Objective:To evaluate the role of peptidylarginine deiminase 4 (PAD4)-mediated development of neutrophil extracellular traps (NETs) in lung ischemia-reperfusion injury (LIRI) in mice.Methods:Ninety-six clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=24 each) using a table of random numbers: sham operation group (group S), sham operation + PAD4 specific inhibitor GSK484 group (group S+ G), lung ischemia-reperfusion group (group L), and lung ischemia-reperfusion + GSK484 group (group L+ G). After anesthesia and mechanical ventilation, mice were subjected to left hilum occlusion for 1 h followed by 2 h of reperfusion to establish the LIRI model in L and L+ G groups. Mice underwent thoracotomy for 3 h without left hilum occlusion in S and S+ G groups. In S+ G and L+ G groups, GSK484 4 mg/kg was intraperitoneally injected once a day for 3 days before developing the model. At the end of reperfusion, blood samples were collected from the abdominal aorta for blood gas analysis to record arterial partial pressure of oxygen (PaO 2). Mice were then sacrificed to collect bronchoalveolar lavage fluid (BALF) and to obtain lung tissues. The concentrations of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) in BALF were measured using enzyme-linked immunosorbent assay. The wet/dry lung weight (W/D) ratio was calculated. The lung tissues were obtained for microscopic examination of pathological changes (with a light microscope) which were scored after hematoxylin-eosin staining and for determination of the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) (by colorimetric assay) and expression of PAD4, neutrophil elastase (NE), high-mobility group box 1 (HMGB1), and citrullinated histone 3 (Cit-H3) (by Western blot). Results:Compared with group S, lung injury scores and W/D ratios were significantly increased, PaO 2 was decreased, the concentrations of IL-1β, IL-6, TNF-α and MPO in BALF were increased, the content of SOD was decreased, the content of MDA was increased, and the expression of PAD4, NE, HMGB1 and Cit-H3 was up-regulated in L and L+ G groups ( P<0.05), and no significant changes were observed in the aforementioned parameters in group S+ G ( P>0.05). Compared with group L, lung injury scores and W/D ratios were significantly decreased, PaO 2 was increased, concentrations of IL-1β, IL-6, TNF-α, and MPO in BALF were decreased, the content of SOD was increased, the content of MDA was decreased, and the expression of PAD4, NE, HMGB1 and Cit-H3 was down-regulated in group L+ G ( P<0.05). Conclusions:Up-regulated PAD4 expression can promote the development of NETs and aggravate oxidative stress and inflammatory responses in lung tissues, thereby participating in LIRI in mice.

Objective:To reveal the differences in the transcriptome maps of brain tissues in mice subjected to Flash irradiation and conventional dose rate irradiation with electron beams and to explain the biological effect and mechanisms of Flash irradiation from multiple perspectives.Methods:Following the principle of grouping based on approximate body weights, 36 female C57BL/6J mice were divided into three groups, i. e., the control, conventional dose rate irradiation (CONV), and Flash irradiation (Flash) groups, with 12 mice in each group. Both the CONV and Flash groups received a single 15 Gy whole-brain irradiation with 9 MeV electron beams. At 3 d post-irradiation, the whole-brain tissue specimens were collected for hematoxylin-eosin (HE) staining to observe pathological changes. At 1, 3, and 10 weeks post-irradiation, the motion function, cognitive ability, depression level, and spatial memory capacity of the mice were assessed using ethology. At 1 and 10 weeks after behavioral experiments, brain tissue samples were collected and snap-frozen in liquid nitrogen for reference-based transcriptome sequencing. Accordingly, the differences in the transcriptome maps of radiation-induced brain injury between CONV and Flash groups were analyzed.Results:The HE staining-based pathological result revealed that compared to the CONV group, the Flash group exhibited reduced glial cell hyperplasia and inflammatory cell infiltration in brain tissues. Ethological research result at 1 week post-irradiation showed that the CONV group manifested a significantly decreased total traveled distance compared to the control and Flash groups ( t = 5.51, 2.38, P < 0.05) and a significantly increased immobility time compared to the control group ( t = 3.60, P < 0.05). Ethological research result at 3 weeks post-irradiation indicated that compared to the CONV group, the Flash group displayed significantly alleviated cognitive impairment ( t = 3.35, P < 0.05) and reduced depression levels ( t = 2.39, P < 0.05). Ethological research result at 10 weeks post-irradiation demonstrated that the CONV group showed the worst cognitive performance, significantly differing from the control group ( t = 4.53, P < 0.05). Transcriptome sequencing result revealed that besides immune-related pathways, the Flash group also exhibited multiple upregulated metabolic pathways and fibroblast growth factor (FGF)-related pathways compared to the CONV group. Conclusions:Compared to conventional dose rate irradiation, Flash irradiation can effectively alleviate radiation-induced brain injury in mice. This effect is associated with various metabolic pathways (including amino acid metabolism) and FGF-related pathways besides immune pathways.

