In the ever-evolving landscape of cancer therapy, while cancer treatments such as chemotherapy, radiotherapy, and targeted therapy aim to eradicate malignant cells, they also inadvertently trigger cellular senescence in both cancerous and microenvironmental tissues. Therapy-induced senescence (TIS) can act as a barrier against tumor growth by halting cell proliferation in the short term, but the long-term persistence of therapy-induced senescent (TISnt) cells may pose a significant challenge in cancer management. Their distinct characteristics, like senescence-associated secretory phenotype (SASP), metabolic dysregulation, and immune evasion, make them exhibit remarkable heterogeneity to orchestrate the tumor microenvironment (TME), resulting in therapy resistance. However, how these TISnt cells functioning differently in cancer progression, and the intricate mechanisms by which they remodel the senescence-associated immunosuppressive microenvironment present challenges for improving anticancer therapy. Therefore, this review summarizes the heterogeneous TISnt cell phenotypes contributing to an accumulated senescent state, outlines their multidimensional interactions in the senescent microenvironment, and discusses current senescence-targeting strategies. Building on the current understanding of TIS, we propose potential avenues for improving TIS-targeting methodologies in the context of head and neck cancer, a representative heterogeneous malignancy, which can substantially enhance the efficacy of the "one-two punch" sequential treatment approach for head and neck cancer.
Humans ; Cellular Senescence/drug effects* ; Tumor Microenvironment ; Neoplasms/pathology* ; Senescence-Associated Secretory Phenotype

Objective:To investigate the value of the ratio of heparin binding protein (HBP) to albumin (ALB) in diagnosis and predict the severity of Kawasaki disease shock syndrome (KDSS).Methods:This study was a retrospective study. Pediatric patients with Kawasaki disease (KD) admitted to the Children's Intensive Care Unit and department of Pediatric Emergency Center of Hunan Children's Hospital from January 2019 to May 2022 were enrolled. The HBP/ALB ratio was calculated according to HBP and serum ALB. The children were divided into three groups (low, medium, and high ratio groups) according to the median and upper and lower quartiles of the HBP/ALB ratio. The differences of each index among the three groups were compared. The receiver operating characteristic curves were drawn to evaluate the clinical value of the HBP/ALB ratio in diagnosis of KDSS and the severity of the disease.Results:A total of 111 cases were included in this study, including 28 cases in the low ratio group, 56 cases in the medium ratio group, and 27 cases in the high ratio group. There were 24 cases with coronary artery damage, 87 cases without coronary artery damage, 27 cases with abnormal ECG findings, and 17 children with KDSS (including 5 cases in the medium ratio group, and 12 cases in the high ratio group). The incidence of KDSS, coronary involvement, and abnormal electrocardiogram proportions in the high ratio group were significantly higher than those in the other two groups. Compared with low and medium ratio groups, the levels of cardiac troponin I, N-terminal pro-brain natriuretic peptide, lactate, stroke output variation, trends in thoracic fluid content, white blood cell count, C-reactive protein, procalcitonin, and D-dimer levels were higher in the high ratio group, while ALB and blood sodium levels were lower in the high ratio group (all P<0.05). There was no significant difference in above indicators between the low and medium ratio groups (all P>0.05). The HBP/ALB ratio had a higher area under the curve, sensitivity, and specificity (0.942, 0.882, and 0.883, respectively) in predicting KDSS compared to HBP alone (0.776, 0.842, and 0.670, respectively). Conclusion:The HBP/ALB ratio could reflect the severity of children with KD and has certain clinical value for prognostic evaluation.

Sepsis is a common critical illness in pediatric intensive care unit,and its prognosis assessment has always been a challenge in pediatric critical care researches.In 2016,Sepsis 3.0 defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.The diagnostic criteria were revised to include a sequential organ failure assessment (SOFA) score increase ≥2 points from baseline in infected/suspected infected patients.However,aforementioned guidelines primarily focus on adults.Considering the unique physiological characteristics of children,the pediatric sequential organ failure assessment (pSOFA) was developed.Currently,the definition of pediatric sepsis has not been updated to include organ dysfunction,and the use of the pSOFA score is not widespread.This review introduced the background,content,and application of the pSOFA score,and compared it with other scoring systems to determine its advantages and application range in prognosis assessment.Finally,it summarized the value of pSOFA score in the prognosis assessment of pediatric sepsis,aiming to provide references for clinical applications.

