Radiopharmaceuticals involve the local delivery of radionuclides to targeted lesions for the diagnosis and treatment of multiple diseases. Radiopharmaceutical therapy, which directly causes systematic and irreparable damage to targeted cells, has attracted increasing attention in the treatment of refractory diseases that are not sensitive to current therapies. As the Food and Drug Administration (FDA) approvals of [177Lu]Lu-DOTA-TATE, [177Lu]Lu-PSMA-617 and their complementary diagnostic agents, namely, [68Ga]Ga-DOTA-TATE and [68Ga]Ga-PSMA-11, targeted radiopharmaceutical-based theranostics (radiotheranostics) are being increasingly implemented in clinical practice in oncology, which lead to a new era of radiopharmaceuticals. The new generation of radiopharmaceuticals utilizes a targeting vector to achieve the accurate delivery of radionuclides to lesions and avoid off-target deposition, making it possible to improve the efficiency and biosafety of tumour diagnosis and therapy. Numerous studies have focused on developing novel radiopharmaceuticals targeting a broader range of disease targets, demonstrating remarkable in vivo performance. These include high tumor uptake, prolonged retention time, and favorable pharmacokinetic properties that align with clinical standards. While radiotheranostics have been widely applied in tumor diagnosis and therapy, their applications are now expanding to neurodegenerative diseases, cardiovascular diseases, and inflammation. Furthermore, radiotheranostic-empowered precision medicine is revolutionizing the cancer treatment paradigm. Diagnostic radiopharmaceuticals play a pivotal role in patient stratification and treatment planning, leading to improved therapeutic outcomes in targeted radionuclide therapy. This review offers a comprehensive overview of the evolution of radiopharmaceuticals, including both FDA-approved and clinically investigated agents, and explores the mechanisms of cell death induced by radiopharmaceuticals. It emphasizes the significance and future prospects of theranostic-based radiopharmaceuticals in advancing precision medicine.

背景  为了推进国家基本公共卫生服务考核评估从过程到结果的转变，课题组前期从理论上构建了“效果导向的基本公共卫生服务综合评价指标体系”，但该指标体系实践应用尚不充分。目的  为了进一步完善该指标体系的实践应用，本研究利用该指标体系对深圳市2017—2022年基本公共卫生服务实施效果进行回顾性评价。方法  于2022年7月—2023年4月通过文献资料法、函调法收集指标数据，采用综合指数法，计算2017—2022年深圳市基本公共卫生服务综合指数及各维度指数。结果  指标体系的54个指标，共收集到49个，完成率为91.8%。2017年至2022年，深圳市基本公共卫生服务综合指数从46.62增加到51.37，项目投入指数从3.75增加到10.40，项目执行指数从11.23增加至的19.36，项目效果指数31.65降低至21.61。单从各子项目的效果指数来看，健康教育效果指数有较大增幅，从2017年的0.067增加到2022年的4.079；慢性病患者健康管理效果指数从2017年的13.469降低至2022年的3.571，最低为3.223（2021年），最高为14.970（2019年），儿童健康管理、知晓率与满意度效果指数最低值分别为3.374、1.987，均出现在2019年。孕产妇健康管理效果指数最低值在2022年（4.052）。结论  以效果为导向的基本公共卫生综合评价指标体系应用于评价市级层面基本公共卫生服务具有一定的可行性和科学性，但部分反映人群健康危险因素及健康状况的指标还存在可获得性低的问题。信息化全量考核能解决数据虚报的问题，提高项目的督导效率。但在服务覆盖率趋近饱和的情况下，其促进作用是有限的，未来基本公共卫生服务应该以提高服务质量、增进人群健康效益为目标，特别要以知晓率与满意度为重点，不断提升居民的获得感。

