Near-frictionless ion transport within triazine framework membranes.

The enhancement of separation processes and electrochemical technologies such as water electrolysers1,2, fuel cells3,4, redox flow batteries5,6 and ion-capture electrodialysis7 depends on the development of low-resistance and high-selectivity ion-transport membranes. The transport of ions through these membranes depends on the overall energy barriers imposed by the collective interplay of pore architecture and pore-analyte interaction8,9. However, it remains challenging to design efficient, scaleable and low-cost selective ion-transport membranes that provide ion channels for low-energy-barrier transport. Here we pursue a strategy that allows the diffusion limit of ions in water to be approached for large-area, free-standing, synthetic membranes using covalently bonded polymer frameworks with rigidity-confined ion channels. The near-frictionless ion flow is synergistically fulfilled by robust micropore confinement and multi-interaction between ion and membrane, which afford, for instance, a Na+ diffusion coefficient of 1.18 × 10-9 m2 s-1, close to the value in pure water at infinite dilution, and an area-specific membrane resistance as low as 0.17 Ω cm2. We demonstrate highly efficient membranes in rapidly charging aqueous organic redox flow batteries that deliver both high energy efficiency and high-capacity utilization at extremely high current densities (up to 500 mA cm-2), and also that avoid crossover-induced capacity decay. This membrane design concept may be broadly applicable to membranes for a wide range of electrochemical devices and for precise molecular separation.

A small proton charge radius from an electron-proton scattering experiment.

Elastic electron-proton scattering (e-p) and the spectroscopy of hydrogen atoms are the two methods traditionally used to determine the proton charge radius, rp. In 2010, a new method using muonic hydrogen atoms1 found a substantial discrepancy compared with previous results2, which became known as the 'proton radius puzzle'. Despite experimental and theoretical efforts, the puzzle remains unresolved. In fact, there is a discrepancy between the two most recent spectroscopic measurements conducted on ordinary hydrogen3,4. Here we report on the proton charge radius experiment at Jefferson Laboratory (PRad), a high-precision e-p experiment that was established after the discrepancy was identified. We used a magnetic-spectrometer-free method along with a windowless hydrogen gas target, which overcame several limitations of previous e-p experiments and enabled measurements at very small forward-scattering angles. Our result, rp = 0.831 ± 0.007stat ± 0.012syst femtometres, is smaller than the most recent high-precision e-p measurement5 and 2.7 standard deviations smaller than the average of all e-p experimental results6. The smaller rp we have now measured supports the value found by two previous muonic hydrogen experiments1,7. In addition, our finding agrees with the revised value (announced in 2019) for the Rydberg constant8-one of the most accurately evaluated fundamental constants in physics.

Continuous Space-Time Crystal State Driven by Nonreciprocal Optical Forces.

We show that the continuous time crystal state can arise in an ensemble of linear oscillators from nonconservative coupling via optical radiation pressure forces. This new mechanism comprehensively explains observations of the time crystal state in an array of nanowires illuminated with light [T. Liu et al., Nat. Phys. 19, 986 (2023).NPAHAX1745-247310.1038/s41567-023-02023-5]. Being fundamentally different from regimes of nonlinear synchronization, it has relevance to a wide range of interacting many-body systems, including in the realms of chemistry, biology, weather, and nanoscale matter.

Autogenous and efficient acceleration of energetic ions upstream of Earth's bow shock.

Earth and its magnetosphere are immersed in the supersonic flow of the solar-wind plasma that fills interplanetary space. As the solar wind slows and deflects to flow around Earth, or any other obstacle, a 'bow shock' forms within the flow. Under almost all solar-wind conditions, planetary bow shocks such as Earth's are collisionless, supercritical shocks, meaning that they reflect and accelerate a fraction of the incident solar-wind ions as an energy dissipation mechanism1,2, which results in the formation of a region called the ion foreshock3. In the foreshock, large-scale, transient phenomena can develop, such as 'hot flow anomalies'4-9, which are concentrations of shock-reflected, suprathermal ions that are channelled and accumulated along certain structures in the upstream magnetic field. Hot flow anomalies evolve explosively, often resulting in the formation of new shocks along their upstream edges5,10, and potentially contribute to particle acceleration11-13, but there have hitherto been no observations to constrain this acceleration or to confirm the underlying mechanism. Here we report observations of a hot flow anomaly accelerating solar-wind ions from roughly 1-10 kiloelectronvolts up to almost 1,000 kiloelectronvolts. The acceleration mechanism depends on the mass and charge state of the ions and is consistent with first-order Fermi acceleration14,15. The acceleration that we observe results from only the interaction of Earth's bow shock with the solar wind, but produces a much, much larger number of energetic particles compared to what would typically be produced in the foreshock from acceleration at the bow shock. Such autogenous and efficient acceleration at quasi-parallel bow shocks (the normal direction of which are within about 45 degrees of the interplanetary magnetic field direction) provides a potential solution to Fermi's 'injection problem', which requires an as-yet-unexplained seed population of energetic particles, and implies that foreshock transients may be important in the generation of cosmic rays at astrophysical shocks throughout the cosmos.

