Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.

Objective: To understand the prevalence of elevated blood pressure and its association with dietary patterns in children and adolescents in China, providing evidence for developing dietary intervention of hypertension in children and adolescents. Methods: Data were derived from the China Children s Nutrition and Health System Survey and Application Project(2019-2021). A stratified cluster random sampling method was used to include 7 933 participants from 28 survey sites in seven major regions of Northeast, North, Northwest, East, Central, South and Southwest China. Multivariate Logistic regression models were used to analyze associations between demographic characteristics, nutritional status and elevated blood pressure. Exploratory factor analysis identified dietary patterns, which were divided into three quartile groups (T3, T2, T1) based on factor scores (compliance for dietary pattern) from high to low, and multivariate Logistic regression model assessed the correlation between elevated blood pressure and dietary patterns. Results: The prevalence of elevated blood pressure was 15.4% among Chinese children aged 7-17 years. Significant differences were observed across nutritional status (reference: underweight; normal weight: OR =1.57; overweight: OR = 2.61 ; obesity: OR =3.85), urban/rural residence (reference: rural; urban: OR =0.86), and paternal education (reference: junior high school and below; bachelor degree or above: OR =0.68) ( P <0.05). The detection rates of high blood pressure in T3 group children and adolescents with four dietary patterns (staple food, animal based food, snacks, vegetables and fruits) were 15.7%, 14.6%, 16.8%, and 15.8%, respectively. After adjusting for residence, paternal education, and nutritional status, the "snack dietary pattern" (mainly candy, sugar sweetened beverages, and processed snacks) showed positive associations with elevated blood pressure in T2 ( OR =1.21) and T3 ( OR =1.19) tertiles ( P <0.05). Conclusions The snack dietary pattern is a related factor for elevated blood pressure in children and adolescents. Restricting unhealthy snack intake may promote cardiovascular health.

Objective To analyze the relationship of total imaging burden score with blood pressure variability(BPV)and cognitive function in elderly patients with cerebral small vessel disease(CSVD).Methods Clinical data of 182 elderly CSVD patients admitted in our hospital from December 2022 to January 2024 were collected and analyzed retrospectively.According to the results of Chinese Guidelines for Diagnosis and Treatment of CSVD-Related Cognitive Dysfunc-tion(2019),Montreal Cognitive Assessment(MoCA)and other tools for their cognitive impair-ment,they were divided into cognitively impaired group(76 cases)and cognitively normal group(106 cases).The total burden score and BPV indicators[24 h systolic blood pressure coefficient of variation(24 h SBPCV),24 h diastolic blood pressure coefficient of variation(24 h DBPCV)]were compared between the two groups.ROC curve was plotted to evaluate the diagnostic value of total burden score,24 h SBPCV and 24 h DBPCV on cognitive impairment in elderly CSVD patients.Multivariate logistic regression analysis was used to identify the risk factors of cognitive impairment in the patients.Based on the MoCA score of the cognitively impaired group,these pa-tients were further assigned into mild and moderate-to-severe cognitive impairment subgroups[with a MoCA score of 18-25(43 cases)and＜18(33 cases),respectively].Then the total burden score,24 h SBPCV and 24 h DBPCV were compared between the two subgroups.Pearson correla-tion coefficient was adopted to evaluate the correlation of severity of cognitive impairment with total burden score,24 h SBPCV and 24 h DBPCV in the elderly CSVD patients.Results The total burden score,24 h SBPCV and 24 h DBPCV were significantly higher in the cognitively impaired group than the cognitively normal group(P＜0.01).ROC curve analysis indicated that total bur-den score(AUC=0.953,95％CI:0.926-0.980,P=0.000),24 h SBPCV(AUC=0.850,95％CI:0.795-0.906,P=0.000)and 24 h DBPCV(AUC=0.761,95％CI:0.690-0.832,P=0.000)had good diagnostic efficiency for cognitive impairment in the elderly CSVD patients,with a cut-off value of 1.5,11.82％,and 8.92％,respectively.Multivariate logistic regression analysis revealed that the above three indicators were risk factors for cognitive impairment in the elderly patients with CSVD(P＜0.05,P＜0.01).Their values were significantly lower in the mild than the moder-ate-to-severe cognitive impairment subgroups(P＜0.01).Pearson correlation analysis displayed that MoCA score was negatively correlated with total burden score,24 h SBPCV and 24 h DBPCV in elderly patients with CSVD(r=-0.755,-0.632,-0.601,P＜0.01).Conclusion Detection of total burden score and BPV indicators is beneficial to the assessment of cognitive impairment in elderly CSVD patients.The higher the total burden score and the greater the BPV indicators,the more severe the cognitive impairment is,which may explore new ideas for clinical diagnosis and treatment of CSVD.

