Clinical death refers to the permanent cessation of life functions. This article reviews the definition of clinical death and the various scenarios in which it occurs, classifies the process of clinical death, and discusses the criteria for determining uncontrollable cardiac death, controllable cardiac death and the criteria and workflow for determining brain death. It elaborates on the relationship between brain death and death, and proposes the areas to note when standardizing the medical documentation of death cases. Based on this, it introduces the content of the management system and workflow construction for death determination in medical institutions, including management structure, personnel qualifications, document norms, quality control system and training mechanism. Paying attention to the construction of the management system and workflow for death determination in medical institutions is of great significance for ensuring medical quality and safety, promoting the healthy development of organ donation, and maintaining the seriousness of legal and ethical practices.

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.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Objective To establish a UV method for the determination of the functional compositions(cinnamic acid derivatives,total flavonoids)in Ligustrum robustum,to predict the contents of trans-p-hydroxycinnamic acid,trans-p-hydroxycinnamic acid esters,and rhoifolin based on UV/HPLC,and to optimize the technological conditions of ultrasonic-assistant extraction of L.robustum.Methods ①In the determination of the functional compositions in L.robustum,total cinnamic acid derivatives were determined by dual-wavelength isobestic point UV method(detection wavelength 316 nm,reference wavelength 268 nm),and total flavonoids were determined by single-wavelength UV method(detection wavelength 268 nm),while rhoifolin was determined by HPLC(C 18 column,eluting with methanol-0.1％acetic acid=40∶60,detection wavelength 310 nm).②The conversion factors were used to establish a UV/HPLC-based prediction model,and the precision of the predicted results was evaluated with other 3 test samples.③ The technological conditions of ultrasonic-assisted extraction were optimized by an orthogonal test.Results ① The linear ranges of total cinnamic acid derivatives,total flavonoids,and rhoifolin were 4.64-20.88,8.24-28.84,5.15-51.50 μg·mL-1(r≥0.999 5),respectively.RSDs of the precision,stability,and reproducibility tests were no more than 1.4％.The recoveries were 97.9％-100.5％(RSD≤ 1.2％,n=6).②The relative errors of the values predicted by UV/HPLC from the results measured by HPLC were from-5.3％to 1.7％.There was no significant difference between the UV/HPLC predicted values and the HPLC determined results(P＞0.05)for the contents of trans-p-hydroxycinnamic acid and rhoifolin.③The optimal technological conditions of ultrasonic-assistant extraction of L.robustum were as follows:ethanol concentration 80％,temperature 50 ℃,liquid-solid ratio 20 mL·g 1,extraction frequency 2 times,extraction time 20 min.The total yield of functional compositions under above conditions was 42.0％.Conclusion The above determination methods are accurate and rapid,and the above extraction technology is effective,energy-saving and rapid,which provide an experimental base for the quality control and application of L.robustum.

Objective:To investigate the effects and its related mechanism of placenta-derived mesenchymal stem cells(PMSCs)on the lipopolysaccharides(LPS)damaged astrocytes.Methods:Primary astrocytes were isolated from the cerebral cortex of neonatal rats.The expression of glial fibrillary acidic protein(GFAP)was identified using immu-nofluorescence staining to evaluate the purity of the primary astrocytes.PMSCs were cocultured with LPS-treated astro-cytes.The expression levels of factors related to inflammation including interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),arginase-1(Arg-1),S100 calcium-bind-ing protein A10(S100A10),and TGF-β/Smad signaling pathway-related proteins such as transforming growth factor beta 1(TGF-β1),transforming growth factor beta type I receptor(TβRⅠ),transforming growth factor beta type II re-ceptor(TβRⅡ),phospho-Smad2 and phospho-Smad3(p-Smad2,p-Smad3)in astrocytes from each group were detec-ted using real time RT-PCR or Western blot techniques.Results:Astrocytes at the third passage exhibited an 80%pos-itivity rate for GFAP.After treated with 10 μg/ml LPS,the astrocytes expression levels of pro-inflammatory factors IL-1β,iNOS,IL-6,and TNF-α were significantly increased(P<0.05),while their expression levels of the anti-inflam-matory factors of Arg-1 and S100A10 were significantly decreased(P<0.05).Meanwhile,their expression levels of TGF-β/Smad signaling pathway related proteins of TGF-β1,TβRⅠ,TβRⅡ,p-Smad2 and Smad3 were increased(P<0.05).After the LPS damaged astrocytes were cocultured with PMSCs,their expression levels of pro-inflammatory factors IL-1β,iNOS,IL-6,and TNF-α were significantly decreased(P<0.05),while their expression levels of the anti-inflammatory factors of Arg-1 and S100A10 were significantly increased(P<0.05).Also,their expression levels of TGF-β/Smad signaling pathway related proteins of TGF-β1,TβRⅠ,TβRⅡ,p-Smad2,and Smad3 were decreased(P<0.05).Conclusion:PMSCs may inhibit the activation of A1 astrocytes through the TGF-β/Smad signaling path-way,by which reducing the astrocytic activation.