背景  自2009年启动国家基本公共卫生服务项目以来，全国各地普遍开展各项服务，由于各省市经济发展水平不同，其基本公共卫生服务项目的实施情况和进展也不同。深圳市作为全国性经济中心城市和国家创新性城市，信息化技术位于全国城市前列。目的  梳理并总结深圳市2017—2022年基本公共卫生服务的实施进展与趋势，为进一步推进深圳市基本公共卫生服务高质量发展提供参考。方法  于2022年7月—2023年4月，收集2017—2022年深圳市项目投入、项目执行和项目效果3个维度共计54项的基本公共卫生服务评价指标，分析各指标在2017—2022年六年间的变化趋势。结果  （1）深圳市基本公共卫生服务项目实际到位经费从2017年的80.71元增加到2022年的144.86元，社康工作人员总数由9992人增长到13758人，公卫医师占基层医务人员比例从5.39%提高到5.94%。（2）电子健康档案建档率、新生儿访视率、0~6岁儿童健康管理率、早孕建册率、产后访视率、孕产妇系统管理率、老年人健康管理率、严重精神障碍患者规范管理率、肺结核患者规范服药率、老年人中医药健康管理率、0~36个月儿童中医药健康管理服务率的平均年增长率分别为6.27%、0.32%、2.61%、1.06%、0.07%、0.62%、8.34%、2.11%、0.51%、9.53%、5.01%，而健康档案使用率、高血压患者规范管理率、糖尿病患者规范管理率从2017年的77.40%、72.48%、72.09%减少至2022年的36.58%、64.14%、66.32%。（3）居民健康素养具备率、参加体育锻炼人数比例、6个月内婴儿纯母乳喂养率的平均年增长率分别为23.75%、15.86%、5.35%，且新生儿死亡率、婴儿死亡率、5岁以下儿童死亡率的平均年增长率分别为-1.71%、-4.25%、-1.63%；管理人群血压控制率、管理人群血糖控制率从2017年的70.84%、67.41%下降至2022年的69.33%、60.82%，剖宫产率、出生缺陷发生率、低出生体重率、5岁以下儿童低体重率、5岁以下儿童贫血患病率、5岁以下儿童肥胖率的平均年增长率分别为0.74%、1.87%、3.97%、3.85%、11.03%、33.50%。2018—2022年群众知晓率从86.26%下降至68.77%，居民满意度从88.51%增加至91.00%。结论  深圳市2017—2022年基本公共卫生服务取得显著成效，组织管理和财政支出不断加强，主体责任得到落实，人力资源队伍不断壮大；各类人群覆盖面广，健康教育效果初显，然而档案利用有待加强，需要进一步推进“老高糖”项目管理高质量发展，不断提高居民的知晓率和获得感。

Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells (PC) in the bone marrow (BM). B-cell maturation antigen (BCMA) is predominantly expressed in malignant plasma cells, and associated with the proliferation, survival, and progression of various myeloma cells. Given these important roles, BCMA emerges as an ideal target antigen for MM therapy. However, effective stratification of patients who may benefit from targeted BCMA therapy and real-time monitoring the therapeutic efficacy poses significant clinical challenge. This study aims to develop a BCMA targeted diagnostic modality, and preliminarily explore its potential value in the radio-immunotherapy of MM. Using zirconium-89 (89Zr, t1/2 = 78.4 h) for labeling the BCMA-specific antibody, the BCMA-targeting PET tracer [89Zr]Zr-DFO-BCMAh230430 was prepared. The EC50 values of BCMAh230430 and DFO-BCMAh230430 were determined by ELISA assay. BCMA expression was assessed in four different tumor cell lines (MM.1S, RPMI 8226, BxPC-3, and KYSE520) through Western blot and flow cytometry. In vitro binding affinity was determined by cell uptake studies of [89Zr]Zr-DFO-BCMAh230430 in these tumor cell lines. For in vivo evaluation, PET imaging and ex vivo biodistribution studies were conducted in tumor-bearing mice to evaluate imaging performance and systemic distribution of [89Zr]Zr-DFO-BCMAh230430. Immunochemistry analysis was performed to detect BCMA expression in tumor tissues, confirming the specificity of our probe. Furthermore, we explored the anti-tumor efficacy of Lutetium-177 labeled BCMA antibody, [177Lu]Lu-DTPA-BCMAh230430, in tumor bearing-mice to validate its radioimmunotherapy potential. The radiolabeling of [89Zr]Zr-DFO-BCMAh230430 and [177Lu]Lu-DTPA-BCMAh230430 showed satisfactory radiocharacteristics, with a radiochemical purity exceeding 99

