Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Objective:To investigate the disease-modifying effect of long-course use of Omalizumab (OMZ) on children and adolescents with allergic asthma.Methods:Retrospective cohort study.The clinical data of 66 children with moderate to severe allergic asthma treated with OMZ in the Department of Pediatrics, the Second Hospital of Tianjin Medical University from April 2019 to June 2024 were analyzed.According to the course of OMZ, the patients were divided into a short course group (33 cases), a medium course group (21 cases), and a long course group (12 cases).The courses of treatment of the 3 groups were 6-<12, 12-<24 and 24 months or more, respectively.Pulmonary ventilation functions [including the percentage of forced expiratory volume in the first second to the expected value (FEV 1%pred), the peak expiratory flow rate to the expected value (PEF%pred), and the maximum mid-expiratory flow to the expected value (MMEF%pred)], fractional exhaled nitric oxide (FeNO) and the absolute value of peripheral blood eosinophils (EOS) were analyzed before and after OMZ treatment.Moreover, whether allergic asthma and comorbidities such as allergic rhinitis (AR), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU) were controlled was explored.Changes in inhaled corticosteroids (ICS) and serum total immunoglobulin E (TIgE) levels were measured.The paired t-test was used for testing measurement data with normal distribution, and the rank sum test for testing non-normally distributed data. Results:(1)Changes of pulmonary ventilation function, FeNO and EOS: the pulmonary ventilation function in the short course group, the FEV 1%pred and MMEF%pred in the medium course group, and the PEF%pred and MMEF%pred in the long course group were improved compared with those at baseline (all P<0.05).FeNO levels in all the 3 groups decreased, compared with those at baseline (all P<0.05).There was no significant difference in peripheral blood EOS between the 3 groups compared with those at baseline (all P>0.05).(2)Control status of allergic asthma and comorbidities: the Asthma Control Test/Childhood Asthma Control Test (ACT/C-ACT), Asthma Control Questionnaire (ACQ) scores and the visual analogue scores (VAS) of rhinitis improved in all 3 groups, compared with those at baseline (all P<0.05).Among 4 patients complicated with AD, 3(75.0%) showed decreased Scoring Atopic Dermatitis Index(SCORAD) scores, compared with those at baseline.Of the 6 children complicated with CSU, 5(83.3%) did not develop rash after injection.(3)Frequency of acute exacerbations of asthma: the number of acute exacerbations of asthma after treatment was lower than that before treatment in all the 3 groups (all P<0.05).The number of attacks in the long course group was decreased in the third year, compared with that in the first year ( P<0.05).(4)The ICS consumption: the ICS consumption in all the 3 groups was significantly decreased, compared with that at baseline (all P<0.05).Six patients (28.6%) in the medium course group had no recurrence within 1 year after stopping ICS therapy.One of the 7 patients (14.3%) in the long course group had stopped ICS for more than 2 years, and 3 patients (42.9%) had stopped ICS for more than 1 year.These 4 children had no recurrence.(5)The change of TIgE: in the short and medium course groups, serum TIgE levels at the end of treatment were higher than those at baseline (all P<0.05).The serum TIgE level in the second year of treatment was higher than that at baseline in the long course group ( P<0.05).The serum TIgE level in the third year of treatment was decreased, compared with that in the second year ( P<0.05). Conclusions:OMZ can improve lung function and FeNO levels, reduce the incidence of acute exacerbations of asthma, and lower ICS usage in children.At the same time, it can also improve the allergic diseases AR, AD and CSU.The prolonged treatment of OMZ can bring long-term sustained benefits to children.The changes in serum TIgE and FeNO levels may suggest that the long-term application of OMZ plays a disease-modifying role in allergic asthma.

