Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Objective:To investigate the differential impact of ultra-high-resolution photon-counting detector CT (UHR PCD-CT) and energy-integrating detector CT (EID-CT) on image quality and calcified plaque-induced luminal stenosis in coronary CT angiography (CCTA).Methods:This retrospective analysis was conducted on patients who underwent both EID-CT and UHR PCD-CT CCTA at the Geriatric Hospital of Nanjing Medical University between January 2021 and November 2024. A total of 141 patients were included in the study, within 46 patients having scans within a 12-month interval. Image quality of all coronary artery segments was subjectively evaluated. Patients with paired scans (interval≤12 months) were included for calcified plaque analysis. Subjective visualization of calcified plaques evaluated. The blooming artifact was calculated as an objective evaluation index for assessing the calcified plaques. Additionally, the degree of coronary artery lumen stenosis resulting from calcified plaques was assessed, along with the measurement of plaque volume and the Agatston score. Changes in lumen stenosis between the two scans were also evaluated. The Wilcoxon signed-rank test was used to compare the subjective scores of coronary artery image quality and calcified plaques between the two groups, and paired-sample t-tests were used to compare the blooming artifact and lumen stenosis degree. Results:The PCD-CT image quality score was significantly higher than that of EID-CT [PCD-CT : 5 (4,5), EID-CT: 4 (4,5); Z=-21.38, P<0.001]. Compared to EID-CT, PCD-CT reduced the blooming artifact (PCD-CT: 38.88%±9.09%, EID-CT: 50.11%±11.52%; t=-12.97, P<0.001), significantly improving the subjective score for visualization of calcified plaques [PCD-CT: 5 (4,5), EID-CT: 3 (2,3); Z=-9.68, P<0.001], and the measured lumen stenosis was notably lower in PCD-CT(PCD-CT:34.88%±18.20%, EID-CT:45.31%±23.42%; t=-9.93, P<0.001). Among 129 analyzed calcified plaques, luminal stenosis was reduced on PCD-CT in 110 plaques (85.3%) and increased in 19 (14.7%), including 4 plaques that had unclear boundaries with the adjacent lumen in EID-CT CCTA images, making the stenosis difficult to assess. Conclusion:Compared to EID-CT, UHR PCD-CT for CCTA significantly improves coronary artery image quality, provides clearer visualization of calcified plaques and adjacent lumen details, and it can reduce the overestimation of coronary artery caleified plaque stenosis.

Objective:To investigate the differential impact of ultra-high-resolution photon-counting detector CT (UHR PCD-CT) and energy-integrating detector CT (EID-CT) on image quality and calcified plaque-induced luminal stenosis in coronary CT angiography (CCTA).Methods:This retrospective analysis was conducted on patients who underwent both EID-CT and UHR PCD-CT CCTA at the Geriatric Hospital of Nanjing Medical University between January 2021 and November 2024. A total of 141 patients were included in the study, within 46 patients having scans within a 12-month interval. Image quality of all coronary artery segments was subjectively evaluated. Patients with paired scans (interval≤12 months) were included for calcified plaque analysis. Subjective visualization of calcified plaques evaluated. The blooming artifact was calculated as an objective evaluation index for assessing the calcified plaques. Additionally, the degree of coronary artery lumen stenosis resulting from calcified plaques was assessed, along with the measurement of plaque volume and the Agatston score. Changes in lumen stenosis between the two scans were also evaluated. The Wilcoxon signed-rank test was used to compare the subjective scores of coronary artery image quality and calcified plaques between the two groups, and paired-sample t-tests were used to compare the blooming artifact and lumen stenosis degree. Results:The PCD-CT image quality score was significantly higher than that of EID-CT [PCD-CT : 5 (4,5), EID-CT: 4 (4,5); Z=-21.38, P<0.001]. Compared to EID-CT, PCD-CT reduced the blooming artifact (PCD-CT: 38.88%±9.09%, EID-CT: 50.11%±11.52%; t=-12.97, P<0.001), significantly improving the subjective score for visualization of calcified plaques [PCD-CT: 5 (4,5), EID-CT: 3 (2,3); Z=-9.68, P<0.001], and the measured lumen stenosis was notably lower in PCD-CT(PCD-CT:34.88%±18.20%, EID-CT:45.31%±23.42%; t=-9.93, P<0.001). Among 129 analyzed calcified plaques, luminal stenosis was reduced on PCD-CT in 110 plaques (85.3%) and increased in 19 (14.7%), including 4 plaques that had unclear boundaries with the adjacent lumen in EID-CT CCTA images, making the stenosis difficult to assess. Conclusion:Compared to EID-CT, UHR PCD-CT for CCTA significantly improves coronary artery image quality, provides clearer visualization of calcified plaques and adjacent lumen details, and it can reduce the overestimation of coronary artery caleified plaque stenosis.