Wearable biosensors have gained huge interest due to their potential for real-time physiological information. The development of a non-invasive blood glucose device is of great interests for health monitoring in reducing the diabetes incidence. Here, we report a sandwich-structured biosensor that is designed for glucose levels detection by using sweat as the means of monitoring. The Prussian blue nanoparticles (PBNPs) and carboxylated carbon nanotubes (MWCNT-COOH) were self-assembled on the electrode to improve the electrochemical performance and as the sensor unit, glucose oxidase (GOx) was immobilized by chitosan (CS) as the reaction catalysis unit, and finally encapsulated with Nafion to ensure a stable performance. As a result, the GOx/PBNPs/MWCNT-COOHsensor displays a low detection limit (7.0 mu M), high sensitivity (11.87 mu A mM-1 cm-2) , excellent interference resistance for a full sweat glucose application range (0.0-1.0 mM) for both healthy individuals , diabetic patients. Additionally, the glucose sensor exhibits stable stability for two weeks and can be successfully applied to screen-printed carbon electrodes (SPCE), demonstrating its great potential for personalized medical detection and chronic disease management.

The immunosuppressive microenvironment of malignant tumors severely hampers the effectiveness of anti-tumor therapy. Moreover, abnormal tumor vasculature interacts with immune cells, forming a vicious cycle that further interferes with anti-tumor immunity and promotes tumor progression. Our pre-basic found excellent anti-tumor effects of c-di-AMP and RRx-001, respectively, and we further explored whether they could be combined synergistically for anti-tumor immunotherapy. We chose to load these two drugs on PVA-TSPBA hydrogel scaffolds that expressly release drugs within the tumor microenvironment by in situ injection. Studies have shown that c-di-AMP activates the STING pathway, enhances immune cell infiltration, and reverses tumor immunosuppression. Meanwhile, RRx-001 releases nitric oxide, which increases oxidative stress injury in tumor cells and promotes apoptosis. Moreover, the combination of the two presented more powerful pro-vascular normalization and reversed tumor immunosuppression than the drug alone. This study demonstrates a new design option for anti-tumor combination therapy and the potential of tumor environmentally responsive hydrogel scaffolds in combination with anti-tumor immunotherapy.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [64Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [64Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [64Cu]QM-2303 from the bloodstream. Administration of a single dose of [177Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [64Cu]/[177Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [64Cu]/[177Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Fibroblast activation protein (FAP) is a serine protease characterized by its high expression in cancer-associated fibroblasts (CAFs) and near absence in adult normal tissues and benign lesions. This unique expression pattern positions FAP as a prospective biomarker for targeted tumor radiodiagnosis and therapy. The advent of FAP-based radiotheranostics is anticipated to revolutionize cancer management. Among various types of FAP ligands, peptides and antibodies have shown advantages over small molecules, exemplifying prolonged tumor retention in human volunteers. Within its scope, this review summarizes the recent research progress of the FAP radiopharmaceuticals based on antibodies and peptides in tumor imaging and therapy. Additionally, it incorporates insights from recent studies, providing valuable perspectives on the clinical utility of FAP-targeted radiopharmaceuticals.

