Spatially clustered type I interferon responses at injury borderzones.

Sterile inflammation after myocardial infarction is classically credited to myeloid cells interacting with dead cell debris in the infarct zone1,2. Here we show that cardiomyocytes are the dominant initiators of a previously undescribed type I interferon response in the infarct borderzone. Using spatial transcriptomics analysis in mice and humans, we find that myocardial infarction induces colonies of interferon-induced cells (IFNICs) expressing interferon-stimulated genes decorating the borderzone, where cardiomyocytes experience mechanical stress, nuclear rupture and escape of chromosomal DNA. Cardiomyocyte-selective deletion of Irf3 abrogated IFNIC colonies, whereas mice lacking Irf3 in fibroblasts, macrophages, neutrophils or endothelial cells, Ccr2-deficient mice or plasmacytoid-dendritic-cell-depleted mice did not. Interferons blunted the protective matricellular programs and contractile function of borderzone fibroblasts, and increased vulnerability to pathological remodelling. In mice that died after myocardial infarction, IFNIC colonies were immediately adjacent to sites of ventricular rupture, while mice lacking IFNICs were protected from rupture and exhibited improved survival3. Together, these results reveal a pathological borderzone niche characterized by a cardiomyocyte-initiated innate immune response. We suggest that selective inhibition of IRF3 activation in non-immune cells could limit ischaemic cardiomyopathy while avoiding broad immunosuppression.

A binary pulsar in a 53-minute orbit.

Spider pulsars are neutron stars that have a companion star in a close orbit. The companion star sheds material to the neutron star, spinning it up to millisecond rotation periods, while the orbit shortens to hours. The companion is eventually ablated and destroyed by the pulsar wind and radiation1,2. Spider pulsars are key for studying the evolutionary link between accreting X-ray pulsars and isolated millisecond pulsars, pulsar irradiation effects and the birth of massive neutron stars3-6. Black widow pulsars in extremely compact orbits (as short as 62 minutes7) have companions with masses much smaller than 0.1 M⊙. They may have evolved from redback pulsars with companion masses of about 0.1-0.4 M⊙ and orbital periods of less than 1 day8. If this is true, then there should be a population of millisecond pulsars with moderate-mass companions and very short orbital periods9, but, hitherto, no such system was known. Here we report radio observations of the binary millisecond pulsar PSR J1953+1844 (M71E) that show it to have an orbital period of 53.3 minutes and a companion with a mass of around 0.07 M⊙. It is a faint X-ray source and located 2.5 arcminutes from the centre of the globular cluster M71.

A repeating fast radio burst associated with a persistent radio source.

The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4 and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately [Formula: see text] parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.

A fast radio burst source at a complex magnetized site in a barred galaxy.

Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref. 9). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (AU; Earth-Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.

A bimodal burst energy distribution of a repeating fast radio burst source.

The event rate, energy distribution and time-domain behaviour of repeating fast radio bursts (FRBs) contain essential information regarding their physical nature and central engine, which are as yet unknown1,2. As the first precisely localized source, FRB 121102 (refs. 3-5) has been extensively observed and shows non-Poisson clustering of bursts over time and a power-law energy distribution6-8. However, the extent of the energy distribution towards the fainter end was not known. Here we report the detection of 1,652 independent bursts with a peak burst rate of 122 h-1, in 59.5 hours spanning 47 days. A peak in the isotropic equivalent energy distribution is found to be approximately 4.8 × 1037 erg at 1.25 GHz, below which the detection of bursts is suppressed. The burst energy distribution is bimodal, and well characterized by a combination of a log-normal function and a generalized Cauchy function. The large number of bursts in hour-long spans allows sensitive periodicity searches between 1 ms and 1,000 s. The non-detection of any periodicity or quasi-periodicity poses challenges for models involving a single rotating compact object. The high burst rate also implies that FRBs must be generated with a high radiative efficiency, disfavouring emission mechanisms with large energy requirements or contrived triggering conditions.

Very-high-frequency oscillations in the main peak of a magnetar giant flare.

