Background In 2021, chronic obstructive pulmonary disease (COPD) emerged as the forth leading cause of death in the world. However, the impact of air pollutants on COPD is still inconsistent across current studies. Objective To analyze the relationship between ambient sulfur dioxide (SO₂) exposure and hospital admissions for COPD in Lanzhou, and to examine the modified effects of SO₂ across different genders, age groups, and seasons. Methods A total of 20718 hospital admission records for COPD were collected from Lanzhou between 2016 and 2020, alongside synchronized data on SO₂ concentration and meteorological variables. A generalized additive model integrated with a distributed lag nonlinear model was used to assess the relationship and the lag effects between SO₂ exposure and COPD admissions. Potential confounders, including meteorological factors, day-of-the-week effect, and holidays, were controlled for, with a maximum lag period set at 7 d. Two-pollutant models and sensitivity analyses were conducted to ensure robustness. Results are expressed as relative risks (RR) with 95% confidence intervals (95%CI). Results During the study period, the average daily number of COPD admissions was 11.34±7.03. The average mass concentration of SO₂ was (23.72±12.35) μg·m⁻³. SO₂ exposure was positively correlated with COPD admissions; specifically, each 10 μg·m⁻³ increase in SO₂ concentration was associated with an RR of 1.440 (95%CI: 1.317, 1.573). Stratified analyses found that at a cumulative lag of 7 d, the RRs were higher among females, individuals aged ≥65 years, and during the cold season. Conversely, no significant increase in COPD admission risk related to SO₂ was observed during the warm season. For every 10 μg·m⁻³ increase in SO₂ concentration, the RR was 1.483 (95%CI: 1.311, 1.678) for females, 1.441 (95%CI: 1.311, 1.583) for those aged > 65 years， and 1.595 (95%CI: 1.313, 1.937) during the cold season. Conclusion Short-term exposure to ambient SO₂ exposure in Lanzhou is associated with an increased risk of COPD admission. The association is more pronounced among females, the elderly (aged> 65 years) and during the cold season.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Major depressive disorder in adolescents is a serious psychiatric condition characterized by profound impairment in psychosocial functioning. Its primary symptoms include low mood, irritability, and anhedonia. Although pharmacological treatments and psychotherapy are currently recommended as first-line treatments, their effectiveness is limited, and pharmacological treatments may carry the risk of increased suicidal ideation. Therefore, exploring new, effective, and safe treatment options is an urgent priority. In recent years, intermittent theta burst stimulation (iTBS), a novel form of transcranial magnetic stimulation, has shown promising results in treating treatment-resistant depression in adults, drawing growing interest in its potential use in adolescents. iTBS modulates neural activity through magnetic stimulation of the cerebral cortex and has been shown to alleviate depressive symptoms, particularly when targeting the left dorsolateral prefrontal cortex (DLPFC). Given the high neuroplasticity of the adolescent brain during this critical developmental stage, adolescents may exhibit heightened sensitivity to iTBS, resulting in more enduring neuroregulatory effects. Research highlights the importance of precise targeting and individualized adjustment of stimulation intensity for optimal therapeutic outcomes. Additionally, accelerated iTBS (aiTBS) protocols have demonstrated faster clinical effects in treating acute or severe depression in adolescents, improving treatment adherence and partially mitigating suicidal tendencies. This review summarizes recent progress in the application of iTBS in adolescent depression, with a focus on its mechanisms, treatment parameters, and related research. The goal is to provide theoretical support and practical guidance for the clinical application of iTBS in adolescent depression care.