Objective:To investigate the effects and its related mechanism of placenta-derived mesenchymal stem cells(PMSCs)on the lipopolysaccharides(LPS)damaged astrocytes.Methods:Primary astrocytes were isolated from the cerebral cortex of neonatal rats.The expression of glial fibrillary acidic protein(GFAP)was identified using immu-nofluorescence staining to evaluate the purity of the primary astrocytes.PMSCs were cocultured with LPS-treated astro-cytes.The expression levels of factors related to inflammation including interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),arginase-1(Arg-1),S100 calcium-bind-ing protein A10(S100A10),and TGF-β/Smad signaling pathway-related proteins such as transforming growth factor beta 1(TGF-β1),transforming growth factor beta type I receptor(TβRⅠ),transforming growth factor beta type II re-ceptor(TβRⅡ),phospho-Smad2 and phospho-Smad3(p-Smad2,p-Smad3)in astrocytes from each group were detec-ted using real time RT-PCR or Western blot techniques.Results:Astrocytes at the third passage exhibited an 80%pos-itivity rate for GFAP.After treated with 10 μg/ml LPS,the astrocytes expression levels of pro-inflammatory factors IL-1β,iNOS,IL-6,and TNF-α were significantly increased(P<0.05),while their expression levels of the anti-inflam-matory factors of Arg-1 and S100A10 were significantly decreased(P<0.05).Meanwhile,their expression levels of TGF-β/Smad signaling pathway related proteins of TGF-β1,TβRⅠ,TβRⅡ,p-Smad2 and Smad3 were increased(P<0.05).After the LPS damaged astrocytes were cocultured with PMSCs,their expression levels of pro-inflammatory factors IL-1β,iNOS,IL-6,and TNF-α were significantly decreased(P<0.05),while their expression levels of the anti-inflammatory factors of Arg-1 and S100A10 were significantly increased(P<0.05).Also,their expression levels of TGF-β/Smad signaling pathway related proteins of TGF-β1,TβRⅠ,TβRⅡ,p-Smad2,and Smad3 were decreased(P<0.05).Conclusion:PMSCs may inhibit the activation of A1 astrocytes through the TGF-β/Smad signaling path-way,by which reducing the astrocytic activation.

Objective To establish a UV method for the determination of the functional compositions(cinnamic acid derivatives,total flavonoids)in Ligustrum robustum,to predict the contents of trans-p-hydroxycinnamic acid,trans-p-hydroxycinnamic acid esters,and rhoifolin based on UV/HPLC,and to optimize the technological conditions of ultrasonic-assistant extraction of L.robustum.Methods ①In the determination of the functional compositions in L.robustum,total cinnamic acid derivatives were determined by dual-wavelength isobestic point UV method(detection wavelength 316 nm,reference wavelength 268 nm),and total flavonoids were determined by single-wavelength UV method(detection wavelength 268 nm),while rhoifolin was determined by HPLC(C 18 column,eluting with methanol-0.1％acetic acid=40∶60,detection wavelength 310 nm).②The conversion factors were used to establish a UV/HPLC-based prediction model,and the precision of the predicted results was evaluated with other 3 test samples.③ The technological conditions of ultrasonic-assisted extraction were optimized by an orthogonal test.Results ① The linear ranges of total cinnamic acid derivatives,total flavonoids,and rhoifolin were 4.64-20.88,8.24-28.84,5.15-51.50 μg·mL-1(r≥0.999 5),respectively.RSDs of the precision,stability,and reproducibility tests were no more than 1.4％.The recoveries were 97.9％-100.5％(RSD≤ 1.2％,n=6).②The relative errors of the values predicted by UV/HPLC from the results measured by HPLC were from-5.3％to 1.7％.There was no significant difference between the UV/HPLC predicted values and the HPLC determined results(P＞0.05)for the contents of trans-p-hydroxycinnamic acid and rhoifolin.③The optimal technological conditions of ultrasonic-assistant extraction of L.robustum were as follows:ethanol concentration 80％,temperature 50 ℃,liquid-solid ratio 20 mL·g 1,extraction frequency 2 times,extraction time 20 min.The total yield of functional compositions under above conditions was 42.0％.Conclusion The above determination methods are accurate and rapid,and the above extraction technology is effective,energy-saving and rapid,which provide an experimental base for the quality control and application of L.robustum.

