assisted surgery were analyzed, and the setup time and localization error of MRN system were measured. The changes of postoperative neurological function were recorded. Results: MRN based on multimodal imaging was achieved in all patients. The MRN system setup time (M(IQR)) was 36 (12) minutes (range: 20 to 44 minutes), and the localization error was 3.2 (2.0) mm (range: 2.6 to 6.7 mm). The reliability of eloquent white matter fiber tracts localization based on MRN was rated as "excellent" in 11 cases, "medium" in 3 cases, and "poor" in 1 case. There were no perioperative death and no new impairment in motor, language, or visual functions after operation. Transient limb numbness occurred in 1 patient after operation, and recovered to the preoperative state in 2 weeks after operation. Conclusion: The MRN system based on multimodal imaging can improve the surgical accuracy and safety, and reduce the incidence of iatrogenic neurological dysfunction.

[Consistency evaluation between patient-completed and physician-completed Caprini scores].

Objective: To evaluate the consistency of patient-completed and physician-completed Caprini scores. Methods: This study was a diagnostic study. We prospectively recruited 200 inpatients (including respiratory and critical care medicine, rheumatology and immunology, obstetrics and gynecology, and orthopedics). Clinical data of the recruited patients were collected. The Wechat applet was developed based on the Chinese version of the patient-completed Caprini score. Patient could enter the Wechat applet by scanning the QR code, and enter the height, weight and other contents to the Wechat applet. The applet could automatically calculate the score and make the risk stratification according to total score. At the same time, physicians would calculate the traditional Caprini score for the same patient and make risk stratification to evaluate the consistency of scores derived from the two methods. Results: The average age of these 200 patients was (59.6±13.9) years, 112(56.0%) of them were female and 184(92.0%) with high school education or above. There was no significant difference between the patient-completed and physician-completed scores (4.8±2.5 vs. 4.7±2.5,P=0.336). The time of physician-completed score was shorter than that of patient-completed score ((2.0±1.0) minutes vs.(2.4±1.2) minutes, P<0.000 1). There was no significant difference on the number of high-highest venous thromboembolism risk patients assessed by the patient-completed and the physician-completed scores: 84.5% (169/200) vs. 83.0%(166/200)(χ2=0.165, P=0.684).There was strong positive correlations between patient-completed and physician-completed scores (r=0.98, P<0.000 1). Cohen's ĸ evaluation showed that the patient-completed Caprini score was in excellent consistency with physician-completed Caprini score(κ=0.97,P<0.000 1). The result of Bland Altman method showed that only 3.0% (6/200) of the scores biased greatly, which was not within the 95% confidence interval, the result proved that the bias belonged to a small probability event. It was inferred that the scores of patient-completed were consistent with those of the physician-completed. Conclusions: The patient-completed Caprini score is in good agreement with the physician-completed Caprini score in this patient cohort.

[Investigation on status of dyslipidemia in Chinese females aged 35 years or above].

Objective: To investigate the prevalence, awareness, treatment and control status of dyslipidemia among females aged ≥35 years old across China. Methods: Participants were selected by stratified multistage random sampling method in the "Twelfth Five-Year Plan" National Science and Technology Support Project "Survey on the Prevalence of Important Cardiovascular Diseases and Key Technology Research in China" project. This study is a retrospective, cross-sectional study. A total of 17 418 females aged 35 years and over were included in the current study. The basic information such as age, medical history and menopause was collected by questionnaire. The blood lipid parameters were derived from clinical laboratory examinations. The prevalence of dyslipidemia and the rate of awareness, treatment, and control of dyslipidemia were analyzed in females aged 35 years and over. Results: The age of participants was (56.2±13.0) years old, and the prevalence of dyslipidemia was 33.1% (5 765/17 418). The prevalence rates of high total cholesterol, hypertriglyceridemia, low HDL-C and high LDL-C were 9.7% (1 695/17 418), 11.1% (1 925/17 418), 10.9% (1 889/17 418) and 7.3% (1 262/17 418), respectively. The prevalence of dyslipidemia increased with age and the prevalence of dyslipidemia in women who were not married, Han, menarche age>16 years, obesity, central obesity, alcohol consumption, diabetes, hypertension and family history of cardiovascular disease were higher than those without such characteristics (P<0.05). There were 10 432 (59.9%) menopausal females in this cohort and prevalence of dyslipidemia of these participants was 38.8% (4 048/10 432), which was higher than that of non-postmenopausal females (24.6%, 1 717/6 986) (P<0.05). The awareness rates, treatment rates and control rates of dyslipidemia were 33.9% (1 953/5 765), 15.1% (870/5 765) and 2.5% (143/5 765) respectively among females aged 35 years and over in China. Conclusion: The prevalence of dyslipidemia in Chinese females aged 35 years and over is high, and its awareness, treatment, and control rates need to be optimized.

