Objective To explore the effect of sex on the incidence of immune-related cutaneous adverse event (ircAE) during immunotherapy for gastric cancer, and to further analyze the correlation between sex, ircAE and prognosis. Methods A retrospective analysis was conducted on patients with advanced gastric cancer who received immune checkpoint inhibitors at the Department of Oncology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Medical School, Nanjing University, from February 1, 2022, to December 31, 2024. Clinicopathological characteristics, occurrence of ircAE, and survival data were collected. The incidence of ircAE was compared between male and female patients. Kaplan-Meier method was used to plot survival curves, and univariate Cox regression analysis was performed to assess prognostic factors. Results A total of 116 patients with advanced gastric cancer were enrolled, including 76 males (65.5%) and 40 females (34.5%). The overall incidence of ircAE was 23.28%, with a higher incidence in male patients than in female patients (28.95% vs 12.50%, P＝0.046). Kaplan-Meier survival analysis on 86 patients with complete follow-up data indicated that patients with ircAE had longer overall survival (OS) than those without ircAE (P＝0.045). Univariate Cox regression analysis showed that male (HR＝0.43, 95%CI 0.22–0.83, P＝0.012) was associated with prolonged OS. Conclusions In gastric cancer immunotherapy, male patients are more likely to develop ircAE and have longer OS than female patients, and the occurrence of ircAE may be related to prolonged OS.

ObjectiveTo explore the efficacy and mechanism of Euphorbia humifusa on acute kidney injury （AKI） based on network pharmacology， molecular docking and experimental verification. MethodsThe active components and targets of E. humifusa were retrieved from TCMSP and SwissTargetPrediction database， and the AKI targets were screened by GeneCards and Online Mendelian Inheritance in Man（OMIM） databases. The drug targets and disease targets were intersected to construct a protein-protein interaction network， and the intersection targets were subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis. Discover Studio software was used to verify the molecular docking of key components and core targets. Gentamicin （GM） was used to induce AKI rat model. Control group， model group， verapamil （16 mg·kg^-1） group， E. humifusa extract （18， 54， 162 mg·kg^-1·d^-1） group and E. humifusa 70% ethanol extract （423 mg·kg^-1） group were continuously administered for 14 days. Urine volume was detected 24 h after modeling and administration. Serum creatinine （SCr）， Blood urea nitrogen （BUN）， 24-hour urine protein （24 hUTP） and uric acid （UA） content； the contents of malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase （SOD）， carbon monoxide synthase （NOS） and lactate dehydrogenase （LDH） in kidney were measured. The levels of interleukin （IL）-6 and tumor necrosis factor （TNF）-α in serum were detected by enzyme linked immunosorbent assay（ELISA） kit. The pathological changes of renal tissue were detected by hematoxylin-eosin （HE） and Masson staining. Western blot was used to detect the expression of PI3K/protein kinase B（Akt）/NF-κB signaling pathway-related proteins. ResultsIn this study， 13 active components such as kaempferol， luteolin， apigenin， gallic acid and quercetin were screened and identified from E. humifusa. Through bioinformatics analysis， these components and AKI have a total of 289 targets， of which 62 are core targets， including Akt1， TNF， tumor protein p53（TP53） and IL-1β. These targets are mainly involved in the regulation of biological processes such as NF-κB signaling pathway， HIF-1 signaling pathway， TNF signaling pathway， PI3K/Akt signaling pathway and mitogen-activated protein kinase（MAPK） signaling pathway. In animal experiments， we successfully constructed a GM-induced AKI model in rats. Compared with the model group， E. humifusa extract could significantly reduce the levels of 24 hUTP， BUN and SCr in rats （P<0.01）， indicating its improvement effect on renal function. In addition， the extract of E. humifusa also significantly reduced LDH activity and MDA content in rat kidney tissue （P<0.05， P<0.01）， and significantly increased SOD， NOS activity and GSH content （P<0.05）， indicating that the extract of E. humifusa has the potential of anti-oxidation and protection of renal function. Further analysis of inflammatory factors showed that the levels of IL-6 and TNF-α in serum of rats treated with E. humifusa extract were significantly decreased （P<0.01）， indicating that E. humifusa extract had anti-inflammatory effects. In addition， the extract of E. humifusa can also regulate the protein expression of PI3K/Akt/NF-κB signaling pathway， which further confirmed its mechanism of reducing GM-induced AKI. ConclusionThe extract of E. humifusa has a significant therapeutic effect on acute kidney injury through its multi-component and multi-target mechanism. Its effect is reflected in improving renal function， anti-oxidation， anti-inflammation and regulating immune response. These findings provide a scientific basis for the application of E. humifusa in the treatment of acute kidney injury， and point out the direction for future drug development and clinical research.

