Objective: To investigate the status of heat illness, knowledge awareness and adaptive behaviors of heat wave knowledge among food delivery riders, so as to provide a basis for optimizing heat wave response measures for food delivery riders. Methods: In November 2022, food delivery riders from a large food delivery platform in Ningbo City, Zhejiang Province were selected as survey subjects using a cluster sampling method. A self-designed electronic questionnaire was used to select demographic information, work status, lifestyle behaviors and disease history, heat illness status, knowledge awareness and adaptive behaviors of heatwave. Results: A total of 911 questionnaires were distributed, and 830 valid questionnaires were recovered, resulting in a valid response rate of 91.11%. Among the respondents, 796 (95.90%) were male, and 818 (98.55%) worked full-time. The mean age was (27.75±8.00) years. A total of 470 respondents (56.63%) had a work tenure of less than 1 year. The primary working hours were 8-<12 hours, with 504 people accounting for 60.72%. There were 108 cases of heatstroke, with an occurrence rate of 13.01%. And 286 people reported heat-related symptoms, with an occurrence rate of 34.46%. The overall awareness rate of heat wave knowledge was 73.22%, while the awareness rate of heat warning signal classification was relatively low at 9.04%. The heat wave cognition score was (5.86±1.31) points. There were statistically significant differences in heat wave cognition scores among food delivery riders of different ages, educational levels, family annual income, work tenures, and work durations (all P<0.05). Regarding positive adaptive behaviors, the number of riders paying attention to weather forecasts and actively learning about preventive measures was higher (734 people each, accounting for 88.43%). Regarding negative adaptive behaviors, the number of riders who often drank ice-cold beverages was higher (509 people, accounting for 61.33%). The heat wave adaptive behavior score was (6.88±1.77) points. There were statistically significant differences in adaptive behavior scores among riders with different educational levels, family annual income, work tenures, and smoking frequency (all P<0.05). Conclusions The occurrence rates of heatstroke and heat-related symptoms among food delivery riders are relatively high. The knowledge awareness and adaptive behaviors regarding heat wave are at a moderate level. It is suggested to strengthen health education, reinforce risk cognition of heat wave, and promote positive adaptive behaviors among food delivery riders.

Geniposide， the primary active component of the traditional Chinese medicine Gardeniae Fructus， is a water-soluble iridoid glycoside. Pharmacological studies have demonstrated that geniposide exhibits various biological activities， including hepatoprotective， anti-inflammatory， analgesic， neuroprotective， antidepressant effects， and inhibitory activity against ischemia-reperfusion injury. Recent research has revealed its promising potential in preventing and treating diseases such as atherosclerosis and osteoporosis， indicating broad application prospects. Numerous in vitro and in vivo studies indicate that the pharmacodynamic mechanisms of geniposide are primarily associated with the inhibition of inflammatory responses and oxidative stress， improvement of lipid metabolism， and regulation of apoptosis. However， due to its high water solubility and rapid metabolism in vivo， geniposide suffers from low oral bioavailability， which limits its therapeutic efficacy and clinical application. In recent years， various formulations， such as creams， cubic liquid crystals， hydrogels， and liposomes， have been developed to address its bioavailability issues. This article reviewed the latest research progress on the pharmacological activities and formulation development of geniposide by analyzing domestic and international literature from the past decade， aiming to provide a theoretical basis for further research， development， and utilization of geniposide and its formulations.