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.

[The value of intraoperative monitoring of cerebral oxygen saturation on postoperative cognitive function in elderly patients undergoing cardiac surgery].

Objective: To investigate the effect of cerebral oxygen saturation (rSO2) on postoperative cognitive dysfunction (POCD) in elderly patients undergoing cardiac anesthesia. Methods: Retrospective analysis was performed on 113 elderly patients (age 65-89) underwent cardiac surgery in Peking University International Hospital from June 2017 to December 2019, 67 male and 46 female patients were included. All operations were performed under general anesthesia, cardiopulmonary bypass, rSO2 and other relevant monitoring. Statistical analysis of the elderly patients with complications, cardiac surgery history, time of CPB, baseline value of rSO2 (rSO2 baseline), lowest intraoperative value of rSO2 (rSO2 min), time of operation, length of stay in CCU, length of hospital stay; Preoperative and postoperative NSE values; number of postoperative POCD and postoperative deaths were recorded. All data were obtained from the medical records system and anesthesia information system of Peking University International Hospital and risk factors related to POCD were analyzed by Logistic regression. Results: POCD occurred in 19 patients (16.8%), and also, intraoperative rSO2 decreased by more than 30% over the baseline. The variance of rSO2 (rSO2 baseline-rSO2 min) in POCD group and non-POCD group was (18.0±2.7) and (6.6±2.3), the variance of NSE (NSE after surgery-NSE before surgery) was (31.3±9.7) and (9.5±3.0) µg/L, respectively. The differences were statistically significant (t=18.35, 17.70, all P<0.05). rSO2 variability was positively correlated with NSE variability (r=0.697, P<0.05). Logistic regression analysis showed that the variation degree of rSO2 [OR(95%CI)was 0.374(0.059-1.895)]、 patients combined with diabetes mellitus [OR(95%CI)was 0.493 (0.041-1.812), history of stroke [OR(95%CI)was 0.325 (0.084-0.917)] and atrial fibrillation [OR(95%CI)was 0.176 (0.091-0.943)] were the risk factors for POCD. Conclusion: POCD can be predicted by monitoring the decline range of rSO2 intraoperatively. rSO2 is recommended as a routine monitoring item for elderly patients undergoing cardiac surgery.

[Study on the prognostic value of preoperative anti hepatitis B virus therapy in patients with hepatocellular carcinoma complicated with microvascular tumor thrombus and establishment of survival prediction model].

Objective: To explored the effect of preoperative antiviral therapy on the prognosis of microvascular tumor thrombi patients, and to established a prognostic prediction model for these patients after radical resection of liver cancer. Methods: The clinicopathological and survival data of hepatocellular carcinoma patients with microvascular tumor thrombus who underwent radical resection in the Third Affiliated Hospital of Sun Yat-sen University from January 1, 2013 to December 31, 2015 were retrospectively collected. Kaplan-Meier method was used to calculate the survival curve, and log-rank test was used to compare the prognosis of patients with and without antiviral treatment before operation. Univariate and multivariate Cox proportional hazard regression model was used to screen predictive factors. R software was used to make predictive nomogram, and discrimination and calibration degree were used to evaluate the prediction model. Results: Among all 153 patients, 22 were female and 131 were male, aged (51.3±11.7) years. The preoperative antiviral therapy significantly improved overall survival and recurrence-free survival (χ2=41.423, 54.389; both P<0.001). According to the results of multivariate and regression analysis, preoperative antiviral therapy (HR=0.301,95%CI:0.171-0.532,P<0.001), alpha fetoprotein (HR=1.226,95%CI:1.157-1.776,P=0.032) and tumor size (HR=1.008,95%CI:1.001-1.016,P=0.02) were important prognostic factors for overall survival. The area under curve value of 3-year survival prediction model was 0.749(95%CI: 0.712-0.782), and that of 5-year survival prediction model was 0.755(95%CI: 0.724-0.793), with good calibration. Conclusions: Preoperative anti hepatitis B virus(HBV) therapy can significantly improve the prognosis of patients with hepatocellular carcinoma complicated with microvascular tumor thrombus, we develope the prediction models of 3-year and 5-year survival rate that can improve the reference for clinical work and benefit patients.