Objective To analyze the effectiveness of a tele-diet combined exercise intervention program in elderly patients with type 2 diabetes mellitus combined with sarcopenia.Methods The selection of 80 cases of elderly patients with type 2 diabetes mellitus combined with sarcopenia was conducted from December 2022 to February 2023 in 2 communities in Urumqi City,and the 2 communities were randomly divided into an experimental group and a control group,with 40 cases in each group.The experimental group carried out the intervention of dietary combined with exercise through tele-technology on the basis of the routine health education,and the control group implemented the routine health education.The scores of somatic functions,muscle strength and quality of life of patients with sarcopenia were compared between the 2 groups before and after the intervention.Results After the intervention,6-meter step speed,5 sit-to-stand tests,grip strength index,and quality of life in the experimental group were better than those in the control group,and the difference was statistically significant(P＜0.05).Conclusion Tele-diet combined with exercise intervention positively affects somatic function,muscle strength,and quality of life in elderly patients with T2DM combined with sarcopenia.

Objective:To analyze the characteristics of child cases admitted to accidental injury and provide reliable basis for the prevention of accidental injury.Methods:The clinical data of children admitted to Hunan Children′s Hospital aged 0-18 due to accidental injuries from January 1, 2018 to December 31, 2021 were retrospectively analyzed. The type of accidental injury and characteristic factors such as prognosis, gender, age, time, and location of the child were analyzed.Results:A total of 9 049 children with accidental injury were admitted, accounting for 3.72%(9 049/33 697) of the total number of hospitalized children. The top three types of accidental injuries were falls/drop (3 695 cases), foreign bodies/suffocation (2 639 cases) and traffic accidents (1 165 cases), accounting for 82.87%(7 499/9 049). There were 8 760 cases (96.81%) of improvement and recovery, 178 cases (1.97%) of disability, and 111 cases (1.23%) of unhealed/dead. Among the accidental injuries, 5 833 cases (64.46%) were boys and 3 216 cases (35.54%) were girls, and the incidence ratio was 1.81∶1. There was significant difference between boys and girls in the composition ratio of the type of accidental injury such as falls/falls, foreign bodies/suffocation, poisoning, sharp object injury, drowning ( χ2 values were 3.90-20.56, all P<0.05). Among the accidental injuries, the children aged 1 to<3 years had higher accidental injuries than the other age groups (3 263 cases, accounting for 36.06%), and the composition ratio of accidental injuries in different age groups was different ( χ2 values were 12.98-573.97, all P<0.05). Among the accidental injuries, the accidental injuries occurred in the second quarter and the third quarter were higher than those in the other two quarters (4 892 cases, accounting for 54.06%), and the composition ratio of accidental injuries such as falls/falls, foreign bodies/suffocation, burn and scald, drowning occurred in different quarters was different ( χ2 values were 10.79-18.88, all P<0.05). In the case of accidental injuries, the family was the most likely place of accidental injury, with different types of accidental injuries occurring in different places ( χ2 values were 10.08-2 186.54, all P<0.05). Conclusions:Children′s unintentional injuries are most likely to occur in boys aged 1-<3 years, and fall/fall is the main injury type. Traffic accidents are the most important unintentional injury type leading to children′s unhealed/dead. Different injury types were related to child gender, age, quarter, and place of occurrence.Due to the differences in the occurrence mechanism and injury mode of accidental injuries in different countries and regions, and the majority of accidental injuries can be prevented, targeted preventive measures should be taken according to the characteristics of children′s accidental injuries in different regions, and a comprehensive prevention system for children′s accidental injuries should be constructed to ensure children′s safety.

