Background Air pollution is a major environmental factor threatening respiratory health. Different pollutants exhibit varying degrees of lag effects on respiratory diseases, and synergistic effects may exist among multiple pollutants. There is an urgent need to identify the key air pollutants influencing respiratory diseases and their interactive effects at specific lags. Objective To identify key pollutants affecting hospital admissions for respiratory diseases, to analyze their lag effect characteristics, and to quantify the impact of multi-pollutant synergistic effects on respiratory disease admissions. Methods Daily air pollution data, meteorological data, and respiratory disease hospitalization records were collected from multiple national monitoring stations in Hefei City from 2019 to 2024. A two-stage analytical framework was employed. First, a distributed lag model (DLM) was used to construct pollutant lag matrices, followed by least absolute shrinkage and selection operator (LASSO) regression to select key variables among fine particulate matter (PM_2.5), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and ozone (O₃). Second, a generalized additive model (GAM) was established, incorporating product interaction terms and excess relative risk (ERI) to quantitatively assess synergistic effects among the selected pollutants. Results Through LASSO regression, 24 pollutant lag terms with non-zero coefficients were identified, among which NO₂, PM_2.5, and SO₂ accounted for 66.7% of the total positive effects and exhibited distinct lag patterns. Exposure to NO₂ showed acute risk, with a relative risk of 1.040 (95%CI: 1.023, 1.057) at lag0. Conversely, PM_2.5 and SO₂ exhibited delayed effects, with peak impacts observed at lag7 (RR=1.012, 95%CI: 1.0002, 1.024) and lag3 (RR=1.015, 95%CI: 1.0004, 1.03), respectively. Short-term NO₂ exposure (lag0–1) exhibited a significant positive interaction with medium-term PM_2.5 exposure (lag4–7). When both pollutants coexisted at high exposure levels, the combined health risk exceeded the sum of their independent effects by 4.40%. Stratified analysis showed that the interaction effects of pollutants were higher in females (ERI=5.00%), children (<18 years, ERI=5.50%), and older adults (≥65 years, ERI=3.90%)Conclusion There are significant lag heterogeneity and synergistic mechanisms in the health effects of air pollution in Hefei. It is recommended to implement real-time early warning responses for NO₂, prioritize medium-to-long-term management for PM_2.5 and SO₂, and adopt coordinated emission reduction measures when NO₂ and PM_2.5 concentrations rise simultaneously. Concurrently, enhanced health protection should be provided for sensitive populations such as women, children, and the elderly.

Objective:To observe the expression of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain(TIGIT)in tumor tissue and peripheral blood CD8+T cells in patients with triple-negative breast cancer(TNBC),and to explore the ef-fect of tiragolumab on the function of CD8+T cells in the peripheral blood of these patients.Methods:The expression of TIGIT in tumor tissue of patients with TNBC was analyzed using The Cancer Genome Atlas(TCGA)database and immunohistochemical staining.Flow cytometry was employed to assess the co-expression of TIGIT and programmed death-1(PD-1)in peripheral blood CD8+T cells,as well as their cytokine secretion.A co-culture model of CD8+T cells and TNBC cell lines,HCC-1937 and MDA-MB-231,was estab-lished.The effect of tiragolumab on the anti-tumor activity of CD8+T cells in patients with TNBC was investigated using flow cytometry and confocal fluorescence imaging.Results:The expression of TIGIT in tumor tissue and peripheral blood CD8+T cells of patients with TNBC was significantly increased(P<0.05).Compared with the healthy control group,the TNBC group showed a significantly larger number of TIGIT+PD-1+CD8+T cells in the peripheral blood and significantly reduced secretion of interferon gamma(IFN-γ),tumor necrosis factor-α(TNF-α),and ginkgolide B(GB)by CD8+T cells;specifically,TIGIT+CD8+T cells demonstrated significantly re-duced secretion compared with TIGIT-CD8+T cells(P<0.05).Fol-lowing treatment with tiragolumab,TIGIT+CD8+T cells exhibited increased secretion of IFN-γ and TNF-α(P<0.05).In the co-culture model,tiragolumab restored the apoptosis-inducing ability of CD8+T cells in patients with TNBC,and this ability was further enhanced when it was combined with envafolimab.Conclusion:Ti-ragolumab restores the tumor-killing function of CD8+T cells by im-proving their immunosuppression.The combination of tiragolumab with envafolimab can further enhance its anti-tumor effect.

