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 analyze the sequence of a novel HLA- DPB1 allele in an individual. Methods:A individual identified from the database of blood donors for matched platelet transfusion at the Blood Center of Zhejiang Province in May 2022 was selected as the study subject. HLA genotype of the individual was determined by next-generation sequencing (NGS) on an Ion Torrent S5 platform. The sequence of the HLA- DPB1 locus was also determined by NGS on an Illumina Miseq platform and third generation sequencing using Oxford Nanopore MinION. This study was approved by Medical Ethics Committee of the Blood Center of Zhejiang Province (Ethics No. 2021-001). Results:A novel HLA- DPB1*02 allele was identified in the specimen, for which the closest genotype was HLA- DPB1*02: new, 17: 01: 01G, with the variant located in exon 3. Meanwhile, the NGS also revealed a novel HLA- DPB1*17 allele, with the closest genotype being HLA- DPB1*02: 01: 02G, 17: new. Both the HLA- DPB1*17: 01: 01: 01 and novel HLA- DPB1*02 alleles were identified by third-generation sequencing. Compared with the HLA- DPB1*02: 01: 02: 01 allele, the novel allele had a G>A variation at position 369 in the exon 3, which did not result in amino acid change. Conclusion:A novel HLA- DPB1 allele has been identified and validated by both NGS and TGS, which has been named as HLA- DPB1*02: 01: 69 by the World Health Organization Committee on Nomenclature of Factors of the HLA System.

Objective:To investigate the association between triglyceride-glucose (TyG) index and all-cause mortality in elderly patients with hypertension and coronary artery disease.Methods:This was a retrospective cohort study, a total of 5 640 elderly inpatients (≥65 years) with hypertension and coronary artery disease who were admitted to the Department of Cardiology, Liberation Army General Hospital from August 2008 to July 2018 were enrolled in this study. The baseline clinical data of the patients were collected and the TyG index was calculated. Patients were divided into four groups according to their TyG index quartiles: TyG index<8.31 ( Q1 group, n=1 392), 8.31≤TyG index<8.67 ( Q2 group, n=1 417), 8.67≤TyG index<9.07 ( Q3 group, n=1 427), and TyG index≥9.07 ( Q4 group, n=1 404). All patients were followed up by obtaining outpatient/rehospitalization records or by telephone. The primary endpoint was all-cause mortality. Log-rank test was used to compare the cumulative all-cause mortality among groups. Cox proportional hazard regression model was used to analyze the risk of all-cause mortality in each group (the Q2 group with the lowest all-cause mortality was used as a reference), after adjusting for confounding factors, Restricted cubic spline analysis (RCS) was used to determine the association between TyG index and risk of all-cause mortality. Results:During a follow-up of 6.44 (4.70, 8.85) years, 1 037 all-cause deaths (18.39 %) were documented. The cumulative all-cause mortality in Q1- Q4 groups was 16.52%, 16.51%, 17.59% and 22.93%, respectively, and the difference was statistically significant ( χ2=26.49, P<0.01). In the Cox regression model, compared with Q2 group (reference), the HR (95% CI) for all-cause mortality was 1.06 (0.88-1.28) in the Q1 group, 1.23 (1.02-1.48) in the Q3 group and 1.48 (1.23-1.77) in the Q4 group, respectively ( P for trend<0.01). RCS curve analysis showed that when the TyG index was greater than 8.67, the risk of all-cause mortality increased with the TyG index, and there was a linear relationship between TyG index and all-cause mortality in this patient cohort (non-linearity P=0.31). Conclusion:The elevated TyG index is significantly associated with a higher risk for all-cause mortality in elderly hypertension and coronary artery disease patients.