Objective:To explore the clinical value of serum insulin combined with cardiac-related markers in evaluating the severity of sepsis associated encephalopathy (SAE).Methods:The clinical data of 130 children with sepsis who admitted to the Pediatric Intensive Care Unit of Hunan Children's Hospital from January 2018 to December 2021 were analyzed retrospectively, and the differences of serum insulin and cardiac-related markers in children with sepsis and SAE were compared.Results:The levels of serum insulin, creatine kinase isoenzyme, hypersensitive troponin T, and N-terminal cerebral urine peptide in the SAE group were significantly higher than those in the non-SAE group ( P<0.05), but there was no significant difference in heart rate and lactic acid ( P>0.05). The levels of serum insulin, creatine kinase isoenzyme, hypersensitive troponin T, N-terminal cerebral urine peptide and lactic acid in the death group were significantly higher than those in the survival group ( P<0.05), while the heart rate was not significantly different ( P>0.05). The area under ROC curve of serum insulin, creatine kinase isoenzyme, hypersensitive troponin T, and N-terminal cerebral urine peptide in predicting SAE were 0.841, 0.599, 0.700, and 0.667, respectively; in terms of judging the prognosis of sepsis, the area under ROC curve were 0.647, 0.669, 0.645, and 0.683, respectively; and in terms of judging the prognosis of children with SAE, the areas under the ROC curve were 0.509, 0.682, 0.666 and 0.555, respectively. Binary logistic regression equation was established with serum insulin, creatine kinase isoenzyme, hypersensitive troponin T, and N-terminal cerebral urine peptide: Y=8.153×NT-proBNP+1.704×CTnT-hs+27.121×insulin+0.946×CK-MB+1.573. The area under the ROC curve of the new variable Y in predicting sepsis SAE, evaluating the prognosis of sepsis, and predicting the prognosis of children with sepsis and SAE was 0.890, 0.756, and 0.729, respectively. Conclusions:Serum insulin, creatine kinase isoenzyme, hypersensitive troponin T, and N-terminal cerebral urine peptide can be used alone to determine the severity of sepsis and sepsis in children with SAE. The combined value of the four indicators is obviously better than that of the single indicator. The combined application of the four indicators may better evaluate the severity of sepsis and SAE.

Objective:To study the clinical features of children with pertussis and the risk factors of severe pertussis.Methods:A retrospective analysis was performed based on clinical data and laboratory examination results of hospitalized children with pertussis who admitted to the intensive care unit, respiratory department, and emergency general department at Hunan Children′s Hospital from January 2019 to March 2020.According to the age, the patients were divided into age ≤3 months group( n=58)and age >3 months group( n=64). According to sputum culture, 63 cases were divided into negative sputum culture group and 59 cases were positive sputum culture group.The patients were also divided into vaccinated group( n=19)and unvaccinated group( n=103). Severe disease was seen in 28 cases, and the other 94 cases had the modest disease.The clinical characteristics between two groups were compared, and the risk factors of severe pertussis pneumonia were analyzed. Results:The hospitalization days in age ≤3 months group was higher than that in age >3 months group.It was also found that shortness of breath, apnea, cyanosis after coughing, heart rate decline were more common in age ≤3 months group than those in age >3 months group( P<0.05). The incidences of respiratory failure and heart failure in positive sputum culture group were higher than those in negative sputum culture group.Clinical characteristics such as hospitalization days, hospitalization expenses, peak white blood cell count, peak lymphocyte count, and incidence of bacterial infection were higher in severe pertussis group than those in non-severe pertussis group( P<0.05). Four patients were treated with exchange blood transfusion, and one patient died.Logistic regression analysis revealed that fever, wheezing, cyanosis after coughing and white blood cell count>20×10 9/L were risk factors for severe pertussis.White blood cell count of 20×10 9/L and lymphocyte count of 14×10 9/L had the highest sensitivity and specificity in predicting severe pertussis(0.71, 0.78; 0.54, 0.79). Conclusion:The younger the children are, the more likely they have shortness of breath, apnea, cyanosis, heart rate falls, and the longer the hospital stay.Bacterial infection will aggravate pertussis.Patients with fever, wheezing, cyanosis after coughing, and white blood cell count>20×10 9/L are more likely to develop severe pertussis.The white blood cell count >20×10 9/L and the lymphocyte count >14×10 9/L are associated with severe pertussis.