Impact of polygenic risk score for triglyceride trajectory and diabetic complications in subjects with type 2 diabetes based on large electronic medical record data from Taiwan: a case control study.

BACKGROUND: The prevalence of diabetic dyslipidemia has gradually increased worldwide and individuals with hypertriglyceridemia often have a high polygenic burden of triglyceride (TG)-increasing variants. However, the contribution of genetic variants to dyslipidemia in patients with type 2 diabetes (T2D) remains limited. Therefore, in this study, we aimed to investigate the genetic characteristics of longitudinal changes in TG levels among patients with T2D and summarize the genetic effects of polygenic risk score (PRS) on TG trajectory and risk of diabetic complications. METHODS: We conducted a case-control study. A total of 11,312 patients with T2D with longitudinal TG and genetic data were identified from a large hospital database in Taiwan. We then performed a genome-wide association study and calculated the relative PRS. RESULTS: In total, 21 single-nucleotide polymorphisms (SNPs) related to TG trajectory were identified and yielded an area under the receiver operating characteristic curve (ROC) of 0.712 for high TG trajectory risk among Taiwanese patients with T2D. A cumulative genetic effect was observed for high TG trajectory, even when considering the adherence of a lipid-lowering agent in stratified analysis. An increased PRS increases high TG trajectory risk in a logistic regression model (odds ratio = 1.55; 95% confidence interval [CI] = 1.31-1.83 in the validation cohort). The TG-specific PRS was associated with the risk of diabetic microvascular complications, including diabetic retinopathy and nephropathy (with hazard ratios of 1.11 [95% CI = 1.01-1.21, P = 0.027] and 1.05 [95% CI = 1.01-1.1, P = 0.018], respectively). CONCLUSIONS: This study may contribute to the identification of patients with T2D who are at risk of abnormal TG levels and diabetic microvascular complications using polygenic information.

Iatrogenic urinary injuries in colorectal surgery: outcomes and risk factors from a nationwide cohort.

BACKGROUND: Iatrogenic urinary injury (IUI) can lead to significant complications after colorectal surgery, especially when diagnosis is delayed. This study analyzes risk factors associated with IUI and delayed IUI among patients undergoing colorectal procedures. METHODS: Adults undergoing colorectal surgery between 2012 and 2021 were identified in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP®) database. Multivariable regression analysis was used to determine risk factors and outcomes associated with IUI and delayed IUI. RESULTS: Among 566,036 patients, 5836 patients (1.0%) had IUI after colorectal surgery, of whom 236 (4.0%) had delayed IUI. Multiple preoperative risk factors for IUI and delayed IUI were identified, with disseminated cancer [adjusted odds ratio (aOR) 1.4, 95% confidence interval (CI) 1.2-1.5; p < 0.001] and diverticular disease [aOR 1.1, 95% CI 1.0-1.2; p = 0.009] correlated with IUI and increased body mass index [aOR 1.6, 95% CI 1.2-2.1; p = 0.003] and ascites [aOR 5.6, 95% CI 2.1-15.4; p = 0.001] associated with delayed IUI. Laparoscopic approach was associated with decreased risk of IUI [aOR 0.4, 95% CI 0.4-0.5; p < 0.001] and increased risk of delayed IUI [aOR 1.8, 95% CI 1.4-2.5; p < 0.001]. Both IUI and delayed IUI were associated with significant postoperative morbidity, with severe multiorgan complications seen in delayed IUI. CONCLUSIONS: While IUI occurs infrequently in colorectal surgery, unrecognized injuries can complicate repair and cause other negative postoperative outcomes. Patients with complex intra-abdominal pathology are at increased risk of IUI, and patients with large body habitus undergoing laparoscopic procedures are at increased risk of delayed IUI.

