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 normal reference range of perchlorate content in the urine of primary school students, and compare whether there are differences in their urine perchlorate contents among different populations, and to provide reference for the health care of primary school students. Methods A total of 441 primary school students aged 6 to 15 years old in a certain city were selected, and their urine samples were collected. The contents of perchlorate in the urine were determined by ultra-high performance liquid chromatography coupled with mass spectrometry, and the measurement data was statistically analyzed using SPSS software. Results There was no significant gender difference in the content of perchlorate in the urine of primary school students, but there was an age difference. The normal reference range for the content of perchlorate in the urine of primary school students aged 6-9 years old was 0-99.09 μg/L, and the normal reference range for the content of perchlorate in the urine of primary school students aged 10-15 years old was 0-74.56 μg/L. Conclusion Through the measurement and analysis of a large number of samples, a normal reference range for the content of urinary perchlorate in primary school students have been recommended.

Objective:To investigate the clinical characteristics, treatment status, and disease outcomes of Chinese patients with multifocal motor neuropathy (MMN).Methods:Inpatients with MMN who were admitted to Huashan Hospital, Shanghai Medical College, Fudan University between January 2014 and April 2024 were enrolled. Baseline information, clinical features, and treatment history were recorded. Disability and functional impairment were assessed using the Inflammatory Neuropathy Cause and Treatment (INCAT) scale.Results:A total of 39 MMN patients were included and classified according to the 2010 European Federation of Neurological Societies/Peripheral Nerve Society criteria: definite MMN (27 cases), probable MMN (3 cases), and possible MMN (9 cases). At onset, 29 cases (29/39, 74.4%) had unilateral upper limb involvement, 5 cases (5/39, 12.8%) had unilateral lower limb involvement, 1 case (1/39, 2.6%) had bilateral lower limb involvement, and 4 cases (4/39, 10.3%) had simultaneous upper and lower limb involvement. By the last follow-up, follow-up duration was 3.4 (5.4) years (range: 0-14.3 years), disease duration was 8.3 (5.9) years (range: 1.2-31.3 years); 27 patients (27/39, 69.2%) exhibited increased limb involvement compared to onset. Segmental conduction block was detected in 35 cases (35/39, 89.7%). Anti-GM1 IgM antibodies were positive in 14 cases (14/31, 45.2%), and cerebrospinal fluid protein-cell dissociation was observed in 6 cases (6/32, 18.8%). Among them, 38 patients were treated with intravenous immunoglobulin (IVIG) during the disease course. Among the 24 patients followed up for>1 year after IVIG initiation, long-term efficacy (≥1 year), medium-short-term efficacy (<1 year), and no efficacy were observed in 16.7% (4/24), 62.5% (15/24), and 20.8% (5/24) of cases, respectively. Patients with persistently positive anti-GM1 IgM antibodies tended to have medium-short-term relief. Cyclophosphamide was used in 7 cases, with long-term improvement in 1 case. One patient achieved sustained improvement after two courses of rituximab. No benefit was observed with plasma exchange, corticosteroids, or other immunosuppressants. The median INCAT score at disease onset was 1 (range: 0-4), while the median pre-immunotherapy INCAT score was 3 (range: 0-5), and at the last follow-up after treatment, the median INCAT score remained 3 (range: 0-5). A statistically significant increase in INCAT scores was observed from disease onset to pretreatment ( U=229.000, P<0.001). However, no statistically significant difference was found between pretreatment and posttreatment INCAT scores ( U=491.500, P=0.880). Conclusions:MMN is a slowly progressive immune-mediated peripheral neuropathy. Early diagnosis and treatment with IVIG are crucial. Evidence for the efficacy of cyclophosphamide and rituximab remains limited.

Objective:To investigate the clinical characteristics, treatment status, and disease outcomes of Chinese patients with multifocal motor neuropathy (MMN).Methods:Inpatients with MMN who were admitted to Huashan Hospital, Shanghai Medical College, Fudan University between January 2014 and April 2024 were enrolled. Baseline information, clinical features, and treatment history were recorded. Disability and functional impairment were assessed using the Inflammatory Neuropathy Cause and Treatment (INCAT) scale.Results:A total of 39 MMN patients were included and classified according to the 2010 European Federation of Neurological Societies/Peripheral Nerve Society criteria: definite MMN (27 cases), probable MMN (3 cases), and possible MMN (9 cases). At onset, 29 cases (29/39, 74.4%) had unilateral upper limb involvement, 5 cases (5/39, 12.8%) had unilateral lower limb involvement, 1 case (1/39, 2.6%) had bilateral lower limb involvement, and 4 cases (4/39, 10.3%) had simultaneous upper and lower limb involvement. By the last follow-up, follow-up duration was 3.4 (5.4) years (range: 0-14.3 years), disease duration was 8.3 (5.9) years (range: 1.2-31.3 years); 27 patients (27/39, 69.2%) exhibited increased limb involvement compared to onset. Segmental conduction block was detected in 35 cases (35/39, 89.7%). Anti-GM1 IgM antibodies were positive in 14 cases (14/31, 45.2%), and cerebrospinal fluid protein-cell dissociation was observed in 6 cases (6/32, 18.8%). Among them, 38 patients were treated with intravenous immunoglobulin (IVIG) during the disease course. Among the 24 patients followed up for>1 year after IVIG initiation, long-term efficacy (≥1 year), medium-short-term efficacy (<1 year), and no efficacy were observed in 16.7% (4/24), 62.5% (15/24), and 20.8% (5/24) of cases, respectively. Patients with persistently positive anti-GM1 IgM antibodies tended to have medium-short-term relief. Cyclophosphamide was used in 7 cases, with long-term improvement in 1 case. One patient achieved sustained improvement after two courses of rituximab. No benefit was observed with plasma exchange, corticosteroids, or other immunosuppressants. The median INCAT score at disease onset was 1 (range: 0-4), while the median pre-immunotherapy INCAT score was 3 (range: 0-5), and at the last follow-up after treatment, the median INCAT score remained 3 (range: 0-5). A statistically significant increase in INCAT scores was observed from disease onset to pretreatment ( U=229.000, P<0.001). However, no statistically significant difference was found between pretreatment and posttreatment INCAT scores ( U=491.500, P=0.880). Conclusions:MMN is a slowly progressive immune-mediated peripheral neuropathy. Early diagnosis and treatment with IVIG are crucial. Evidence for the efficacy of cyclophosphamide and rituximab remains limited.

Dry eye,also known as keratoconjunctivitis sicca,is clinically manifested as dry eyes,itching,burning,blurred vision and other symptoms,which seriously affects the life quality of patients.In recent years,the incidence of dry eye has increased year by year,and it has become one of the common clinical diseases in ophthalmology.At present,the treatment methods of dry eye mainly include drug treatment,surgical treatment and clinical nursing,among which drug is the most commonly used method for the treatment of dry eye.Therefore,this paper summarizes the application and research progress of clinical medication of dry eye based on permeation pathways and inflammatory pathways in recent years,so as to provide some ideas for the follow-up treatment of dry eye and drug development.