Objective:To explore the application value of heparin-binding protein (HBP) in the early diagnosis and assessment of severe adenovirus pneumonia.Methods:A total of 90 children diagnosed with adenovirus pneumonia admitted in the Department 1 of Emergency and Pediatric Intensive Care Unit 1 in Hunan Children′s Hospital from January 2019 to March 2020 were recruited.HBP levels in children with adenovirus pneumonia were detected.The correlation between HBP with white blood cell count (WBC), neutrophil ratio (N), C-reactive protein (CRP), interleukin-6(IL-6) and erythrocyte sedimentation rate (ESR) were examined.Receiver operating characteristic(ROC) curve analysis was conducted to explore the value of HBP in the early diagnosis and assessment of severe adenovirus pneumonia.Children with adenovirus pneumonia were divided into severe adenovirus pneumonia group (severe group) and non-severe adenovirus pneumonia group (non-severe group) according to their severity.Those in the severe group were further divided into bronchiolitis obliterans(BO) group and non-BO group according to the occurrence of BO.Results:(1) The HBP level in children with adenovirus pneumonia was (49.47±34.19) μg/L, which was significantly higher in the severe group than that of non-severe group[(82.88±44.02) μg/L vs.(35.15±13.08) μg/L, t=15.349, P<0.05]. Children in the severe group were significantly younger, and they had a significantly longer length of stay, lower Pediatric Critical Illness Scores (PCIS), and higher inflammatory markers like HBP, WBC, N, CRP, IL-6, and ESR compared with those of the non-severe group (all P<0.05). No significant difference in the procalcitonin (PCT) level was detected between groups.(2) The HBP was positively correlated with inflammatory markers like WBC ( r=0.38, P<0.05), N ( r=0.26, P<0.05), CRP ( r=0.47, P<0.05), IL-6 ( r=0.76, P<0.05), and ESR ( r=0.35, P<0.05). However, HBP did not have a significant correlation with PCT ( r=0.097, P>0.05). (3) In the severe group, the HBP level of the children with invasive mechanical ventilation, oxygenation index(P/F index)≤ 200 mmHg (1 mmHg=0.133 kPa) and BO was significantly higher than that of the non-invasive mechanical ventilation, P/F index> 200 mmHg and non-BO (all P<0.05). (4) The area under the ROC curve of HBP, WBC, N, CRP, ESR and IL-6 in predicting the severity of adenovirus pneumonia were 0.915, 0.748, 0.770, 0.740, 0.820 and 0.798, respectively.When the cut-off value of HBP was 45 μg/L, the sensitivity and specificity of HBP were 81.48% and 85.71%, respectively. Conclusions:As an inflammatory mediator, HBP is involved in the inflammatory response of the body.It may be a useful new marker for the early diagnosis of severe adenovirus infection, which also has a certain value in the evaluation of the severity and prognosis of the disease.The findings provide a basis for early clinical intervention and treatment of adenovirus infection in children.