Effects of different stocking densities on the development of reproductive and immune functions in young breeder pigeons during the rearing period.

1. Stocking density (SD) is closely related to animal performance. This experiment was designed to evaluate the development of reproductive and immune functions of young pigeons under different SDs.2. A total of 288 (half male and half female) 40-day-old pigeons (body weight 400 ± 15 g) were allocated into four groups: High stocking density (HSD; 0.308 m3/bird), standard stocking density (SD; 0.616 m3/bird), and low stocking density (LSD; 1.232 m3/bird) and a caged (control; 0.04125 m3/bird). Every group had six replicates of the same sex.3. The results showed that caged male pigeons had the highest testis index, testosterone content, and gene expression of the androgen receptor gene. LSD treatment induced the highest concentrations of oestradiol, progesterone and mRNA levels of reproductive hormone receptor genes in female pigeons. In male pigeons, the spleen index (organ weight calculated as a percentage of total body weight) showed a peak level (0.09 ± 0.020) in the LSD group, and the thymus index peaked (0.23 ± 0.039) in SD group. However, the index for ovary, spleen, thymus and bursa of Fabricius in female pigeons showed no significant changes among different groups.4. The IL-1ß, IL-8, IFN-γ, TGF-ß and toll-like receptor 2 (TLR-2) mRNA levels reached their maximum values in both male and female pigeon spleens in the LSD group.5. Young male pigeons housed in cages showed increased testicular development while low stocking density increased the development of reproductive function in young female pigeons. A larger activity space could help enhance the immune function of both male and female pigeons.

[Establishment and verification of invasion syndrome prediction model in patients with diabetes complicated with Klebsiella pneumoniae liver abscess].

Objective: To analyze the correlative factors of invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess, and to construct and verify the online nomographic prediction model. Methods: A case control study. The clinical data of 213 diabetic patients with Klebsiella pneumoniae liver abscess admitted to the Third Affiliated Hospital of Soochow University from January 1, 2015 to December 31, 2021 were retrospectively analyzed. The patients were divided into the training set (149 cases) and the test set (64 cases) by stratified random sampling method at a ratio of 7∶3. Synthetic minority over-sampling technique(SMOTE) was used to process the imbalanced data, then Lasso regression was used to screen out the optimal feature variables in the training set and multivariate logistic regression model was used to construct the prediction model of invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess, and verify it in the training set and test set. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the prediction efficiency of the model, and the simple and online interactive dynamic web page column graph was constructed. Results: Among the 213 patients, 60 were males and 153 were females, aged of (61.4±12.0) years. A total of 25(11.74%) diabetic patients with Klebsiella pneumoniae liver abscess developed invasion syndrome, which were included in divided into invasive K.pneumoniae liver abscesses syndrome (IKPLAS) group, and the other 188 cases were in without invasive K.pneumoniae liver abscesses syndrome (NIKPLAS) group. SMOTE algorithm was used for oversampling processing, so that the ratio of positive and negative samples was 1∶1. In the oversampling training set, 5 main risk factors were screened based on Lasso regression, namely fasting blood glucose (λ=0.063), hemoglobin (λ=-0.042), blood urea nitrogen (λ=-0.050), abscess size (λ=-0.025) and sequential organ failure assessment (SOFA) score (λ=0.450), respectively. Multivariate logistic regression model showed that fasting blood glucose (OR=1.20, 95%CI: 0.98-1.48, P=0.006), hemoglobin (OR=0.90, 95%CI: 0.86-0.95, P<0.001), blood urea nitrogen (OR=1.22, 95%CI: 1.03-1.43, P=0.017), abscess diameter (OR=0.76, 95%CI: 0.61-0.94, P=0.010), SOFA score (OR=3.08, 95%CI: 2.18-4.36, P<0.001) were associated with invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess. The area under the curve of ROC in the training set was 0.966 (95%CI: 0.943-0.989), the sensitivity was 90.5%, and the specificity was 91.3%. The area under the curve of the validation set ROC was 0.946 (95%CI: 0.902-0.991), with a sensitivity of 79.6% and a specificity of 88.9%. The calibration curves drawn in the training set and the test set fit well with the ideal curve. DCA showed that the neomorph prediction model had a good clinical net benefit when predicting the risk of IKPLAS in patients with diabetes complicated with Klebsiella pneumoniae liver abscess was 0.10-0.40. Conclusions: Fasting blood glucose, hemoglobin, urea nitrogen, abscess size and SOFA score are the related factors for invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess. The constructed column graph can effectively predict the risk of invasion syndrome in patients with diabetes complicated with Klebsiae pneumoniae liver abscess.

