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.

[Purpose]To analyze the incidence and mortality of liver cancer in cancer registration areas of Zhejiang Province in 2021 and the epidemiological trends of liver cancer from 2000 to 2021.[Methods]Using liver cancer data from 2000 to 2021 reported by Zhejiang Provincial Can-cer Registries,stratified by sex,age,and urban-rural areas,indicators including crude incidence rate,crude mortality rate,age-standardized incidence rate by Chinese standard population(ASIRC),age-standardized mortality rate by Chinese standard population(ASMRC),age-standardi-zed incidence rate by world standard population(ASIRW),age-standardized mortality rate by world standard population(ASMRW)were calculated.Joinpoint Regression Program(Version 5.3.0)was used to fit the log-linear relationship between rates and years,and calculate the annual percentage change(APC)and average annual percentage change(AAPC)with 95％confidence interval(CI).[Results]In 2021,the crude incidence rate of liver cancer in Zhejiang cancer registration areas was 26.93/105(ASIRC:13.35/105),and the crude mortality rate was 20.87/105(ASMRC:9.52/105).The number of new cases and deaths of liver cancer accounted for 5.07％and 11.33％of all malig-nant tumor cases and deaths,respectively.The incidence and mortality rates of liver cancer in male were significantly higher than those in female(crude incidence rate:40.17/105 vs 13.85/105;ASIRC:20.60/105 vs 6.34/105;crude mortality rate:30.78/105 vs 11.07/105;ASMRC:14.67/105 vs 4.57/105),and those in rural areas were higher than those in urban areas(crude incidence rate:30.39/105 vs 24.79/105;ASIRC:15.35/105 vs 12.10/105;crude mortality rate:24.32/105 vs 18.72/105;ASMRC:11.30/105 vs 8.40/105).In 2021,the incidence rate of liver cancer was low before the age of 30 years old,and increased significantly with age after 30 years old,reaching the peak in male aged 85 years old and above(170.04/105)and in female aged 80～84 years old(84.74/105).The mortality rate showed a similar trend to the incidence rate,which was low before the age of 30 years old and increased significantly with age after 30 years old,peaking in male aged 85 years old and above(211.64/105)and in female aged 80～84 years old(98.31/105).From 2000 to 2021,the crude incidence rate of liver cancer in Zhejiang Province showed an overall upward trend(AAPC=1.01％,95％CI:0.44％～1.58％),while the ASIRC remained relatively stable(AAPC=-0.81％,95％CI:-1.48％～0.02％)with a significant remained relatively stable(AAPC=-0.81％,95％CI:-1.48％～0.02％),after 2010,the ASIRC remained relatively stable(AAPC=-0.81％,95％CI:-1.48％～0.02％)with a significant decreased significantly.Both the crude mortality rate(AAPC=-0.84％,95％CI:-1.23％～-0.36％)and ASMRC(AAPC=-2.78％,95％CI:-3.28％～-2.20％)showed sig-nificant downward trends,and the decline of ASMRC was more obvious.[Conclusion]From 2000 to 2021,the incidence of liver cancer in cancer registration areas of Zhejiang Province showed a fluctuating downward trend,and the mortality showed a steady downward trend,but the disease burden remains heavy.Rural areas,the elderly,and males are high-risk populations,which should be the key targets of liver cancer prevention and control.

Objective:To study and establish the quality standard of Polyoxyl 15 hydroxystearate(HS15),a phar-maceutical excipient,and systematically evaluate its functionality-related characteristics and safety.HS15 was applied to the preparation of docetaxel(DTX)injection to further investigate the safety and pharmacokinetic char-acteristics of the injection in vitro and in vivo.Methods:Based on the general USP-NF2024,EP11.0 and the fourth general rules of the Chinese Pharmacopoeia 2020 edition,the quality standards of HS15 were studied.Combined with the functional properties of surfactants,the critical micelle concentration of HS15 was investigated,and its safety was investigated by hemolysis test and vascular irritation test in vitro.HS15 was further applied to the preparation of DTX injection,and the safety and efficacy of the preparation were comprehensively evaluated by in vitro cytotoxicity test and in vivo pharmacokinetic study.Results:According to the experimental results and the pharmacopoeia of various countries,the quality standard of HS15 was preliminarily formulated.When the concen-tration of HS15 was 1 mg·mL-1,the hemolysis rate was about0.2%,the vascular irritation was small,and the DTX injection was safe in vitro and in vivo.The pharmacokinetic behavior was in line with expectations.Conclusion:This study successfully established the quality standard of HS15,and its functional correlation index research and safety evaluation strategy can provide reference for the quality control of similar excipients.The appli-cation of HS15 in the preparation of DTX injection provides a theoretical and experimental basis for its application in the development of insoluble antitumor drug injection.

According to the work goals and tasks determined by edition outline of the Chinese Pharmacopoeia 2025 Edition, the Chinese Pharmacopoeia 2025 Edition has been completed. Among them, 52 new pharmaceutical excipients monographs have been added, an increase of 15.5% compared with the 2020 Edition, and the total number has reached 387. This article focuses on the general framework and the main characteristics of the standards of pharmaceutical excipients in the Chinese Pharmacopoeia 2025 Edition, which can contribute to accurately understand and utilize the standards in Chinese Pharmacopoeia.