[Clinical characteristics of 21 infertile women with non-classic 21-hydroxylase deficiency].

Objective: To investigate the clinical features of infertile women with non-classic 21-hydroxylase deficiency (21-OHD). Methods: The study enrolled 21 infertile women with non-classic 21-OHD in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2009 to December 2018. The clinical presentation, endocrine hormone, glucolipid metabolism and treatment outcome were retrospectively analyzed. The diagnosis of non-classic 21-OHD was comprehensively based on clinical and hormonal characteristics. Results: Among 21 cases, the age was (29.9±2.9) years, the mean age at menarche was (13.6±2.0) years, body mass index was (22.1±2.9) kg/m2, and 38% (8/21) had oligomenorrhea. Hirsutism was diagnosed in 3 cases (14%, 3/21). Clitoromegaly was seen in 14% (3/21) and polycystic ovarian morphology was found in 33% (7/21) of the patients. The mean serum level of basal progesterone was (11.3±21.0) nmol/L, with 48% (10/21) having high basal progesterone level; after therapy by glucocorticoid, the level of progesterone was (1.9±2.0) nmol/L. Serum 17-hydroxyprogesterone concentration was (66.4±123.6) nmol/L; after therapy by glucocorticoid, it was (2.4±1.8) nmol/L. In the study increased testosterone, androstenedione and dehydroepiandrosterone sulfate were present in 62% (13/21), 52% (11/21) and 43% (9/21), respectively; and 52% (11/21) of patients manifested androgen excess and basal progesterone elevation; androgen levels decreased after therapy by glucocorticoid. The pregnancy rate was 76% (16/21). Out of 19 pregnancies, 6/19 ended in spontaneous miscarriages. Conclusions: Infertile women with non-classic 21-OHD are characterized by hyperandrogenism and basal progesterone elevation, whereas gonad axis disorder is not apparent. After no response to conventional therapy, adult infertile women with non-classic 21-OHD could achieve a desirable pregnancy outcome with proper treatment of glucocorticoid.

[Explore the value of whole exome sequencing in early diagnosis for children with language delay/disorder].

Objective: To evaluate the utility of whole-exome sequencing (WES) in early diagnosis for children with language delay/disorder. Methods: Children with language delay/disorder who were admitted to the Department of Health Care, Children's Hospital Affiliated to the Capital Pediatric Institute from January 2019 to December 2020 were analyzed retrospectively. Based on informed consent, the peripheral blood of the children and their parents was collected for WES. Combining the clinical phenotypes of the children, the candidate variants, including single nucleotide variants (SNVs) and copy number variations (CNVs), were selected for validation and family segregation analysis using Sanger sequencing, real-time PCR or CNV-Seq. The pathogenicity of variants was evaluated based on ACMG guideline following with finial genetic diagnosis. Based on whether genetic diagnosis was achieved or not, 125 children with comprehensive examination of the Children Neuropsychological and Behavioral Scale(CNBS-R2016) were sub-grouped (positive/negative group), and the total scores and the detailed scores of five developmental sections (gross motor, fine motor, adaptive ability, language and social behavior ability) between two subgroups were compared. Results: A total of 165 children with language delay/disorder were recruited, including 109 males and 56 females. The ratio of boys to girls was 1.95∶1.The age of the children was (3.2±1.2) years old, the median age was 3.0 years. 45 children carry disease-related pathogenic/likely pathogenic variants, including 36 SNVs and 9 CNVs. The genetic diagnostic yield of this cohort was 27.3% (45/165). The inheritance analysis for core family members showed de novo variant accounted for 86% of genetic diagnosis (31/36). The positive diagnosis rate in girls was 45% (25/56), which was significantly higher than that in boys (18.3%, 20/109, χ²=12.171, P<0.05). There was no significant difference in the rate of positive diagnosis among all age groups (χ²=4.349, P>0.05). Interestingly, the scores of gross motors of positive group were significantly lower than that of negative group (61.5 vs. 69.4, t=-2.610, P<0.05). Otherwise, no significant difference was seen between two groups(t=-0.933, -1.298, -0.114, -0.214, all P>0.05). Conclusions: Language delay/disorder has complex genetic heterogeneity. WES has important application value in early etiological diagnosis for children with language delay/disorder.

