Population pharmacokinetic modeling of sotatercept in healthy participants and patients with pulmonary arterial hypertension.

Sotatercept is a breakthrough, first-in-class biologic, that is FDA-approved for the treatment of pulmonary arterial hypertension (PAH). A population pharmacokinetic (PopPK) model was developed using data from two phase 1 studies in healthy participants, and two phase 2 studies and one phase 3 study in participants with PAH. The pooled sotatercept PK data encompassed single intravenous (IV) or subcutaneous (SC) doses ranging from 0.01 to 3.0 mg/kg, as well as multiple SC doses ranging from 0.03 to 1.0 mg/kg, with PK samples collected up to a maximum of ~150 weeks following Q3W and Q4W dosing regimens. The final PopPK analysis included 350 participants, with 30 and 320 participants receiving sotatercept IV and SC, respectively. A two-compartment model with a first-order absorption rate constant and a linear disposition from central compartment well-described sotatercept PK. The estimated bioavailability is ~66%; bioavailability, clearance (CL), and central volume (VC) have low to moderate inter-individual variability. Time-varying body weight and baseline albumin concentration were statistically significant predictors of PK; CL and VC were predicted to increase with increasing body weight, while CL was predicted to decrease with increasing baseline albumin concentration. However, the magnitude of covariate effects is not predicted to meaningfully alter the disposition of sotatercept. Altogether, the PopPK modeling results demonstrate favorable PK characteristics (low to moderate variability and typical bioavailability), supporting sotatercept as a SC biological agent for the treatment of patients with PAH.

AMPK signaling pathway regulated the expression of the ApoA1 gene via the transcription factor Egr1 during G. parasuis stimulation.

Glaesserella parasuis (G. parasuis) is the causative agent of porcine Glässer's disease, resulting in high mortality rates in pigs due to excessive inflammation-induced tissue damage. Previous studies investigating the protective effects of G. parasuis vaccination indicated a possible role of ApoA1 in reflecting disease progression following G. parasuis infection. However, the mechanisms of ApoA1 expression and its role in these infections are not well understood. In this investigation, newborn porcine tracheal (NPTr) epithelial cells infected with G. parasuis were used to elucidate the molecular mechanism and role of ApoA1. The study revealed that the AMPK pathway activation inhibited ApoA1 expression in NPTr cells infected with G. parasuis for the first time. Furthermore, Egr1 was identified as a core transcription factor regulating ApoA1 expression using a CRISPR/Cas9-based system. Importantly, it was discovered that APOA1 protein significantly reduced apoptosis, pyroptosis, necroptosis, and inflammatory factors induced by G. parasuis in vivo. These findings not only enhance our understanding of ApoA1 in response to bacterial infections but also highlight its potential in mitigating tissue damage caused by G. parasuis infection.

Clinical characteristics and prognosis of SARS-CoV-2 infection in lung transplant recipients.

Objective: This study aimed to investigate the clinical manifestations and prognosis of lung transplant (LTx) recipients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease (COVID-19) pandemic. Methods: The research participants were LTx recipients who underwent surgery and were regularly followed up at our center. From 1 December 2022 to 28 February 2023, during the COVID-19 pandemic in China, research participants were interviewed either online or in person. SARS-CoV-2 nucleic acid or self-tested antigens were detected according to accessibility. Diagnosis and treatment were performed according to the Diagnosis and Treatment Plan for COVID-19 (10th edition) issued by the National Health Commission of the People's Republic of China. Hospitalized patients underwent chest imaging examinations, routine blood tests, biomarkers for infection and inflammation, and biochemical tests, all of which were taken and recorded. Data were analyzed to describe the features of COVID-19 in LTx recipients. Results: In total, 52 patients were enrolled in this study, comprising 48 men and 4 women, with a mean age of 51.71 ± 11.67 years. By 1 December 2022, the mean survival period was 33.87 ± 25.97 months, of which 84.61% of the patients (44/52) had a survival period longer than 12 months. The SARS-CoV-2 infection rate in these LTx recipients was 82.69% (43/52), with 3.85% (2/52) of the infected recipients being asymptomatic, 50.00% (26/52) of the infected recipients experiencing mild COVID-19, 11.54% (6/52) having moderate COVID-19, and 17.31% (9/52) having severe or critical COVID-19. The mortality rate among severe and critical patients was 66.67% (6/9). Conclusion: LTx recipients in this cohort exhibited a notable susceptibility to SARS-CoV-2, with 82.69% of individuals diagnosed with COVID-19. Moreover, the mortality rate among critically ill patients was high.