OBJECTIVE To establish the HPLC fingerprint of Xintong granules and the quantitative analysis of multi-components by single-marker method(QAMS)to determine the contents of 7 components,so as to provide a scientific basis for their quality control.METHODS HPLC method was used to establish the fingerprints for 10 batches of Xintong granules(No.S1-S10),and similarity evaluation,cluster analysis(CA)and partial least squares-discriminant analysis(PLS-DA)were performed.At the same time,the contents of seven components,including puerarin,daidzin,calycosin-7-O-β-D-glucoside,stilbene glycoside,naringin,icariin and tanshinone ⅡA,were determined by QAMS method,and were compared with the results of external standard method.RESULTS A total of 18 common peaks were marked and 7 peaks were identified in the HPLC fingerprints for 10 batches of Xintong granules,namely puerarin(peak 4),daidzin(peak 7),calycosin-7-O-β-D-glucoside(peak 9),stilbene glycoside(peak 10),naringin(peak 12),icariin(peak 17),and tanshinone ⅡA(peak 18);the similarities among them were more than 0.990,and CA and PLS-DA results showed that S4-S5,S8-S10,S1-S3 and S6-S7 were clustered into three categories,respectively.Using naringin as the internal standard,the contents of puerarin,daidzin,calycosin-7-O-β-D-glucoside,stilbene glycoside,icariin and tanshinone ⅡA were determined to be 7.868 1-10.181 2,1.709 2-2.374 1,0.285 2-0.326 3,1.024 1-1.523 9,0.140 2-0.290 4,and 0.077 1-0.219 4 mg/g,respectively,by the QAMS.These results showed no significant differences compared to those obtained by the external standard method.CONCLUSIONS Established HPLC fingerprint and QAMS method are convenient,stable and accurate,which can provide a basis for the quality evaluation of Xintong granules.

Objective:To investigate the gene expression of pulmonary metastatic papillary thyroid cancer (PTC) and its association with lung metastasis, facilitating risk assessment and personalized therapeutic strategies.Methods:A retrospective cohort study was conducted on 269 PTC patients (61 males, 208 females, age (38.9±11.9) years) treated at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University from January 2017 to June 2020, including 60 cases with lung metastasis and 209 without. Primary tumor tissues underwent targeted next-generation sequencing (tNGS). Univariate and multivariate logistic regression analyses were performed to identify risk factors for lung metastasis, and χ2 test was used to evaluate the differences between the effective and ineffective groups of radioactive iodine (RAI) therapy. Results:In 60 PTC patients with lung metastasis, the mutation rates of B-Raf proto-oncogene, serine/threonine protein kinase (BRAF) V600E, telomerase reverse transcriptase (TERT) promoter, and rearranged in transformation (RET) fusion mutations were 28.3%(17/60), 25.0%(15/60), and 26.7%(16/60), respectively. Univariate analysis demonstrated that age≥55 years, multifocality, lateral cervical lymph node metastasis, extrathyroidal extension, BRAF V600E mutation, RET fusion, and TERT promoter mutation were significantly associated with lung metastasis in PTC ( Wald χ2 values: 4.13-31.28, all P<0.05). However, no significant statistical associations were observed between lung metastasis and gender, rat sarcoma type GTPase family (RAS) mutation, tumor protein p53 (TP53) mutation, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation, neurotrophic tyrosine receptor kinase 1 (NTRK1) fusion, or anaplastic lymphoma kinase (ALK) fusion ( Wald χ2 values: 0.01-3.50, all P>0.05). Multivariate analysis identified TERT promoter mutation (odds ratio ( OR)=11.86, 95% CI: 3.68-38.29, P<0.001), multifocality ( OR=5.30, 95% CI: 2.41-11.69, P<0.001), extrathyroidal extension ( OR=3.98, 95% CI: 1.77-8.98, P=0.001), and lateral cervical lymph node metastasis ( OR=3.13, 95% CI: 1.28-7.68, P=0.013) as independent risk factors for lung metastasis in PTC. Conversely, BRAF V600E mutation emerged as a potential protective factor ( OR=0.09, 95% CI: 0.04-0.21, P<0.001). The proportions of BRAF V600E mutation ( χ2=20.49, P<0.001) and TERT promoter mutation ( χ2=4.91, P=0.027) were higher in the RAI ineffective group. Conclusions:BRAF V600E mutation, TERT promoter mutation and RET fusion are related gene expression in lung metastasis of PTC. Multifocality, extrathyroidal extension, lateral cervical lymph node metastasis and TERT promoter mutation are risk factors for lung metastasis of PTC (TERT is an independent molecular risk marker), while BRAF V600E mutation may be a protective factor. RAI treatment efficacy of PTC patients with lung metastasis and BRAF V600E mutation/TERT promoter mutation is worse.