Magnetars are strongly magnetized, isolated neutron stars1-3 with magnetic fields up to around 1015 gauss, luminosities of approximately 1031-1036 ergs per second and rotation periods of about 0.3-12.0 s. Very energetic giant flares from galactic magnetars (peak luminosities of 1044-1047 ergs per second, lasting approximately 0.1 s) have been detected in hard X-rays and soft γ-rays4, and only one has been detected from outside our galaxy5. During such giant flares, quasi-periodic oscillations (QPOs) with low (less than 150 hertz) and high (greater than 500 hertz) frequencies have been observed6-9, but their statistical significance has been questioned10. High-frequency QPOs have been seen only during the tail phase of the flare9. Here we report the observation of two broad QPOs at approximately 2,132 hertz and 4,250 hertz in the main peak of a giant γ-ray flare11 in the direction of the NGC 253 galaxy12-17, disappearing after 3.5 milliseconds. The flare was detected on 15 April 2020 by the Atmosphere-Space Interactions Monitor instrument18,19 aboard the International Space Station, which was the only instrument that recorded the main burst phase (0.8-3.2 milliseconds) in the full energy range (50 × 103 to 40 × 106 electronvolts) without suffering from saturation effects such as deadtime and pile-up. Along with sudden spectral variations, these extremely high-frequency oscillations in the burst peak are a crucial component that will aid our understanding of magnetar giant flares.

No pulsed radio emission during a bursting phase of a Galactic magnetar.

Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances1-3. It has long been speculated that magnetars are the engine powering repeating bursts from FRB sources4-13, but no convincing evidence has been collected so far14. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts15. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare18-21. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.

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.

A magnetar-powered X-ray transient as the aftermath of a binary neutron-star merger.

Mergers of neutron stars are known to be associated with short γ-ray bursts1-4. If the neutron-star equation of state is sufficiently stiff (that is, the pressure increases sharply as the density increases), at least some such mergers will leave behind a supramassive or even a stable neutron star that spins rapidly with a strong magnetic field5-8 (that is, a magnetar). Such a magnetar signature may have been observed in the form of the X-ray plateau that follows up to half of observed short γ-ray bursts9,10. However, it has been expected that some X-ray transients powered by binary neutron-star mergers may not be associated with a short γ-ray burst11,12. A fast X-ray transient (CDF-S XT1) was recently found to be associated with a faint host galaxy, the redshift of which is unknown13. Its X-ray and host-galaxy properties allow several possible explanations including a short γ-ray burst seen off-axis, a low-luminosity γ-ray burst at high redshift, or a tidal disruption event involving an intermediate-mass black hole and a white dwarf13. Here we report a second X-ray transient, CDF-S XT2, that is associated with a galaxy at redshift z = 0.738 (ref. 14). The measured light curve is fully consistent with the X-ray transient being powered by a millisecond magnetar. More intriguingly, CDF-S XT2 lies in the outskirts of its star-forming host galaxy with a moderate offset from the galaxy centre, as short γ-ray bursts often do15,16. The estimated event-rate density of similar X-ray transients, when corrected to the local value, is consistent with the event-rate density of binary neutron-star mergers that is robustly inferred from the detection of the gravitational-wave event GW170817.

Misprogramming of glucose metabolism impairs recovery of hippocampal slices from neuronal GLT-1 knockout mice and contributes to excitotoxic injury through mitochondrial superoxide production.