Evaluation of Left Ventricular Flow Kinetic Energy by Four-Dimensional Blood Flow MRI in Nondialysis Chronic Kidney Disease Patients.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased, and early cardiovascular disease risk. Changes in hemodynamics within the left ventricle (LV) respond to cardiac remodeling. The LV hemodynamics in nondialysis CKD patients are not clearly understood. PURPOSE: To use four-dimensional blood flow MRI (4D flow MRI) to explore changes in LV kinetic energy (KE) and the relationship between LV KE and LV remodeling in CKD patients. STUDY TYPE: Retrospective. POPULATION: 98 predialysis CKD patients (Stage 3: n = 21, stage 4: n = 21, and stage 5: n = 56) and 16 age- and sex-matched healthy controls. FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession (SSFP) cine sequence, 4D flow MRI with a fast field echo sequence, T1 mapping with a modified Look-Locker SSFP sequence, and T2 mapping with a gradient recalled and spin echo sequence. ASSESSMENT: Demographic characteristics (age, sex, height, weight, blood pressure, heart rate, aortic regurgitation, and mitral regurgitation) and laboratory data (eGFR, Creatinine, hemoglobin, ferritin, transferrin saturation, potassium, and carbon dioxide bonding capacity) were extracted from patient records. Myocardial T1, T2, LV ejection fraction, end diastolic volume (EDV), end systolic volume, LV flow components (direct flow, delayed ejection, retained inflow, and residual volume) and KE parameters (peak systolic, systolic, diastolic, peak E-wave, peak A-wave, E/A ratio, and global) were assessed. The KE parameters were normalized to EDV (KEiEDV). Parameters were compared between disease stage in CKD patients, and between CKD patients and healthy controls. STATISTICAL TESTS: Differences in clinical and imaging parameters between groups were compared using one-way ANOVA, Kruskal Walls and Mann-Whitney U tests, chi-square test, and Fisher's exact test. Pearson or Spearman's correlation coefficients and multiple linear regression analysis were used to compare the correlation between LV KE and other clinical and functional parameters. A P-value of <0.05 was considered significant. RESULTS: Compared with healthy controls, peak systolic (24.76 ± 5.40 µJ/mL vs. 31.86 ± 13.18 µJ/mL), systolic (11.62 ± 2.29 µJ/mL vs. 15.27 ± 5.10 µJ/mL), diastolic (7.95 ± 1.92 µJ/mL vs. 13.33 ± 5.15 µJ/mL), peak A-wave (15.95 ± 4.86 µJ/mL vs. 31.98 ± 14.51 µJ/mL), and global KEiEDV (9.40 ± 1.64 µJ/mL vs. 14.02 ± 4.14 µJ/mL) were significantly increased and the KEiEDV E/A ratio (1.16 ± 0.67 vs. 0.69 ± 0.53) was significantly decreased in CKD patients. As the CKD stage progressed, both diastolic KEiEDV (10.45 ± 4.30 µJ/mL vs. 12.28 ± 4.85 µJ/mL vs. 14.80 ± 5.06 µJ/mL) and peak E-wave KEiEDV (15.30 ± 7.06 µJ/mL vs. 14.69 ± 8.20 µJ/mL vs. 19.33 ± 8.29 µJ/mL) increased significantly. In multiple regression analysis, global KEiEDV (ß* = 0.505; ß* = 0.328), and proportion of direct flow (ß* = -0.376; ß* = -0.410) demonstrated an independent association with T1 and T2 times. DATA CONCLUSION: 4D flow MRI-derived LV KE parameters show altered LV adaptations in CKD patients and correlate independently with T1 and T2 mapping that may represent myocardial fibrosis and edema. TECHNICAL EFFICACY: Stage 3.