Objective:To compare the burden of benign prostatic hyperplasia（BPH）between China and the United States from 1990 to 2021.Methods:The prevalence，incidence，years lived with disability（YLD），and their age-standardized rates for BPH in China and the United States from 1990 to 2021 were obtained from the Global Burden of Disease Study 2021（GBD 2021）. The average annual percentage change（AAPC）of the age-standardized incidence rate（ASIR）and the age-standardized YLD rate（ASYR）was calculated using Joinpoint regression analysis. In addition，the YLD burden of BPH，prostate cancer，kidney cancer，bladder cancer，and three other urological diseases were compared between the two countries.Results:From 1990 to 2021，the number of BPH cases in China increased from 1.460 4 million to 3.244 5 million，the number of prevalent cases rose from 9.940 5 million to 23.111 2 million，and YLDs grew from 0.2 million person-years to 0.460 2 million person-years，with AAPCs of 2.63%，2.78%，and 2.75%，respectively. In 2021，the numbers of incident cases，prevalent cases，and YLDs were 0.577 9 million，4.930 3 million，and 0.095 9 million person-years in the United States，and 13.787 6 million，112.502 million，and 2.235 7 million person-years globally. China’s ASIR decreased from 363.07/100 000 to 299.14/100 000（AAPC -0.60%），and ASYR from 57.33/100 000 to 45.84/100 000（AAPC -0.70%），both of which were higher than those in the United States but lower than the global level. Age-specific analyses showed declining incidence and YLD rates across all age groups in China，while certain age groups in the United States demonstrated increasing trends. From 1990 to 2021，the proportion of YLDs attributable to BPH among seven urological diseases in China rose from 61.4% to 69.2%. In 2021，YLDs due to prostate cancer accounted for the highest proportion among seven urinary system diseases in the United States，reaching 54.5%. Projections indicate that although ASIR and ASYR in China will decline from 2022 to 2040，the absolute numbers of incident cases and YLDs are projected to continue to rise，reaching 4.97 million and 0.78 million，respectively，by 2040.Conclusions:Between 1990 and 2021，the number of incidence cases，prevalence cases，and YLDs of BPH in China increased markedly，while ASIR and ASYR declined. The disease burden of BPH remains substantial，with a higher proportion of YLDs among urological diseases compared with the United States. By 2040，the number of BPH cases and YLDs in China is projected to further increase，underscoring the need for greater public health attention.

Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective To explore the expression of peripheral blood Nod-like receptor protein 3(NLRP3)inflammasomes,serum caveolin-1(Cav-1),and sphingosine 1-phosphate receptor 1(S1P1)in children with Kawasaki disease(KD),and to elucidate their associations with coronary artery lesion(CAL).Methods A total of 223 children diagnosed with KD were recruited from our hospital between March 2023 and December 2024 and served as the KD study group.These children were classified into the CAL group(n=71)and the non-CAL group(n=152)based on their CAL status.Additionally,223 healthy children who underwent physical examinations at our hospital were selected as the healthy control group.Clinical data,levels of routine laboratory test indices,peripheral blood NLRP3 inflammasomes,serum Cav-1,and S1P1 were compared among the groups.Risk factors for CAL in children with KD were analyzed,and the diagnostic value of peripheral blood NLRP3 inflammasomes,serum Cav-1,and S1P1 levels for CAL in children with KD was evaluated.Results The levels of NLRP3,caspase-1,ASC in peripheral blood and messenger ribonucleic acid(mRNA)of serum Cav-1 were significantly higher in the KD study group than in the healthy control group(P<0.05).Conversely,the serum level of S1P1 was significantly lower in the KD study group compared to the healthy control group(P<0.05).In the CAL group,the levels of peripheral blood white blood cell count(WBC),NLRP3,caspase-1,ASC mRNA,serum C-reactive protein(CRP),and Cav-1 were all higher than those in the non-CAL group(P<0.05),while the serum level of S1P1 was lower than that in the non-CAL group(P<0.05).The levels of NLRP3,caspase-1,ASC mRNA in peripheral blood,along with serum Cav-1 and S1P1,were identified as independent risk factors for CAL in children with KD(P<0.05).The results of receiver operating characteristic(ROC)analysis indicated that the combined test of the levels of NLRP3,caspase-1,ASC mRNA in peripheral blood,serum Cav-1,and S1P1 for diagnosing CAL in children with KD had an area under the curve(AUC)value of 0.926.This value was significantly higher than that of each individual index(0.844,0.785,0.821,0.843,0.833,P<0.05).Conclusions The levels of NLRP3 inflamma-tory vesicles in peripheral blood and serum Cav-1 were highly expressed in children with KD,whereas the serum S1P1 was poorly expressed.These indices may be involved in the development process of CAL in children with KD.Moreover,the combination of these indices is more beneficial for the diagnosis of CAL in children with KD.