Objective:To establish an HPLC-DAD wavelength-switching method for the determination of aspirin dipyridamole tablets and free salicylic acid.Methods:An Agilent ZORBAX SB C18 column(250 mm ×4.6 mm,5 μm)was adopted with acetonitrile-tetrahydrofuran-glacial acetic acid-water(20∶5∶5∶70)as the mobile phase,and isocratic elution was performed at the flow rate of 1.0 mL·min-1,the column temperature of 30 ℃,and the detection wavelengths were 276 nm for aspirin,284 nm for dipyridamole and 303 nm for salicylic acid.Results:Aspirin,dipyridamole and free salicylic acid had a good linear relationship in the range of 38.37-383.71,9.60-96.05 and 1.02-10.21 μg·mL-1 respectively.The average recoveries were 99.88％(RSD=0.23％),99.01％(RSD=0.46％)and 100.99％(RSD=0.75％),respectively.There was no signif-icant difference for the content resuls between the established method and the standard method.The content uni-formity of A+2.2S ranges from 4.7 to 6.4.Conclusion:The established method is simple and suitable for the quality control of aspirin dipyridamole tablets.

ObjectiveTo investigate the mechanism of Lycium barbarum polysaccharides （LBP） in promoting the activation of RAW264.7 macrophages. MethodRAW264.7 macrophages were stimulated with LBP at different concentrations （50， 100， 200 mg·L^-1）， and those stimulated with lipopolysaccharide （LPS） at 100 μg·L^-1 and galactose （Gal） at 100 mg·L^-1 as positive controls. After 24 h of LBP stimulation， the cell counting kit-8 （CCK-8） was used to detect the survival rate of RAW264.7 macrophages treated with LBP （0， 50， 100， 200， 400， 800 mg·L^-1）. The levels of interleukin-6 （IL-6） and interleukin-12 （IL-12） in cell culture supernatant were detected by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA expression of p38 mitogen-activated protein kinase （MAPK）， extracellular signal-regulated kinase （ERK）， c-Jun N-terminal kinase （JNK）， and nuclear factor κB （NF-κB） in Toll-like receptor 4 （TLR4）/Toll-like receptor 2 （TLR2）/macrophage galactose-type lectin （MGL） pathway of RAW264.7 macrophages was detected by Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCCK-8 results showed that compared with the results in the blank group， the survival rate of RAW264.7 macrophages decreased in the 400， 800 mg·L^-1 LBP groups （P<0.05）. ELISA results showed that compared with the blank group， 50 mg·L^-1 LBP could promote the secretion of IL-12 in RAW264.7 macrophages （P<0.01）. Compared with the blank group， 100 mg·L^-1 LBP and 200 mg·L^-1 LBP could promote the secretion of IL-6 in RAW264.7 macrophages （P<0.05， P<0.01）. Western blot results showed that compared with the blank group， the LBP groups （50， 100， 200 mg·L^-1） enhanced protein expression levels of MAPK key molecules （p-p38 MAPK， p-ERK， p-NF-κB， and p-JNK） in TLR4， TLR2， and MGL pathways （P<0.05， P<0.01）. Compared with the model group， the 200 mg·L^-1 LBP group could promote the expression level of p-NF-κB protein in RAW264.7 macrophages （P<0.01）. Real-time PCR results showed that compared with the blank group， the LBP groups （50， 100， and 200 mg·L^-1） enhanced the mRNA expression levels of MAPK key molecules （p38 MAPK， ERK， NF-κB， and JNK） in TLR4 and TLR2 pathways （P<0.05， P<0.01）. Compared with the model group， the 50 and 200 mg·L^-1 LBP groups could promote the mRNA expression levels of JNK and ERK2 in RAW264.7 macrophages （P<0.05， P<0.01）. ConclusionLBP can regulate the activation of RAW264.7 macrophages and participate in the immune response through the TLR2/TLR4/MGL pathway.