Objective To investigate the impact of a high-salt diet on blood pressure level and the prevalence of hypertension in individuals with varying salt-sensitive phenotypes.Methods In 2004,339 participants from northern China were subjected to a chronic salt loading diet intervention study,and their salt-sensitive phenotypes were determined based on the study results.The participants were divided into salt-sensitive and salt-insensitive groups.In 2018,we randomly selected 152 participants for follow-up from the original cohort,and assessed their salt intake through 24-hour urine sodium level.The participants were divided into different groups based on various criteria to comprehensively investigate the effects of high-salt diet on blood pressure level and hypertension prevalence in individuals with different salt-sensitive phenotypes.Results Among the 339 subjects,154 were identified as salt-sensitive,accounting for 45.4％,while 185 were classified as salt-insensitive,accounting for 54.4％.The average arterial pressure response to high-salt intake after switching from low-salt intake in salt-sensitive individuals was 8.31(7.60,9.02),while the average arterial pressure response in salt-insensitive individuals was-1.09(-1.49,-0.68).A follow-up visit was conducted in 152 participants,It was found that the systolic blood pressure and diastolic blood pressure[divided according to the average daily salt intake(＞11 g).SBP:140.8 mmHg vs.132.9 mmHg,DBP:85.9 mmHg vs.81.6 mmHg,P＜0.05;divided according to the quartile of daily salt intake,SBP:140.8 mmHg vs.132.9 mmHg,DBP:85.9 mmHg vs.81.6 mmHg,P＜0.05]were significantly higher in the high-salt diet group than in the normal salt diet group in salt-sensitive individuals,but there was no significant difference in salt-insensitive individuals(P＞0.05).Additionally,the high-salt diet could significantly increase the incidence of hypertension among salt-sensitive individuals[divided according to the average daily salt intake(＞11 g):58.8％vs.32.8％,P＜0.05;divided according to the quartile of daily salt intake:58.8％vs.32.8％,P＜0.05],but had no effect on salt-insensitive individuals(P＞0.05).Conclusion A high-salt diet can increase systolic blood pressure and diastolic blood pressure in salt-sensitive individuals,and significantly increase the long-term prevalence of hypertension in salt-sensitive individuals,but not in salt-insensitive individuals.Therefore,the salt-sensitive phenotype plays a crucial role in the relationship between salt intake and salt-sensitive hypertension.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Purpose To investigate the correlation between molecular typing of urothelial carcinoma(UC)and its clinicopathologic features and prognosis,in order to explore the prognostic markers and therapeutic targets for UC.Methods 115 patients with UC were retrospectively analyzed.Immunohistochemical markers GATA-3,CK20,CK5/6 and CD44 were used for molecular typing of UC(luminal-like type,basal-like type and null).Correlations between molecular typing and clinicopathological features were analyzed using the Chi-square test and Fisher precise test.Sur-vival analysis was performed using the Kaplan-Meier test and Log-rank test.Results The expression of GATA-3 and CK20 was negatively correlated with the clinical stage of UC,while the expression of CD44 was positively correlated with the clinical stage of UC(both P＜0.05).CK20 was a marker of good prognosis(P=0.03).The proportion of clinically advanced UC with basal-like type was significantly higher than that of luminal-like type(78.4％vs 53.4％,P=0.033).Among the histologic variants,UC with neuroendocrine differentiation(100％),sarcomatoid carcinoma(80.0％)and squamous differentiation(77.8％)were basal-like type.All plasmacytoid and lymphoepithelioma-like types,as well as 81.8％of micropapillary UC.Among the null phenotypes,the differential variant predominated(66.7％).Compared with the luminal-like type,although the prognosis of basal-like UC was worse,there was no sta-tistically significant difference(P＞0.05).Conclusion Patients with CK20-expressing UC had a significantly better prognosis.The main histologic variants types of basal-like type and coelomofacial type are different.Molecular typing of UC using immunohistochemical markers is suggestive of clinical staging and prognosis of patients.