We have previously reported a failure of recovery of synaptic function in the CA1 region of acute hippocampal slices from mice with a conditional neuronal knockout (KO) of GLT-1 (EAAT2, Slc1A2) driven by synapsin-Cre (synGLT-1 KO). The failure of recovery of synaptic function is due to excitotoxic injury. We hypothesized that changes in mitochondrial metabolism contribute to the heightened vulnerability to excitotoxicity in the synGLT-1 KO mice. We found impaired flux of carbon from 13C-glucose into the tricarboxylic acid cycle in synGLT-1 KO cortical and hippocampal slices compared with wild-type (WT) slices. In addition, we found downregulation of the neuronal glucose transporter GLUT3 in both genotypes. Flux of carbon from [1,2-13C]acetate, thought to be astrocyte-specific, was increased in the synGLT-KO hippocampal slices but not cortical slices. Glycogen stores, predominantly localized to astrocytes, are rapidly depleted in slices after cutting, and are replenished during ex vivo incubation. In the synGLT-1 KO, replenishment of glycogen stores during ex vivo incubation was compromised. These results suggest both neuronal and astrocytic metabolic perturbations in the synGLT-1 KO slices. Supplementing incubation medium during recovery with 20 mM D-glucose normalized glycogen replenishment but had no effect on recovery of synaptic function. In contrast, 20 mM non-metabolizable L-glucose substantially improved recovery of synaptic function, suggesting that D-glucose metabolism contributes to the excitotoxic injury in the synGLT-1 KO slices. L-lactate substitution for D-glucose did not promote recovery of synaptic function, implicating mitochondrial metabolism. Consistent with this hypothesis, phosphorylation of pyruvate dehydrogenase, which decreases enzyme activity, was increased in WT slices during the recovery period, but not in synGLT-1 KO slices. Since metabolism of glucose by the mitochondrial electron transport chain is associated with superoxide production, we tested the effect of drugs that scavenge and prevent superoxide production. The superoxide dismutase/catalase mimic EUK-134 conferred complete protection and full recovery of synaptic function. A site-specific inhibitor of complex III superoxide production, S3QEL-2, was also protective, but inhibitors of NADPH oxidase were not. In summary, we find that the failure of recovery of synaptic function in hippocampal slices from the synGLT-1 KO mouse, previously shown to be due to excitotoxic injury, is caused by production of superoxide by mitochondrial metabolism.

Notch signaling regulates Th17 cells differentiation through PI3K/AKT/mTORC1 pathway and involves in the thyroid injury of autoimmune thyroiditis.

PURPOSE: Autoimmune Thyroiditis (AIT) is the most common thyroid disease; however, there were no measures to prevent the progression of the disease. The present study attempts to identify that Notch signaling regulates the differentiation of T helper 17 (Th17) cells by activating downstream Phosphatidylinositol-3 kinase/protein kinase/mechanistic target of rapamycin complex 1 (PI3K/AKT/mTORC1) pathway participating in the thyroid injury of the experimental autoimmune thyroiditis (EAT). METHODS: In vivo experiments, mice were randomly divided into 4 groups: a control group, an EAT group, and two groups with LY294002 treatment (pTg plus 25 mg/kg or 50 mg/kg LY294002, respectively). The degrees of thyroiditis were evaluated, and the percentage of Th17 cells, expression of interleukin-17A (IL-17A), and the main components of the Notch-PI3K signaling pathway were detected in different groups. In vitro experiments, two different dosages of LY294002 (25 and 50 µM) were used to intervene splenic mononuclear cells (SMCs) from EAT mice to further evaluate the regulatory effect of Notch-PI3K pathway on Th17 cells. RESULTS: Our data demonstrate that the infiltration of Th17 cells and the expressions of IL-17A, Notch, hairy and split 1 (Hes1), p­AKT (Ser473), p­AKT (Thr308), p­mTOR (Ser2448), S6K1, and S6K2 increased remarkably in EAT mice. After PI3K pathway was blocked, the degrees of thyroiditis were significantly alleviated, and the proportion of Th17 cells, the expression of IL-17A, and the above Notch-PI3K pathway-related molecules decreased in a dose-dependent manner. Additionally, the proportion of Th17 cells was positively correlated with the concentration of serum thyroglobulin antibody (TgAb), IL-17A, and Notch-PI3K pathway-related molecules mRNA levels. CONCLUSIONS: Notch signal promotes the secretion of IL-17A from Th17 cells by regulating the downstream PI3K/AKT/mTORC1 pathway through Hes-Phosphatase and tensin homolog (PTEN) and participates in thyroid autoimmune damage, and the PI3K pathway inhibitor may play important effects on AIT by affecting Th17 cells differentiation.