Objective:To investigate the disease-modifying effect of long-course use of Omalizumab (OMZ) on children and adolescents with allergic asthma.Methods:Retrospective cohort study.The clinical data of 66 children with moderate to severe allergic asthma treated with OMZ in the Department of Pediatrics, the Second Hospital of Tianjin Medical University from April 2019 to June 2024 were analyzed.According to the course of OMZ, the patients were divided into a short course group (33 cases), a medium course group (21 cases), and a long course group (12 cases).The courses of treatment of the 3 groups were 6-<12, 12-<24 and 24 months or more, respectively.Pulmonary ventilation functions [including the percentage of forced expiratory volume in the first second to the expected value (FEV 1%pred), the peak expiratory flow rate to the expected value (PEF%pred), and the maximum mid-expiratory flow to the expected value (MMEF%pred)], fractional exhaled nitric oxide (FeNO) and the absolute value of peripheral blood eosinophils (EOS) were analyzed before and after OMZ treatment.Moreover, whether allergic asthma and comorbidities such as allergic rhinitis (AR), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU) were controlled was explored.Changes in inhaled corticosteroids (ICS) and serum total immunoglobulin E (TIgE) levels were measured.The paired t-test was used for testing measurement data with normal distribution, and the rank sum test for testing non-normally distributed data. Results:(1)Changes of pulmonary ventilation function, FeNO and EOS: the pulmonary ventilation function in the short course group, the FEV 1%pred and MMEF%pred in the medium course group, and the PEF%pred and MMEF%pred in the long course group were improved compared with those at baseline (all P<0.05).FeNO levels in all the 3 groups decreased, compared with those at baseline (all P<0.05).There was no significant difference in peripheral blood EOS between the 3 groups compared with those at baseline (all P>0.05).(2)Control status of allergic asthma and comorbidities: the Asthma Control Test/Childhood Asthma Control Test (ACT/C-ACT), Asthma Control Questionnaire (ACQ) scores and the visual analogue scores (VAS) of rhinitis improved in all 3 groups, compared with those at baseline (all P<0.05).Among 4 patients complicated with AD, 3(75.0%) showed decreased Scoring Atopic Dermatitis Index(SCORAD) scores, compared with those at baseline.Of the 6 children complicated with CSU, 5(83.3%) did not develop rash after injection.(3)Frequency of acute exacerbations of asthma: the number of acute exacerbations of asthma after treatment was lower than that before treatment in all the 3 groups (all P<0.05).The number of attacks in the long course group was decreased in the third year, compared with that in the first year ( P<0.05).(4)The ICS consumption: the ICS consumption in all the 3 groups was significantly decreased, compared with that at baseline (all P<0.05).Six patients (28.6%) in the medium course group had no recurrence within 1 year after stopping ICS therapy.One of the 7 patients (14.3%) in the long course group had stopped ICS for more than 2 years, and 3 patients (42.9%) had stopped ICS for more than 1 year.These 4 children had no recurrence.(5)The change of TIgE: in the short and medium course groups, serum TIgE levels at the end of treatment were higher than those at baseline (all P<0.05).The serum TIgE level in the second year of treatment was higher than that at baseline in the long course group ( P<0.05).The serum TIgE level in the third year of treatment was decreased, compared with that in the second year ( P<0.05). Conclusions:OMZ can improve lung function and FeNO levels, reduce the incidence of acute exacerbations of asthma, and lower ICS usage in children.At the same time, it can also improve the allergic diseases AR, AD and CSU.The prolonged treatment of OMZ can bring long-term sustained benefits to children.The changes in serum TIgE and FeNO levels may suggest that the long-term application of OMZ plays a disease-modifying role in allergic asthma.