[Clinical features and outcomes of digestive tract perforation in pediatric mature B-cell non-Hodgkin lymphoma].

To summarize the clinical features and prognosis of pediatric mature B-cell non-Hodgkin lymphoma (mB-NHL) with digestive tract perforation. The clinical manifestations, laboratory and imaging examinations, treatment and outcomes of mB-NHL children complicated with digestive tract perforation admitted to Beijing Children's Hospital of Capital Medical University from January 2016 to June 2023 were retrospectively analyzed. A total of 12 patients were included, with 11 males and 1 female, aged 0.8-16.0 (7.5±5.4) years. Among them, there were 10 cases of Burkitt lymphoma, 1 case of high-grade B-cell lymphoma (HGBL) and 1 case of diffuse large B-cell lymphoma (DLBCL), respectively. Intestinal involvement was involved in all cases, with St.Jude staging ranging from stage Ⅲ to Ⅳ. Eleven cases had large abdominal mass. In 7 cases, abdominal X-ray examination showed free gas under the diaphragm. Eleven cases experienced digestive tract perforation after chemotherapy, and the time of perforation after initiation of chemotherapy was 2.0-111.0 (41.2±33.6) days. The most common site of perforation was ileum (6 cases), followed by gastric wall (2 cases), jejunum (1 case), colon (1 case) and appendix (1 case). Eight patients underwent surgery, and the time between surgery and re-chemotherapy was 7.0-45.0 (17.6±12.0) days. One case with perforation before chemotherapy died after giving up treatment. The remaining 11 cases received conservative treatment or surgical intervention, followed by regular chemotherapy after symptom and infection control. The follow-up time was 6.0-82.0 (45.0±26.1) months, and all survived.

[The safety and efficacy of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia in children].

To explore the safety and efficacy of blinatumomab in the treatment of CD19 positive (CD19+) B-cell acute lymphoblastic leukemia (B-ALL) in children. A retrospective analysis was conducted on the clinical data of pediatric B-ALL patients who received blinatumomab treatment from Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences from August 2021 to October 2023. Based on their disease status, the patients were divided into refractory/relapsed(RR) group, minimal residual disease clearance (MC) group, and chemotherapy intolerance (IC) group. Clinical data of the children were collected to evaluate the adverse drug reactions, therapeutic efficacy and survival of the children. In total, 35 patients were included, with 20 males and 15 females, aged from 0.6 to 16.4 (9.9±4.2) years old. There were 10 cases in the RR group, 20 cases in the MC group and 5 cases in the IC group. A total of 56 cycles of infusion were completed, with one cycle in 24 cases, two cycles in 5 cases, three cycles in 2 cases and four cycles in 4 cases. The median infusion time [M (Q1, Q3)] from the first to the fourth cycle was 14 (14, 28) days, 28 (28, 28) days, 28 (28, 28) days and 28 (26, 28) days, respectively. In terms of adverse reactions, the incidence of grade 1-2 cytokine release syndrome(CRS) was 57.1% (32/56), with grade 1 CRS accounting for 84.4% (27/32). The incidence rate of immune effector cell-associated neurotoxicity syndrome(ICANS) (grade 4) was 1.8% (1/56). In the RR group, 6 cases were treated effectively, and minimal residual disease(MRD) turned negative, before treatment, MRD levels were all less than 20%. Among them, 3 cases had MRD turning positive again 14 to 42 days after discontinuation of Belintoumab. Four cases were treated ineffectively, with MRD >20% before treatment. All MRD positive cases in MC group turned negative and all MRD negative cases in the IC group remained negative after treatment. The median follow-up time of RR group was 5.7 (3.8, 9.4) months, and 1 year median survival rate and event-free survival rate were 40.0%±21.9% and 33.3%±19.2%, respectively. The median follow-up time for MC and IC group patients was 6.7 (5.2, 12.5) months and 7.1 (5.1, 7.6) months, respectively, with an event free survival rate of 100%. The safety and efficacy of using belintoumab in partial RR, MRD clearance, and chemotherapy intolerance are good.