VHL mutation drives human clear cell renal cell carcinoma progression through PI3K/AKT-dependent cholesteryl ester accumulation.

BACKGROUND: Cholesteryl ester (CE) accumulation in intracellular lipid droplets (LDs) is an essential signature of clear cell renal cell carcinoma (ccRCC), but its molecular mechanism and pathological significance remain elusive. METHODS: Enabled by the label-free Raman spectromicroscopy, which integrated stimulated Raman scattering microscopy with confocal Raman spectroscopy on the same platform, we quantitatively analyzed LD distribution and composition at the single cell level in intact ccRCC cell and tissue specimens in situ without any processing or exogenous labeling. Since we found that commonly used ccRCC cell lines actually did not show the CE-rich signature, primary cancer cells were isolated from human tissues to retain the lipid signature of ccRCC with CE level as high as the original tissue, which offers a preferable cell model for the study of cholesterol metabolism in ccRCC. Moreover, we established a patient-derived xenograft (PDX) mouse model that retained the CE-rich phenotype of human ccRCC. FINDINGS: Surprisingly, our results revealed that CE accumulation was induced by tumor suppressor VHL mutation, the most common mutation of ccRCC. Moreover, VHL mutation was found to promote CE accumulation by upregulating HIFα and subsequent PI3K/AKT/mTOR/SREBPs pathway. Inspiringly, inhibition of cholesterol esterification remarkably suppressed ccRCC aggressiveness in vitro and in vivo with negligible toxicity, through the reduced membrane cholesterol-mediated downregulations of integrin and MAPK signaling pathways. INTERPRETATION: Collectively, our study improves current understanding of the role of CE accumulation in ccRCC and opens up new opportunities for treatment. FUNDING: This work was supported by National Natural Science Foundation of China (No. U23B2046 and No. 62027824), National Key R&D Program of China (No. 2023YFC2415500), Fundamental Research Funds for the Central Universities (No. YWF-22-L-547), PKU-Baidu Fund (No. 2020BD033), Peking University First Hospital Scientific and Technological Achievement Transformation Incubation Guidance Fund (No. 2022CX02), and Beijing Municipal Health Commission (No. 2020-2Z-40713).

Deficient gait function despite effect index of the Western Ontario and McMaster university osteoarthritis index score considered cured one year after bilateral total knee arthroplasty.

BACKGROUND: To clarify the value of gait analysis and its consistency with traditional scoring scales for the evaluation of knee joint function after total knee arthroplasty (TKA). METHODS: This study included 25 patients with knee osteoarthritis (KOA) who underwent bilateral TKA, and 25 conditionally matched healthy individuals, categorised into the experimental and control groups, respectively. Patients in the experimental group underwent gait analysis and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) evaluation before and 1 year after TKA. Weight-bearing balance and walking stability were assessed using discrete trends of relevant gait indicators. Pearson's correlation analysis was performed on the gait and WOMAC score data of the experimental group before and after TKA. RESULTS: One year after TKA, patients' gait indices (except gait cycle) were significantly better than before surgery, but significantly worse than that of the control group (P < 0.01). The shape of patients' plantar pressure curves did not return to normal. Additionally, the discrete trend of related gait indicators reflecting weight-bearing balance and walking stability were smaller than before TKA, but still greater than that of the control group. The WOMAC scores of patients 1 year after TKA were significantly lower than those before TKA (P < 0.001), and the efficacy index was > 80%. The WOMAC scores and gait analysis results were significantly correlated before TKA (P < 0.05). CONCLUSIONS: Gait analysis should be used in conjunction with scoring scales to assess joint functions.