Objective To study the effects of different pellet feed hardness on the growth and reproduction,feed utilization rate,and environmental dust in laboratory mice.Methods One hundred of fifty 50 3-week-old SPF-grade C57BL/6JGpt and 150 ICR laboratory mice were randomly divided into three groups,with an equal number of males and females.They were fed diets with different hardness of 18.62 kg,23.15 kg,and 27.89 kg.Body weight,feed utilization rate,and dust levels in cages were recorded and calculated for mice aged 3-10 weeks.Forty-five 6-week-old male mice and ninety 4-week-old female mice from each strain were randomly divided into three groups and fed pellet feeds with three different hardness levels.After 2 weeks of adaptation to the same hardness feed,the mice were paired at a 1:2 male-to-female ratio and monitored for reproductive data for 3 months.Results At the age of 4 weeks,the body weight of male C57BL/6JGpt mice in 23.15 kg group was significantly higher than that in the 18.62 kg and 27.89 kg groups(P＜0.01),and the body weight of females in the 18.62 kg group was significantly higher than that in the 27.89 kg group(P＜0.05).There was no significant difference in body weight among ICR mice aged 3-10 weeks across different feed hardness groups(P＞0.05).For both strains,feed utilization rate for males was higher than that for females across different feed hardness groups at all weeks of age(P＜0.01).Compared to the 27.89 kg group,both the 18.62 kg and 23.15 kg groups showed a significant increase in the 50-mesh dust levels in cages for both strains aged 4-8 weeks(except for 7-week-old C57BL/6JGpt mice)(P＜0.05).For both C57BL/6JGpt and ICR mice,there was no significant difference in basic reproductive performance such as interval between the first litter and the monthly production index among the three feed hardness groups during the experimental period(P＞0.05).However,the monthly production index of C57BL/6JGpt mice first increased and then decreased with the increase of feed hardness,while that of ICR mice increased with increasing feed hardness,though these differences were not statistically significant(P＞0.05).Conclusion Different strains and genders had different tolerance to feed hardness.C57BL/6JGpt mice are more adapted to lower hardness feeds,while ICR mice are better suited to slightly higher hardness feeds.

Objective:To investigate the epidemiological and clinical characteristics of Keshan disease current cases in Qingyang City, Gansu Province.Methods:Full coverage monitoring data of all Keshan disease affected villages in Qingyang City from January to December 2022 were collected from the database of the Qingyang City Center for Disease Prevention and Control. A retrospective analysis was conducted to analyze the epidemiological distribution and clinical manifestations (including electrocardiography, classification of cardiac function, chest X-ray, B-mode ultrasound of the heart, etc) of 132 current cases of Keshan disease.Results:Among the 132 current cases of Keshan disease, there were 5 cases of latent type and 127 cases of chronic type, and 25 new cases were identified in 2022; with a male-to-female ratio of 1.03 ∶ 1.00 (67 ∶ 65), a median age of 62 years (interquartile range of 12). The area with the highest number of current cases was Heshui County, with a Keshan disease incidence rate of 3.37/10 000; the lower areas were Xifeng District and Zhenyuan County, with a Keshan disease incidence rate of 0.08/10 000 and 0.03/10 000, respectively. The abnormal electrocardiogram of the current cases was mainly characterized by T-wave and/or ST-segment changes, with a total of 78 cases, accounting for 59.09% of the total cases. Heart function impairment (grade Ⅱ and above) was found in 124 cases, accounting for 93.94%. The results of B-mode ultrasound and chest X-ray examination showed that there were 107 cases of heart enlargement, accounting for 81.06% of the total cases.Conclusions:The Keshan disease current cases in Qingyang City are predominantly chronic in elderly, with a balanced gender distribution but regional distribution differences. Abnormal electrocardiogram is common in patients, and their cardiac function is often impaired. Given the persistent presence of pathogenic factors, continued monitoring is necessary to achieve early intervention and improve prognosis.