BackgroundPatients with cold tumors gain limited benefits from immune checkpoint blockade (ICB) therapy owing to low programmed cell death protein ligand 1 (PD‐L1) expression and minimal immune cell infiltration. Mild photothermal therapy (PTT) using black phosphorus nanosheets (BPNSs) is a promising approach to enhance the efficacy of ICB therapy. However, to ensure that BPNS‐based PTT‐enhanced ICB therapy is clinically adaptable, a noninvasive, bedside‐accessible imaging tool capable of monitoring the status of PD‐L1 is imperative. We demonstrated that positron emission tomography (PET) using [64Cu]HKP2202 precisely delineated PD‐L1 expression in tumors receiving PTT.MethodsBPNSs were modified with polyethylene glycol to prepare BPNS@PEG, which were then characterized. MC38 cells and tumor allografts were treated with BPNS@PEG followed by 808 nm near‐infrared light exposure. PET using [64Cu]HKP2202 was performed to monitor PD‐L1 expression in vivo. We also evaluated whether the efficacy of ICB therapy improved after delivering BPNS@PEG‐based PTT.ResultsBPNS@PEG had a well‐defined lamellar structure with clear edges and an average size of 150 nm. PET and Western blotting assays indicated that PD‐L1 expression was upregulated after BPNS@PEG and NIR‐light treatment. Notably, the antitumor effect of anti PD‐L1 therapy was enhanced in mice treated with BPNS@PEG‐based PTT.ConclusionsBPNS@PEG had the capacity to convert cold tumors into hot tumors to facilitate the efficacy of ICB therapy. Importantly, the complementary diagnostic PET radiotracer targeting PD‐L1 allowed real‐time monitoring of PD‐L1 expression in the tumor microenvironment to guide ICB administration, holding great potential to achieve efficient and precise tumor immunotherapy.

Flexible sensors are capable of converting multiple human physiological signals into electrical signals for various applications in clinical diagnostics, athletics, and human-machine interaction. High-performance flexible strain sensors are particularly desirable for sensitive, reliable, and long-term monitoring, but current applications are still constrained due to high response threshold, low recoverability properties, and complex preparation methods. In this study, we present a stable and flexible strain sensor by a cost-effective self-assemble approach that demonstrates remarkable sensitivity (2169), ultrafast response and recovery time (112 ms), and wide dynamic response range (0-50%), as confirmed in human pulse and human-computer interaction. These excellent performances can be attributed to the design of a Polydimethylsiloxane (PDMS) substrate integrated with multiwalled carbon nanotubes (MWCNT) and graphene nanosheets (GNFs), which results in high electrical conductivity. The MWCNT serves as a bridge, connecting the GNFs to create an efficient conductive path even under a strain of 50%. We also demonstrate the strain sensor's capability in weak physiological signal pulse measurement and excellent resistance to mechanical fatigue. Moreover, the sensor shows diverse sensitivities in various tensile states with different signal patterns, making it highly suitable for full-range human monitoring and flexible wearable systems.

The development of immune checkpoint blockade therapy based on programmed cell death-protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) has revolutionized cancer therapies in recent years. However, only a fraction of patients responds to PD-1/PD-L1 inhibitors, owing to the heterogeneous expression of PD-L1 in tumor cells. This heterogeneity presents a challenge in the precise detection of tumor cells by the commonly used immunohistochemistry (IHC) approach. This situation calls for better methods to stratify patients who will benefit from immune checkpoint blockade therapy, to improve treatment efficacy. Positron emission tomography (PET) enables real-time visualization of the whole-body PD-L1 expression in a noninvasive way. Therefore, there is a need for the development of radiolabeled tracers to detect PD-L1 distribution in tumors through PET imaging. Compared to their L-counterparts, dextrorotary (D)-peptides have properties such as proteolytic resistance and remarkably prolonged metabolic half-lives. This study designed a new method to detect PD-L1 expression based on PET imaging of 68Ga-labeled PD-L1-targeted D-peptide, a D-dodecapeptide antagonist (DPA), in tumor-bearing mice. The results showed that the [68Ga]DPA can specifically bind to PD-L1-overexpressing tumors in vivo, and showed favorable stability as well as excellent imaging ability, suggesting that [68Ga]DPA-PET is a promising approach for the assessment of PD-L1 status in tumors.