Frontiers in all electrical control of magnetization by spin orbit torque.

Achieving all electrical control of magnetism without assistance of an external magnetic field has been highly pursued for spintronic applications. In recent years, the manipulation of magnetic states through spin-orbit torque (SOT) has emerged as a promising avenue for realizing energy-efficient spintronic memory and logic devices. Here, we provide a review of the rapidly evolving research frontiers in all electrical control of magnetization by SOT. The first part introduces the SOT mechanisms and SOT devices with different configurations. In the second part, the developments in all electrical SOT control of magnetization enabled by spin current engineering are introduced, which include the approaches of lateral symmetry breaking, crystalline structure engineering of spin source material, antiferromagnetic order and interface-generated spin current. The third part introduces all electrical SOT switching enabled by magnetization engineering of the ferromagnet, such as the interface/interlayer exchange coupling and tuning of anisotropy or magnetization. At last, we provide a summary and future perspectives for all electrical control of magnetization by SOT.

YAP-mediated GPER signaling impedes proliferation and survival of prostate epithelium in benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) occurs when there is an imbalance between the proliferation and death of prostate cells, which is regulated tightly by estrogen signaling. However, the role of G protein-coupled estrogen receptor (GPER) in prostate cell survival remains ambiguous. In this study, we observed that prostates with epithelial hyperplasia showed increased yes-associated protein 1 (YAP) expression and decreased levels of estrogen and GPER. Blocking YAP through genetic or drug interventions led to reduced proliferation and increased apoptosis in the prostate epithelial cells. Interestingly, GPER agonists produced similar effects. GPER activation enhanced the phosphorylation and degradation of YAP, which was crucial for suppressing cell proliferation and survival. The Gαs/cAMP/PKA/LATS pathway, downstream of GPER, transmitted signals that facilitated YAP inhibition. This study investigated the interaction between GPER and YAP in the prostate epithelial cells and its contribution to BPH development. It lays the groundwork for future research on developing BPH treatments.

Clinical efficacy of acupuncture in treating postoperative gastrointestinal dysfunction of colorectal cancer, a systematic review and Meta analysis. / é’ˆåˆºæ²»ç–—ç»“ç›´è‚ ç™Œæœ¯åŽèƒƒè‚ åŠŸèƒ½éšœç¢ç–—æ•ˆçš„ 系统评价和Meta分析.

OBJECTIVES: To evaluate the efficacy of acupuncture in the treatment of postoperative gastrointestinal dysfunction(POGD) of colorectal cancer. METHODS: Randomized controlled trials of acupuncture in the treatment of POGD were retrieved from 7 databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP Chinese Journal Service Platform, WanFang Data Knowledge Service Platform, and China Biology Medicine disc. The search period ranged from the inception of the databases to November 10th, 2022. The quality of the included literature was assessed using the Cochrane bias risk assessment tool and the modified Jadad scale. Meta analysis was conducted using RevMan 5.4. Regression analysis and bias risk analysis were performed using Stata 16.0. Trial sequential analysis was conducted using TSA 0.9 software. RESULTS: A total of 27 randomized controlled trials involving 2 629 patients were included. Intervention measures included manual acupuncture, electroacupuncture, transcutaneous acupoint electrical stimulation, warm acupuncture, and thumb-tack needle. The results showed that acupuncture treatment significantly reduced time to tolerance of liquid diet after surgery (MD=-13.70, 95% CI=ï¼»-17.94, -9.46ï¼½, P<0.000 01), time to first defecation (MD=-18.20, 95% CI=ï¼»-22.62, -13.78ï¼½, P<0.000 01), time to first flatus (MD=-16.31, 95% CI=ï¼»-20.32, -12.31ï¼½, P<0.000 01), time to bowel sounds recovery (MD=-11.91, 95% CI=ï¼»-14.01, -9.81ï¼½, P<0.000 01), and length of hospital stay (MD=-1.49, 95% CI=ï¼»-2.27, -0.70ï¼½, P=0.000 2). Regression analysis indicated that cancer type, study quality and number of acupuncture were the main sources of heterogeneity. Bias analysis suggested potential publication bias risks. Trial sequential analysis indicated that the required number of cases had been met and the conclusion was reliable. CONCLUSIONS: Acupuncture is an effective intervention for promoting gastrointestinal recovery in patients undergoing colorectal cancer surgery. Further large-sample and well-designed clinical trials are still needed to compare different acupuncture techniques.

