Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Objective:To evaluate the feasibility of the novel programmed death-ligand 1 (PD-L1)-targeted PET/CT molecular probe for evaluating PD-L1 expression and tumor heterogeneity in patients with non-small cell lung cancer (NSCLC).Methods:From October 2023 to October 2024, 30 patients (21 males, 9 females; age 69(58, 75) years) with newly diagnosed NSCLC at the First Affiliated Hospital of Xiamen University were prospectively enrolled. All patients underwent PET/CT imaging 1 h after intravenous administration of 68Ga-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-DK224, and SUV max was calculated. Immunohistochemical staining on biopsy samples of patients were performed and the PD-L1 tumor proportion score (TPS) was calculated. The differences of SUV max between two groups were compared by using Mann-Whitney U test. Results:Of 30 patients, 31 biopsy specimens were obtained including 24 primary lesion biopsies, 1 lymph node lesion biopsy, and 6 metastatic lesion biopsies, with 16 TPS<1%, 9 1%≤TPS<50% and 6 TPS≥50%. PD-L1-positive tumors showed relatively high uptake of 68Ga-NOTA-DK224. The SUV max of TPS≥1% group was significantly higher than that of TPS<1% group (6.9(5.1, 7.7) vs 3.8(3.1, 4.2); Z=-4.47, P<0.001), and SUV max of TPS≥50% group was significantly higher than that of TPS<50% group (8.6(7.3, 12.4) vs 4.2(3.7, 5.3); Z=-3.65, P<0.001). Of 30 patients, 24 had multiple metastatic lesions with 212 lesions in total. The median fold difference was 2.3 (range: 1.4-6.0), and the median CV was 28.3% (range: 11.7%-61.6%). Conclusion:68Ga-NOTA-DK224 PET/CT is able to accurately and comprehensively reflect PD-L1 expression and tumor heterogeneity in primary and metastatic NSCLC.

Objective:To evaluate the feasibility of the novel programmed death-ligand 1 (PD-L1)-targeted PET/CT molecular probe for evaluating PD-L1 expression and tumor heterogeneity in patients with non-small cell lung cancer (NSCLC).Methods:From October 2023 to October 2024, 30 patients (21 males, 9 females; age 69(58, 75) years) with newly diagnosed NSCLC at the First Affiliated Hospital of Xiamen University were prospectively enrolled. All patients underwent PET/CT imaging 1 h after intravenous administration of 68Ga-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-DK224, and SUV max was calculated. Immunohistochemical staining on biopsy samples of patients were performed and the PD-L1 tumor proportion score (TPS) was calculated. The differences of SUV max between two groups were compared by using Mann-Whitney U test. Results:Of 30 patients, 31 biopsy specimens were obtained including 24 primary lesion biopsies, 1 lymph node lesion biopsy, and 6 metastatic lesion biopsies, with 16 TPS<1%, 9 1%≤TPS<50% and 6 TPS≥50%. PD-L1-positive tumors showed relatively high uptake of 68Ga-NOTA-DK224. The SUV max of TPS≥1% group was significantly higher than that of TPS<1% group (6.9(5.1, 7.7) vs 3.8(3.1, 4.2); Z=-4.47, P<0.001), and SUV max of TPS≥50% group was significantly higher than that of TPS<50% group (8.6(7.3, 12.4) vs 4.2(3.7, 5.3); Z=-3.65, P<0.001). Of 30 patients, 24 had multiple metastatic lesions with 212 lesions in total. The median fold difference was 2.3 (range: 1.4-6.0), and the median CV was 28.3% (range: 11.7%-61.6%). Conclusion:68Ga-NOTA-DK224 PET/CT is able to accurately and comprehensively reflect PD-L1 expression and tumor heterogeneity in primary and metastatic NSCLC.