Objective:To evaluate the safety and effectiveness of the model repair strategy for preputial defect in hypospadias surgery.Methods:From February 2017 to December 2022, 59 children in our hospital with an average age of (6.9±3.2) years were retrospectively analyzed. All of them were children with multiple failed hypospadias operations. According to the condition of penile scrotum skin, different methods of penile skin reconstruction were selected. Among them, 20 patients underwent penile skin flap reconstruction with simple foreskin and multiple small incision reduction, 22 patients with penile and scrotal transposition underwent penile lateral scrotum flap to complete ventral penis coverage, and 12 patients underwent middle scrotum flap with pedicled flap to cover ventral urethra. The penis was covered by inferior epigastric artery perforator flap in 5 patients.Results:The wound healed completely one week after the operation and no obvious scar formation was observed. The ventral flap of the penis was covered by the lateral scrotal flap of the penis, and no flap necrosis and wound infection were observed. The ventral urethra was covered with pedicled skin flap in the middle scrotal suture. The flap survived without scrotal hematoma. The inferior epigastric artery perforator flap was used to cover the patients with penile defect, all the flaps survived, and no complications such as wound infection and abdominal hernia occurred. No urethral fistula or urethral diverticulum was reported in all the patients. Urethral stricture occurred in 1 case of scrotal suture pedicled flap group and 1 case of lateral penis scrotal flap group, which was cured after expansion. One case with small incision and one case with lateral scrotal skin were cured after secondary repair by Mathieu method.Conclusions:For children with a history of multiple hypospadias operations, coverage of ventral skin defects of the penis is essential to reduce complications and obtain good appearance. This study summarized four effective strategies for covering penile defect from simple to complex. The small incision was used to reduce the expansion of all flaps. The lateral penile scrotal flap is more suitable for patients with penile scrotal transposition. The pedicled flap of scrotal suture and inferior superficial artery perforator flap are suitable for the repair of larger defect area.

Objective:To explore the effect of systematic diagnosis and treatment model based on new classification on primary hypospadias.Methods:The data of 689 patients with primary hypospadias admitted to Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from March 2010 to June 2021 were retrospectively analyzed. Of all, 349 cases from March 2010 to June 2016 were treated with traditional treatment methods, and 340 cases from July 2016 to June 2021 were treated with systematic diagnosis and treatment model based on new hypospadias classification. Traditional treatment group of patients according to the European Society of Urology (EAU) guide classification, were divided into the distal-anterior type (located on the glans or distal shaft of the penis), intermediate-middle type (penile) and proximal-posterior type (penoscrotal, scrotal, perineal). For distal type, tubularized incised plate (TIP) or dorsal inlay urethroplasty (Inlay) was performed. Patients with intermediate-middle type underwent Inlay, and patients with proximal-posterior type underwent Bracka staging. In the systematic diagnosis and treatment group, hypospadias was reclassified into distal type (located on the glan or in the first third of the shaft of the penis), junctional type (the back two-thirds of the shaft of the penis and the base of the penis), and proximal type (scrotum or perineum). For distal type, TIP or Inlay was used. Patients with junctional type were treated with urethroplasty with union free graft and local flap method (Montage). Patients with proximal type were treated with Montage or Bracka staging. Patients with testicular volume <0.8 ml and glans width <1.0 cm were treated with human chorionic gonadotropin (HCG) before surgery. There were 349 patients in the traditional group, with an average age of (18.58±7.59) months. There were 157 cases of distal-anterior type, 47 cases of intermediate-middle type and 145 cases of proximal-posterior type. There were 181 cases with penile curvature < 30° and 168 cases with penile curvature ≥30°. There were 340 cases in the systematic diagnosis and treatment group, with an average age of (18.94±6.05) months. According to EAU classification, 160 cases were distal-anterior type, 42 cases were intermediate-middle type and 138 cases were proximal-posterior type. There were 197 cases with penile curvature < 30° and 143 cases with penile curvature ≥30°. There was no significant difference in the above indicators between the two groups ( P>0.05). The surgical methods, incidence of postoperative complications and the time of hospital stay between the two groups compared. The changes in penis size and testis volume before and after the use of hormones in the systematic treatment group were compared. Results:In the traditional group, 139 patients underwent TIP, 65 patients underwent Inlay, and 145 patients underwent Bracka staging. In the systematic diagnosis and treatment group, 187 cases were reclassified as distal type (153 cases underwent TIP and 34 cases underwent Inlay). Of the 69 cases of junctional type, 10 cases underwent Inlay, and 59 cases underwent Montage. Of the 84 cases of proximal type, 77 cases underwent Montage, and 7 cases underwent Bracka staging. There was significant difference between the two groups ( P<0.01). In the traditional group, there were 31 cases of urinary fistula (8.9%), 43 cases of urethral stricture (12.3%), 21 cases of urethral diverticulum (6.1%), 45 cases of penile recurvature (12.9%), and the total incidence of complications was 40.1% (140/349). There were 19 cases of urinary fistula (5.6%), 28 cases of urethral stricture (8.2%), 15 cases of urethral diverticulum (4.4%) and 24 cases of penile recurvature (7.1%) in the systematic diagnosis and treatment group. The total incidence of complications was 25.3%(86/340). There were statistically significant differences in the incidence of the above complications between the two groups ( P<0.05). There was a significant difference in the duration of hospital stay between the traditional group and the systematic diagnosis and treatment group [(4.3±1.2) d vs. (1.5±0.5) d, P=0.01]. The width of glans penis after HCG treatment was (1.35±0.14) cm, which was significantly higher than that before HCG treatment [(0.96±0.24) cm, P=0.03]. The length of penis [(2.55±0.19) cm vs. (2.29±0.16) cm] and the volume of testis [(0.76±0.24) ml vs. (0.64±0.15) ml] were not significantly different from those before treatment ( P>0.05). Conclusions:The new classification has clarified the choice of surgical methods, avoiding the amplification of surgical indications. The systematic diagnosis and treatment model based on new classification has significantly improved the treatment effect of hypospadias and effectively reduced postoperative complications. It provides an optional diagnosis and treatment model for hypospadias.