Objective: Blood safety surveillance is a critical measure for the objective assessment of blood quality and enhancing transfusion safety. This study aims to comprehensively understand the current status of blood safety surveillance and management in blood collection and supply institutions in Sichuan Province, systematically analyze existing problems and vulnerabilities, and provide a basis for optimizing management strategies and improving capabilities to ensure blood safety. Methods: The Blood Safety Surveillance questionnaire was designed, covering adverse donor reaction reporting, management of adverse events, and transfusion adverse reaction feedback. An online survey was conducted via Questionnaire Star platform among 21 blood collection and supply institutions in the province, gathering information on management systems, process implementation, and utilization of monitoring data. The collected data were organized and statistically analyzed using Excel. Results: The questionnaire response rate and validity rate were both 100%. Blood collection and supply institutions in Sichuan Province have generally established a blood safety surveillance system and achieved positive outcomes. Regarding adverse events in blood collection and supply, 95.24% (20 institutions) have established reporting procedures, and 66.67% (14) collect information through multiple channels such as internal reports, external reports, and statistical trend feedback. A total of 90.48% (19) institutions regularly summarize and analyze adverse event data, and 85.71% (18) produce reports with improvement recommendations based on this analysis.71.43% (15) institutions implement reward and penalty measures, and 71.43% (15) report underreporting or omission due to accountability or performance concerns. In terms of monitoring adverse blood donation reactions, all blood collection and supply institutions have established full-process management systems.76.19% (16) collect data through multiple approaches, including on-site donation records, voluntary donor reports, and donor follow-ups. Adverse reactions were followed up in 95.24% (20) of institutions with 65% (13) completing follow-ups within 24 hours.80.95% (17) have established investigation procedures, while 66.67% (14) believe underreporting or omission still occurs. All blood collection and supply institutions regularly compile statistics on adverse donation reactions. Of these, 85.71% (18) institutions providing feedback to management departments and 90.48% (19) analyzing the data and making recommendations.76.19% (16) institutions use monitoring data for return donor management and targeted care, and 71.43% (15 stations) incorporate it into management reviews. Regarding adverse transfusion reactions, 95.24% (20) institutions have established and implemented procedures for isolating, recalling, and tracing of problematic blood units. However, only 42.86% (9) have established feedback mechanisms of adverse transfusion reaction with hospitals, and only 19.05% (4) support direct reporting via information systems.47.62% (10) institutions regularly analyze adverse transfusion reaction data, and 19.05% (4) provide feedback and recommendations to relevant hospitals. All blood collection and supply institutions reported challenges in collecting hospital feedback, citing complexities in data collection and reporting processes. Conclusion: Blood safety surveillance systems have been preliminarily established in Sichuan Province. However, further strengthening is still required, including conducting in-depth data analysis and utilization, standardizing the configuration of emergency medications and equipment, and improving feedback mechanisms for adverse transfusion reactions. To improve the overall level of blood safety management, it is recommended to strengthen closed-loop data management, improve feedback mechanisms between blood collection and supply institutions and hospitals, foster a non-punitive reporting culture, and systematically advance the regionalization and standardization of the monitoring system. These efforts will contribute to sustainably improving the overall effectiveness and sustainability of blood safety management.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

BACKGROUND:3D organoids have characteristics that resemble physiological tissues and to some extent mimic organ function,making them excellent models for applications ranging from basic development/stem cell research to personalized medicine. OBJECTIVE:To review and discuss the types of diseases and application areas such as tumor modeling that organoids can be applied to,as well as their regulatory status and challenges. METHODS:With"organoid,stem cell,disease model,3D printing technology,medical field"as Chinese and English search terms,we searched PubMed,Elsevier,WanFang,and CNKI databases to summarize and analyze organoid products at home and abroad,summarize the application of organoid technology in the medical field,and prospect the future development of organoid products in the medical field. RESULTS AND CONCLUSION:Organoids can break the limitations of traditional cell and animal models,avoid the ethical problems existing in clinical research,and have a high similarity to the source organ,a more similar performance to the physiology and pathology of human systems,and genetic stability,which has great advantages in current research.Organoids have been applied in the following fields:efficacy evaluation studies(preclinical models),including intestinal organoids,kidney organoids,liver organoids,gallbladder organoids,lung organoids,brain organoids,heart organoids,skin organoids,and reproductive system organoids;research on infectious diseases;cancer research and precision therapy;regenerative medicine;immune organoids.Although the United States,the European Union and China do not have perfect regulatory provisions,they are trying to promote the formulation of organoid regulatory laws and regulations.In China,although no organoid medical device products have been listed for the time being,its related regenerative medicine products have made breakthroughs.