White matter microstructure alterations in type 2 diabetes mellitus and its correlation with cerebral small vessel disease and cognitive performance.

Microstructural abnormalities of white matter fiber tracts are considered as one of the etiology of diabetes-induced neurological disorders. We explored the cerebral white matter microstructure alteration accurately, and to analyze its correlation between cerebral small vessel disease (CSVD) burden and cognitive performance in type 2 diabetes mellitus (T2DM). The clinical-laboratory data, cognitive scores [including mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), California verbal learning test (CVLT), and symbol digit modalities test (SDMT)], CSVD burden scores of the T2DM group (n = 34) and healthy control (HC) group (n = 21) were collected prospectively. Automatic fiber quantification (AFQ) was applied to generate bundle profiles along primary white matter fiber tracts. Diffusion tensor images (DTI) metrics and 100 nodes of white matter fiber tracts between groups were compared. Multiple regression analysis was used to analyze the relationship between DTI metrics and cognitive scores and CSVD burden scores. For fiber-wise and node-wise, DTI metrics in some commissural and association fibers were increased in T2DM. Some white matter fiber tracts DTI metrics were independent predictors of cognitive scores and CSVD burden scores. White matter fiber tracts damage in patients with T2DM may be characterized in specific location, especially commissural and association fibers. Aberrational specific white matter fiber tracts are associated with visuospatial function and CSVD burden.

Improving the capturing ability of swirl-based microfluidic chip by introducing baffle wall.

Microfluidics technology is promising in developing microparticle manipulation technology due to its nondestructive control and notable adaptability. The manipulation of microparticle based on swirling stagnation point is one of the feasible microfluidics biotechnologies. Aiming to improve the regulation and control of microparticle, baffle wall is introduced into the 2-microchannel flow field. The theory of wall attachment jet is employed to elucidate the effect of baffle wall. Subsequently, finite volume method simulation is conducted by modeling the swirling flow region (SFR), and the swirling strength is calculated to characterize the SFR's particle-capturing ability. Experimental validation of the modeling and simulation methods is performed using a printed microfluidic chip, which has demonstrated exceptional reliability. Simulation results show that the baffle wall makes considerable influence on the SFR. Strikingly, a global range adjustment of stagnation point is realized when the baffle wall is configured with a convex shape, which has remarkably outperformed our previous work, where the stagnation point could only move within half range of the field. This work significantly contributes to advanced flow field structure and provides insight into better regulation of stagnation point as well as microparticles. These findings have potential applications in the analysis of the effect of bio/chemical substances on single cell.

Parameterization of optical properties for liquid cloud droplets containing black carbon based on neural network.

This paper introduces a novel back propagation (BP) neural network method to accurately characterize optical properties of liquid cloud droplets, including black carbon. The model establishes relationships between black carbon volume fraction, wavelength, cloud effective radius, and optical properties. Evaluated on a test set, the value of the root mean square error (RMSE) of the asymmetry factor, extinction coefficient, single-scattering albedo, and the first 4 moments of the Legendre expansion of the phase function are less than 0.003, with the maximum mean relative error (MRE) reaching 0.2%, which are all better than the traditional method that only uses polynomials to fit the relationship between the effective radius and optical properties. Notably, the BP neural network significantly compresses the optical property database size by 37,800 times. Radiative transfer simulations indicate that mixing black carbon particles in water clouds reduces the top-of-atmosphere (TOA) reflectance and heats the atmosphere. However, if the volume fraction of black carbon is less than 10-6, the black carbon mixed in the water cloud has a tiny effect on the simulated TOA reflectance.

Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis.

Purpose: This study aimed to explore the clinical efficacy of transarterial chemoembolization (TACE) in combination with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (triple therapy) compared to TACE alone (monotherapy) for advanced hepatocellular carcinoma (HCC). Material and Methods: Data of consecutive advanced HCC patients receiving triple therapy or monotherapy at our center between January 2019 and December 2022 were collected and retrospectively analyzed. Propensity score matching (PSM) and subgroup analyses were performed to reduce the bias between the two groups. The primary outcomes of the study were the overall survival (OS) and progression-free survival (PFS). The secondary outcomes were the objective response rate (ORR) and disease control rate (DCR). Results: A total of 104 patients were enrolled in this study: 41 in the triple therapy group and 63 in the monotherapy group. After PSM analysis, each group included 37 patients. The median OS and PFS were significantly longer in the triple therapy group than in the monotherapy group in the whole cohort (median OS, 18.8 vs 11.7 months, P = 0.022; median PFS, 10.5 vs 6.4 months, P = 0.012) and after PSM (median OS, 19.6 vs 12.5 months, P = 0.030; median PFS, 10.5 vs 6.7 months, P = 0.008). Furthermore, the treatment modality was an independent prognostic factor for OS (hazard ratio [HR]: 0.449, 95% confidence interval [CI]: 0.240-0.840, P = 0.012) and PFS (HR: 0.406, 95% CI: 0.231-0.713, P = 0.002) according to the multivariate cox regression analysis. A greater ORR was also observed in the triple therapy group (ORR: 56.7% vs 32.4%, P = 0.035). No significant difference was observed in DCR between the two groups (83.7% vs 72.9%, P = 0.259). Conclusion: The triple therapy was superior to the monotherapy regarding OS, PFS, and ORR of advanced HCC patients.

Residue dissipation dynamics and dietary risk assessment of emamectin benzoate, chlorantraniliprole, chlorfenapyr, and lufenuron in cabbage.

Emamectin benzoate (EB), chlorantraniliprole (CTP), chlorfenapyr (CFP), and lufenuron (LFR) are widely used to control Spodoptera exigua on cabbage. This study is aimed at establishing a universal, sensitive, accurate, and efficient method for the determination of these pesticide residues in cabbage using QuEChERS pretreatment combined with ultra-performance liquid chromatography or gas chromatography-tandem mass spectrometry (UPLC‒MS/MS or GC‒MS/MS). The recoveries of these pesticides (containing metabolites) in cabbage detected by the optimized method ranged between 80.9% and 99.9%, with relative standard deviations (RSDs) of 0.164-12.5%. The limit of quantification (LOQ) of the four pesticides was determined to be 0.01 mg/kg. The standard curve, accuracy, precision, and LOQ of the analysis method all met the requirements of pesticide residue detection. The optimized method was used to detect the dissipation dynamics and terminal residues in 12 regions. The dissipation half-lives of CTP, CFP, and LFR were 3.35-7.01 d, 2.29-4.75 d, and 3.24-6.80 d, respectively. The terminal residues of all these pesticides were below the maximum residue limits (MRLs). The dietary risk assessment indicated that the dietary risk probabilities for EB, CTP, CFP, and LFR were all less than 1 and were within the acceptable range. This study provides a comprehensive assessment of the residues and dietary risks of EB, CTP, CFP, and LFR for the scientific use of pesticides.

Particle sorting method based on swirl induction.

