Objective To investigate the improvement effect of Necrostatin-1 (Nec-1) on mouse models with immune checkpoint inhibitor (ICI) -associated myocarditis (ICIAM) and potential mechanism. Methods Ten male BALB/c mice aged 6-8 weeks were selected to construct the ICIAM models. The echocardiography and serum myocardial injury markers were used to assess cardiac function of mice. The levels of inflammatory markers including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Hematoxylin-eosin (HE) staining was used to evaluate myocardial inflammation, and Masson staining was used to evaluate myocardial fibrosis. The expressions of myocardial necroptosis proteins including receptor-interacting protein kinase 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL) and their phosphorylated forms were detected by Western blotting. The spleen lymphocytes were extracted and co-cultured with HL-1 cell line. Cell viability was measured by cell counting kit-8 (CCK-8). The release of reactive oxygen species (ROS) and changes of mitochondrial membrane potential were observed. RIP1, RIP3, MLKL and their phosphorylated forms were determined. The levels of markers of oxidative stress, including malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were measured. Results Nec-1 significantly improved the cardiac function injury of mice induced by ICI, and inhibited the release of TNF-α and IL-1β in plasma of ICIAM mice (P＜0.001); inhibited expressions of phosphorylated RIP1, RIP3 and MLKL (P＜0.05); decreased MDA activity, and increased SOD and GSH-Px activity (P＜0.001). In HL-1 cells, Nec-1 intervention inhibited the RIP1-RIP3-MLKL pathway (P＜0.05), improved decrease of the cell viability induced by lymphocytes (P＜0.001), decreased ROS release, increased mitochondrial membrane potential, inhibited MDA activity, and increased SOD and GSH-Px activities (P＜0.001). Conclusions Necroptosis plays an important role in the occurrence and development of ICIAM，but Nec-1 could alleviate the progression of ICIAM by inhibiting necroptosis induced by oxidative stress in cardiomyocytes; RIP1 maybe a new target in treatment of ICIAM.

To investigate the distribution of common inhalant and food allergens test results in children in Suzhou by gender, age and disease group, and to analyse the changes in allergen distribution in the different years, to provide theoretical guidance for the diagnosis, treatment and monitoring of children′s allergic diseases in Suzhou City. A retrospective cross-sectional study was conducted to analyze the 2 736 children (1 654 males and 1 082 females) who were diagnosed and tested serum content of specific immunoglobulin E (sIgE) antibodies to inhalant and food allergens in the Children′s Hospital of Soochow University between October 2017 and June 2024. The allergen sIgE positive rates epidemiological characteristics were statistically analyzed by Chi square test by grouping based on different year, gender, age and disease. The results showed that a total of 2 736 children screened for allergens, with an overall positive allergen sIgE rate of 73.06%(1 999/2 736), and the top five allergen sIgE positive rates were Dermatophagoides farinae (40.75%, 1 115/2 736), Dermatophagoides pteronyssinus (38.78%, 1 061/2 736), milk (34.65%, 948/2 736), egg whites (32.68%, 894/2 736) and molds and yeasts mixes (mx2) (24.82%, 679/2 736). The positive rates of food allergen sIgE were higher in the 2017-2019 (60.46%, 370/612) than the 2020-2022 (53.79%, 149/227) and after the 2023-2024 (48.46%, 895/1 847) ( χ2=27.059, P<0.001); The positive rates of inhaled allergen sIgE were lower in the 2017-2019 (40.03%, 245/612) than the 2020-2022 (52.71%, 146/227) and the 2023-2024 (56.04%, 1 035/1 847)( χ2=47.223, P<0.001). The positive rates of inhaled allergen sIgE in males (54.96%, 909/1 654) were higher than those in females (47.78%, 517/1 082) ( χ2=13.497, P<0.001). The total positive rate for the food allergen sIgE was highest at 1-3 years of age (67.55%, 589/872) and then gradually decreased with age ( χ2=194.095, P<0.001); The total positive rate of inhaled allergen sIgE was lowest at the age of less than 1 year (8.33%, 22/206) and then gradually increased with age ( χ2=300.329, P<0.001). The positive rates of food allergen sIgE, in descending order from high to low were asthma (59.40%), atopic dermatitis and eczema (48.10%), other groups (48.02%), allergic rhinitis (45.73%) and urticaria (40.00%); The positive rates of inhaled allergen sIgE were asthma (71.05%), allergic rhinitis (63.57%), atopic dermatitis and eczema (62.17%), urticaria (40.00%) and other groups (49.76%), and the difference between disease subgroups were statistically significant( χ2 were 64.841 and 19.055, P<0.05). In conclusion, the top four allergen sIgE positive rates for children in the Suzhou area were Dermatophagoides farinae, Dermatophagoides pteronyssinus, milk and egg white. Total sIgE positive rates for food allergens decreased progressively in the 2017-2019, 2020-2022 and 2023-2024, and total positive rates for inhalant allergens increased progressively in the 2017-2019, 2020-2022 and 2023-2024. The distribution of allergen positive varies with gender, age and disease.

Objective:To analyze the pathogen spectrum and epidemiological characteristics of acute respiratory infections in Yantai from 2024 to 2025.Methods:Influenza-like illness（ILI）and severe acute respiratory infection（SARI）patients were enrolled from the national sentinel hospitals for acute respiratory infectious diseases in Yantai between January 2024 and April 2025. Oropharyngeal swab samples were collected and 16 common respiratory pathogens were tested using real-time quantitative PCR. Descriptive epidemiological methods were used to analyze the detection results.Results:A total of 1 499 cases were included in the study，including 1 070 ILI cases and 429 SARI cases. The overall positive rate of respiratory pathogens was 52.57%（788/1 499）. All of the 16 targeted respiratory pathogens were detected，with influenza virus A（FluA），SARS-CoV-2， Haemophilus influenzae（ Hi），and human adenovirus（HAdV）being the predominant pathogens. The co-infection rate was 6.27%（94/1 499），with FluA combined with Hi infection being the predominant type. Statistically significant differences in the positive rates of influenza B virus and SARS-CoV-2 were observed between male and female patients（both P<0.05）. The overall positive rates varied significantly across different age groups（ P<0.001），with the highest rate（64.62%，84/130）observed in the 4-14 year age group. The overall positive rates also varied significantly among different months（ P<0.001），with the highest rate in December（69.93%，107/153）. The overall positive rate was 57.48%（615/1 070）in ILI cases and 40.33%（173/429）in SARI cases，with statistically significant difference between the two groups（ P<0.001）. Influenza viruses and SARS-CoV-2 were the predominant pathogens in ILI cases，whereas HAdV and Mycoplasma pneumoniae were more common in SARI cases. Conclusions:FluA，SARS-CoV-2， Hi，and HAdV are the predominant pathogens causing acute respiratory infections in Yantai from January 2024 to April 2025. The positive rates of respiratory pathogens varies across different gender and age groups，and shows distinct seasonal patterns. There are significant differences in pathogen spectra between ILI and SARI cases.

Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

Noggin is a protein secreted by human cells and belongs to the bone morphogenetic protein (BMP) family, which can inhibit the formation and proliferation of bone tissue. The initial research found that Noggin is mainly involved in the development of the embryonic skeletal and nervous systems in vertebrate embryos. Subsequent studies have found that Noggin also plays an important role in bone metabolism and bone mineral density regulation in adults, mainly by regulating the activities of signaling pathways such as Wnt/β-catenin, notch and hedgehog. Meanwhile, there is also a certain mutual influence among various channels. This article mainly reviews the relevant research on the regulation of osteoporosis by Noggin in signaling pathways, clarifies the related mechanism of Noggin in various signaling pathways, and analyzes the current research status and prospects of Noggin.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Objective To study the predictive value of adenosine monophosphate-activated protein kinase(AMPKα)and hepatocyte nuclear factor 4(HNF4)expression for local recurrence and distant metastasis after laparoscopic radical gastrectomy for gastric cancer.Methods Two hundred and ninety-four patients who underwent laparoscopic radical gastric cancer surgery admitted to Suining Central Hospital from January 2020 to August 2022 were selected.These patients were categorized into a recurrence and metastasis group(n=59)and a non-recurrence and non-metastasis group(n=235)based on postoperative local recurrence and distant metastasis.Gastric cancer tissue specimens obtained from surgical resection were used to detect and compare the cancer tissues of AMPKα mRNA and HNF4 mRNA between the two groups,and the data were statistically analyzed.Results The AMPKα mRNA and HNF4 mRNA in the recurrence and metastasis group were lower than those in the non recurrence and metastasis group(P<0.05);the point-biserial correlation showed that AMPKα mRNA(r=-0.816)and HNF4 mRNA(r=-0.803)were negatively correlated with postoperative local recurrence and distant metastasis(P<0.001),and the net correlation analysis showed that this relationship still existed after excluding confounding factors(P<0.001).Logistic regression analysis showed that AMPKα mRNA and HNF4 mRNA were postoperative local recurrence and distant metastasis related influencing factors(P<0.001);the interaction analysis showed that AMPKα mRNA and HNF4 mRNA were in a super multiplication model,and the decrease of HNF4 mRNA had a positive interaction effect on the decrease of AMPKα mRNA(P<0.05);the AUC of AMPKα mRNA+HNF4 mRNA was higher than that of AMPKα mRNA or HNF4 mRNA(Z=4.261,4.275,P<0.05).Conclusion Co-mbined detection of AMPKα and HNF4 expression can predict the risk of local recurrence and distant metastasis after laparoscopic radical gastrectomy for gastric cancer.

Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

Background and Aims:Pancreatic cancer is one of the most aggressive malignancies of the digestive system and is associated with an inferior prognosis.In recent years,its incidence has shown a trend toward younger onset.Early-onset pancreatic cancer(EOPC),defined as pancreatic cancer diagnosed at≤50 years of age,has been increasing annually and may possess distinct biological and prognostic characteristics.Given the limited data from China,this study aimed to investigate the clinicopathological features and prognostic outcomes of EOPC patients.Methods:Clinical data of 113 patients with EOPC admitted to Xiangya Hospital,Central South University,from January 2017 to December 2023 were retrospectively analyzed.Variables included demographic characteristics,clinicopathological features,and survival information.Kaplan-Meier survival curves were plotted,and differences in survival between the surgical and non-surgical groups were compared.Results:The median age at diagnosis was 46(42-49)years,and males accounted for 65.49%of cases.Blood type A(40.71%)and type O(34.51%)were most common.The main presenting symptoms were abdominal pain(69.91%),weight loss(62.83%),jaundice(43.36%),and abdominal distension(36.28%).Imaging findings showed bile duct dilation in 32.74%,pancreatic duct dilation in 39.82%,vascular invasion in 59.29%,and distant metastasis in 52.21%of patients.Histopathology revealed that adenocarcinoma and ductal adenocarcinoma accounted for 93.81%of all cases,with predominantly moderate or poor differentiation(76.10%).Tumors were the most frequently located in the pancreatic head(65.42%).TNM staging showed lymph node metastasis in 77.88%and stage Ⅳ disease in 52.21%.Laboratory tests demonstrated markedly elevated CA19-9 levels.Kaplan-Meier analysis indicated a median overall survival of 18.6 months for the entire cohort,with significantly longer survival in the surgical group compared with the non-surgical group(29.4 months vs.13.8 months,P=0.001 5).Conclusion:EOPC predominantly affects males and tends to arise in the pancreatic head.It is often diagnosed at an advanced stage or with distant metastasis and is characterized by poor differentiation and strong invasiveness.Surgical resection markedly improves survival and remains the key to prolonged prognosis.Young individuals presenting with unexplained abdominal pain,weight loss,or jaundice should be carefully evaluated through imaging to enable early diagnosis and timely surgical intervention.Future multicenter,large-sample prospective studies are warranted to validate these findings further.