Climate change has led to an increasing frequency and intensity of extreme climate events such as heat and drought extremes with considerable global public health burden. This systematic review collected 87 domestic and international studies from 2000 to 2023, considering the impacts of heat extremes, drought extremes, and compound hot-dry events on infectious diseases attributable to various transmission pathways such as waterborne, foodborne, insect-borne, airborne, and contact-transmitted diseases. Our results showed that high temperature was associated with increased transmission risks of waterborne and foodborne diseases including infectious diarrheal diseases (cholera, dysentery, typhoid, and paratyphoid) and infectious gastroenteritis; vector-borne diseases including dengue fever, Zika virus (ZIKV) disease, chikungunya fever, malaria, West Nile fever, and Rift Valley fever; airborne diseases including influenza-like diseases, influenza A, measles, and mumps; and contact-transmitted diseases including HIV/AIDS, schistosomiasis, and leptospirosis. Additionally, drought conditions also amplified the transmission risks of waterborne and foodborne diseases including cholera, Escherichia coli infection, rotavirus infection, and hepatitis E; vector-borne diseases such as scrub typhus, schistosomiasis, hemorrhagic fever with renal syndrome, and West Nile fever; airborne diseases including meningococcal meningitis, pertussis, measles, and upper respiratory infections; and contact-transmitted diseases such as HIV/AIDS. Along with global warming, the frequency of compound high temperature and drought events shows a considerably increasing trend, causing more adverse health effects than heat or drought alone. However, there is limited research quantifying their effects on infectious diseases. These associations may be mediated through temperature and precipitation on infectious disease pathogens, transmission vectors, population susceptibility, public health services, and behaviors. In the context of climate change, the increasing occurrence of compound events of high temperatures and droughts raises health concerns, and further studies are needed to enhance our understanding of the impacts of climate change on infectious diseases and improve human adaption to climate change.

Objective:To develop a tetramer probe targeting fibroblast activation protein (FAP), named 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-4P(FAP inhibitor (FAPI)) 4, evaluate its biodistribution and PET image in FAP-positive-tumor bearing nude mice, and explore its feasibility as a novel radio-regent for treatment of FAP-positive tumor. Methods:FAP tetramer probe was constructed on the FAPI-46 motif with four mini-polyethylene glycol (PEG)(PEG 3) spacers between the four FAPI motifs, denoted as 4P(FAPI) 4. DOTA was used as the chelator for radiolabeling with 68Ga and 177Lu. The FAP binding characteristics were test by in vitro cell competitive binding experiment. Small-animal PET, in vivo biodistribution, and radionuclide targeting therapy were performed in HT-1080-FAP tumor bearing nude mice ( n=39). Independent-sample t test was performed to analyze tumor uptake data, and two-factor repeated measures analysis of variance was utilized to compare tumor volume data in radioactive isotope therapy. Results:Cell experiment showed that FAPI-tetramer and FAPI-monomer had similar half maximal inhibitory concentration values (3.29 and 2.15 nmol/L). 68Ga/ 177Lu radiolabeled FAPI-tetramer had better tumor uptake and retention than FAPI-monomer in small-animal PET and in vivo biodistribution experiment, with the tumor uptake for 177Lu-DOTA-4P(FAPI) 4 and 177Lu-FAPI-46 at 48 h of (18.72±1.32) vs (2.72±1.20) percentage activity of injection dose per gram of tissue (%ID/g) ( t=15.55, P<0.001). 177Lu-DOTA-4P(FAPI) 4 group showed best anti-tumor efficacy compared with 177Lu-FAPI-46 and control group in radionuclide targeting therapy. On the 2nd day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the control group (mean difference 67.19 mm 3, P=0.049); on the 14th day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the monomer treatment group (mean difference 414.33 mm 3, P=0.005). Conclusion:FAPI-tetramer can improve tumor uptake and retention ability compared with FAPI-46, and 177Lu-DOTA-4P(FAPI) 4 can be a promising radio-agent for FAP-positive tumor therapy.

AIM: To screen the active constituents in Taohong Siwu Decoction(THSWD) by Systems Pharmacology and to study its protective effect on myocardial injury through cell experiments. METHODS: The TCMSP database and Pharmmaper database were used to retrieve the constituents and active constituent targets of THSWD. The Genecards database was used to retrieve the myocardial injury related targets gene. Then construct and analyze the constituents-disease intersection target network and the contribution value of constituents, and screen out the main active constituents of THSWD acting on the myocardium. Furthermore, CoCl