Objective:To analyze the application effect of quality management of diabetes special nursing based on index orientation in geriatric hospital.Methods:The evaluation index of diabetes special nursing quality management was established based on PDCA cycle management and Donabedian model. This index was applied to conduct training, supervision and assessment of diabetes special nursing in 25 nursing units of Beijing Geriatric Hospital from January to December 2019, and the homogenized management of diabetes special nursing in the whole hospital was finally realized. The knowledge and skills of diabetes of in-hospital nurses and patients at 3, 6, 9 and 12 months before and after the implementation were compared, as well as the quality management examination of diabetes special nursing in 25 nursing units. SPSS 17.0 software was used in statistical analysis.Results:The constructed evaluation index of diabetes special nursing quality management included 2 first-level indexes, 7 second-level indexes and 11 third-level indexes. After the implementation of homogeneous management, the scores of nurses and patients in diabetes specialist knowledge and skills were higher than those before implementation, and the differences were statistically significant ( P<0.01) . The scores of quality examination of diabetes special nursing (insulin management, insulin pen management, glucose meter management, hypoglycemic drug taking method) were higher than those before the implementation, and the differences were statistically significant ( P<0.01) . After 12 months of implementation, the scores of quality examination of diabetes special nursing (quality management manual writing, nurse training) were all higher than those after 3 months of implementation, and the differences were statistically significant ( P<0.01) . Conclusions:Establishing evaluation index of quality management of diabetes special nursing in geriatric hospitals and adopting homogeneous management can effectively promote non-endocrinology department nurses to master the knowledge and skills of diabetes special nursing and help improve the management quality of diabetes special nursing.

Objective To evaluate the safety and efficacy of induced hypotension and hypotension in carotid endarterectomy (CEA).Methods Data of 1 486 patients who underwent CEA in multicenters from Aug 2012 to Aug 2018 were retrospectively analyzed.After screening,a total of 1 448 patients met the inclusion criteria.Induced hypertension and hypotension was used in all thees patients.Results 87.8％ of the patients were with severe carotid stenosis.The average operative time was (51.8 ± 6.1) min,and the internal carotid artery clamping time was (11.4 ± 3.1) min.After induced hypertension,the stump pressure were higher than that before,of which 1 438 (99.3％) were greater than 50 mmHg.Monitoring of EEG oxygen saturation showed that the value of ipsilateral rSO2 was significantly lower than that of the contralateral [(56％ ± 3％) vs.(64％ ± 4％),P ＜ 0.05] before induced hypertension.After induced hypertension and clamp removal,the value of ipsilateral rSO2 was lower than that of the contralateral,but there was not significant difference (all P ＞ 0.05).Perioperative cerebral infarction occurred in 2 cases,ipsilateral cerebral hemorrhage in 1 case,contralateral cerebral hemorrhage in 1 case and myocardial infarction in 2 cases.Connclusion The technique of induced hypotension and hypotension play a temporary role in brain protection for patients undergoing CEA.This study demonstrated the safety and effectiveness of induced hypertension and hypotension technique.