Objective: To analyze the consumption frequency of major foods among Chinese children aged 6-17 years old, and to provide a basis for optimizing the dietary structure of children in China. Methods: Using data from the China Nutrition and Health System Survey and Application Program for Children 0-18 years old, 56 734 children aged 6-17 years old from North, Norththeast East, Central, South, Southwest and Northwest seven regions in China were selected for the study using stratified cluster random sampling from 2019 to 2021. A food frequency questionnaire was used to investigate the intake frequency of eight food groups in a month, including fresh vegetables, fresh fruits, livestock and poultry meats, aquatic products, eggs, dairy products, legumes, and cereals and potatoes. The foods were grouped according to whether they met the recommended intake criteria outlined in the Dietary Guidelines for Chinese Residents 2022. The〖KG*2〗χ2 test was used to compare the differences in the proportion of childrens intake frequency of each food group meeting the standard in different regions and age groups. Results: The proportions of Chinese children aged 6-17 years who consumed fresh vegetables and cereals and potatoes ≥3 times/d were 12.1% and 67.2%, respectively. The proportions of children who consumed fresh fruits, livestock and poultry meats, eggs and dairy products ≥1 time/d were 50.8%, 58.8%, 36.0% and 54.3%, respectively. The proportion of legumes consumed ≥4 times/week was 37.4%, and the proportion of aquatic products consumed ≥2 times/week was 39.7%. Fresh vegetables (5.5%), fresh fruits (33.1%), and dairy products (36.4%) had the lowest frequency of meeting the recommended standards in South China, and aquatic products (27.4%) and eggs (21.1%) had the lowest frequency of meeting the recommended standards in Northwest (P<0.008 3). Conclusion The overall intake frequency of fresh vegetables, fresh fruits, legumes, and dairy products are insufficient among Chinese children, with significant regional variations.

