Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

Objective·To optimize iSeroSnFR,a genetically encoded 5-hydroxytryptamine(5-HT)fluorescent sensor based on bacterial periplasmic binding proteins(PBPs),to enhance its performance for both in vivo and in vitro 5-HT detection.Methods·iSeroSnFR1.2 was engineered by replacing the circularly permuted superfolder green fluorescence protein(cpsfGFP)sequence in iSeroSnFR1.0 with that from the acetylcholine sensor iAChSnFR using Gibson assembly.The fluorescence response and kinetic properties of iSeroSnFR1.0 and iSeroSnFR1.2 were compared by overexpressing the sensors in HEK293 cells and puffing with exogenous 5-HT.Additionally,to mimic physiological conditions,cultured mouse cortical neurons infected with Sindbis virus carrying each sensor were electrically stimulated to induce endogenous 5-HT release and further evaluate sensor performance.Results·iSeroSnFR1.2 showed significantly improved performance over iSeroSnFR1.0.In HEK293 cells,it exhibited a 1.5-fold increase in fluorescence response(ΔF/F0)to exogenous 5-HT,along with faster kinetics(rise time:36.3 ms vs 44.9 ms;decay time:1 003.6 ms vs 1 730.4 ms).In cortical neurons,it demonstrated a 2.7-fold increase in response to endogenously released 5-HT,with rise and decay times reduced by 44.0%and 26.7%,respectively.Notably,iSeroSnFR1.2 showed increased basal fluorescence,enabling better imaging in high-background environments.Conclusion·The optimized iSeroSnFR1.2 sensor offers a markedly improved fluorescent response and temporal resolution for 5-HT detection,providing an advanced tool for studying 5-HT dynamics in neuroscience and psychiatric research.

Objective:To analyze the diagnostic value of bedside capsule endoscopy in patients with acute or severe gastrointestinal bleeding.Methods:Clinical data from patients who underwent bedside capsule endoscopy due to acute or severe suspected gastrointestinal bleeding in Nanfang Hospital, Southern Medical University from June 2018 to September 2021 were analyzed retrospectively. The efficacy of capsule endoscopy in detecting upper gastrointestinal tract and small intestinal bleeding was evaluated.Results:A total of 74 patients underwent bedside capsule endoscopy for suspected acute or severe gastrointestinal bleeding. Five patients were excluded due to failure of examination due to retention of capsule endoscope in the gastric lumen, and 69 were included in the study, of whom 54 patients with a definitive diagnosis of gastrointestinal hemorrhage. The positive detection rate of the capsule endoscopy was 83.33% (45/54), including 17 cases of ulcer, 5 cases of erosion, 5 cases of vascular malformation, 4 protrusion mass, 4 diverticulum, 5 obscure gastrointestinal bleeding, 1 stenosis , 1 active mucosal blood exudation, 1 gastric retention, 1 mucosal swelling, and 1 mucosal wrinkle change. The sensitivity and specificity of capsule endoscopy in the diagnosis of upper gastrointestinal bleeding were 92.31% (12/13) and 75.00% (3/4) respectively. The sensitivity and specificity of capsule endoscopy for diagnosing small intestinal bleeding were 80.49% (33/41) and 90.91% (10/11) respectively.Conclusion:Bedside capsule endoscopy demonstrates high sensitivity and specificity in the diagnosis of gastrointestinal bleeding, showing potential advantages in bedside applications for acute and severe gastrointestinal bleeding.