Purpose To investigate the relationship between the expression of POSTN and NECTIN-3 in urothelial carcinoma(UC)and its clinicopathologic features and prognosis.Methods Clinical data of 115 UC patients were col-lected.EnVision two-step method was used for immunohistochemical analysis to determine the expression of POSTN and NECTIN-3 in UC and their correlation with clinicopathological features and prognosis.Transcriptomic data from TCGA database were used to analyze the correlation between the expression of POSTN and NECTIN-3 in bladder cancer and the pathological stage and prognosis of bladder cancer.qPCR and Western blot were used to detect the expression levels of POSTN and NECTIN-3 in tumor tissues and adjacent tissues of patients.Results TCGA database analysis showed that the expression level of NECTIN-3 in urinary bladder urothelial carcinoma(UBUC)was significantly lower than that in paracancer tissues,and POSTN expression was positively correlated with pathological stage.Prognostic a-nalysis showed that POSTN expression was negatively correlated with the overall survival of UBUC(P＞0.05),and NECTIN-3 expression was negatively correlated with disease-free survival of UBUC(P＞0.05).The experimental re-suits showed that patients with positive POSTN expression were more prone to perineural invasion[25 cases(86.2％)vs 4 cases(13.8％),P=0.019],vascular invasion[36 cases(83.7％)vs 7 cases(16.3％),P=0.007],and lymph node metastasis[24 cases(88.9％)vs 3 cases(11.1％),P=0.033].Additionally,the positive expression rate of POSTN in UBUC was significantly higher than that in upper tract urothelial carcinoma(UTUC)(75.0％vs 54.3％,P=0.028).Higher expression levels of POSTN and NECTIN-3 were associated with shorter overall survival,but the difference was not statistically significant(P＞0.05).Conclusion There is no significant correlation between NECTIN-3 and the clinicopathological features and prognosis of urothelial carcinoma,while the expression of POSTN is correlated with the invasive clinicopathological features of UC,which has certain suggestive significance for clinical stage and prognosis.

Objective To explore the impact of different moving patterns during the dip-coating process on thickness distributions of polymer heart valves.Methods Based on the volume of fluid(VOF)multiphase flow model,the Eulerian wall-film(EWF)model,and dynamic mesh technology,the dip-coating manufacturing process of polymer heart valves were numerically simulated.The effects of vertical,horizontal,and circular moving patterns on flow characteristics of the surface impregnation liquid and liquid film distributions under self-rotation conditions of the models were mainly studied.Subsequently,seven identical test points were set on each valve leaflet to collect thickness data,and the coefficient of variation(CV)was calculated to evaluate the uniformity of the liquid film thickness.Given that the vertical and horizontal patterns had fewer moving planes,limiting the optimization space,the circular pattern(45°)with richer moving planes was selected as the basis for optimization,and comparative analysis of numerical simulation was conducted.Results In the vertical pattern,the peak CV was 0.461 3;in the horizontal pattern,the CV was 0.060 8;and in the circular pattern,the CV at 30°,45° and 60° were 0.457 5,0.272 8,and 0.255 6,respectively.After optimization,the CV for the circular pattern(45°)decreased to 0.052 5,representing an 80.7％reduction compared to the pre-optimization value.Conclusions The moving patterns significantly affect the uniformity of dip-coating thickness distributions.The horizontal pattern demonstrates the best uniformity,while the vertical pattern shows the poorest uniformity.The CV for the circular pattern decreases as the angle increases,with its uniformity between that of the vertical and horizontal patterns.Optimization of moving pattern parameters based on simulation results has improved the uniformity of thickness distributions.

Objective:To observe the therapeutic effect of combining low-frequency pulsed electrical stimulation with Beckman oral muscle exercise training in relieving drooling among persons with Parkinson′s disease (PD).Methods:A random number table was used to divide 120 PD patients with drooling into a mouth muscle training group, an electrical stimulation group, and an observation group, with 40 patients in each group. In addition to routine medication, the oral muscle training group was given Beckman oral muscle exercise training, the electrical stimulation group underwent low-frequency pulsed electrical stimulation treatment, while the observation group was provided with both. Before and after 4 weeks of treatment, the severity of salivation, the frequency of repeated empty swallowing, oral motor function, saliva secretion, and life quality of the three groups were evaluated using the Saliva Rating Scale (DRS), the Repeated Saliva Swallowing Test (RSST), oral motor function grading, the Parkinson′s Disease Saliva Clinical Scale (SCS-PD), saliva weighing, and the PD Quality of Life Scale (PDQ-39).Results:After the treatment the average DRS, SCS-PD, saliva weighing and PDQ-39 results of the observation group were significantly better than those before treatment and better than the other 2 groups′ averages. That group′s average RSST and oral motor function scores had increased significantly compared to before treatment, and compared with the other 2 groups′ averages at the same time point.Conclusions:Combining low-frequency pulsed electrical stimulation with Beckman oral muscle exercise can improve oral motor function, swallowing, and the life quality of PD patients who drool. It is more effective than electrical stimulation or oral muscle exercise training alone. Such combination therapy is worthy of clinical promotion and application.