Determinants of depressive symptoms at individual, school and province levels: a national survey of 398,520 Chinese children and adolescents.

OBJECTIVES: The aims of this study were to describe the national distribution of depressive symptoms in Chinese children and adolescents, to examine the determinants of depressive symptoms at individual, school and province levels and to assess the gender and age differences in the effect of school factors on depressive symptoms. STUDY DESIGN: This was a national cross-sectional study. METHODS: A school-based online survey was conducted in mainland China from between December 1, 2021, and January 1, 2022. A total of 398,520 eligible participants were included in the analysis. School-level data were drawn from students, headteachers and Baidu Maps, and province-level data were obtained from the national human development report. The Patient Health Questionnaire-2 was used to measure depressive symptoms. RESULTS: Areas with the highest mean scores for depressive symptoms were in the northeastern, inner central and southwestern regions of China. At the individual level, younger age, male sex, being an only child, Han ethnicity, lower body mass index, more days of exercise, less drinking and smoking behaviours, higher subjective family socio-economic status (SES) and popularity in school were related to fewer depressive symptoms; however, objective family SES and maternal education were not related to fewer depressive symptoms. The school-level variables of public status, psychological activities and psychological courses and province-level variable of higher Human Development Index were associated with fewer depressive symptoms. The effect of psychological courses and activities on depressive symptoms was greater in females. CONCLUSIONS: The results showed multilevel factors related to depressive symptoms and emphasised the importance of implementing school-based psychological activities to ameliorate depressive symptoms in Chinese children and adolescents across age and gender.

A risk-prediction score about colorectal lesions based on the Chinese population of high-risk participants aged 50-65 years.

OBJECTIVES: The present study aims to develop an effective risk-prediction score (RPS) to improve screening efficiency and contribute to secondary prevention of colorectal cancer (CRC). STUDY DESIGN: Screening for colorectal lesions. METHODS: 14,398 high-risk individuals aged 50-65 years were included. The baseline characteristics of participants with and without colorectal lesions (CL) were compared using a Chi-squared test. The overall population was randomly split into a training set and a test set in the ratio of 80% and 20%. One-factor and multifactor logistic regression analyses were performed in the training set to construct the RPS (scores of 0-9.62). Area under curve (AUC) was calculated as an estimate of predictive performance using the receiver-operating characteristic (ROC) curve in the test set. RESULTS: In the study population, being male, advanced age, current or previous smoking, weekly alcohol consumption, high body mass index (BMI ≥24 kg/m2), and previously detected colonic polyp were associated with higher risk of CL. Compared to the low-risk group (0-2.31 points), the ORs and 95% confidence intervals (CIs) for the moderate-risk group (2.31-3.85 points) and high-risk group (3.85-8.42 points) were 1.58 (1.44, 1.73) and 2.52 (2.30, 2.76), respectively. For every 1-point increase in score, participants had a 27% increased risk of CL (OR:1.27, 95% CI: 1.24, 1.30). For participants with CL predicted by RPS, the area under the working characteristic curve was 0.61 (P < 0.001). CONCLUSION: Our RPS can quickly and efficiently identify multiple lesions of the colorectum. Combining RPS with existing screening strategies facilitates the identification of very high-risk individuals and may help to prevent CRC.

Prognostic significance of serum cystatin C in acute brainstem infarctions patients.