Objective:To evaluate the relationship between breast cancer resistance protein (BCRP)-blood brain barrier (BBB) and dexmedetomidine-induced improvement in postoperative cognitive function in patients with mild hyperbilirubinemia.Methods:This was a prospective study. Ninety patients of both sexes with mild hyperbilirubinemia caused by choledocholithiasis, aged 55-69 yr, with body mass index of 22-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with preoperative Mini-Mental State Examination (MMSE) scores≥20, scheduled for elective cholecystectomy, exploratory choledocholithotomy and T-tube drainage from December 2022 to August 2023 in the Third Central Hospital of Tianjin, were divided into 2 groups( n=45 each) using a random number table method: control group (C group) and dexmedetomindine group (D group). After induction of anesthesia, dexmedetomidine was intravenously infused at a loading dose of 0.5 μg/kg over 10 min, followed by an infusion of 0.6 μg·kg -1·h -1 until the end of operation in group D, and the equal volume of normal saline was given instead in group C. At 2 days before operation and 1, 3, 5, 7 and 14 days after operation, the cognitive function was assessed using MMSE and Montreal Cognitive Assessment, and the serum BCRP concentration, concentrations of cognitive function serological indicators (serum S100β, β amyloid 42, malondialdehyde), and concentrations of BBB serological indicators (serum glial fibrillary acidic protein, thrombospondin 1, claudin 5) were determined using enzyme-linked immunosorbent assay. Results:Compared with group C, MMSE and Montreal Cognitive Assessment scores were significantly increased, the incidence of cognitive impairment was decreased, the serum concentrations of S100β, β amyloid 42 and malondialdehyde were decreased, the serum concentrations of BCRP were increased, and the serum concentrations of glial fibrillary acidic protein, claudin-5 and thrombospondin 1 were decreased in group D ( P<0.05). Conclusions:The mechanism by which dexmedetomidine improves postoperative cognitive function may be related to up-regulating BCRP levels and improving BBB function in patients with mild hyperbilirubinemia.

Objective:To investigate the clinical utility of 68Ga-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in the detection of primary and metastatic gastric signet-ring cell carcinoma (GSRCC) and compared the results with those of 18F-FDG PET/CT. Methods:A total of 21 patients (10 males, 11 females, average age 52 years) with primary and metastatic GSRCC who underwent 68Ga-FAPI and 18F-FDG PET/CT at the First Affiliated Hospital of Xiamen University from June 2020 to May 2022 were retrospectively analyzed. Pathological results of surgery and (or) biopsy were used as the " gold standard" for final diagnosis. In cases whose surgery or tissue biopsies were not available, clinical and radiographic follow-up results were used as the reference standards. Wilcoxon signed-rank test was used to compare the SUV max of 18F-FDG and 68Ga-FAPI. McNemar χ2 test was used to compare the detection rate between 18F-FDG and 68Ga-FAPI PET/CT. Results:68Ga-FAPI PET/CT showed higher SUV max than 18F-FDG in primary tumors (5.3(2.4, 15.7) vs 2.4(1.8, 2.5); z=2.31, P=0.021), local recurrences (7.8(6.0, 8.9) vs 2.4(1.9, 3.4); z=2.20, P=0.028), lymph nodes metastases (7.7(4.5, 12.2) vs 2.4(1.9, 3.6); z=6.01, P<0.001) and bone/visceral metastases (6.7(5.3, 11.1) vs 2.4(2.0, 3.4); z=11.36, P<0.001). Regarding diagnostic accuracy, 68Ga-FAPI PET/CT showed higher sensitivities than 18F-FDG for primary tumors (7/9 vs 2/9; χ2=3.20, P=0.063) and local recurrences (7/7 vs 2/7; χ2=3.20, P=0.063). It also demonstrated higher lesion detection rates than 18F-FDG for suspicious lymph node metastases (86%(65/76) vs 32%(24/76); χ2=31.37, P<0.001) and bone/visceral metastases (99%(184/185) vs 39%(73/185); χ2=107.08, P<0.001). Conclusions:68Ga-FAPI PET/CT showed higher tumor uptake and lesion detection rate than 18F-FDG in the primary and metastatic GSRCC. 68Ga-FAPI PET/CT demonstrates good diagnostic performance for tumor detection, staging, and restaging of GSRCC, which is helpful to further guide clinical treatment strategy.

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.

