OBJECTIVE: To investigate the biological activity and antitumor effect of pegylated recombinant human interleukin 2 (PEG-rhIL-2) obtained by site-specific conjugation of polyethylene glycol (PEG) with non-natural amino acids, and to explore its antitumor mechanism. METHODS: The binding activities of PEG-rhIL-2 at three different sites (T41, Y45, and V91) to human interleukin 2 receptors α (IL-2R_α) and β (IL-2R_β) and were detected by surface plasmon resonance (SPR) technology. Western blot was used to detect the levels of the Janus kinase-signal transducer and activator of transcription 5 (JAK-STAT5) signaling pathway activated by different doses of rhIL-2 and PEG-rhIL-2 in CTTL-2 and YT cells. Blood was collected after a single administration in mice to detect the drug concentration at different time points and evaluate the pharmacokinetic parameters of Y45-PEG-rhIL-2. Mouse hepatoma cell line Hepa1-6, pancreatic cancer cell line Pan-02, and colon cancer cell line MC-38 were selected. Tumor models were constructed in C57BL/6 mice. Different doses of Y45-PEG-rhIL-2 and excipient control were administrated respectively to evaluate the tumor suppression effect of the drug. In the MC-38 colon cancer model, the tumor suppression effect of Y45-PEG-rhIL-2 combined with anti-programmed death-1 (PD-1) monoclonal antibody was evaluated. Hepa1-6 mouse tumor models were constructed and rhIL-2, Y45-rhIL-2 and Y45-PEG-rhIL-2 were administrated respectively. The proportion of tumor-infiltrating lymphocytes was analyzed by flow cytometry. RESULTS: The SPR detection results showed that the binding activities of PEG-rhIL-2 to IL-2R_α/IL-2R_β were both reduced. The affinity of Y45-PEG-rhIL-2 to IL-2R_α was reduced to approximately 1/250, and its affinity to IL-2R_β was reduced to 1/3. Western blot results showed that the activity of Y45-PEG-rhIL-2 in stimulating JAK-STAT5 signaling in CTLL-2 cells expressing heterotrimeric IL-2 receptor complex IL-2R_αβγwas reduced to approximately 1/300, while its activity in YT cells expressing heterodimeric IL-2 receptor complex IL-2R_βγwas reduced to approximately 1/3. The pharmacokinetic evaluation after a single dose in the mice showed that the elimination half-life of Y45-PEG-rhIL-2 was 17.7 h. Y45-PEG-rhIL-2 has pharmacokinetic characteristics superior to those of rhIL-2. Y45-PEG-rhIL-2 showed dose-dependent tumor suppression activity, and the combination of Y45-PEG-rhIL-2 and anti-PD-1 antibody had a better tumor-inhibiting effect than the single use of Y45-PEG-rhIL-2 or anti-PD-1 antibody. Flow cytometry analysis demonstrated that 72 h after the administration of Y45-PEG-rhIL-2, the proportion of tumor-infiltrating cytotoxic T lymphocytes (CD8⁺T cells) increased by 86.84%. At 120 h after administration, the ratio of CD8⁺T cells to regulatory T cells (Treg) increased by 75.10%. CONCLUSION Y45-PEG-rhIL-2 obtained by site-specific conjugation via non-natural amino acids changed its receptor binding activity and inhibited tumor growth in dose-dependent manner in multiple tumor models by regulating CD8⁺T cells.
Interleukin-2/pharmacokinetics* ; Animals ; Mice ; Humans ; Recombinant Proteins/pharmacology* ; Polyethylene Glycols/chemistry* ; Cell Line, Tumor ; Antineoplastic Agents/pharmacokinetics* ; Signal Transduction/drug effects* ; STAT5 Transcription Factor/metabolism* ; Interleukin-2 Receptor alpha Subunit/metabolism* ; Interleukin-2 Receptor beta Subunit/metabolism*