[摘 要] 目的：探讨RNA结合基序蛋白15（RBM15）是否通过含跨膜Bax抑制基序蛋白6（TMBIM6）/TGF-β/Smad轴促进宫颈癌细胞增殖、迁移及侵袭。方法：收集2023年1月至2025年1月在苏州大学附属张家港医院接受手术治疗的82例宫颈癌患者的肿瘤组织与癌旁组织。应用R语言分析癌症基因组图谱（TCGA）数据库中RBM15、TMBIM6 mRNA的表达；采用免疫组织化学法和Western blotting法检测RBM15、TMBIM6蛋白表达；采用Kaplan-Meier曲线分析RBM15、TMBIM6 mRNA表达与宫颈癌患者预后的关系；采用CCK-8法、划痕实验及Transwell侵袭实验检测RBM15、TMBIM6对宫颈癌细胞增殖、迁移及侵袭的影响；利用基于序列的RNA腺苷甲基化位点预测工具（SRAMP）预测TMBIM6 mRNA的N6-甲基腺苷（m6A）修饰位点；采用RNA免疫共沉淀（RIP）实验、RNA衰变和挽救实验鉴定RBM15与TMBIM6 mRNA的相互作用；采用甲基化RNA免疫共沉淀定量PCR（MeRIP-qPCR）检测TMBIM6 mRNA的m6A富集；采用Western blotting法检测RBM15通过TMBIM6对宫颈癌细胞TGF-β/Smad通路相关蛋白表达的影响。结果：宫颈癌组织中RBM15 mRNA、TMBIM6 mRNA表达均高于癌旁组织（均P < 0.05），癌组织RBM15、TMBIM6阳性率均高于癌旁组织（均P < 0.001）。宫颈癌细胞系HeLa、MS-751、SiHa中RBM15、TMBIM6蛋白表达均高于正常宫颈上皮细胞系Ect1/E6E7（均P < 0.05）。国际妇产科联盟（FIGO）分期ⅠB2～ⅡB期宫颈癌组织中RBM15、TMBIM6蛋白阳性率高于ⅠA～ⅠB1期（P均 < 0.05）。RBM15 mRNA高表达组、TMBIM6 mRNA高表达组5年无进展生存率分别低于各自的低表达组（均P < 0.05）。宫颈癌组织中RBM15 mRNA与TMBIM6 mRNA表达呈正相关（P < 0.05）。SRAMP预测结果显示，TMBIM6 mRNA序列的960、24876、25203位点为高可信度m6A修饰位点。在HeLa、SiHa细胞中过表达RBM15后，TMBIM6 mRNA和蛋白表达升高（P < 0.05）；敲低RBM15后，TMBIM6 mRNA和蛋白表达降低（P < 0.05）。与IgG组相比，RBM15抗体免疫沉淀物中TMBIM6 mRNA显著富集。MeRIP-qPCR结果显示，TMBIM6 mRNA的960、24876、25203位点均存在明显的m6A富集。敲低RBM15可缩短TMBIM6 mRNA半衰期并降低其稳定性。敲低RBM15可抑制宫颈癌细胞增殖、迁移及侵袭，过表达TMBIM6可逆转上述影响。在HeLa、SiHa细胞中过表达TMBIM6后，TGF-β1、Smad2、Smad3蛋白表达升高；敲低RBM15后，上述蛋白表达降低，过表达TMBIM6可逆转该影响。结论：RBM15可能通过m6A修饰提高TMBIM6 mRNA稳定性并激活TGF-β/Smad通路，从而促进宫颈癌细胞增殖、迁移及侵袭。

BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
Humans ; China/epidemiology* ; Hearing Loss/epidemiology* ; Prevalence ; Middle Aged ; Male ; Female ; Adult ; Aged ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Aged, 80 and over ; Cost of Illness