Background::The clinical characteristics of patients with the comorbidities of hypertension and coronary artery disease (HT-CAD) and atrial fibrillation (AF) are largely unknown. This study aimed to investigate the prevalence of AF in patients with HT-CAD and clinical characteristics of patients with both HT-CAD and AF.Methods::This cross-sectional study was conducted in Chinese People’s Liberation Army General Hospital in Beijing, China, and included 20,747 inpatients with HT-CAD with or without AF from August 2008 to July 2018. We examined the overall prevalence, clinical characteristics, comorbidity profiles, treatment patterns, and blood pressure (BP) control of patients with both HT-CAD and AF. Multivariate logistic regression was used to investigate the associations of cardiovascular risk factors with AF in patients with HT-CAD.Results::The overall prevalence of AF in patients with HT-CAD was 4.87% (1011/20,747), and this increased with age; to be specific, the prevalence in women and men increased from 0.78% (2/255) and 1.02% (26/2561) at the age of <50 years to 8.73% (193/2210) and 10.28 % (298/2900) at the age of ≥70 years, respectively. HT-CAD patients who had AF had a higher prevalence of cardiovascular-related comorbidities than those without AF. Multivariate logistic regression showed that age, gender (male), body mass index, heart failure, and chronic kidney disease were independently associated with the risk of AF in patients with HT-CAD. For those with both HT-CAD and AF, 73.49% (743/1011) had a CHA 2DS 2-VASc score of ≥4, and only about half of them had the BP controlled at <140/90 mmHg, which indicated a high risk of thromboembolism and stroke. The use of oral anticoagulation increased during the study period (10.00% [20/200] in 2008 to 2011 vs. 30.06% [159/529] in 2015 to 2018, P < 0.01), but remained at a relatively low level. Conclusions::AF is highly prevalent among patients with HT-CAD. Patients with both HT-CAD and AF have a higher prevalence of cardiovascular-related comorbidities, lower BP control rate, and lower use of oral anticoagulation.

This paper reviews the status quo of recent years’ research on autophagy and damage of chondrocytes in Kashin-Beck disease （KBD） and osteoarthritis （OA）. PI3K/AKT signaling pathway and mTOR regulate the autophagy activity of chondrocytes. PI3K/AKT signaling pathway can promote the proliferation of chondrocytes and cause their damage by inhibiting their autophagy activity. This might play an important role in the occurrence and progression of bone and joint diseases such as KBD and OA， and provide scientific basis for revealing the pathogenesis and treatment plan of them.

Carrying out the optimal location selection of medical equipment in the medical community plays an important role in scientifically allocating equipment resources and improving the service capacity of medical community. Aiming at minimizing the operating cost of the location selection and configuration of the portable color Doppler ultrasound instrument in the county medical community and the shortest time spent on medical visits for residents, the authors established the total value objective function of the medical community configuration according to the value engineering method; and considered the relevant constraints such as distance, time and personnel quality, the mathematical model of optimal planning for the selection and configuration of portable color Doppler ultrasound equipment in county medical community was constructed. The empirical research results showed that based on the established constraints, after 5 000 iterations, the model output 5 relatively optimized allocation points among the 9 allocation points, and when the allocation number of each allocation point was 1, the total allocation value in the medical community reached the maximum. This study could provide a new idea and feasible method for the allocation of equipment resources of county medical community in China.

Chondroitin sulfate (CS) is a sulfurated glycosaminoglycan, a major component of the extracellular matrix, widely distributed in skin, cartilage and vascular tissue. CS plays an important role in the physiological state regulation of articular cartilage, which affects tensile strength and elasticity of tissues by influencing aggrecan. Previous studies have shown that CS sulfate modification may be related to the growth and development disorders of cartilage tissue and the occurrence of osteoarticular diseases. At the same time, CS is also a common joint supplement, often used in the treatment of osteoarthritis and Kashin-Beck disease. In this paper, the research progress of CS sulfate modification characteristics in Kashin-Beck disease and osteoarthritis and the application of the preparation in the treatment of Kashin-Beck disease and osteoarthritis are reviewed, aiming to provide help for the investigation of the etiology of Kashin-Beck disease and the treatment of osteoarthritis and Kashin-Beck disease.