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 explore the visualization effect of different walking fibers and anatomical positions of the basal nucleus in the postcentral gyrus based on the diffusion tensor imaging(DTI)fiber bundle of the precentral gyrus and internal capsule reconstruction model.Methods A set of diffusion tensor volume(DTV)data was used to visualize and export a mesh model by a 3DSlicense 5.6.2 software.The basal nucleus were reconstructed by 3DSlicense through T1W1 data from the same scan,and exported the mesh model,and thus imported the above model into DTIANALYSIS 1.51 software for visualization.By adjusting the RGB component threshold,the fiber bundles were screened to obtain fiber bundles that mainly run left and right,front and back,and up and down.The anatomical relationship between the fiber bundles and the basal nucleus was observed.Results The fiber bundles originating from the precentral gyrus were mainly distributed in the inner and lower parts,and run above and outside the basal nucleus;The fiber bundles that mainly run forward and backward are distributed on the outer side and run on the outer side of the basal nucleus;The fiber bundles that mainly run up and down were distributed in the upper and middle parts of the precentral gyrus,with some fibers running towards the hypothalamus.They intersect in the corpus callosum and ventral pons,and run along the posterior part of the space between the lentiform nucleus and the dorsal thalamus.Conclusion Based on the RGB components in DTI,fibers with different walking directions in the precentral gyrus can be screened to display their anatomical position relationship with the basal ganglia.

Objective:To explore the early effects and safety of using a hybrid fixation strategy with 3D-printed porous tantalum metal augments to reconstruct substantial bone defects in complex primary total knee arthroplasty (TKA).Methods:A retrospective analysis was performed on the clinical data from August 2019 to September 2023, encompassing 20 patients (21 knees) with significant bone loss who underwent hybrid fixation with 3D-printed porous tantalum augments. The procedures were conducted at two medical centers: the First Affiliated Hospital, School of Medicine, Zhejiang University (11 cases) and Xiangya Hospital of Central South University (9 cases). The study cohort comprised 6 males (6 knees) and 14 females (15 knees), with a mean age of 61.05±11.23 years (range, 42-80 years). The distribution of cases was 7 on the left side and 14 on the right side. All cases were categorized as type 3 according to the Anderson Orthopaedic Research Institute (AORI) classification system. The cohort included 19 unilateral and 1 bilateral case, with 5 involving complex primary replacements (3 with Charcot arthropathy, 1 with syphilitic arthropathy, and 1 with severe valgus deformity) and 16 revision surgeries (13 for aseptic loosening and 3 for infection). Preoperative assessments included routine CT scans and digital three-dimensional reconstructions to identify large metaphyseal defects exceeding 50% of the metaphyseal area or those thicker than 10 mm. For such defects, 3D-printed standardized porous tantalum augments were implemented. In cases of extensive cavitary bone defects or severe metaphyseal defects where the medial and lateral defects collectively exceeded 80% of the metaphyseal region or where the residual bone stock was insufficient for screw fixation of standardized augments, 3D-printed personalized custom-made porous tantalum augments were employed for hybrid fixation and repair. Comparative analyses were conducted on pre- and postoperative imaging data (prosthesis positioning and complications), knee range of motion (ROM), visual analogue scale (VAS) for pain, and Knee Society score (KSS).Results:Of the cases, 17 were repaired using standardized 3D-printed porous tantalum augments, while 4 underwent repairs with customized augments for hybrid fixation. Follow-up averaged 26.5±15.0 months (range, 12-62 months). There was a significant increase in knee ROM, improving from 72.8°±31.9° preoperatively to 113.2°±6.8° at 12 months postoperatively ( P<0.05). VAS scores decreased from 6.6±1.4 preoperatively to 2.5±1.0 at 12 months postoperatively ( P<0.05). Similarly, KSS improved from 52.8±6.4 preoperatively to 80.7±7.9 at 12 months postoperatively ( P<0.05). There were no incidences of prosthesis displacement, poor bone integration, or postoperative infections. Conclusion:The hybrid fixation strategy employing 3D-printed porous tantalum augments has been found to be effective in addressing significant bone defects in TKA. The follow-up results indicate a satisfactory biological integration of the porous tantalum metal augments with the host bone, which has resulted in substantial improvements in pain relief and knee joint functionality.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To explore the current status of H.pylori infection in the natural population of Sanya City,analyze its influencing factors,and provide a reference basis for the prevention and control of H.pylori infection.Methods A total of 677 residents from four districts of Sanya City were selected by overall stratified random sampling method,and were subjected to urea 14C breath test and questionnaire survey to calculate the positive rate of H.pylori in the natural population and analyze the influencing factors of H.pylori infection.Results A total of 606 residents were included,and the number of H.pylori positive detections was 261,with a positive detection rate of 38.5％.Among them,different ethnicity,marital status,smoking,eating vegetables and fruits,and literacy level were associated with H.pylori infection(P＜0.05);gender,age,BMI,alcohol consumption,drinking water source,betel quid chewing,and the number of cohabitants were not significantly associated with H.pylori infection(P＞0.05).Family infection was an independent risk factor for H.pylori infection in the natural population of Sanya City,and Li ethnicity,frequent consumption of fruits and vegetables,and college and higher education level were independent protective factors for H.pylori infection in the natural population of Sanya City.Conclusion The rate of H.pylori infection in the natural population of Sanya City is lower than the national average.Consuming more fruits and vegetables and improving the awareness of hygiene protection are conducive to the prevention of H.pylori infection;and the promotion of the family and related members with the same examination and treatment is important to avoid aggregation of infection within the family.