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

Objective To construct an aptamer-functionalized carboxylated graphene oxide(CGO)fluo-rescent sensor to achieve highly sensitive and specific detection of ketamine(KET)and its metabolite norketamine(NK)using an aptamer capable of simultaneously recognizing KET and NK.Methods A specific aptamer for simultaneous recognition of KET and NK was screened using graphene oxide-sys-tematic evolution of ligand by exponential enrichment(GO-SELEX)and molecular docking tech-niques.The aptamer,labeled with Cy5 fluorescence,was chemically conjugated to CGO to construct an aptamer-functionalized CGO fluorescent sensor.By optimizing detection conditions,including the mass concentration of CGO,aptamer concentration,reaction temperature,and incubation time,quantita-tive analysis of the target analytes was achieved using the ratio of fluorescence intensity changes be-fore and after target addition.The stability of the sensor in biological matrices was evaluated by moni-toring fluorescence intensity changes over incubation time in blank blood and urine,in comparison with the traditional physical adsorption-based CGO fluorescent sensor.Spiked recovery experiments in blank blood and urine were conducted to compare performance with that of HPLC-MS/MS.Results A specific aptamer A5 was selected and chemically conjugated with CGO to construct the aptamer-functionalized CGO fluorescent sensor.Under optimized conditions,the proposed fluorescent sensor ex-hibited a linear detection range of 1.0-5.0 ng/mL for KET,with a limit of detection(LOD)of 0.86 ng/mL;while for NK,the linear detection range was 1.0-5.0 ng/mL,with an LOD of 0.70 ng/mL.Com-pared with the CGO fluorescent sensor constructed via physical adsorption,this sensor demonstrated greater stability in blood and urine.The spiked recovery rates of KET and NK in blank blood and urine ranged from 81.50%to 110.03%,exhibiting detection performance comparable to that of HPLC-MS/MS.Conclusion The aptamer screening method offers a novel approach for selecting aptamers tar-geting drugs and their metabolites.The constructed aptamer-functionalized CGO fluorescent sensor pro-vides an efficient and reliable strategy for the high-performance detection of KET and NK.

Objective To establish a chromatography-tandem mass spectrometry method for detecting chlorfenapyr and its metabolite tralopyril in blood,and to investigate the toxicokinetics in rats.Methods Chlorfenapyr(8 mg/kg)was administered orally to rats,and blood samples were collected from rats'canthus vein at 5 min,15 min,30 min,1 h,3 h,6 h,12 h,24 h and 48 h after administration.The blood samples were extracted using 100 μL of 5%formic acid solution and 400 μL of acetonitrile.Chlorfena-pyr was qualitatively and quantitatively detected by triple quadrupole gas chromatography-tandem mass spectrometry(GC-MS/MS)and tralopyril was detected by triple quadrupole liquid chromatography-tandem mass spectrometry(LC-MS/MS).The DAS 3.0 software was used to fit the toxicokinetic equa-tions and calculate the toxicokinetic parameters.Results Chlorfenapyr was detectable from 5 min to 24 h with a peak time of 1 h.Tralopyril was detectable from 15 min to 48 h with a peak time of 3 h.The toxicokinetic process of chlorfenapyr in rat blood conformed to a first-order absorption one-compartment open model,with the toxicokinetic equation described as C=e-0.265t-e-0.175t.Tralopyril con-formed to the first-order absorption three-compartment model,and the toxicokinetic equation was C=47 361.069e-2.209t-35 404.962e-1.486t+11 956.363e-0.512t.In the equations,C stands for the concentration of the target substance in the blood,e is the natural constant(≈2.718 28),and t stands for time.Conclu-sion This study optimized the detection method for chlorfenapyr and its metabolite tralopyril in blood.The toxicokinetic equations and parameters of chlorfenapyr and tralopyril can provide a reference for the estimation of oral intake time of chlorfenapyr.