ObjectiveTo evaluate the quality of research and evidence related to antihypertensive Chinese patent medicines combined with western medicines for the treatment of hypertension， synthesize and update the evidence， form expert consensus， and provide evidence for clinical decision-making. MethodThe databases of China National Knowledge Infrastructure （CNKI）， WanFang Data Knowledge Service Platform （WanFang）， Vip Chinese Science and Technology Journal Database （VIP）， Chinese Biomedical Literature Service System （Sinomed）， National Library of Medicine （PubMed）， Cochrane Library， Web of Science， and US Clinical Trials Registry were searched for randomized controlled trials of antihypertensive Chinese medicine combined with western medicine for the treatment of hypertension from database construction to July 31， 2022. The quality of the literature was evaluated using the bias risk assessment tool in Cochrane Handbook 6.3. Evidence synthesis of main outcome indicators was performed using R software. The Grading of Recommendations Assessment， Development， and Evaluation profiler （GRADEprofiler） 3.6 was employed to evaluate the quality of evidence. Expert consensus was formed based on the Delphi method after two rounds of voting. Result64 pieces of literature were included， and the results of literature quality evaluation and risk of bias showed that 70.31% （45/64） of the studies indicated some risks， and 29.69% （19/64） indicated high risks. Compared with conventional western medicines， the combination of Chinese patent medicines with western medicines can significantly lower systolic pressure （SBP） and diastolic pressure （DBP）， increase the effective rate of antihypertensive， reduce the incidence of adverse reactions， endothelin-1， and traditional Chinese medicine syndrome scores. Egger's test showed that Songling Xuemaikang capsules reduced SBP and DBP. Tianma Gouteng granules reduced SBP and DBP and increased the effective rate of antihypertensive， and Xinmaitong capsules reduced SBP and increased the effective rate of antihypertensive， without significant publication bias. Songling Xuemaikang capsules increased the effective rate of antihypertensive， and Xinmaitong capsules decreased DBP， with significant publication bias. The results of the GRADE evidence quality evaluation showed that most evidence was at grades B and C. Finally， four strong recommendations and 14 weak recommendations were formed. ConclusionCompared with conventional western medicines for the treatment of hypertension， antihypertensive Chinese patent medicines combined with western medicines have advantages in reducing blood pressure and improving drug use safety， but they are mostly weak recommendations in terms of efficacy， and more high-quality evidence is needed.

Oral allergy syndrome（OAS），also known as pollen-food allergy syndrome，is a type of food allergy caused by the cross-reaction of inhaled allergens with food allergens.The clinical manifestations are oral symptoms such as itching，pain and numbness after ingestion of food allergens，and systemic symptoms may be accompanied in severe cases.The main cross-reactive antigens are PR-10 family，lipid transfer proteins，prefibrins and storage proteins.The diagnosis of OAS is mainly based on clinical history，oral food challenge，skin prick test，antigen specific IgE detection，allergen component diagnosis，basophil activation test，etc.OAS patients should strictly avoid allergic foods，and use antihistamines and epinephrine when necessary.Biologics，specific immunotherapy，and oral tolerance induction can also be used to treat OAS，but the efficacy is still controversial.

To construct a recombinant attenuated Salmonella strain carrying the p57 and BLID genes and to evaluate its inhibitory effect on breast cancer cells and apoptosis induction in vitro,the recombinant attenuated Salmonella LH430/pEGFP-p57-BLID was constructed.RT-PCR and Western blot were used to detect the transcription and expression of the recombinant attenuated Salmonella in cancer cells.The CCK-8 method was used to assess the safety of the recombinant at-tenuated Salmonella and its impact on the activity of breast cancer cells.The cell scratch assay was used to analyze the influence of the recombinant attenuated Salmonella on the migratory ability of cancer cells.Flow cytometry and Western blot were used to analyze the effect of the recombinant attenuated Salmonella on the apoptosis of MDA-MB-231 cells.The bands of target genes carried by the recombinant attenuated Salmonella could be amplified by PCR,and these target genes could be transcribed and expressed in MDA-MB-231 cells.The recombinant attenuated Salmonella showed good growth characteristics and genetic stability.Compared with the PBS group,recombi-nant attenuated Salmonella LH430/pEGFP-p57-BLID significantly reduced(P＜0.01)the activity of MDA-MB-231 cells and significantly inhibited(P＜0.01)the migration of MDA-MB-231 cells.Recombinant attenuated Salmonella LH430/pEGFP-p57-BLID can obviously increase the number of apoptosis in MDA-MB-231 cells,significantly upregulate(P＜0.01)the expression of apoptotic protein Bax,and significantly downregulate(P＜0.01)the expression of apoptotic protein Bcl-2.The results showed that the recombinant attenuated Salmonella had an inhibitory effect on breast cancer MDA-MB-231 cells and could induce apoptosis,which laid a foundation for the subsequent study of anti-tumor in vivo.