[Advances in the study of the role of adenosine 2A receptor in liver injury].

Adenosine, as an endogenous purine nucleoside, is widely distributed in various tissues and organs of the body. It binds to adenosine receptors to regulate a variety of important biological processes. Adenosine 2A receptors have a close relationship with the occurrence and development of various clinical diseases. This article reviews the research progress of adenosine 2A receptors in non-alcoholic fatty liver disease, acute immune hepatitis, liver ischemia-reperfusion injury, liver fibrosis, etc., in order to provide new research strategies for the prevention and treatment of these diseases.

[Management protocol and outcome assessment of ruptured intracranial aneurysm emergency surgery during coronavirus disease 2019 pandemic].

Objective: To explore the improvement of emergency admission screening and perioperative management protocols in the scenario of the coronavirus disease 2019 (COVID-19) pandemic and its regular prevention and control for patients with ruptured intracranial aneurysms, which are the most common emergency cases with the most urgent needs for emergent surgery. Methods: The response protocol of the emergency surgical management of ruptured intracranial aneurysm during the epidemic period (from January to March, 2020) at Beijing Tiantan Hospital, Capital Medical University was reviewed. The prognosis of emergent aneurysm surgery under different levels of protection or during the same period of 2019 and 2020 was further compared to describe the operation and prognosis under the new management protocol. Results: A total of 127 emergency cases with aneurysmal subarachnoid hemorrhage were referred to Beijing Tiantan Hospital, Capital Medical University from January 20 to March 25, 2020, and 42 cases(33.1%) underwent emergent aneurysm clipping after multi-desciplinary consultation. Admissions of emergency cases required epidemiological, laboratory, and imaging screenings for COVID-19, with additional throat swab virus nucleic acid screening afterwards. During the same period, 9 cases of COVID-19 were confirmed in the emergency screening, and no false negative cases were found. Compared with the same period in 2019, the interval between emergency visits and emergency craniotomy did not increase significantly due to the preoperative screening ((37±17) hours during the epidemic period versus (29±12) hours at the same period in 2019, P=0.058). There was no significant difference in the incidence of perioperative adverse events and postoperative neurological dysfunction (P=0.779). According to the screening results, the corresponding operative and postoperative management protocol and protection standards were adopted. There was no significant difference in the prognosis of emergent surgery between patients with a negative initial screening and those who were to be excluded or suspected in the initial screening (P=0.678). Although viral nucleic acid screening tended to prolong the time interval before surgical intervention ((36±15) hours before nucleic acid screening versus (40±20) hours after nucleic acid screening, P=0.453), there was no statistically significant difference in the preoperative adverse events and postoperative neurological function (P=0.653). Conclusion: The current protocol of COVID-19 screening and stratified emergent surgery management based on screening results can effectively identify suspected and confirmed COVID-19 cases, thereby ensuring timely, safe and effective emergent surgery and prohibiting nosocomial spread.

[Effect of lncRNA-AC013472.3 on LPS-stimulated secretion of tumor necrosis factor-α in NR8383 rat alveolar macrophages].