Objective To investigate the types of diseases examined by ultrasonography in a certain island clinic,and to summarize the experience of ultrasound medical support in island area.Methods The ultrasound examination results of patients who were admitted to a certain island clinic from January 2017 to August 2022 were reviewed,and the types and characteristics of diseases examined by ultrasound were analyzed.Results A total of 2 043 patients underwent ultrasound examination.There were 76 disease categories and 1 579 diseases.The top five diseases were fatty liver(13.24%),kidney crystals(12.10%),kidney stones(10.70%),gallbladder polyps(6.33%)and ureteral stones with hydronephrosis(6.02%).Ultrasound could predict the pathological types of appendicitis and guide the clinical decision by observing the width of the appendiceal lumen and the layers of the appendiceal wall.Doppler-assessed ureteric jet could be used to determine the renal function of the affected side of ureteral calculi.Conclusion There are wide and varied disease categories in islands.Sonographers should have comprehensive abilities and qualities.This study can provide reference for the follow-up medical support on island area.

Objective To explore the relationship between axillary artery and axillary vein by combining computed tomography angiography computed tomography angiography(CTA)and computed tomography venography(CTV),and to provide imaging data for establishing an effective blood circulation pathway for vascular injury in clinical transaxillary surgery.Methods The image data of 30 patients who underwent left upper limb and axillary CTA and CTV at the same time were collected.After three-dimensional reconstruction of the images by GE AW4.6 workstation,the course,branch type and variation of axillary artery,the course of axillary vein,the reflux of subordinate branches and the relationship between axillary artery and axillary vein were observed.The length of the whole segment,the length of segment and the inner diameter of the starting point of each segment were measured and statistically analyzed.Results According to the number of branches from the main trunk,the axillary artery was divided into 7 types.According to the variation of the number of blood vessels,the axillary vein was divided into 5 types;The unknown vein branches converge into 32 branches,of which the first segment accounted for 37.5％,the second segment accounted for 46.9％,and the third segment accounted for 15.6％.According to the absence of arterial branches,the relationship between axillary artery and axillary vein was divided into 2 types.Conclusion There are many types of branches of axillary arteries and branches of axillary veins,and the variation types are complex.The changes of branches of axillary arteries affect the distribution of branches of axillary veins.Combined with CTA and CTV images,the relationship between axillary vessels can be reflected clearly and intuitively,which can provide imaging reference for the establishment of new ways of blood supply and reflux in clinical axillary treatment.

Objective:To explore the current therapeutic status of rhythm control versus rate control in elderly patients with atrial fibrillation(AF)and the related factors that may influence treatment decisions.Methods:A retrospective study was conducted on AF patients aged ≥75 years old who were hospitalized in the Healthcare Department of Beijing Hospital from January 2010 to May 2020.The patients were grouped and compared according to whether they underwent rhythm control or rate control.Multivariate logistic regression analysis was used to investigate the factors that may influence the treatment decision of rhythm control or rate control.Results:A total of 167 patients was included, with a median age of 90 years old.Among them, 21 patients(12.6%)received rhythm control, and 109 patients(65.3%)received rate control.Compared with the group not receiving rhythm control, the rhythm control group had a younger age, higher BMI, higher diastolic blood pressure, a higher proportion of multiple medication use, a lower proportion of chronic kidney disease stage 3 or above, and higher hemoglobin levels(all P<0.05). Compared with the group not receiving rate control, the rate control group had a lower proportion of paroxysmal AF, a faster resting ventricular rate, a higher proportion of smoking history, a higher proportion of multiple medication use, coronary heart disease, pacemaker treatment, chronic obstructive pulmonary disease and/or asthma, and a lower proportion of cognitive impairment(all P<0.05). Multivariate logistic regression analysis revealed that multiple drug use( OR=11.578, 95% CI: 1.341-99.993, P=0.026)was positively associated with rhythm control therapy, while chronic kidney disease stage 3 or above( OR=0.248, 95% CI: 0.063-0.968, P=0.045)was negatively associated with rhythm control therapy.For rate control therapy, multiple drug use( OR=5.056, 95% CI: 2.253-11.347, P<0.001), resting ventricular rate( OR =1.033, 95% CI: 1.005-1.062, P=0.021), and chronic obstructive pulmonary disease(COPD)and/or asthma( OR=2.739, 95% CI: 1.124-6.672, P=0.027)showed positive associations. Conclusions:The application rate of rhythm control therapy is low in elderly AF patients, and ventricular rate control is the main treatment.Complex clinical conditions are the main constraints, and it is urgent to optimize individualized strategies based on prospective studies and develop new treatment techniques to improve clinical practice.