[The distribution of biomarkers for Behcet syndrome and their clinical relevance in real-world studies].

Objective: To explore the distribution of different biomarkers for Behcet's syndrome (BS) and their correlation with distinct clinical phenotypes of BS patients in real-world studies. Methods: This study was a retrospective cross-sectional study. A total of 483 patients diagnosed with BS in the Department of Rheumatology and Immunology, Peking University People's Hospital from 2019 to 2022 were enrolled. The baseline information and clinical features of the patients were recorded at their first diagnosis and tested the level of HLA-B51, several auto-antibodies, antistreptolysin-O(ASO), immune globulin, complement in blood serum and interleukin-6 (IL-6). Logistic regression was used to analyze the correlation of biomarkers and phenotypes. Results: Among BS patients, the number of positive cases for HLA-B51, anti-endothelial cell antibody (AECA), antinuclear antibodies (ANA) and ASO was 129, 115, 79 and 54, respectively. The positive rate of other biomarkers was less than 5.0%. About 12.6% of patients with BS had an increased level of IgA (n=61), and 10.8% of patients had an increased level of IgG (n=52). About 41.0% of patients had increased levels of IL-6 (n=198), and 6.4% of patients had decreased levels of IgM (n=31). About 11.2% of patients had decreased levels of C3 (n=54), and 6.0% of patients had decreased levels of C4 (n=29). Elevated IgA was a risk factor for the articular phenotype of BS (OR=2.652, P=0.011). Decreased complement C4 was a risk factor for the neurological phenotype of BS (OR=3.594, P=0.039). Positive ASO was a risk factor for the gastrointestinal phenotype of BS (OR=2.578, P=0.041). Elevated IL-6 was a risk factor for the ocular phenotype of BS (OR=7.560, P=0.016). Conclusion: HLA-B51 and AECA are common biomarkers in BS. Elevated IgA, decreased complement C4, positive ASO, and elevated IL-6 are risk factors for different phenotypes of BS.

[Analysis of the change in human resources of centers for disease control and prevention in different regions of China from 2010 to 2020].

Objective: To analyze the change in human resources within China's Centers for Disease Control and Prevention (CDC) from 2010 to 2020. Methods: The self-reported information from provincial, prefectural (city), and county (district) levels of China's CDC, covering employee counts, staff composition, professional qualifications, educational backgrounds, technical titles, and tenure, were extracted from the China Disease Prevention and Control Information System. The demographic context was provided by the annual population figures from the China Statistical Yearbook (2010-2020). The profile of CDC personnel was described, and the average annual percentage rate change (AAPC), average annual percentage rate change (APC), human resource agglomeration degree (HRAD) and the difference between HRAD and population agglomeration degree (PAD) were calculated. The Joinpoint regression model was used to analyze the time trend. Results: The decade under review witnessed a net increase of 17 300 active and 18 300 enrolled personnel in the CDC, surpassing the national population growth rate with AAPCs of 0.93% and 1.03%, respectively. This upward trajectory was statistically significant (P<0.05). The ratio of disease control personnel per 10 000 population escalated from 1.14 to 1.21. An initial decline in active CDC workforce density (from 1.31 to 1.27 per 10 000 population between 2010 and 2017) was followed by an increase (from 1.28 to 1.37 between 2018 and 2020), with APCs of -0.40% and 3.73%, respectively. The proportion of professional and technical staff in 2019 was highest in the eastern region (86.01%), followed by the western (83.75%) and central regions (79.54%). The period also saw an enhancement in the average academic degree (from 1.91 to 2.43 points) and professional title scores (from 1.39 to 1.53 points) of CDC personnel. While the average tenure in the eastern and western regions showed a slight decline, the central region experienced an increase, with HRAD values indicating a higher concentration in the eastern and central regions compared to the western region. The HRAD-PAD discrepancy revealed a negative value in the eastern region, nearing zero in the central and western regions. Conclusion: Between 2010 and 2020, China's CDC experienced notable growth in human resources and underwent structural optimization, albeit with significant regional disparities in concentration.

[Effects of retinopathy on visual function in type 2 diabetes mellitus].