Objective: To analyze the association of eating dining locations and their association with nutritional status among Chinese children aged 6-17 years,so as to provide reference for guiding children s reasonable diet. Methods: Stratified random cluster sampling was used to select children aged 6 to 17 years from 28 cities and rural areas of 14 provinces in East, North, Central, South, Southwest, Northwest, Northeast of China, and a total of 52 535 children were included in the study from 2019 to 2021. Information including dining locations, demographic characteristics, dietary intakes and physical activity were collected through a questionnaire survey. Fasting body height and weight were measured in the morning. Unordered multiclass Logistic regression analysis was conducted to assess the relationship between dining locations and nutritional status in children. Results: Regarding children s dining locations, 66.3% ate breakfast at home,25.8% ate breakfast at school,7.9% ate breakfast outside (small dining tables, restaurants, stalls, etc.); 67.7% ate dinner at home,29.0% ate dinner at school,3.3% ate dinner outside; and 63.6% ate lunch at school,30.8% ate lunch at home,5.7% ate lunch outside. The prevalence rates of overweight/obesity and undernutrition were 28.6% and 9.3%, respectively. The adjusted multiclass Logistic regression analysis (controlling for age, region, parental education, household income, total energy intake, and moderate-to-vigorous physical activity) demonstrated that, compared to eating at home, school based breakfast and dinner consumption was associated with significantly lower overweight/obesity risks for both genders (boys: breakfast OR =0.70, 95% CI =0.65-0.75; dinner OR =0.80, 95% CI = 0.74- 0.86; girls: breakfast OR = 0.89 , 95% CI = 0.82-0.96; dinner OR =0.88, 95% CI =0.81-0.95), whereas eating lunch away from home significantly increased overweight/obesity risks (boys: OR =1.32, 95% CI =1.17-1.48; girls: OR =1.43, 95% CI =1.26- 1.62 ), with all associations being statistically significant ( P <0.05). After adjusting for confounding factors, boys who ate breakfast away from home showed a significantly reduced risk of undernutrition ( OR =0.80,95% CI =0.66-0.97), while those consuming lunch away from home had an increased risk ( OR =1.26, 95% CI =1.01-1.57) ( P <0.05). Conclusions The choice of dining locations for children is becoming more diverse, and a relatively high proportion of children eat meals outside the home and at school. Eating out have a higher risk of malnutrition for children. School feeding may be beneficial to children s physical health.

Objective:To investigate community residents' utilization preferences for "Internet + Nursing Service" and provide evidence for improving service uptake.Methods:Based on literature review, semi-structured interviews, and expert consultation, six service attributes and their levels were identified. Using a discrete choice experiment, 12 choice sets were generated through orthogonal design. Convenience sampling was employed to recruit 294 community residents in Nanjing from January to October 2024. A structured questionnaire was administered, and a conditional logit model was used to explore residents' preferences for "Internet + Nursing Service".Results:A total of 294 questionnaires were distributed, and all were validly returned, with an effective response rate of 100.0%. Preference analysis revealed that nurse type, service continuity, hospital classification, medical insurance coverage, and service price significantly influenced residents' preferences for "Internet + Nursing Service" ( P<0.05). Relative importance analysis indicated that the most valued attributes, in descending order, were medical insurance coverage (41.7%), nurse type (17.9%), service price (12.7%), hospital classification (12.1%), service continuity (11.7%), and waiting time (3.9%). When the proportion of medical insurance coverage reached 80%, residents' willingness to pay was the strongest. Conclusions:Medical insurance coverage is the key factor affecting community residents' choice of "Internet + Nursing Service". Residents prefer services provided by general hospitals and expert nurses. It is recommended to improve medical insurance and pricing policies, allocate resources precisely, and enhance service quality to promote the development of "Internet + Nursing Service".

Objective:To investigate community residents' utilization preferences for "Internet + Nursing Service" and provide evidence for improving service uptake.Methods:Based on literature review, semi-structured interviews, and expert consultation, six service attributes and their levels were identified. Using a discrete choice experiment, 12 choice sets were generated through orthogonal design. Convenience sampling was employed to recruit 294 community residents in Nanjing from January to October 2024. A structured questionnaire was administered, and a conditional logit model was used to explore residents' preferences for "Internet + Nursing Service".Results:A total of 294 questionnaires were distributed, and all were validly returned, with an effective response rate of 100.0%. Preference analysis revealed that nurse type, service continuity, hospital classification, medical insurance coverage, and service price significantly influenced residents' preferences for "Internet + Nursing Service" ( P<0.05). Relative importance analysis indicated that the most valued attributes, in descending order, were medical insurance coverage (41.7%), nurse type (17.9%), service price (12.7%), hospital classification (12.1%), service continuity (11.7%), and waiting time (3.9%). When the proportion of medical insurance coverage reached 80%, residents' willingness to pay was the strongest. Conclusions:Medical insurance coverage is the key factor affecting community residents' choice of "Internet + Nursing Service". Residents prefer services provided by general hospitals and expert nurses. It is recommended to improve medical insurance and pricing policies, allocate resources precisely, and enhance service quality to promote the development of "Internet + Nursing Service".