Atherosclerosis, a chronic disease associated with metabolism, poses a significant risk to human well-being. Currently, existing treatments for atherosclerosis lack sufficient efficiency, while the utilization of surface-modified nanoparticles holds the potential to deliver highly effective therapeutic outcomes. These nanoparticles can target and bind to specific receptors that are abnormally over-expressed in atherosclerotic conditions. This paper reviews recent research (2018–present) advances in various ligand-modified nanoparticle systems targeting atherosclerosis by specifically targeting signature molecules in the hope of precise treatment at the molecular level and concludes with a discussion of the challenges and prospects in this field. The intention of this review is to inspire novel concepts for the design and advancement of targeted nanomedicines tailored specifically for the treatment of atherosclerosis.

背景 国家基本公共卫生服务项目自2009年至今已开展13年，是我国迄今为止针对高血压患者开展的最大范围的人群干预实践，了解该人群对干预实践的反馈，对于推动国家基本公共卫生服务的持续发展非常重要。目的 探讨高血压患者的国家基本公共卫生服务自评受益率与满意度，为促进国家基本公共卫生服务实现高质量发展提供科学依据。方法 采用多阶段分层抽样方式，于2019年11—12月在我国东、中、西部地区5市10区（县）20个社区卫生服务中心或乡镇卫生院抽取2 419例≥35岁的高血压患者进行问卷调查。问卷由两部分组成：一般人口学信息和高血压患者健康管理情况。结果 86.26%（2 072/2 402）的调查对象认为其所接受的基本公共卫生服务对其健康改善具有帮助。分别有97.15%（2 349/2 418）、94.09%（2 275/2 418）、88.16%（2 129/2 415）、87.81%（2 118/2 412）、61.36%（1 469/2 394）、95.04%（2 297/2 417）、83.67%（2 013/2 406）、82.34%（1 981/2 406）、95.53%（2 310/2 418）的高血压患者对医护人员服务态度、医护人员服务水平、体格检查、健康教育、中医药治疗、随访服务、高血压并发症筛查、血压控制效果及总体服务表示满意。不同文化程度、不同自评健康状况、是否在基层首次发现血压异常、过去1年内接受不同随访服务次数的高血压患者的自评获益率比较，差异有统计学意义（P＜0.05）；不同文化程度、是否在基层首次发现血压异常、过去1年内接受不同随访服务次数的高血压患者总体服务满意度比较，差异有统计学意义（P＜0.05）。结论 高血压患者的国家基本公共卫生服务自评受益率及满意度较高，应注重国家基本公共卫生服务的规范提供及城乡同质化，以促进国家基本公共卫生服务实现高质量、可持续的发展。

As an important measure to deepen the reform of the medical and pharmaceutical health system, the national essential public health services programs has been carried out for more than ten years. Therefore, it is of great significance to evaluate the effect and remaining problems of the programs over the decade of implementation period (2009-2019) and to further promote the country's basic public health services. With reference to Donabedian quality theory, this paper summarized and analyzed the key problems existing in China's basic public health services from the aspects of project objectives, project contents, operation mechanisms, implementation processes and effects, and make relevant suggestions from six aspects, mainly as follows: based on scientific reasoning, dynamically adjusting the programs; suggestion that the national basic public health services should be graded and managed by classification; timely revision of project specifications to improve service quality and efficiency; gradually promoting the effectiveness-oriented evaluation and assessment system; improving operational mechanisms and promoting sustainable development; fully playing the role of county medical community, and enhancing service coordination; establishing a scientific and long-term monitoring mechanism for national essential public health services programs. It provides reference for further improvement and optimization of national essential public health services progjects.