Fluid-based methods for particle sorting demonstrate increasing appeal in many areas of biosciences due to their biocompatibility and cost-effectiveness. Herein, we construct a microfluidic sorting system based on a swirl microchip. The impact of microchannel velocity on the swirl stagnation point as well as particle movement is analyzed through simulation and experiment. Moreover, the quantitative mapping relationship between flow velocity and particle position distribution is established. With this foundation established, a particle sorting method based on swirl induction is proposed. Initially, the particle is captured by a swirl. Then, the Sorting Region into which the particle aims to enter is determined according to the sorting condition and particle characteristic. Subsequently, the velocities of the microchannels are adjusted to control the swirl, which will induce the particle to enter its corresponding Induction Region. Thereafter, the velocities are adjusted again to change the fluid field and drive the particle into a predetermined Sorting Region, hence the sorting is accomplished. We have extensively conducted experiments taking particle size or color as a sorting condition. An outstanding sorting success rate of 98.75% is achieved when dealing with particles within the size range of tens to hundreds of micrometers in radius, which certifies the effectiveness of the proposed sorting method. Compared to the existing sorting techniques, the proposed method offers greater flexibility. The adjustment of sorting conditions or particle parameters no longer requires complex chip redesign, because such sorting tasks can be successfully realized through simple microchannel velocities control.

Inhibiting CBP Decreases AR Expression and Inhibits Proliferation in Benign Prostate Epithelial Cells.

(1) Background: CREB-binding protein (CBP) is a key transcriptional coactivator of androgen receptors (AR). We conducted this study to investigate the effects of CBP on AR expression and proliferation in benign prostatic hyperplasia (BPH) prostate epithelial cells. (2) Methods: By analyzing a published data set, we found that CBP was closely related to the gene expression of AR in prostate cells. We enrolled 20 BPH patients who underwent transurethral resection of the prostate (TURP) in Peking University First Hospital in 2022, and analyzed the expressions of CBP and AR in BPH prostate tissues. Then, we used ICG-001 and shRNA to inhibit CBP in prostate epithelial cells (BPH-1 cells and RWPE-1 cells), and conducted immunofluorescence, cell viability assay, flow cytometry analysis, and Western blot to analyze the effects of CBP on AR expression and proliferation in prostate epithelial cells. We also studied the interaction between CBP and AR through a co-immunoprecipitation assay. (3) Results: CBP is consistent with AR in expression intensity in prostate tissues. Inhibiting CBP decreases AR expression, and induces proliferation inhibition, apoptosis, and cell cycle arrest in BPH prostate epithelial cells. The co-immunoprecipitation assay showed that CBP binds with AR to form transcription complexes in prostate epithelial cells. (4) Conclusions: Inhibiting CBP decreases AR expression and inhibits proliferation in benign prostate epithelial cells. CBP may be a potential target to affect AR expression and the proliferation of prostate epithelial cells in BPH.

Epidemiology of asthma exacerbation in children before and after the COVID-19 pandemic: a retrospective study in Chengdu, China.

PURPOSE: To examine the numbers and characteristics of children affected by asthma exacerbation in Chengdu, China, before and after the COVID-19 pandemic to inform efforts to manage childhood asthma in the post epidemic era. METHODS: Data were retrospectively collected from children admitted for asthma exacerbation to Chengdu Women and Children's Central Hospital between January 2017 and December 2022. Rates of hospitalization, ages of the affected children, comorbidities and infections, and relationships between hospitalization and seasonal or environmental factors were examined before and after the epidemic. RESULTS: Fewer children were hospitalized for asthma exacerbation, yet more hospitalized children had severe exacerbation after the epidemic than before. Rates of hospitalization varied considerably with time of year, and the timing of peak hospitalizations differed before and after the epidemic. Only before the epidemic, rates of hospitalization for asthma exacerbation were positively correlated with humidity. Infants made up a smaller proportion of hospitalized children after the epidemic than before, with preschool children accounting for most hospitalizations after the epidemic. The proportion of children hospitalized for asthma exacerbation who also had pneumonia was significantly smaller after the epidemic than before. Conversely, the proportion of children hospitalized for asthma exacerbation who also had allergic diseases was significantly greater after the epidemic than before. CONCLUSION: The epidemiology of asthma exacerbation in children changed after the epidemic. Future efforts to manage the condition in the paediatric population should focus on severe asthma exacerbation, prevention and management of allergic diseases, and the influence of meteorological and environmental factors.