Objective The aim of this study is to explore the changes of expression of integrin αvβ3 in bovine u-terine epithelial cells in vitro induced by estrogen or/and progesterone alone or in combination,and to provide a new refer-ence marker for determining bovine uterine receptivity state. Methods RT-PCR was used to analyze the transcriptional changes of αvβ3 expression in bovine endometrium treated by different concentrations of estrogen,progesterone alone or in combination. Results The expression of integrin αvβ3 reached the highest level when the culture medium was added with progesterone at the concentration of 10 -7mg/mL,and the expression of αv and β3 in the 10 -7mg/mL concentration group was significantly higher than that of the control one(P<0.05). Moreover,the expression of αv was highest in the 10 -10 mg/mL E2group,but the expression of β3 was the lowest in that one. In addition,adding with both estrogen and progester-one,the transcriptional level of integrin αvβ3 was significantly higher than that in the control one. The transcriptional level of αv in the treatment group was significantly higher than that in the control group(P<0.05),but the transcriptional level of β3 in this group was not(P>0.05). Conclusions It can be concluded that integrin αvβ3 can be used as a new poten-tial reference marker gene for detecting the bovine uterine receptive status.

Objective To investigate the influence on biological characteristics in human pancreatic cancer cells after beding transfected by two anti-carcinoma miRNAs at the same time.Methods Pancreatic cancer cells PANC1,SW1990 and normal pancreatic cells AR42J were transfected by miR-34a and(or) miR-let7 by liposome.Cells transfected with negative control miRNA (miR-NC) and untransfected were as controls.The expression of miR-34a and miR-let7 were detected by real-time fluorescent quantitative RT-PCR.The cell proliferation was detected by MTT test and the migration and invasion were evaluated by transwell assay.The apoptosis rate was measured by flow cytometric analysis.Results After being transfected with miRNAs,the expression of miR-34a and miR-let7 in double transfection group (miR-34a and miR-let7 were transfected at the same time),miR-34a transfection group,miR-let7 transfection group was significantly up-regulated than those in miRNA-NC transfection group and untransfected group in PANC1 cells,SW1990 cells and AR42J cells,repectively.The difference which was statistically significant (P ＜0.05)indicating that cells were successfully transfected.The cell proliferation in double transfection group of PANC1 cells and SW1990 cells were (0.665 ± 0.01,0.6375 ± 0.03),which were significantly inhibited compared with (0.974 ± 0.03,0.971 ±0.05) in miR-NC group and (0.8875 ±0.05,0.8625 ±0.06) in miR-let7 group.The difference was statistically significant(P ＜ 0.05).The cell proliferation activity in double transfection group was lower than those in miR-34a group (0.795 ±0.06,0.7925 ±0.06),but did not have statistically significant difference.There was no significant change in AR42J cells.Cell invasion assay showed that the number of PANC1 cells permeating substrate membrane in miR34a group (103.7 ± 3.28) and miR-let7 group (100.7 ± 1.76) were significantly fewer than miR-NC group (231.3 ±2.6) and untransfected group (153.7 ±2.6).The number of cells permeating substrate membrane in double transfection group(61.67 ± 3.18)was fewer than miR-34a group and miR-let7 group,respectively.The difference was statistically significant (P ＜ 0.01).The migration test had consistent results with invasion test.The changes of invasion and migration in SW1990 cells were similar to those in PANC1 cells.The apoptosis rate of PANC1 cells in miR-34a group,miR-let7 group,double transfection group,miR-NC group and untransfected group was (16.66 ± 1.27) ％,(15.46 ± 0.33) ％,(23.35 ± 1.80) ％,(9.33 ± 0.31) ％ and (8.83 ± 0.36) ％ respectively.Single transfection group had higher apoptosis rate than miR-NC group and untransfected group (P ＜0.05).Double transfection group had a significantly higher apoptosis rate than miR-let7 group (P ＜ 0.05),while there was no significant difference between double transfection group and miR-34a group.Conclusions The cell proliferation,invasion and migration in double miRNAs transfected pancreatic cancer cells were significantly down-regulated compared with those in single miRNA transfected cells,while apoptosis rate in double miRNAs transfection group was higher than single miRNA transfection group.Thus,the combination of two anti-cancer miRNAs may exert a more significant synergistic antitumor effect.