Objective To assess the patient enablement level in a general hospital and its related factors,to investigate the relationship of patient enablement with patient's overall satisfaction and doctor's empathy levels.Methods Patients attending the Family Medicine Clinic of HKU-Shenzhen Hospital in September 2014 and met the inclusion criteria were asked to complete a questionnaire survey which included general characteristics,overall satisfaction;the Patient Enablement Instrument (PEI) and the Consultation and Relational Empathy Measure Scale (CARE) after the consultation.Results Total 2 326 questionnaires were issued and 1 818 were retrieved,of which 1 478 were qualified questionnaires.The qualified rate of PEI was 81.3％ and the qualified rate of patient overall satisfaction was 96.28％.The positive rate of patient enablement was 97.70％ (1 444/1 478),and the mean score of PEI was 8.21 ±3.33.Multivariate linear regression analysis showed that the PEI scores were not influenced by gender and education level of the patients,gender of the consulting doctors and initial/follow up consultation.The PEI scores were influenced by the age of the patients,the types of clinic (general practice/chronic practice clinic) and the reasons for consulting (P ＜ 0.05).There were correlations between PEI score and overall satisfaction of patients (r =0.383,P ＜ 0.001),patient's recommendation of the clinic (r =0.595,P ＜ 0.001) and CARE scores (r =0.546,P ＜ 0.001).Conclusion The results show that the PEI scores of patients visiting family medicine clinic of this hospital are higher than those reported in other studies.The PEI score may be influenced by the age of the patients,the types of clinic and the reasons for consulting.Positive correlations between patient enablement and the overall satisfaction,patient's recommendation and doctor empathy were observed.

Objective To assess the empathy level of general practitioners (GPs) in the outpatient clinics of a general hospital,and to investigate the related factors.Methods Patients attending the Family Medicine Clinic of HKU-Shenzhen Hospital in September 2014 and met the inclusion criteria were asked to complete the questionnaire which included general characteristics,overall satisfaction and the Measure-Consultation and Relational Empathy Measure (CARE) Scale after the consultation.Results Of the 1 818 questionnaires retrieved,1 690 CARE scales were completed (intact rate was 92.96%).The overall satisfaction rate was 95.92% (1 621/1 690).And 97.28% (1 644/1 690) of the patients would recommend family medicine service to their friends or relatives.The total score of CARE scale was (45.47±6.26),and the scores of 4 CARE components were (4.63 ± 0.59),(4.43 ± 0.81),(4.54 ± 0.69) and (4.55 ± 0.66),which showed significant difference (P<0.01).The multivariate linear regression analysis showed that the mean CARE scores were not influenced by gender and education levels of the patients,gender of the consulting doctors,initial/follow up consultation,and the location of the consultation.The mean CARE scores were influenced by age of patients and the reasons for consulting (P<0.05).There was a moderate correlation of the CARE scores with the overall satisfaction of patients (r=0.613,P<0.001) and patient's recommendation of the clinic (r=0.466,P<0.001).Conclusion Doctors who were evaluated in this study have a higher empathy level than results from other countries.There is positive correlation between doctor's empathy level and patient's overall satisfaction.The result of doctor's empathy level may be influenced by patient's age and the reasons for consulting.

Objective To analyze the patients with infection before transfusion in onder to avoid misdiagnosis and blood transfusion caused by cross-infection and remind medical staff attention to operation and self-protection.Methods HBsAg,Anti-HCV,Anti-TP,Anti-HIV1/2 were detecced by 2 576 cases of pre-operative,prenatal,blood transfusions before the patient's blood ELISA assay.Results 2 576 cases of infectious markers in patients with serum positive rate was 12.15％.The positive rates of was HBsAg,Anti-HCV,Anti-TP,Anti-HIV1/2:11.06％,2.13％,1.67％,0.00％,HBsAg and Anti-HCV were positive for both the percentage of 0.54％.Conclusion The transfusion of pre-infection detection is necessary for patients with early diagnosis and treatment of infectious diseases to avoid and prevent hospital infections,medical personnel,as well as occupational infection to reduce or avoid blood transfusion caused by medical disputes.

Objective To investigate the influence of service-learning model on medical graduates' ethical behavioral tendency. Methods A self-designed questionnaire was conducted among 302 medical students who have graduated in the last five years including the basic information, ethical behavioral tendency and participation of service-learning. The acquired data was analyzed and com-pared using chi-square test and unconditional logistic multiple regression. Results 68.2%(206/302) undergraduates participated in service-learning. Undergraduates participated in service-learning be-haved more ethical than those did not participated when facing the situation of patient' vomits (P=0.037). There were statistical differences in taking bribes from patients between those participated in service-learning and those did not (P=0.031). According to the results of unconditional logistic multiple regression analysis, whether participating in the service-learning is one of significant factors influenc-ing undergraduates' attitude towards bride-taking. Conclusions Medical students educated by service-learning model will exhibited more ethically accepted medical behaviors after becoming doctors. Ser-vice-learning model, a new medical education model, is worth promoting.