Objective:To systematically review recent domestic and international literature on the use of extracorporeal membrane oxygenation (ECMO) in obstetric critical care and provide evidence-based support for clinical decision-making.Methods:Literature published between January 1, 2014, and December 31, 2024, in both Chinese and English was retrieved from databases including CNKI, Wanfang Medical Network, Chinese Medical Journal Network, PubMed, and Embase. Data on maternal age, gestational age, diagnosis, ECMO type, ECMO duration, pregnancy outcomes, and maternal and neonatal survival rates were extracted from relevant studies.Results:Among 1 306 retrieved articles, 214 met the inclusion criteria, involving a total of 355 obstetric patients who received ECMO treatment. The majority of patients (58.9%, 209/355) were treated postpartum. The most common indications for ECMO initiation included pulmonary infection (32.7%, 116/355), pulmonary embolism (24.5%, 87/355), pulmonary hypertension (12.4%, 44/355), sepsis (9.6%, 34/355), and peripartum cardiomyopathy (6.2%, 22/355). The modes of ECMO used in the obstetric population were venovenous (VV) in 49.6%(176/355) and venoarterial (VA) in 44.2%(157/355) of cases. The overall maternal survival rate was 82.0%(291/355), while the fetal/neonatal survival rate was 74.4%(264/355). Bleeding was the most common complication (35.5%, 126/355), followed by thrombosis (14.6%, 52/355) and infections related to ventilator or cannulation sites (19.2%, 68/355).Conclusions:ECMO can serve as an effective temporary organ support therapy for critically ill patients during pregnancy and the postpartum period.

Objective:To analyze the diagnostic value of bedside capsule endoscopy in patients with acute or severe gastrointestinal bleeding.Methods:Clinical data from patients who underwent bedside capsule endoscopy due to acute or severe suspected gastrointestinal bleeding in Nanfang Hospital, Southern Medical University from June 2018 to September 2021 were analyzed retrospectively. The efficacy of capsule endoscopy in detecting upper gastrointestinal tract and small intestinal bleeding was evaluated.Results:A total of 74 patients underwent bedside capsule endoscopy for suspected acute or severe gastrointestinal bleeding. Five patients were excluded due to failure of examination due to retention of capsule endoscope in the gastric lumen, and 69 were included in the study, of whom 54 patients with a definitive diagnosis of gastrointestinal hemorrhage. The positive detection rate of the capsule endoscopy was 83.33% (45/54), including 17 cases of ulcer, 5 cases of erosion, 5 cases of vascular malformation, 4 protrusion mass, 4 diverticulum, 5 obscure gastrointestinal bleeding, 1 stenosis , 1 active mucosal blood exudation, 1 gastric retention, 1 mucosal swelling, and 1 mucosal wrinkle change. The sensitivity and specificity of capsule endoscopy in the diagnosis of upper gastrointestinal bleeding were 92.31% (12/13) and 75.00% (3/4) respectively. The sensitivity and specificity of capsule endoscopy for diagnosing small intestinal bleeding were 80.49% (33/41) and 90.91% (10/11) respectively.Conclusion:Bedside capsule endoscopy demonstrates high sensitivity and specificity in the diagnosis of gastrointestinal bleeding, showing potential advantages in bedside applications for acute and severe gastrointestinal bleeding.

Objective:To systematically review recent domestic and international literature on the use of extracorporeal membrane oxygenation (ECMO) in obstetric critical care and provide evidence-based support for clinical decision-making.Methods:Literature published between January 1, 2014, and December 31, 2024, in both Chinese and English was retrieved from databases including CNKI, Wanfang Medical Network, Chinese Medical Journal Network, PubMed, and Embase. Data on maternal age, gestational age, diagnosis, ECMO type, ECMO duration, pregnancy outcomes, and maternal and neonatal survival rates were extracted from relevant studies.Results:Among 1 306 retrieved articles, 214 met the inclusion criteria, involving a total of 355 obstetric patients who received ECMO treatment. The majority of patients (58.9%, 209/355) were treated postpartum. The most common indications for ECMO initiation included pulmonary infection (32.7%, 116/355), pulmonary embolism (24.5%, 87/355), pulmonary hypertension (12.4%, 44/355), sepsis (9.6%, 34/355), and peripartum cardiomyopathy (6.2%, 22/355). The modes of ECMO used in the obstetric population were venovenous (VV) in 49.6%(176/355) and venoarterial (VA) in 44.2%(157/355) of cases. The overall maternal survival rate was 82.0%(291/355), while the fetal/neonatal survival rate was 74.4%(264/355). Bleeding was the most common complication (35.5%, 126/355), followed by thrombosis (14.6%, 52/355) and infections related to ventilator or cannulation sites (19.2%, 68/355).Conclusions:ECMO can serve as an effective temporary organ support therapy for critically ill patients during pregnancy and the postpartum period.