Objective:To explore the clinical, imaging, and pathological features of glottic squamous cell carcinoma of the larynx and their relationship with prognosis. Methods:A retrospective analysis was conducted on the clinical, imaging, and pathological data of 130 patients with glottic squamous cell carcinoma of the larynx who were treated at the First People's Hospital of Yinchuan and the General Hospital of Ningxia Medical University from January 2018 to March 2023. Imaging examinations （CT and MRI） were used to evaluate the lesion boundary clarity, density, enhancement nature, and enhancement degree. Postoperative pathological examination was used to determine the pathological nature, immunohistochemistry, etc. Statistical methods such as χ² test, Spearman correlation analysis, multivariate logistic regression analysis, and Kaplan-Meier method were used to analyze the data. Results:Among the 130 patients, 127 were male and 3 were female, with an average age of （61.92±9.595） years. There was a correlation between clinical, imaging, and pathological features. Multivariate analysis showed that heterogeneous MRI density （OR=12.414;P=0.019） and squamous cell carcinoma as a subtype were correlated. The initial symptom of non-hoarseness （HR=6.045;P=0.010） and unclear MRI boundary （HR=12.559; P=0.029） were independent risk factors for poor prognosis in patients with glottic squamous cell carcinoma of the larynx. Conclusion:There is a correlation between the clinical, imaging, and pathological features of patients with glottic squamous cell carcinoma of the larynx, and they can affect prognosis. The initial symptom of non-hoarseness and unclear MRI boundary of the tumor are independent risk factors for poor prognosis.
Humans ; Laryngeal Neoplasms/diagnosis* ; Prognosis ; Male ; Female ; Retrospective Studies ; Middle Aged ; Carcinoma, Squamous Cell/diagnosis* ; Magnetic Resonance Imaging ; Glottis/pathology* ; Tomography, X-Ray Computed ; Aged

Objective:To investigate the clinical characteristics and major allergens of patients with pollen-food allergy syndrome（PFAS） and their correlation with the severity of symptoms, and to provide a basis for identifying high-risk patients, optimizing the allergen testing process and developing individualized dietary management strategies. Methods:The clinical data of 166 patients with PFAS admitted to our hospital from January 2021 to July 2023 were retrospectively analyzed. The clinical symptoms, pollen types and food allergy of the patients were analyzed by questionnaire survey and serum specific IgE detection. phi coefficient, Apriori algorithm modeling and multivariate logistic regression analysis were used to evaluate the association between allergen and symptom severity. Results:Artemisia pollen was the most common allergen in this area, with a positive rate of 96.39%. Peach and mango were the most common food allergens, which caused allergic reactions in 24.10% and 22.89% of patients, respectively. Oral mucosal symptoms were the main symptoms. Correlation analysis showed that there was a correlation between pollen allergens and allergenic food. Association rule analysis showed that when the patient was allergic to the combination of peanuts and trees, the probability of high severity of symptoms was 82.35%. Multivariate analysis showed that ragweed allergy was significantly positively correlated with the severity of PFAS symptoms. Conclusion:Artemisia pollen and related food allergens play an important role in the pathogenesis of PFAS. Association rule mining and network map analysis revealed direct associations between peanut and tree combination allergy and symptom severity, as well as potential links between other inhaled allergens and specific food allergies. Ragweed and peach allergy are independent risk factors for the aggravation of PFAS symptoms, which can be used as early warning indicators. These results help to improve the screening of high-risk patients and the construction of regional allergen databases.
Humans ; Food Hypersensitivity/immunology* ; Allergens/immunology* ; Retrospective Studies ; Pollen/immunology* ; Cross Reactions ; Immunoglobulin E/blood* ; Rhinitis, Allergic, Seasonal/immunology* ; Artemisia/immunology* ; Male ; Female ; Adult ; Prunus persica/immunology* ; Arachis/immunology* ; Middle Aged ; Surveys and Questionnaires ; Oral Allergy Syndrome

Background Asthma poses a serious threat to children's growth, development, and mental health, thus there has been an increasing focus on the control of asthma morbidity in children and the assessment of its risk factors. A growing body of research has found that exposure to ambient air pollutants an significatly increase the risk of childhood asthma. Objective To understand the changes of ambient air pollutant concentrations in Nanjing and asthma outpatient visits to Nanjing Children's Hospital, and to quantitatively analyze the effects of exposure to different ambient air pollutants on children's asthma outpatient visits. Methods Daily data of ambient air pollutants fine particulate matter (PM_2.5), inhalable particle (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), ozone (O₃), meteorological factors (air temperature & relative humidity), and outpatient visits due to asthma in the hospital from January 1, 2019 to December 31, 2023 were collected, and a generalized additive model based on quasi poisson distributions was used to quantitatively analyze the short-term effects of ambient air pollutant exposure on outpatient visits due to asthma in the hospital. Results The annual average concentrations of PM_2.5, PM₁₀, SO₂, and NO₂ in Nanjing from 2019 to 2023 did not exceed the national limits. For single-day lagged effects, the single-pollutant model showed that the effects of PM_2.5, PM₁₀, NO₂, and CO on children's asthma outpatient visits were greatest for every 10 units increase at lag0, with excess risk (ER) of 1.39% (95%CI: 0.65%, 2.14%), 1.46% (95%CI: 0.97%, 1.95%), 5.46% (95%CI: 4.36%, 6.57%), and 0.18% (95%CI: 0.11%, 0.26%), respectively, and SO₂ reached the maximum effect at lag1, with an ER of 23.15% (95%CI: 13.57%, 33.53%) for each 10 units increase in concentration. Different pollutants reached their maximum cumulative lag effects at different time. The PM₁₀, PM_2.5, SO₂, NO₂, and CO showed the largest cumulative lag effects at lag01, lag01, lag02, lag02, and lag03, respectively, with ERs of 1.35% (95%CI: 0.77%, 1.92%), 0.96% (95%CI: 0.10%, 1.83%), 28.50% (95%CI: 15.49%, 42.98%), 6.92% (95%CI: 5.53%, 8.33%), and 0.31% (95%CI: 0.20%, 0.42%), respectively. The influences of PM_2.5 and PM₁₀ on outpatient visits due to asthma in the hospital became more pronounced with advancing age, while the associations with NO₂, SO₂, and CO were weakened as children grew older. Conclusion Ambient air pollutants (PM_2.5, PM₁₀, SO₂, NO₂, CO) can increase childhood asthma visits, and different pollutants have varied effects on the number of asthmatic children's visits at different ages.