Malignant tumor metastasis is the key factor leading to poor prognosis of patients， and it is a difficult problem to be overcome in the field of tumor therapy. Metabolic reprogramming， as a key link in the regulation of tumor metastasis activity， affects the growth， invasion， and metastasis of tumor cells by changing the metabolic pathways of intracellular substances （such as glucose， amino acids， lipids， and nucleotides）. In particular， metabolic reprogramming plays a key role in the multistage linked steps related to tumor metastasis and can play a crucial role in several key stages of tumor tissue dissociation in situ， hematogenous metastasis， and remote colonization. Malignant tumor cells can selectively adjust their own metabolic state to adapt to the growth conditions of different metastatic microenvironments and colonization sites and then choose the most favorable growth and metabolism strategy. According to the holistic concept of traditional Chinese medicine （TCM）， the metastasis of malignant tumors is generally closely related to the metabolic state of the whole body. One of the advantages of TCM in the treatment of malignant tumors is systemic regulation. With its multi-pathway， multi-target， and multi-component therapeutic characteristics， TCM can effectively control the metastasis of malignant tumors by regulating the degradation of tumor epithelial mesenchymal transformation （EMT） and extracellular matrix （ECM）， anchoring the independent growth of tumor cells and the tumor microenvironment. In this paper， the potential regulatory effects of metabolic reprogramming on the metastasis of malignant tumors were discussed， and the latest research progress of the regulation of metabolic reprogramming by TCM on tumor metastasis was reviewed. At the same time， the key targets of TCM and its bioactive components in the process of tumor metastasis intervention were reviewed. This study aims to provide a more valuable basis and clearer idea for the treatment of malignant tumor metastasis by regulating metabolic reprogramming with TCM.

[Objective] To compare the clinical efficacy of super pulse thulium laser enucleation of the prostate (SPThuLEP) with "open tunnel" and transurethral holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH), in order to provide reference for the treatment options of BPH. [Methods] The clinical data of 112 BPH patients treated in our hospital during Jan.2023 and Jul.2023 were retrospectively analyzed, including 65 treated with SPThuLEP with "open tunnel" and 57 with HoLEP.The operation time, postoperative hemoglobin decrease, postoperative bladder irrigation, catheter indwelling time, hospitalization time and complications were compared between the two groups.The changes of maximum urine flow rate (Qmax), international prostate symptom score (IPSS), quality of life score (QoL), postvoid residual (PVR) and prostate-specific antigen (PSA) were compared between the two groups before operation and one month after operation. [Results] All operations were successful without conversion to open or transurethral plasmakinetic resection.The postoperative decrease of hemoglobin in SPThuLEP group was lower than that in HoLEP group [(13.12±6.72) g/L vs. (21.02±6.51) g/L], with statistical difference (P<0.05). There were no significant differences in the operation time [(63.35±15.73) min vs.(61.02±17.55) min], postoperative bladder irrigation time [(1.07±0.45) d vs. (1.06±0.36) d], catheter indwelling time [(2.98±0.56) d vs. (3.01±0.63) d] and hospitalization time [(3.63±0.61) d vs.(3.79±0.76) d] between the two groups (P>0.05). No blood transfusion, secondary bleeding or unplanned hospitalization occurred, and there were no serious complications such as transurethral electroresection syndrome (TURS), urethral stricture and urinary incontinence.One month after operation, the Qmax, IPSS, QoL, PVR and PSA of the two groups were significantly improved compared with those before operation (P<0.05), but with no statistical difference between the two groups (P>0.05). [Conclusion] SPThuLEP with "open tunnel" has comparable efficacy as HoLEP in the treatment of BPH.With advantages of small amount of bleeding and high safety, this minimally invasive technique can be widely popularized in clinical practice.

Objective To assess the clinical value of a novel surgical technique—Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in the resection of anterior mediastinal masses. Methods Patients who underwent tubeless subxiphoid uniportal video-assisted thoracoscopic surgery via balance-shaped sternal elevation device in anterior mediastinal masses process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to April 2025 were included, and their clinical data were analyzed. Results A total of 4 patients were included, with 2 males and 2 females, aged 58-75 years. The diameter of the tumor was 2.5-3.0 cm. The operation time was 60.0-150.0 min, intraoperative blood loss was 5-10 mL, pain score on the 3rd day after surgery was 0 points, and postoperative hospital stay was 2-3 days. All patients achieved complete resection of the masses and thymus without perioperative complications. Conclusion The tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device technique optimizes surgical visualization and instrument maneuverability while avoiding complications related to conventional anesthesia and tubing, thereby markedly enhancing the minimally invasive profile of anterior mediastinal masses resections. In addition to maintaining procedural safety, this approach effectively reduces postoperative pain and accelerates patient recovery, highlighting its potential for widespread clinical adoption.