Objective·To optimize iSeroSnFR,a genetically encoded 5-hydroxytryptamine(5-HT)fluorescent sensor based on bacterial periplasmic binding proteins(PBPs),to enhance its performance for both in vivo and in vitro 5-HT detection.Methods·iSeroSnFR1.2 was engineered by replacing the circularly permuted superfolder green fluorescence protein(cpsfGFP)sequence in iSeroSnFR1.0 with that from the acetylcholine sensor iAChSnFR using Gibson assembly.The fluorescence response and kinetic properties of iSeroSnFR1.0 and iSeroSnFR1.2 were compared by overexpressing the sensors in HEK293 cells and puffing with exogenous 5-HT.Additionally,to mimic physiological conditions,cultured mouse cortical neurons infected with Sindbis virus carrying each sensor were electrically stimulated to induce endogenous 5-HT release and further evaluate sensor performance.Results·iSeroSnFR1.2 showed significantly improved performance over iSeroSnFR1.0.In HEK293 cells,it exhibited a 1.5-fold increase in fluorescence response(ΔF/F0)to exogenous 5-HT,along with faster kinetics(rise time:36.3 ms vs 44.9 ms;decay time:1 003.6 ms vs 1 730.4 ms).In cortical neurons,it demonstrated a 2.7-fold increase in response to endogenously released 5-HT,with rise and decay times reduced by 44.0%and 26.7%,respectively.Notably,iSeroSnFR1.2 showed increased basal fluorescence,enabling better imaging in high-background environments.Conclusion·The optimized iSeroSnFR1.2 sensor offers a markedly improved fluorescent response and temporal resolution for 5-HT detection,providing an advanced tool for studying 5-HT dynamics in neuroscience and psychiatric research.

Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.

Tumor metastasis is the major cause of death for tumor patients and the key bottleneck of clinical treatment. In recent years， basic and clinical studies have recognized that tumor microenvironment （TME） is highly correlated with tumor metastasis， which provides hope for anti-metastatic drug development and clinical treatment. At present， the mainstream studies on TME represented by immune checkpoint inhibitors （ICIs） mainly focus on the rectification of immune function of T cells and B cells. However， a large number of studies have shown that the significance of other members of TME for tumor metastasis cannot be ignored， which greatly reflects the progress of anti-metastatic research based on TME regulation. This review focused on tumor metastasis， summarized the mechanism of action of non-T and non-B immune cells ［tumor-associated macrophages （TAMs） and tumor-associated neutrophils （TANs）］ and non-immune members ［vascular endothelial cells （ECs）， tumor-associated fibroblasts （CAFs）， and blood platelet］ in the process of tumor metastasis in TME based on the literature over the recent five years， and explored their key value in the treatment of metastasis. At the treatment level， this review focused on the perspective of the integration of frontier and traditional methods and took the functional homeostasis remodeling of TME as the entry point to summarize the activity and mechanism of traditional Chinese medicine （TCM） regulation of non-T and non-B immune cells and non-immune members and highlight its advantages and characteristics in clinical intervention of metastasis. This review helps to break through the limitations of over-reliance on T and B immune cells in anti-metastatic research， make the research rely on a wider range of cell groups， explore the potential value of TME in anti-metastatic drug intervention， and enrich the idea and strategy of understanding the anti-metastatic pharmacological activity. The review is also expected to provide a broader vision for the research and development of new anti-metastatic drugs.