BACKGROUND:Type 2 diabetes mellitus impairs renal function,and studies have shown that exercise interventions can protect the kidneys.Irisin can protect renal function in diabetic nephropathy patients by restoring autophagy through inhibition of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway. OBJECTIVE:To explore whether exercise can restore autophagy and ameliorate renal injury by inhibiting over-activation of the renal PI3K/Akt/mTOR signaling pathway,as well as to analyze the differences in the effects of different modalities of exercise. METHODS:Six-week-old Sprague-Dawley rats were randomly divided into a blank control group(normal rats)and a diabetic group,and then the diabetic group was randomly divided into a diabetic model group,a moderate-intensity continuous exercise group,and a high-intensity intermittent exercise group after successful modeling using high-fat,high-sugar feeding plus intraperitoneal administration of low-dose 1%streptozotocin(30 mg/kg).The two exercise groups were subjected to 8 weeks of exercise intervention with different exercise intensities.The fasting blood glucose concentration was detected by glucose oxidase method,glycated hemoglobin levels was measured using a kit,serum insulin concentration was detected by Elisa method,and insulin resistance index was calculated.Gene expression of PI3K,AKT,mTOR,Beclin-1,podocin,and nephrin was detected by RT-PCR.Protein expression of mTOR and autophagy marker proteins LC3-1,LC3-2,and Beclin-1 was detected by western blot RESULTS AND CONCLUSION:Fasting blood glucose and glycosylated hemoglobin levels were highly significantly increased,insulin resistance levels were significantly increased,and insulin levels were significantly decreased in type 2 diabetic rats.Both exercises resulted in highly significant decreases in fasting blood glucose and glycosylated hemoglobin levels,significant decreases in insulin resistance levels and significant increases in insulin levels in type 2 diabetic rats.Insulin levels were significantly higher in the high-intensity intermittent exercise group compared with the moderate-intensity continuous exercise group.The expression of podocin and nephrind genes was significantly reduced in type 2 diabetic rats and two different forms of exercise significantly the gene expression.There was a further trend toward an increase in gene expression of podocyte-associated proteins in the moderate-intensity continuous exercise group compared with the high-intensity intermittent exercise group,but there was no significant difference.The mRNA and protein expression of PI3K,AKT and mTORC1 in kidney tissues of type 2 diabetic rats were significantly increased,and the expression of autophagy marker proteins Beclin-1 and LC3-2 and LC3-2/LC3-1 were significantly decreased.Both different forms of exercise significantly decreased the mRNA and protein expression of PI3K,AKT,and mTORC1,and significantly increased the autophagy marker proteins Beclin-1,LC3-2,and LC3-2/LC3-1 in renal tissues.Compared with the moderate-intensity continuous exercise group,there was a trend toward further decreases in mRNA expression of PI3K,AKT,and mTORC1 and protein expression of mTOR,and a trend toward further elevation of Beclin-1,LC3-2,and LC3-2/LC3-1 in the high-intensity intermittent exercise group,but only Beclin-1 showed a significant difference between groups.In summary,renal podocyte injury in type 2 diabetes mellitus with suppressed autophagy is closely related to aberrant activation of the PI3K/AKT/mTORC1 signaling pathway.Both moderate-intensity continuous exercise and high-intensity intermittent exercise can protect the diabetic kidney,reduce podocyte damage,and restore renal podocyte autophagy,which may be achieved by inhibiting the excessive activation of the PI3K/AKT/mTOR signaling pathway.High-intensity intermittent exercise shows a trend toward more favorable restoration of autophagy compared with moderate-intensity continuous exercise,but with a slight decrease in podocyte protein expression.

Objective To investigate the effects of Aconite decoction （AD） on the viability and polarization of murine RAW264.7 macrophages induced by lipopolysaccharide （LPS） or interleukin-4 （IL-4）. Methods Cytotoxicity of AD was assessed by the CCK-8 assay. RAW264.7 cells were polarized toward M1 phenotype by LPS or M2 phenotype by IL-4, followed by treatment with varying concentrations of AD. Macrophage polarization was analyzed by flow cytometry. Quantitative PCR was performed to measure mRNA expression of polarization-associated markers （IL-6, iNOS, Arg1, and Ym1）. ELISA was used to quantify secreted cytokines （TNF-α and IL-10）in the supernatant. Results At non-toxic concentrations, IL-6 and iNOS mRNA levels in LPS-stimulated cells were significantly upregulated while Arg1 and Ym1 expression in IL-4-treated groups were downregulated by AD. Concurrently, TNF-α secretion in LPS-induced M1 polarization was enhanced but IL-10 production in IL-4-induced M2 polarization was suppressed by AD. Conclusion AD could promote macrophage proliferation and viability, augments LPS-driven M1 polarization, and inhibit IL-4-mediated M2 polarization, which provided experimental evidence for the potential application of AD in tumor immunotherapy.

The structural characteristics and clinical application of embolic microspheres were summarized in this paper. According to evaluation experience and current regulatory registration evaluation requirements, registration evaluation concerns on embolic microsphere as medical device were analyzed from four aspects: administration attributes, product description, non-clinical studies and clinical evaluation, in order to provide references for the development and registration application of such products and improve the efficiency of registration application.
Microspheres ; Device Approval ; Embolization, Therapeutic/instrumentation*

Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE ^-/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.