Objective:To investigate the epidemiological and clinical characteristics of Keshan disease current cases in Qingyang City, Gansu Province.Methods:Full coverage monitoring data of all Keshan disease affected villages in Qingyang City from January to December 2022 were collected from the database of the Qingyang City Center for Disease Prevention and Control. A retrospective analysis was conducted to analyze the epidemiological distribution and clinical manifestations (including electrocardiography, classification of cardiac function, chest X-ray, B-mode ultrasound of the heart, etc) of 132 current cases of Keshan disease.Results:Among the 132 current cases of Keshan disease, there were 5 cases of latent type and 127 cases of chronic type, and 25 new cases were identified in 2022; with a male-to-female ratio of 1.03 ∶ 1.00 (67 ∶ 65), a median age of 62 years (interquartile range of 12). The area with the highest number of current cases was Heshui County, with a Keshan disease incidence rate of 3.37/10 000; the lower areas were Xifeng District and Zhenyuan County, with a Keshan disease incidence rate of 0.08/10 000 and 0.03/10 000, respectively. The abnormal electrocardiogram of the current cases was mainly characterized by T-wave and/or ST-segment changes, with a total of 78 cases, accounting for 59.09% of the total cases. Heart function impairment (grade Ⅱ and above) was found in 124 cases, accounting for 93.94%. The results of B-mode ultrasound and chest X-ray examination showed that there were 107 cases of heart enlargement, accounting for 81.06% of the total cases.Conclusions:The Keshan disease current cases in Qingyang City are predominantly chronic in elderly, with a balanced gender distribution but regional distribution differences. Abnormal electrocardiogram is common in patients, and their cardiac function is often impaired. Given the persistent presence of pathogenic factors, continued monitoring is necessary to achieve early intervention and improve prognosis.

Objective:To investigate the clinical utility of intracavitary electrocardiogram (IC-ECG) localization technique in locating the tip of umbilical venous catheterization (UVC).Methods:From April 2020 to March 2021, premature infants admitted to the Department of Neonatology of the Third Affiliated Hospital of Guangzhou Medical University and received UVC were collected for a prospective study. According to whether IC-ECG was used to determine the position of umbilical vein catheter tip during catheterization, they were divided into IC-ECG group and control group. The differences of catheterization success rate, total incidence of catheter-related complications were compared between the two groups. The relationship between characteristic P waves and the position of the catheter tip in the IC-ECG group was also analyzed.Results:A total of 104 premature infants were enrolled, including 52 cases in IC-ECG group and 52 cases in control group. The catheter placement accuracy rate of the IC-ECG group was higher than that of the control group (53.8% vs. 28.8%, P<0.05). There was no statistically significant difference of the total incidence of catheter-related complications between the two groups ( P>0.05). Among the 40 cases with characteristic P wave changes in the IC-ECG group, 21 cases had normal P wave, of which 13 cases (61.9%) were with the correct position. And 19 cases had low-amplitude bimodal P waves, of which 15 cases (78.9%) were with the correct position. There was no statistically significant difference of the exact position rate of the catheter tips between the two types of P waves ( P>0.05). Conclusions:The use of IC-ECG localization technique in the process of catheterization of umbilical vein can increase the exact position rate of catheterization. Furthermore, when IC-ECG monitoring shows characteristic P wave changes to normal P wave or low-amplitude bimodal P wave, the tip of the UVC catheter may be located accurately.

Objective:To have a better understanding of congenital leukemia by summarizing its clinical features and prognosis.Methods:This study retrospectively recruited 10 neonates with congenital leukemia treated in Beijing Children's Hospital, Capital Medical University from January 2006 to December 2018. Clinical data including clinical manifestations, laboratory examinations, treatment and follow-up were described.Results:The 10 patients consisted of six boys and four girls. In all cases, symptoms presented within 11 d after birth. The admission complaints were jaundice ( n=4), polypnea ( n=3), fever ( n=2) and rash ( n=2). Physical examinations of the 10 patients showed eight with splenomegaly, seven with hepatomegaly and seven with petechia/skin rash. All patients had significantly increased white blood cell count (from 45.8×10 9/L to 553.0×10 9/L), complicated by different degrees of anemia and thrombocytopenia. By bone marrow biopsy, two cases were diagnosed as acute lymphoblastic leukemia and the other eight cases as acute myeloid leukemia. All cases refused chemotherapy on the preliminary diagnosis. Three cases lost follow-up and six died within two months after discharge requested by their parents. One baby had spontaneous remission, but relapsed two years later. Complete remission was achieved after strict management and no relapse was reported until ten years old. Conclusions:Congenital leukemia is a severe condition with high mortality. Some cases may achieve spontaneous remission, but long-term follow-up is needed.