Humans ; Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; Calcinosis/surgery* ; Transcatheter Aortic Valve Replacement ; Heart Valve Prosthesis

To explore the characteristics of big data of patients with allergic rhinitis, including the time, population and spatial distribution of allergic rhinitis in Beijing from 2016 to 2021, so as to provide reference for the prevention and treatment of this disease. Descriptive epidemiological methods were used to analyze the distribution (including gender, age and location)and trend of allergic rhinitis patients in 30 pilot hospitals from January 2016 to December 2021, T test and Kruskal-Wallis rank sum test were used to test the statistical differences. The results showed that the number of patients with allergic rhinitis in 30 hospitals increased year by year from 2016 to 2019, with an increase of 97.9%. In 2020, the number of patients decreased. In 2021, the number of visits returned to the pre-epidemic level (461 332); The number of patients with allergic rhinitis was the highest in September, with a seasonal index of 177.6%, while the lowest number was in February, accounting for only 47.2%; a significant difference was observed in the number of patients in different age groups(H=45 319.48, P<0.05), and patients under 15 years old accounted for the highest proportion(819 284 visits); There were significant differences between patients of different genders in the 45-59 year old group (t=-4.26, P<0.05).There were relatively more patients with allergic rhinitis in Dongcheng District(31.1%) than in Huairou District and Miyun District (0.4%). In conclusion, since 2016, the number of patients increased significantly, with a varied trend in different seasons. Most patients were children. There were more patients in the central urban area than in the outer suburbs.
Child ; Humans ; Female ; Male ; Adolescent ; Middle Aged ; Beijing/epidemiology* ; Big Data ; Epidemics ; Hospitals ; Rhinitis, Allergic/epidemiology*

Humans ; Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; Calcinosis/surgery* ; Transcatheter Aortic Valve Replacement ; Heart Valve Prosthesis

To explore the characteristics of big data of patients with allergic rhinitis, including the time, population and spatial distribution of allergic rhinitis in Beijing from 2016 to 2021, so as to provide reference for the prevention and treatment of this disease. Descriptive epidemiological methods were used to analyze the distribution (including gender, age and location)and trend of allergic rhinitis patients in 30 pilot hospitals from January 2016 to December 2021, T test and Kruskal-Wallis rank sum test were used to test the statistical differences. The results showed that the number of patients with allergic rhinitis in 30 hospitals increased year by year from 2016 to 2019, with an increase of 97.9%. In 2020, the number of patients decreased. In 2021, the number of visits returned to the pre-epidemic level (461 332); The number of patients with allergic rhinitis was the highest in September, with a seasonal index of 177.6%, while the lowest number was in February, accounting for only 47.2%; a significant difference was observed in the number of patients in different age groups(H=45 319.48, P<0.05), and patients under 15 years old accounted for the highest proportion(819 284 visits); There were significant differences between patients of different genders in the 45-59 year old group (t=-4.26, P<0.05).There were relatively more patients with allergic rhinitis in Dongcheng District(31.1%) than in Huairou District and Miyun District (0.4%). In conclusion, since 2016, the number of patients increased significantly, with a varied trend in different seasons. Most patients were children. There were more patients in the central urban area than in the outer suburbs.
Child ; Humans ; Female ; Male ; Adolescent ; Middle Aged ; Beijing/epidemiology* ; Big Data ; Epidemics ; Hospitals ; Rhinitis, Allergic/epidemiology*