Cochlear implantation is the most effective method to restore hearing in patients with severe and profound hearing impairment.There are individual differences in rehabilitation after cochlear implantation.In order to better understand the underlying factors of rehabilitation,machine learning has been gradually applied to the reha-bilitation prediction of cochlear implant patients.Since related literature is still in its infancy,many problems still remain unresolved,such as insufficient sample size and lack of diversification of data features.We suggest that fu-ture research may expand the sample size,optimize machine learning models,and fully explore the predictive factors affecting the rehabilitation of cochlear implantation,and make machine learning a better tool in the area of cochlear implantation.

Research shows that epileptic seizures are essentially due to abnormal functions of neural circuits. Optogenetics regulates neural circuits by specifically expressing light-sensitive proteins in target neurons, which has now become an important tool in the research of temporal lobe epilepsy. Studies have shown that optogenetics focuses on brain regions such as the hippocampus, medial septal nucleus, cerebellum, and basal ganglia in studying temporal lobe epilepsy. This article reviews the research progress of optogenetics in exploring the pathogenesis and therapeutic targets of temporal lobe epilepsy, aiming to provide new ideas for temporal lobe epilepsy treatment.

Objective To study the influence of stent and balloon shape on hemodynamics in tapered vessels with multiple stenosis.Methods The hemodynamic model was established after the implantation of vascular stent in tapered vessel with multiple stenosis.The numerical simulation method was used to study the effect of the combination of different shaped stents and balloons on postoperative hemodynamics.Results When the cylindrical stent was expanded using the cylindrical balloon and tapered balloon respectively,compared with cylindrical balloon expansion,the proportion of low-speed blood flow area generated by tapered balloon expansion was reduced by 0.58％,and the proportion of low time-averaged wall shear stress(TAWSS)area was reduced by 3.22％.The use of tapered balloon for expansion could produce less low-speed blood flow and low TAWSS area.When tapered balloon was used to expand the cylindrical stent and tapered stent respectively,compared with expanding tapered stent,the proportion of low-speed blood flow area generated by expanding cylindrical stent decreased by 1.35％,and the proportion of low TAWSS area decreased by 9.73％.Conclusions The hemodynamic environment of tapered vessel with multiple stenosis was influenced by the shape of stent and balloon.The use of tapered balloon to expand the cylindrical stent in tapered vessels with multiple stenosis can achieve favorable hemodynamic environment and reduce the risk of ISR occurence.This study can provide a scientific basis for the rational formulation of clinical intervention scheme.

Objective To observe early changes of left atrial strain and left atrial stiffness index(LASI)in rabbits with left ventricular myocardial injury induced by adriamycin(ADM).Methods Eighteen New Zealand white rabbits were randomly divided into experimental group(n=12)and control group(n=6),while 2 mg/kg ADM was injected into rabbits in experimental group and 5 ml physiological saline was injected into rabbits in control group every week for a total of 4 weeks.Ultrasound examination was performed before injection of ADM/physiological saline,2 and 4 weeks after injection,respectively.Left atrial anteroposterior diameter(LAAPD),left ventricular end diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),lateral wall of mitral ring of early peak flow velocity(e),mitral valve orifice early peak flow velocity(E)/e,left ventricular global longitudinal strain(LVGLS),right ventricular collectivity long axis strain(RVCLS),left atrial strain during reservoir phase(LASr),left atrial strain during conduit phase(LAScd),left atrial strain during contraction phase(LASct)and LASI were obtained and analyzed.After ultrasound examination,myocardial changes were observed with pathological examination.Results Four weeks after injection,e in experimental group was significantly lower than that before injection,also lower than that 2 and 4 weeks after injection in control group(all P＜0.05).Significant differences of LASr,LAScd,LASct and LASI were found among different time points between groups(all P＜0.05).Two and 4 weeks after injection,the above 4 parameters in experimental group were all significantly different with those in control group(all P＜0.05).LASr,LASct and LASI were different among different time points,while LAScd before injection was higher than that 2 and 4 weeks after injection in experimental group(all P＜0.05).The pathological findings supported ultrasonic changes.Conclusion In early stage of ADM induced left ventricular myocardial injury in rabbits,changes of left atrial strain and LASI could be seen,which were more significant than those of LVGLS,RVCLS and LVEF,etc.