Objective: To observe and compare the clinical effects of different electroacupuncture waveforms on primary dysmenorrhea. Methods: This was a prospective, randomized, three-group, parallel-controlled trial. Participants with primary dysmenorrhea were randomly divided into dense-sparse wave, continuous wave, and discontinuous wave groups in a 1:1:1 ratio. Two lateral Ciliao (BL 32) points were used. All three groups started treatment 3–5 days before menstruation, once a day for six sessions per course of treatment, one course of treatment per menstrual cycle, and three menstrual cycles. The primary outcome measure was the proportion with an average visual analog scale (VAS) score reduction of ≥50% from baseline for dysmenorrhea in the third menstrual cycle during treatment. The secondary outcome measures included changes in dysmenorrhea VAS scores, Cox Menstrual Symptom Scale scores and the proportion of patients taking analgesic drugs. Results: The proportion of cases where the average VAS score for dysmenorrhea decreased by ≥50% from baseline in the third menstrual cycle was not statistically significant (P > .05). Precisely 30 min after acupuncture and regarding immediate analgesia on the most severe day of dysmenorrhea, there was a statistically significant difference in the dense-sparse wave group compared with the other two groups during the third menstrual cycle (P < .05). Additionally, there was a statistically significant difference between the dense-sparse wave and discontinuous wave groups 24 h after acupuncture (P < .05). Conclusions Waveform electroacupuncture can alleviate primary dysmenorrhea and its related symptoms in patients. The three groups showed similar results in terms of short- and long-term analgesic efficacy and a reduction in the number of patients taking analgesic drugs. Regarding achieving immediate analgesia, the dense-sparse wave group was slightly better than the other two groups.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

Objective To analyze the effects of miR-181a-5p overexpression on metabolites in the small intestines of mice with subcutaneous oral cancer by detecting changes in metabolites and metabolic pathways.Methods Three groups were included in study:Control group,negative control and miR-181a-5p overexpression group.To establish a subcutaneous oral cancer model in mice,variously treated cell suspensions were subcutaneously injected into the upper right of the groin in female M-NSG severely immunodeficient mice.Changes in pathology and small intestinal tissues were assessed by HE staining.Changes in mouse body weight were also assessed.Tandem orbitrap mass spectrometry and ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry,were used to examine metabolites in the small intestines.By pre-analyzing the original data and quality rating sample data,XCMS was able to assess which metabolites were different among the groups.To identify unique metabolic pathways,KEGG enrichment analysis was used.Results A total of 170 distinct metabolites were found in the small intestinal tissues of Control and NC groups.Choline metabolism,alanine,aspartate,and glutamate metabolism,GABA synaptic metabolism,glycerophospholipid metabolism,cAMP signaling route,cancer center carbon metabolism,and niacin and niacin amine metabolic pathways were important signaling pathways for metabolite enrichment.In the NC group,16 distinct metabolites with VIP values larger than 2 were found in the small intestines compared with the OE group overexpressing miR-181a-5p.Glycerin phosphorylcholine,palmitic acid,3-hydroxybutyl carnitine,and β-hydroxybutyric acid were among the metabolites that significantly varied.The primary enhanced metabolic pathway was the choline pathway.Conclusions Mouse small intestines underwent slight changes from subcutaneous oral cancer with the greatest effect on metabolites critical for energy metabolism.The choline metabolic pathway was the pathway that selected absolutely metabolites in mouse small intestines with subcutaneous grafts of oral cancer.