OBJECTIVES: Some studies show that high circulating cystatin C (CysC) may predict cardiovascular events and death after ischemic stroke onset. However, the association between serum CysC and outcome in ischemic stroke patients remains contradictory. We sought to assess the association between a specific stroke subgroup, brainstem infarction (BSI) and serum CysC. MATERIALS AND METHODS: A total of 324 acute BSI patients were included in the study. Serum CysC was used to calculate estimated glomerular filtration rate (eGFRCysC) at baseline. Modified Rankin scale score ((mRS) ≥3) six months after acute BSI indicates poor functional outcome. Patients were categorized into two groups according to mRS and eGFRCysC. Logistic regression analyses were performed to determine independent risk factors. RESULTS: Lower eGFRCysC was associated with hemoglobin A1c (HbA1c). This risk remained statistically significant after controlling for age, hypertension, initial National Institutes of Health Stroke Scale (NIHSS) score, HbA1c, fibrinogen and homocysteine. The serum eGFRCysC levels were significantly lower in the poor functional outcome group than the good functional outcome group (P<0.001). Multivariate logistic regression analyses showed that eGFRCysC level was significantly lower in the poor outcome group after adjusting for age, previous infarctions, initial NIHSS score, and HbA1c. CONCLUSIONS: Lower eGFRCysC levels were strongly associated with poor functional outcome of acute BSI patients with a higher HbA1c level. Lower eGFRCysC may be a more helpful serologic biomarker for the prediction of prognosis in BSI.

[Introduction to the 9th edition of TNM classification for lung cancer].

Lung cancer is the second commonly diagnosed cancer and remained the leading cause of cancer-related death, with an estimated 1.8 million deaths in 2020. The identification of driver gene mutation and administration of corresponding tyrosine kinase inhibitor have improved overall survival and quality of life in advanced lung cancer patients. Check point inhibitor has revolutionized treatment strategy of driver gene negative advanced NSCLC patients. TNM staging system is the most widely used classification method, providing an international common language during academic communication and important tool for predicting prognosis and subsequent treatment decision making. Accumulating knowledge about prognostic factors in lung cancer promotes the update of TNM classification. In the World Conference on Lung Cancer (WCLC) held in Singapore, September, 2023, International Association for Study of Lung Cancer (IASLC) released the forthcoming 9th edition of TNM classification for lung cancer, which is supposed to be adopted at January, 2024. The manuscript discussed the history, data resource and limitation of the TNM staging system.

[Effect of HBV DNA load on the safety and prognosis of systematic therapy in advanced hepatocellular carcinoma].

Objective: To study the effect of hepatitis B virus (HBV) infection on the occurrence of liver damage, HBV reactivation (HBVr) and the influence of HBVr on the prognosis of patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. Methods: The clinical data of 403 patients with HBV-related HCC at the Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University et al, from July 2018 to December 2020 were collected. The incidence of liver damage and HBVr during systematic therapy, and the influence of HBVr on survival prognosis were analyzed. Results: Of the 403 patients, 89.1% were male (n=359), with a median age of 51 years (51.5±12.1). Before propensity score matching (PSM), the proportion of patients with cirrhosis, TNM and advanced BCLC stage was higher in high HBV-DNA (baseline HBV-DNA>1000 U/ml, n=147) group comparing with the low HBV-DNA (baseline HBV DNA≤1000 u/ml, n=256) group (P<0.05). There was no significant difference in baseline indexes between the two groups after PSM. In 290 patients after PSM, there was no significant difference in the incidence of liver damage and HBVr between high HBV-DNA group and low HBV-DNA group (P>0.05). Survival analysis was performed on 169 patients with survival data, the median overall survival (OS) was found to be 11.49 months (95%CI: 7.77-12.89) and 16.65 months (95%CI: 10.54-21.99, P=0.008) in the high and low HBV-DNA groups, respectively. And median progression-free survival (PFS) was 7.41 months (95%CI: 5.06-8.67) and 10.55 months (95%CI: 6.72-13.54, P=0.038), respectively, with a statistically significant difference. There were no differences in overall survival (OS) and progression-free survival (PFS) between patients with and without HBVr and those with or without liver damage (P>0.05). Conclusions: HBV-DNA levels above 1 000 U/ml before systemic therapy do not increase the risk of liver damage or HBVr during systemic therapy in patients with HBV-related hepatocellular carcinoma, and such patients can safely receive systemic therapy.

[Epidemiological characteristics of spontaneous subarachnoid hemorrhage cases in Shandong province].