Background The national essential public health services programs (NEPHSP) is an important project led by the Chinese government to benefit the people, which is a Chinese practice towards universal health coverage. In 2009, the project was rolled out across the country, and its coverage and influence are second to none in the field of public health in China. It is necessary to review the 10-year progress of the project and clarify its effectiveness to maintain its sustainable development. Objective To systematically sort out and summarize the progress and achievements of the NEPHSP made over the past decade (2009-2019) . Methods We collected the monitoring data (2009-2016) of basic public health projects in 31 provinces (autonomous regions and municipalities directly under the central government) through correspondence, analyzed the monitoring data of the national basic public health service management platform (2017-2019) and the relevant indicators of the China Health Statistical Yearbook (2010-2020) , and analyzed the coverage of basic public health services in the country over the past ten years from the perspective of providers. From November to December 2019, a ten-year assessment survey of the national essential public health services was carried out in Zhejiang Province, Shanxi Province and Chongqing city to investigate the residents' awareness, utilization, satisfaction and self-assessment benefit rates of NEPHSP from the perspective of the consumers. Results During the past decade, the coverage of various service items of basic public health in China has increased significantly: (1) the rate of construction of health file, the rate of construction of electronic health file, and the utilization rate of health file have increased from 48.78%, 35.07% and 22.14% in 2009 to 88.25%, 86.82% and 55.34% in 2019, with an average annual growth rate of 6.41%, 10.92% and 15.62% respectively; (2) A total of 6.311 billion printed health education materials were distributed nationwide, about 337million audio-visual health education materials were broadcasted, and a total of 1.144 billion people attended health education lectures; (3) By 2019, there were about 109 million registered hypertensive patients and about 31 357 100 diabetes patients nationwide. The standardized management rate of hypertensive / diabetes patients has increased by 29.28% and 27.25% respectively in the past decade. The blood pressure / blood glucose control rate in the population managed for hypertension / diabetes has increased by 16.84% and 24.69% respectively in the past decade, with an average annual growth rate of 3.28% and 5.56% respectively. The gap in each indicator among the eastern, central and western regions was gradually narrowing; (4) The rates of early pregnancy enrollment, antenatal examination, postpartum visit and system management increased by 6.06%, 4.60%, 7.79% and 9.40% respectively. The ten-year rates of neonatal visit and health management of 0-6-year-old children increased by 14.09% and 17.82% respectively, with an average annual growth rate of 1.74% and 2.30%. In 2019, the national elderly health management rate was 67.41%, an increase of 26.23% over 2009, with an average annual growth rate of 5.96%. The average annual growth rate of TCM health management services for the elderly and children was 15.00% and 12.97%, respectively; (5) The rate of establishing vaccination certificates and the vaccination rate of all kinds of vaccines among residents were stable at more than 90%; The standardized management rate of patients with severe mental disorders reached 89.17% in 2019, the management rate of pulmonary tuberculosis patients and the regular drug taking rate of pulmonary tuberculosis patients had been stable at more than 95% since 2015; (6) In 2019, the awareness rate of the national essential public health services programs for participating residents in the survey was 85.4%, the service utilization rate was 98.7%, the service satisfaction of the key groups was more than 90%, and the self-assessment service benefit rate was more than 85%; (7) The service capacity of primary medical and health service institutions had been improved, and the number of institutions had shown a continuous upward trend. The number of personnel in primary medical and health institutions, the proportion of doctors and nurses, and the proportion of Bachelor degree or above had all increased year by year. Conclusion Over the past decade, as an important part of basic health services in China, the population coverage of basic public health services had increased significantly, the goal of wide service coverage had been basically achieved, the health management level of the focused population had been significantly improved, the effect of health management had been presented, the residents' sense of access to basic public health services had been gradually improved, and the service capacity of basic medical and health institutions had been continuously improved. The comprehensive implementation of basic public health services in China is an important initiative towards the goal of "universal health coverage".