Objective: To introduce a combined operation for treating chronical peroneal tendon dislocation and to evalu-ate the clinical outcomes of patients. Methods: Data of 12 ankles in 12 patients (male 9, female 3) with chronical peroneal ten-don dislocation who underwent the fibular groove deepening procedure with transposition of the peroneal longus muscle from June 2006 to August 2013 were retrospectively analyzed. The mean age was 24.6±4.3 years (range, 18-34 years), and there were 3 cas-es on left side, 9 on right side. The mechanism of peroneal tendon injury consisted of sports injuries in 8 and sprains in 4. There were 8 cases of flat fibula sulcus and 4 cases of convex. All patients met the inclusion criteria of a painful snapping or popping sen-sation or palpable clicking and positive provocation maneuver and without fracture and were treated with peroneal sulcus deepen-ing and peroneal longus tendon transposition. The duration of preoperative popping and pain symptoms ranged from 12 to 23 weeks, with an average of 16.9±4.0 weeks. All cases were treated conservatively 3-4 weeks before operation and were not effec-tive. The clinical outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, visual anologue scale (VAS). Results: Twelve patients were followed up with an average period of 37.3±7.0 (range, 25-50) months. The mean VAS scale score of all patients reduced from 5.6±0.9 to 0.5±0.7 at the latest follow-up. The mean AOFAS scale score improved from 61.4±5.6 to 92.6±4.2 at the latest follow-up. The difference between preoperative and postoperative was statis-tically significant. (t=16.250,-18.475; P=0.000). According to the evaluation of symptom and function scoring system, 10 cases were excellent and 2 cases were good, with an excellent rate of 100%. The mean postoperative return-sport time was 26.42±3.06 weeks (range, 23-32 weeks). All patients healed primarily and no infection, skin necrosis and residual redislocation occurred. The osteotomy healed completely without displacement, which was confirmed by imaging examination in three months postoperation. No patients had intractable pain after surgery, and they were able to perform daily activities at 3 months and physical exercise at 6 months after surgery. No slip occurred in all patients at the latest follow-up. Conclusion The fibular groove deepening procedure with transposition of the peroneal longus muscle can effectively treat chronical peroneal tendon dislocation and obtain good medi-um-term results.

Objective To compare the effect of different gastrointestinal motility drugs on capsule endoscopy. Methods Seventy-one patients with suspected small bowel disease were randomly divided into metoclopramide group (24 patients), mosapride group(25 patients) and control group (22 group). The patients in metoclopramide group swallowed capsule endoscopy immediately after intramuscularly injecting 10 mg metoclopramide, the patients in mosapride group swallowed capsule endoscopy 15 min after taking 5 mg mosapride, and the patients in control group did not take any of the gastrointestinal motility drugs. Three groups had the same bowel preparation before checking. The finishing rate of small bowel examinations, stomach and small intestinal transit time, intestinal cleanliness and the detection rates of lesions in three groups were compared. Results The total small bowel examination finishing rate was 94.4%(67/71). The small bowel examination finishing rate in metoclopramide group, mosapride group, and control group was 95.8%(23/24), 96.0%(24/25), and 90.9% (20/22), and there was no significant difference(P>0.05). The stomach transit time in metoclopramide group, mosapride group and control group was(27.5 ± 20.7), (28.1 ± 20.9) and (52.3 ± 33.5) min. The stomach transit time in metoclopramide group and mosapride group had no significant difference (P>0.05), but it was significantly lower than that in control group (P<0.05). The small intestinal transit time in three groups had no significant difference (P>0.05). The image class scores in metoclopramide group, mosapride group and control group was (2.5 ± 0.4), (2.7 ± 0.4) and (1.7 ± 0.3) scores.The scores in metoclopramide group and mosapride group had no significant difference (P>0.05), but they were significantly higher than that in control group (P<0.05). The detection rate of lesions in metoclopramide group, mosapride group and control group was 45.8%(11/24), 56.0%(14/25) and 18.2%(4/22). The detection rate of lesions in metoclopramide group and mosapride group had no significant difference (P>0.05), but it was significantly higher than that in control group (P<0.05). Conclusions The use of gastrointestinal motility drugs before capsule endoscopy can improve the quality of inspection, and metoclopramide and mosapride shows no significant difference.