Objective: To investigate the characteristics and trends of spontaneous subarachnoid hemorrhage (SAH) in Shandong province. Methods: In this study, SAH incidence data of residents from 2012 to 2021 were collected from the chronic disease monitoring information management system of Shandong province, including the basic information of outpatient, emergency or inpatient cases and out-of-hospital deaths (name, gender, ID number, address, etc.) and disease diagnosis information (disease diagnosis, date of onset, date of diagnosis, etc.). The crude incidence rate and age-standardized incidence rate were used as indicators to describe the incidence of SAH in different gender, age groups and regions (urban and rural areas). Joinpoint regression was used to analyze the variation of incidence rate and age by year. The rate difference decomposition method was used to estimate the contribution of population aging to the increase of SAH incidence. Global and local spatial autocorrelation analysis was performed using DeoDa 1.12 software. Results: From 2012 to 2021, a total of 11 629 cases of SAH were reported from 19 provincial monitoring sites in Shandong province. Among them, 54.11% (6 293 cases) were female and 91.87% (10 684 cases) were≥45 years old. The reported crude incidence rate increased from 5.26/100 000 to 9.50/100 000, with an average annual increase of 7.75% (Ztrend=7.30, Ptrend<0.001), and the standardized incidence rate also showed an upward trend (Ztrend=3.92, Ptrend=0.004). The crude incidence rate of women was higher than that of men in all years (all P values<0.05), and the standardized incidence rate of women was higher than that of men in all years except in 2012 and 2021 (all P values<0.05). In 2012, the crude incidence and standardized incidence of urban residents were lower than those in rural areas (P<0.05); from 2013 to 2017, the urban incidence was higher than that in rural areas; and after 2018, the rural incidence exceeded the urban incidence again (all P values<0.05). The median age of onset of SAH increased from 61.9 years in 2012 to 67.2 years in 2021. The age of onset of SAH in men was lower than that in women in all years (all P<0.05), and there was no significant difference between urban and rural residents in most years (P>0.05). The incidence of SAH increased with age (Ptrend<0.001), with a low incidence reported in residents aged<45 years and a rapid increase in residents aged≥45 years. According to the seasonal decomposition, the incidence of SAH had three small peaks in January, March to May and October to November. From 2013 to 2021, the contribution of aging population to the increase of crude incidence of SAH increased from 27.86% to 43.68%. The global spatial autocorrelation analysis showed that the incidence of SAH was in an obvious spatial aggregation distribution (Moran's I>0, P<0.05). Local spatial autocorrelation analysis showed that the counties with high incidence were mainly concentrated in Dezhou City in northwest Shandong Province and Heze city in southwest Shandong province. Conclusions: The crude incidence rate of SAH in Shandong province is increasing, with spatial clustering and seasonal clustering. Residents aged 45 years and older, female residents, and rural residents are at high risk of developing SAH, so targeted prevention and control measures should be taken for high-incidence seasons, high-risk groups, and high-incidence clustered areas.

[Prevalence and intervention effect of arteriovenous graft stenosis].

Objective: To evaluate the prevalence, intervention methods and effect of arteriovenous graft (AVG) stenosis. Methods: The clinical data of patients who received AVG in the Blood Purification Center, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were retrospectively analyzed. The patency rate, prevalence and intervention effect of AVG stenosis were analyzed. Results: A total of 475 patients aged (55.5±11.8) years were included, and there were 193 male cases (40.6%) and 282 female cases (59.4%). The patients were followed up for [M (Q1, Q3)] 19 (12, 30) months, and the primary, assisted primary and secondary patency were 14 (5, 27), 27 (13, 55), and 59 (33, 65) months, respectively. There were 799 access events which needed intervention, with a total standardized intervention rate of 0.90 per patient-year. Totally, 431(53.9%, 431/799) stenosis events occurred in 207 AVG. Among 422 AVG stenosis events with complete clinical data, 57.8% (244/422) were multi-site stenosis and 42.2% (178/422) were single-site stenosis. The most common sites of stenosis were graft-vein anastomosis (47.6%, 340/715), venous outflows (22.7%, 162/715), and puncture zone (20.0%, 143/715). In the 414 stenosis with intact follow-up data, 90.8% (376/414) were treated by balloon angioplasty, 8.5% (35/414) received covered stent insertion, and 0.7% (3/414) were intervened by open surgery. Clinical success rate was 98.1% (406/414). The primary patency time after endovascular treatment was 6 (4, 12) months. Covered stent significantly increased post-intervention primary patency time compared withballoon angioplasty [6 (3, 7) months vs 3 (1, 4) months, P=0.020]. Conclusions: Stenosis is the most common complication of AVG, and the most common sites are graft-vein anastomosis, venous outflows, and puncture zone. Intervention of AVG stenosis has a high clinical success rate, and a relatively low post-intervention patency. Covered stent insertion improves the post-intervention patency of AVG, which has a poor effect using balloon expansion.