Objective: To investigate the effect of long non-coding RNA-AC013472.3 on lipopolysaccharide (LPS)-stimulated secretion of tumor necrosis factor (TNF)-α in NR8383 rat alveolar macrophages. Methods: Silencing and overexpression models of lncRNA-AC013472.3 were established with NR8383 rat alveolar macrophages as the experimental subjects. The silencing models were divided into three groups: random nonsense negative small interfering RNA sequence (si-con) group (si-con group, si-con transfected NR8383 cells), LPS+si-con group (10 µg/L LPS was used to treat si-con transfected NR8383 cells for 24 h), and siRNA group (siRNA transfected NR8383 cells), and LPS+siRNA group (10 µg/L LPS was used to treat siRNA transfected NR8383 cells for 24 h). The overexpression models were divided into the empty plasmid (p-con) group (p-con transfected NR8383 cells), LPS+p-con group (10 µg/L LPS was used to treat p-con transfected NR8383 cells for 24 h), lncRNA overexpression plasmid (plncRNA) group (plncRNA transfected NR8383 cells), and the LPS+plncRNA group (10 µg/L LPS was used to treat plncRNA transfected NR8383 cells for 24 h). The mRNA levels of TNF-α in each group were examined by quantitative real-time PCR (qPCR). The protein levels of tumor necrosis factor receptor-related factor-6 (TRAF-6) and phosphorylated nuclear factor-κB (NF-κB) p65 were examined by Western blot. Results: In the silencing model, the mRNA levels of TNF-α, the protein levels of TRAF-6 and NF-κB p65 in the LPS+si-con group were significantly higher than those in the si-con group (2.040±0.195 vs 1.048±0.207, 0.473±0.022 vs 0.293±0.076 and 0.469±0.062 vs 0.252±0.038)(all P<0.05). The mRNA levels of TNF-α, the protein levels of TRAF-6 and NF-κB p65 in the LPS+siRNA group were significantly higher than those in the siRNA group (4.158±0.119 vs 1.028±0.019, 0.700±0.104 vs 0.231±0.023 and 0.771±0.095 vs 0.258±0.050)(all P<0.05). The relative expression levels of all indexes in the LPS+siRNA group were significantly higher than those in the LPS+si-con group (all P<0.05). In the overexpression model, the mRNA levels of TNF-α, the protein levels of TRAF-6 and NF-κB p65 in the LPS+p-con group were significantly higher than those in the p-con group (1.961±0.169 vs 0.999±0.143, 0.533±0.047 vs 0.247±0.020 and 0.565±0.108 vs 0.276±0.048) (all P<0.05). The mRNA levels of TNF-α, the protein levels of TRAF-6 and NF-κB p65 in the LPS+plncRNA group were significantly higher than those in the plncRNA group (1.322±0.110 vs 1.043±0.093, 0.347±0.035 vs 0.232±0.023 and 0.405±0.072 vs 0.268±0.031) (all P<0.05). The relative expression of all indexes in the LPS+plncRNA group were significantly lower than that in the LPS+p-con group (all P<0.05). Conclusion: LncRNA-AC013472.3 may inhibit the activation of NF-κB signaling pathway, thereby inhibiting the LPS-stimulated secretion of TNF-α in NR8383 rat alveolar macrophages.

[The application of amodified scalp retractor in the craniotomy for intracranial aneurysms].

Objective: To investigate the application of a modified scalp retractor in the craniotomy for intracranial aneurysms withlateral supraorbital approach. Methods: From January 2019 to April 2020, a total of 32 patients with anterior circulation aneurysms clipping by superior lateral orbital approach were selected from Beijing Tiantan Hospital and Peking University International Hospital. The subjects were randomly divided into the traditional scalp retractor group and the modified scalp retractor group utilizing a random number table, with 16 patients in each group. The number of intraoperative retractor adjustment, incision length, postoperative scalp necrosis rate, postoperative wound healing grade, postoperative neurosurgical satisfaction score and patients' satisfaction score for incision were compared between the two groups. Results: The number of retractor adjustment in the modified scalp retractors group was significantly less than that in the traditional scalp retractor group (10.1±2.2 vs 14.2±3.6, P<0.05) . Incision length was also significantly shorter than that of the conventional scalp retractor group ( (10.1±1.0) cm vs (13.9±0.9) cm, P<0.05) .Neurosurgeons were significantly more satisfied with modified scalp retractors than the traditional scalp retractors (8.1±0.9 vs 6.0±0.9, P<0.05). There was no significant difference in postoperative scalp necrosis rate between two groups (P>0.05). Conclusion: The modified scalp retractor group is superior to the traditional scalp retractor group in the craniotomy for intracranial aneurysms with later supraorbital approach, with shorter in cision, less retractor adjustment and shorter surgical time.