BackgroundAttention deficit hyperactivity disorder （ADHD） is a neurodevelopmental disorder characterized by age-inappropriate inattention， excessive activities incongruous with setting， and emotional impulsivity. Subthreshold ADHD （sADHD） is clinically defined as the presence of ADHD symptoms that do not meet the full diagnostic criteria for ADHD. Children with sADHD exhibit deficits in executive function， demonstrate more conduct， learning， and anxiety-related problems compared to typically developing children， and show even poorer working memory performance than children diagnosed with ADHD. Currently， there is limited epidemiological research on sADHD in China， with few studies simultaneously investigating the prevalence of both ADHD and sADHD in children. ObjectiveTo investigate the prevalence of ADHD and sADHD among children aged 6–13 years in Chongqing， analyzing their distribution characteristics within this population， with the aim of providing references for developing preventive measures against both ADHD and sADHD. MethodsFrom October to November 2023， a total of 3 398 students in grades 1–6 from six primary schools in Jiangbei District， Chongqing were selected using a stratified cluster random sampling method. The occurrence of ADHD and sADHD was evaluated by using the short version （18-item version） of the Swanson， Nolan， and Pelham IV rating scales （SNAP-IV） and the Chinese vision of Schedule for Affective Disorder and Schizophrenia for School-aged Children-Present and Lifetime Version （K-SADS-PL）. ResultsThe ADHD detection rate among children in Chongqing was 1.90% （95% CI： 0.014–0.024）. Boys showed a significantly higher ADHD detection rate than girls （χ²=7.733， P=0.005）. No statistically significant differences were found in ADHD detection rates across different grades or age groups （χ²=7.347， 12.362， P>0.05）. The sADHD detection rate was 6.32% （95% CI： 0.054–0.072）. Similarly， boys exhibited significantly higher sADHD detection rates than girls （χ²=21.005， P<0.01）. Significant differences emerged across different grades （χ²=20.559， P=0.001）， while no statistically significant difference was observed in age groups （χ²=12.070， P=0.060）. ConclusionThe ADHD detection rates were comparable across all grade levels and age groups from 6–13 years old. Second-grade children demonstrated notably higher sADHD rates compared to other grades， while boys demonstrated higher prevalence rates than girls for both ADHD and sADHD. ［Funded by Science and Health Joint Medical Research Project in Jiangbei District， Chongqing City in the Second Half of 2023 （number， 2023JBKWLH022）］

According to the work goals and tasks determined by edition outline of the Chinese Pharmacopoeia 2025 Edition,the Chinese Pharmacopoeia 2025 Edition has been completed.Among them,52 new pharmaceutical excip-ients monographs have been added,an increase of 15.5%compared with the 2020 Edition,and the total number has reached 387.This article focuses on the general framework and the main characteristics of the standards of pharmaceutical excipients in the Chinese Pharmacopoeia 2025 Edition,which can contribute to accurately under-stand and utilize the standards in Chinese Pharmacopoeia.

Objective To analyze the medication rules of Chinese herbal concentrated-granule for the treatment of hypertension nationwide using data mining and knowledge graph methods,thus to provide evidence for expanding its application in treating hypertension.Methods From January 2022 to March 2023,Chinese herbal concentrated-granule prescriptions for hypertension prescribed by traditional Chinese medicine experts nationwide were collected.Microsoft Excel was used to analyze the frequency,properties and flavors,meridian tropism,and efficacy categories of the medicinals.Hierarchical clustering was applied for cluster analysis,and the Neo4j graph database was utilized to construct an information knowledge graph illustrating the relationships between regions and medicinals.Results A total of 2 600 Chinese herbal concentrated-granule prescriptions were included,involving 370 medicinals.The top six frequently-used medicinals were Poria(Fuling),Glycyrrhizae Radix et Rhizoma(Gancao),Atractylodis Macrocephalae Rhizoma(Baizhu),Citri Reticulatae Pericarpium(Chenpi),Paeoniae Radix Alba(Baishao),and Angelicae Sinensis Radix(Danggui).The properties of the medicinals were mainly warm and mild,and their flavors were usually sweet,pungent,and bitter.The medicinals frequently have the meridian tropism of the spleen,lung,and liver meridians.Hierarchical clustering yielded seven clusters.The information knowledge graph of region-medicinals relationships revealed that medicinals used in five or more regions were Baishao,Baizhu,Chenpi,Pinelliae Rhizoma(Banxia),Fuling,Gastrodiae Rhizoma(Tianma),Bupleuri Radix(Chaihu),Chuanxiong Rhizoma(Chuanxiong),Salviae Miltiorrhizae Radix et Rhizoma(Danshen),Danggui,Gancao,and Astragali Radix(Huangqi).Conclusion Chinese herbal concentrated-granule for hypertension usually consist of tonifying medicinals,with sweet and warm properties,and having the meridian tropism of the spleen meridian.And the medicinals composed of the prescriptions often have the actions of calming the liver and suppressing yang,strengthening the spleen and removing dampness,and nourishing the liver and kidney.