[Interim efficacy of a multicenter cohort study for China Net Childhood Lymphoma mature B-cell lymphoma 2017 regimen in the treatment of pediatric High-grade-B cell lymphoma].

Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageⅡ, 33(53.2%)patients in stage Ⅲ and 18(29.1%)patients in stage Ⅳ. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.

[Role of mitochondrial autophagy and the curative effect of rehmannia glutinosa leaves total glycoside capsules on nucleos(t)ide drug-induced renal injury].

Objective: To study the curative effect of rehmannia glutinosa leaves total glycoside capsules and the role of mitochondrial autophagy on nucleos(t)ide drug-induced renal injury. Methods: Adefovir dipivoxil (ADV) was used to construct a hepatitis B virus (HBV) transgenic mouse model for renal injury. Renal function was measured in each group at one and two weeks of modeling. Mitochondrial autophagy indicators were measured at two weeks of modeling in renal tissue. Transmission electron microscopy was used to detect mitochondrial autophagy phenomena in renal tissue. The model was established for two weeks. Mouse with renal injury were treated with rehmannia glutinosa leaves total glycoside capsules or isotonic saline for eight weeks by intragastric administration. Renal function was measured. Renal tissue morphology was observed. Mitochondrial autophagy indicators were detected in renal tissue. The protective effect of different concentrations of verbascoside (the main active ingredient of rehmannia glutinosa capsule) was observed on HK-2 cell damage induced by ADV. HK-2 cells were divided into control, ADV, and ADV plus verbascoside groups. The effects of verbascoside at different times and concentrations were observed on the HK-2 mitochondrial autophagy indicators. Fifty patients with chronic hepatitis B were collected who presented with renal injury after treatment with nucleos(t)ide analogs. The random number method was used to divide 29 cases into a control group that received conventional treatment. The treatment group of 21 cases was treated with rehmannia glutinosa leaves total glycoside capsules on the basis of the control group. Serum creatinine (Scr) and urinary protein were detected at eight weeks.The χ(2) test or t-test was used for statistical analysis. Results: Compared with the control group, two weeks of modeling in the ADV group induced renal function injury in HBV mice. The expression of autophagy indicators was higher in the renal tissue of the ADV group than that of the control group. Transmission electron microscopy had revealed mitochondrial autophagy in the renal tissue of the ADV group. Compared with the control group, the renal function of HBV mice treated with rehmannia glutinosa leaves total glycoside capsules improved for two months, and the expressions of autophagy indicators were down-regulated.Verbascoside promoted proliferation in ADV-damaged HK-2 cells, and the expression of autophagy indicators was down-regulated compared with the ADV alone group. In 50 patients with renal function injury, the urinary protein improvement was significantly superior in the treatment group than that in the control group, with eighteen and three cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with a statistically significant difference (χ(2) = 9.975 0, P = 0.001 6). Serum creatinine was decreased in the treatment group compared with the control group, with 11 and 10 cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with no statistically significant difference (χ(2) = 0.593 5, P = 0.441 1). Conclusion: Rehmannia glutinosa leaves total glycoside capsule can improve the nucleos(t)ide drug-induced renal function injury in chronic hepatitis B, possibly playing a role via inhibiting PINK1/Parkin-mediated mitochondrial autophagy.