Objective:To observe the therapeutic effect of echinacoside (ECH) on liver injury and glucose metabolism disorder in sepsis rats induced by cecal ligation and puncture (CLP), and to explore its possible mechanism.Methods:Forty eight male Sprague Dawley (SD) rats were randomly divided into four groups: sham group (sham), model group (CLP), treatment group (CLP+ ECH) and inhibitor group (CLP+ ECH+ EX527). The sham group only received laparotomy, and the model group underwent CLP. The treatment group was intragastric administration of echinacea (30 mg/kg) every day after CLP modeling. The inhibitor group was injected with silence information regulator 1 (SIRT1) inhibitor EX527 (5 mg/kg) one hour before CLP, and then treated the same as the treatment group. Fasting blood glucose, insulin and serum biochemical indexes were detected in virous groups. The serum levels of interleukin (IL)-1 β, IL-6 and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). 2′, 7′- dichlorofluorescein diacetate (DCFH-DA) staining was used to observe the production of reactive oxygen species (ROS) in liver tissue of rats in each group; hematoxylin-eosin (HE) staining was used to observe the pathological changes of liver tissue in each group; The expressions of SIRT1, glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), phosphorylated signal transducers and activators of transcription 3 (p-STAT3) and phosphorylated protein ki-nase B(p-AKT) were detected by Western blot.Results:Compared with sham group, the levels of serum glucose, serum insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), ROS, IL-1β, IL-6 and TNF-α in model group increased, while the liver glycogen and survival rate decreased (all P<0.05). After echinacoside treatment, the serum glucose, serum insulin, ALT, AST, ROS , IL-1β, IL-6 and TNF-α levels decreased, and the liver glycogen and survival rate increased (all P<0.05); After SIRT1 inhibitor intervention, the levels of serum insulin, ALT, AST, IL-6 and ROS in the inhibitor group increased ( P<0.05). HE staining showed that there were infiltration and necrosis of inflammatory cells in the liver tissue of model group, and echinacoside could significantly reduce the focal and massive necrosis; Western blot showed that compared with the sham group, the expression levels of SIRT1, p-STAT3 and p-AKT protein in the model group decreased, while the expression levels of G6Pase and PEPCK protein increased ( P<0.05); After echinacoside treatment, the expression levels of SIRT1, p-STAT3 and p-AKT increased, while the expression levels of G6Pase and PEPCK decreased ( P<0.05). After SIRT1 inhibitor intervention, the expression of SIRT1, p-STAT3 and p-AKT protein decreased, and the expression of G6Pase and PEPCK protein increased in the inhibitor group ( P<0.05). Conclusions:Echinacoside is a potential therapeutic agent for sepsis associated liver injury and glucose metabolism disorders, which may play a role by targeting SIRT1 to activate STAT3 and AKT in the liver.

Objective:To investigate whether miRNA-296-5p can inhibit enterovirus 71 (EV71) virus replication in neural cells SK-N-SH by targeting the phosphatase and tensin homology deleted on chromosome 10 (PTEN)/phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinases (AKT) signaling pathway.Methods:Serum samples were collected from patients with EV71 virus-infected hand-foot-mouth disease and normal physical examination, and the expressions of serum inflammatory factors procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) , interleukin-6 (IL-6), IL-1β, and IL-13 were detected by enzymelinked immunosorbent assay (ELISA). Human neuroblastoma SK-N-SH cells infected by EV71 virus in logarithmic growth phase were set up as control group, miRNA-296-5p mimic group and miRNA-296-5p inhibitor group. The transfection was carried out according to the Lipofectamine 2000tm cell transfection reagent. The expression of EV71-VP1 gene mRNA and protein and PTEN/PI3K/Akt signal pathway related molecules in three groups of cells was observed by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) and Western blot.Results:ELISA test results showed that the levels of serum inflammatory factors PCT, CRP, TNF-α, IL-1β, IL-6 and IL-13 in patients with EV71 virus-infected hand, foot and mouth disease were significantly higher than those in normal physical examination ( P<0.05). The results of qRT-PCR and Western blot showed that the mRNA and protein levels of mirna-296-5p and PTEN in SK-N-SH were significantly decreased after EV71 virus infection, while the mRNA and protein levels of EV71-VP1 and molecules related to PI3K/AKT signaling pathway were significantly increased ( P<0.05). The expression of PTEN was significantly increased in the miRNA-296-5p mimic group, and the expression of EV71-VP1 and the activation of the PI3K/AKT signaling pathway were inhibited, while the effect was reversed in the miRNA-296-5p inhibitor group ( P<0.05). Conclusions:MiRNA-296-5p inhibits the replication of EV71 virus in neural cells SK-N-SH by targeting the PTEN/PI3K/AKT signaling pathway, while reducing the cellular inflammatory response, targeting miRNA-296-5p and downstream PTEN/PI3K/AKT The signal pathway is expected to provide therapeutic targets and theoretical basis for the treatment of hand-foot-mouth disease caused by clinical EV71 virus.