To construct a recombinant attenuated Salmonella strain carrying the p57 and BLID genes and to evaluate its inhibitory effect on breast cancer cells and apoptosis induction in vitro,the recombinant attenuated Salmonella LH430/pEGFP-p57-BLID was constructed.RT-PCR and Western blot were used to detect the transcription and expression of the recombinant attenuated Salmonella in cancer cells.The CCK-8 method was used to assess the safety of the recombinant at-tenuated Salmonella and its impact on the activity of breast cancer cells.The cell scratch assay was used to analyze the influence of the recombinant attenuated Salmonella on the migratory ability of cancer cells.Flow cytometry and Western blot were used to analyze the effect of the recombinant attenuated Salmonella on the apoptosis of MDA-MB-231 cells.The bands of target genes carried by the recombinant attenuated Salmonella could be amplified by PCR,and these target genes could be transcribed and expressed in MDA-MB-231 cells.The recombinant attenuated Salmonella showed good growth characteristics and genetic stability.Compared with the PBS group,recombi-nant attenuated Salmonella LH430/pEGFP-p57-BLID significantly reduced(P＜0.01)the activity of MDA-MB-231 cells and significantly inhibited(P＜0.01)the migration of MDA-MB-231 cells.Recombinant attenuated Salmonella LH430/pEGFP-p57-BLID can obviously increase the number of apoptosis in MDA-MB-231 cells,significantly upregulate(P＜0.01)the expression of apoptotic protein Bax,and significantly downregulate(P＜0.01)the expression of apoptotic protein Bcl-2.The results showed that the recombinant attenuated Salmonella had an inhibitory effect on breast cancer MDA-MB-231 cells and could induce apoptosis,which laid a foundation for the subsequent study of anti-tumor in vivo.

Objective To investigate the effect of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) on the proliferation, migration and tumor immune microenvironment of colorectal cancer cells and its possible molecular mechanism. Methods The Cancer Genome Atlas (TCGA) database was used to analyze the expression levels of IGF2BP2 and MYC in colorectal cancer and adjacent tissues. The expression of IGF2BP2 in HCT-116 and SW480 human colorectal cancer cells was silenced by RNA interference (RNAi), and the silencing effect was detected by quantitative real-time PCR. After knocking down IGF2BP2, colony formation assay, CCK-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were employed to detect cell colony formation and proliferation ability. Transwell^TM assay was used to detect cell migration ability. Quantitative real-time PCR was used to detect the mRNA expression of IGF2BP2, MYC, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and interleukin-10 (IL-10). The protein expression of IGF2BP2 and MYC was detected by western blot. The binding ability of IGF2BP2 and MYC in HCT-116 cells was detected by quantitative real-time PCR after RNA immunoprecipitation. Results The results of TCGA database showed that the expression of IGF2BP2 and MYC in colorectal cancer tissues was significantly higher than that in adjacent tissues, and the survival time of colorectal cancer patients with high expression of IGF2BP2 was shorter. After silencing IGF2BP2, the viability, proliferation and migration of HCT-116 and SW480 cells were decreased. The mRNA expression of MYC, TGF-β and IL-10 in IGF2BP2 knockdown group was significantly decreased, while the expression of TNF-α mRNA was increased. The expression of MYC protein and the stability of MYC mRNA were significantly decreased. RIP-qPCR results showed that IGF2BP2 could bind to MYC mRNA. Conclusion Knockdown of IGF2BP2 inhibits colorectal cancer cell proliferation, migration and promotes tumor immunity by down-regulating MYC expression.
Humans ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Colorectal Neoplasms/metabolism* ; Gene Expression Regulation, Neoplastic ; Interleukin-10/metabolism* ; RNA, Messenger ; RNA-Binding Proteins/metabolism* ; Transforming Growth Factor beta/genetics* ; Tumor Microenvironment/immunology* ; Tumor Necrosis Factor-alpha/metabolism* ; Proto-Oncogene Proteins c-myc/metabolism*

Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.

Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients' lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K⁺ (mitoK-ATP) channels and mitochondrial complex II. Chlorpropamide delayed aging in Caenorhabditis elegans, human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice. In addition, the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms, which is consistent with the function of its reported targets, mitoK-ATP channels. Increased levels of mitochondrial reactive oxygen species (mtROS) were observed in chlorpropamide-treated worms. Moreover, the lifespan extension by chlorpropamide required complex II and increased mtROS levels, indicating that chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal. This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans.