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 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 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 the state of rotator cuff injury in flight crew and to explore the effectiveness of extracorporeal shock wave therapy combined with functional exercise in treating rotator cuff injury.Methods A total of 60 flight crew with rotator cuff injuries in Dalian Rehabilitation Center from June 2022 to June 2023 were enrolled in this study.They were randomly assigned to experimental group(shock wave therapy combined with functional exercise)or the control group(functional exercise).The clinical efficacy was compared between the two groups after 4 weeks of treatment.Results All the research objects were male.There was no significant difference in the general information,such as age,flight duration,or course of the disease between the two groups(P>0.05).The visual analogue scale(VAS)scores were decreased,and Constant-Murley scores(CMS)and range of motion(ROM)were increased in both groups after treatment.The above-mentioned indexes in the experimental group were better than those in the control group(P<0.001).Conclusion The shock wave therapy and functional exercise has a more significant therapeutic effect on rotator cuff injuries than functional exercise alone.

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.

Background::An evidence gap still exists regarding the efficacy and safety of tegoprazan in patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China. Methods::This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement. Results::A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: -1.7%, 95% confidence interval [CI]: -8.5%, 5.0%, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients' diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively. Conclusion::Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

Objective:To report the clinical, electrophysiological, and genetic mutation characteristics of a family with paramyotonia congenita, to enhance clinical understanding of ion channelopathies, provide better guidance for clinical diagnosis, and optimize treatment plans.Methods:The clinical data, nerve conduction studies, needle electromyography, long exercise test, short exercise test, and whole-exome sequencing results of the proband with paramyotonia congenita and his family members admitted to Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, in August 2023 were collected and analyzed.Results:The proband was a 15-year-old male who presented with episodic muscle weakness for 1 year, accompanied by elevated creatine kinase during episodes. Between the ages of 3 and 4, he exhibited facial and bilateral hand myotonia triggered by cold exposure. His mother, sister, maternal grandmother, maternal aunt and uncle also displayed similar cold-induced facial and hand myotonia during childhood. Additionally, his cousin exhibited walking difficulties, frequent falls, mild difficulty in opening eyes after closure, and mild chewing and swallowing difficulties at the age of 1. Electromyography of the proband showed widespread myotonic discharges and myopathic impairment, while the electromyography of his mother and sister revealed only widespread myotonic discharges. The proband′s long exercise test results were consistent with periodic paralysis, while the short exercise test results aligned with paramyotonia congenita. His sister′s long exercise test results were within normal range, while the short exercise test results of his mother and sister were consistent with paramyotonia congenita. Genetic testing of the family revealed that all tested patients carried a heterozygous SCN4A mutation, c.4343G>A (R1448H). Conclusions:The R1448H mutation in the SCN4A gene is the genetic cause of this family. Patients carrying the SCN4A R1448H mutation may exhibit clinical features of cold-induced myotonia with or without episodic muscle weakness. In addition to widespread myotonic discharges on electromyography, certain patients may also show myopathic impairment. The long and short exercise tests can further assist in differentiating various types of myotonia and periodic paralysis for clinical diagnosis.

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.