Objective: To study the influence of the severity of diabetic retinopathy (DR) on the visual function of patients with type 2 diabetes, to provide scientific basis for the early prevention and control of DR. Methods: This study was designed as a cross-sectional study, recruiting already-diagnosed type 2 diabetes patients in four community health service centers in Guizhou Province between February and September 2022. Employing the Chinese version of the Visual Function Index-14 (VF-14), assess the participants' near vision, visual adaptation, subjective visual perception, and stereo vision, with higher scores indicating poorer visual function. Categorize the severity of each eye's damage into no diabetic retinopathy (DR), mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR), and use a 5-level DR grading system to evaluate the overall severity of diabetic retinopathy in both eyes. Employing linear regression analysis to investigate the linear relationship between DR and visual function index. Local weighted regression evaluates the nonlinear relationship between the DR composite score and the scores of visual function, with a steeper slope indicating poorer visual function for that level. Results: A total of 542 patients with type 2 diabetes were investigated, including 244 (45.02%) males, 298 (54.98%) females, and 162 (29.89%) patients with DR. After adjusting for confounders, compared with those without DR, patients with binocular DR Had overall scores (ß=0.136, P=0.003), near vision (ß=0.163, P<0.001), visual adaptation (ß=0.092, P=0.042), subjective vision (ß=0.120, P=0.009) and stereo vision (ß=0.094, P=0.044) were higher than those without DR. There were no differences in visual functions between DR And monocular DR. The local weighted regression curve showed that near vision (slope: 23.78) and overall score (slope: 58.37) increased sharply from mild to moderate NPDR in both eyes. Visual adaptation (slope: 5.37, 7.72), subjective vision (slope: 6.53, 7.93), stereovision (slope: 0.74, 0.91) increased slowly in mild to moderate NPDR in both eyes and in moderate to severe NPDR/PDR in both eyes. Conclusion: Binocular DR is associated with impaired visual function, but there is no difference between monocular DR And non-DR visual function. The early damage of DR To visual function is mainly manifested in near vision. In the prevention and control of DR, more attention should be paid to visual function, especially the change of near vision, and retinal damage should not be assessed solely by visual status.

[Analysis of pollution status and influencing factors of polybrominated diphenyl ethers in household dust in five cities in northern China].

Objective: To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China. Methods: Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust. Results: The M (Q1, Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑12PBDEs in Luoyang and Shijiazhuang (P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ß (95%CI): 0.186 (0.013, 0.359)], infrequent home cooking [ß (95%CI):-0.342 (-0.570, -0.114)], and increased residential PM10 concentration [ß (95%CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ß (95%CI): 0.093 (0.013, 0.172)], house area less than 90 m2 [ß (95%CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ß (95%CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑12PBDEs in household dust. Conclusion: The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.

[Clinicopathological study of 24 cases of monkeypox virus infection-related rashes].

Objective: To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests. Methods: Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope® hybridization and electron microscopy. Results: All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri's bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope® hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions: The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.

[Progress in the treatment of progressive familial intrahepatic cholestasis].

Progressive familial intrahepatic cholestasis (PFIC) is an important cause of liver-related death or transplantation in children. The PFIC spectrum is expanding, twelve types of PFIC are currently included in the Online Mendelian Inheritance in Man (OMIM) database. With the increase of PFIC types and the inconsistence of certain types in numbering, the current numbering classification of PFIC is confusing, so the experts in the field recommend using the corresponding mutant gene/ protein defect to name different type of PFIC except for PFIC type 1-3. The clarification of the genotype-phenotype relationship and/or the establishment of phenotypic predictors significantly improved the management of patients with PFIC. Odevixibat and maralixibat, inhibitors of the apical sodium ion-dependent bile acid transporter on the intestinal epithelial cells, were approved in European Union and the United States for the treatment of PFIC pruritus in 2021, expanding the treatment options for PFIC. Additionally, personalized treatments for specific mutations and novel gene therapy is promising.

[Effect of SHP-1 knockout in airway epithelial cells on emphysema phenotype in chronic obstructive pulmonary disease in mice].