To summarize the nursing experience of a patient with Danon disease after heart transplantation.Nursing key points:closely monitor heart function,prevent right heart failure;phased analgesic and sedative measures were implemented to reduce the occurrence of related complications.Skeletal muscle function was evaluated and rehabilitation training was strengthened to promote the prognosis of patients.The patient was transferred to the general ward 5 days after operation,and was discharged 22 days after operation.

Objective:To summarize and analyze the risk factors associated with bronchial mucus plugs (BMPs) in children with Mycoplasma pneumoniae pneumonia (MPP),providing a clinical basis for the indication of bronchoscopy in children with MPP.Methods:A total of 72 children with MPP admitted to the Department of Pediatrics at the Fourth Affiliated Hospital of Nanjing Medical University from December 2022 to December 2024,who underwent bronchoscopy,were selected for this study.According to the presence or absence of BMPs under tracheoscopy,the patients were divided into the mucus plug group and the non-mucus plug group,and their clinical data were analyzed and compared.Results:Among the 72 children with MPP,30 cases (41.7%) were in the mucus plug group,while 42 cases (58.3%) were in the non-mucus plug group.Univariate Logistic regression analysis showed that thermal peak ( OR 2.086,95% CI 1.029-4.299, P=0.041),thermal duration ( OR 1.453,95% CI 1.197-1.763, P < 0.001),thermal duration ≥10 days ( OR 26.154,95% CI 5.316-128.661, P<0.001),combined with pleural effusion ( OR 4.727,95% CI 1.136-19.677, P=0.033),atelectasis ( OR 5.636,95% CI 2.024-15.699, P<0.001),lymphocyte proportion( OR 0.936,95% CI 0.888-0.978, P=0.014),neutrophil proportion( OR 1.048,95% CI 1.005-1.093, P=0.028),lactatedehydrogenase ( OR 1.005,95% CI 1.001-1.009, P = 0.028),D-dimer ( OR 2.203,95% CI 1.133-4.280, P = 0.020),fibrin degradation products ( OR 1.563,95% CI 1.095-2.231, P=0.014),and no heat regression within 72 hours of hormone use ( OR 0.239,95% CI 0.085-0.667, P=0.006) were significant influencing factors for the formation of BMPs in children with MPP.Multivariate Logistic regression analysis showed that thermal duration ≥10 days and atelectasis were independent risk factors for BMPs formation ( P<0.05). Conclusion:For MPP children with thermal duration≥10 days,especially with atelectasis,BMPs may have been formed,and it is recommended to perform bronchoscopy as soon as possible.

To summarize the nursing experience of a patient with severe pulmonary hypertension complicated with giant heart after lung transplantation.Key nursing points:to set up volume management measures in stages to avoid hemodynamic disorders;to monitor cardiac function closely and be alert to the occurrence of low cardiac output syndrome;to closely observe heart rate and heart rhythm to correct arrhythmia as soon as possible;the sequential ventilation strategy was adopted to promote the recovery of lung function.Progressive implementation of individual rehabilitation was conducted,and the patient activity tolerance was improved.After careful treatment and nursing,the patient was successfully transferred to the general ward 29 days after surgery,recovered from the hospital 41 days after surgery,followed up for 6 months,and recovered well.

Objective To explore the impact of different delay time of umbilical cord ligation on the outcome of preterm infants.Methods A total of 266 preterm infants born in the obstetric department of this hospital from January 2021 to December 2022 were selected as the research subjects and divided into the in-stant group(umbilical cord ligation immediately after birth,n=53),30 s group(delayed umbilical cord liga-tion for 30 s,n=50),60 s group(delayed umbilical cord ligation for 60 s,n=55),90 s group(delayed umbili-cal cord ligation for 90 s,n=55)and 120 s group(delayed umbilical cord ligation for 120 s,n=52)according to the random number table method.The Hb and HCT levels and the incidence rates of anemia,blood transfu-sion,hyperbilirubinemia,intracranial hemorrhage,necrotizing enterocolitis(NEC)and bronchopulmonary dys-plasia(BPD)after birth were compared among 5 groups.Results The Hb and HCT levels at 24 h after birth in the 60,90,120 s groups were higher than those in the instant group and 30 s group,moreover the 120 s group was higher than the 60 s group and 90 s group,and the differences were statistically significant(P＜0.05).The anemia incidence rate and blood transfusion rate in the 60,90,120 s groups were lower than those in the instant group and 30 s group,and the differences were statistically significant(P＜0.05).The hyperbil-irubinemia incidence rate in the 120 s group was higher than that in the other 4 groups,and the difference was statistically significant(P＜0.05).The intracranial hemorrhage incidence rate in the 60,90,120 s groups were lower than those in the instant group and 30 s group,and the differences were statistically significant(P＜0.05).The NEC incidence rate in the 60 s and 90 s group was lower than that in the instant group and 30 s group,but the 120 s group was higher than that in the other 4 groups,and the differences were statistically significant(P＜0.05).The BPD incidence rate had no statistical difference among 5 groups(P＞0.05).Con-clusion Delayed umbilical cord ligation for 60 s or 90 s could improve the outcomes of preterm infants.

Objective To explore the effects of Emotional Freedom Techniques combined with PERMA model intervention on fear of disease progression and quality of life in postoperative liver cancer patients.Methods A total of 58 liver cancer patients admitted from September 2023 to February 2024 were randomly divided into the experimental group(n=29)and the control group(n=29)using a random number table method.The experimental group received Emotional Freedom Techniques combined with PERMA-based positive psychological intervention,while the control group received the holistic nursing and routine psychological guidance.Both groups underwent the continuous intervention for 8 weeks.Outcomes were assessed using the Fear of Progression Questionnaire-Short Form(FoP-Q-SF),Distress Thermometer(DT),Self-Rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS),Cancer Fatigue Scale(CFS),Athens Insomnia Scale(AIS)and Index of Well-Being(IWB).Results After the intervention,the experimental group showed the significantly lower scores than those in the control group in FoP-Q-SF(24.97±2.34/34.10±8.46),DT(2.24±0.95/2.93±1.33),SAS(49.55±1.35/58.55±4.60),SDS(51.86±1.58/61.79±4.00),CFS(4.03±0.94/5.10±1.18),and AIS(2.45±1.12/4.07±0.96)(all P<0.05),while the IWB score(10.56±1.74/7.39±2.05)was significantly higher than that in the control group(P<0.05).Conclusion The combination of Emotional Freedom Techniques and PERMA model intervention can effectively alleviate the disease-related fears,improve the negative emotions,reduce the physical symptoms and enhance the subjective well-being in postoperative liver cancer patients,and it has a significant clinical application value.

This report described the multidisciplinary management of a preterm infant with congenital tracheal agenesis (TA). The infant, delivered via cesarean section at 32 +5 weeks' gestation, had Apgar scores of 6 and 8 at 1 and 5 minutes, respectively. Although skin color improved after 30 seconds of bag-mask ventilation, the infant exhibited no cry, weak spontaneous breathing, and failed multiple intubation attempts. The patient was transferred to Anhui Children's Hospital of Fudan University under continuous bag-mask positive-pressure ventilation at 3 hours after birth (September 10, 2024). Combined imaging and fiberoptic bronchoscopy confirmed TA (Floyd type Ⅱ/Faro type C) with multiple anomalies, including duodenal atresia, aortic coarctation, and butterfly vertebrae. Whole-genome sequencing revealed a suspected mosaic SCN2A c.5317G>A variant (wild-type parents) and an ERCC5 c.2974C>T heterozygous variant inherited from the mother (homozygous). Following esophageal intubation, invasive mechanical ventilation, and continuous gastrointestinal decompression, respiratory distress significantly improved with a stabilized condition. The infant died 30 hours after birth following treatment withdrawal.