Objective: To construct and characterize conditional Src homology region 2 protein tyrosine phosphatase 1 (SHP-1) knockout mice in airway epithelial cells and to observe the effect of defective SHP-1 expression in airway epithelial cells on the emphysema phenotype in chronic obstructive pulmonary disease (COPD). Methods: To detect the expression of SHP-1 in the airway epithelium of COPD patients. CRISPR/Cas9 technology was used to construct SHP-1flox/flox transgenic mice, which were mated with airway epithelial Clara protein 10-cyclase recombinase and estrogen receptor fusion transgenic mice (CC10-CreER+/+), and after intraperitoneal injection of tamoxifen, airway epithelial SHP-1 knockout mice were obtained (SHP-1flox/floxCC10-CreER+/-, SHP-1Δ/Δ). Mouse tail and lung tissue DNA was extracted and PCR amplified to discriminate the genotype of the mice; the knockout effect of SHP-1 gene in airway epithelial cells was verified by qRT-PCR, Western blotting, and immunofluorescence. In addition, an emphysema mouse model was constructed using elastase to assess the severity of emphysema in each group of mice. Results: Airway epithelial SHP-1 was significantly downregulated in COPD patients. Genotyping confirmed that SHP-1Δ/Δ mice expressed CC10-CreER and SHP-1-flox. After tamoxifen induction, we demonstrated the absence of SHP-1 protein expression in airway epithelial cells of SHP-1Δ/Δ mice at the DNA, RNA, and protein levels, indicating that airway epithelial cell-specific SHP-1 knockout mice had been successfully constructed. In the emphysema animal model, SHP-1Δ/Δ mice had a more severe emphysema phenotype compared with the control group, which was manifested by disorganization of alveolar structure in lung tissue and rupture and fusion of alveolar walls to form pulmonary alveoli. Conclusions: The present study successfully established and characterized the SHP-1 knockout mouse model of airway epithelial cells, which provides a new experimental tool for the in-depth elucidation of the role of SHP-1 in the emphysema process of COPD and its mechanism.

[Safety of umeclidinium/vilanterol in Chinese patients in a real-world setting: a prospective, multicenter, single-arm, observational study].

Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.

[Arrhythmias and electrocardiographic characteristics in cancer patients treated with immune checkpoint inhibitors].

Objective: To evaluate the incidence of arrhythmias and electrocardiographic (ECG) characteristics in cancer patients treated with immune checkpoint inhibitors (ICIs). Methods: This was a cohort study conducted in the Fourth Hospital of Hebei Medical University. Cancer patients initiating ICIs treatments from November 2020 to September 2022 were included in this study. Baseline 12-leads ECG before ICIs initiation and post-treatment ECG were analyzed. An abnormal ECG was defined as the presence of any of the following changes: sinus arrhythmias, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia, premature contractions, conduction disorder, and ST-T changes. Results: A total of 87 patients were enrolled, aged 63 (57, 68) years, with 66 (75.9%) males. And 44.8% (39/87) of patients presented with at least one confirmed cardiovascular disease or cardiovascular risk factor at baseline. The incidence of abnormal ECG increased from 31.0% (27/87) at baseline to 65.5% (57/87) after receiving (5.0±2.7) cycles of ICIs treatment (P<0.001). The incidence of sinus arrhythmias was significantly increased after ICIs treatment (23.0% (20/87) vs. 9.2% (8/87), P=0.023), of which only the incidence of sinus tachycardia was significantly increased (11.5% (10/87) vs. 2.3% (2/87), P=0.039). There was also a significantly increased incidence of ST-T changes after ICIs treatment (31.0% (27/87) vs. 17.2% (15/87), P=0.012), which mainly attributed to the T wave changes (29.9% (26/87) vs. 13.8% (12/87), P=0.001). The incidence of premature contractions was also significantly increased after ICIs treatment (9.2% (8/87) vs. 0, P=0.008). Additionally, compared with baseline, the P wave axis was significantly increased after ICIs treatment ((56.94±21.01)° vs. (52.00±22.69)°, P=0.043). After ICIs treatment, the heart rate was significantly increased ((79.07±15.37) beats/min vs. (75.64±13.37) beats/min, P=0.029). Sokolow-Lyon index ((2.21±0.81)mV vs. (2.33±0.75)mV, P=0.138), QTc interval ((431.44±36.04)ms vs. (428.00±30.05)ms, P=0.415) all showed signs of change after treatment, but did not reach the traditional significant level. Conclusions: The incidence of abnormal ECG is significantly increased after ICIs treatment, especially for sinus tachycardia, premature contractions and T wave changes; the P wave axis and heart rate is also significantly increased after treatment. It is important to perform regular ECG monitoring in patients receiving ICIs treatment.

[Preliminary study on the role and mechanism of IL-6 receptor antagonists in improving post-infarction ventricular arrhythmia].

Objective: To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism. Methods: The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining. Results: Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP (P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower (P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group (P all<0.05). Conclusions: TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.