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.

Since the beginning of the 21st century, the severe respiratory infectious diseases worldwide [such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza A H1N1 and novel coronavirus infection have attracted wide attention from all walks of life due to their superior pathogenicity and transmissibility. Aerosols-carrying pathogens are the main transmission route of many severe respiratory infectious diseases, which can lead to severe respiratory failure and even acute respiratory distress syndrome (ARDS) in infected individuals. Mechanical ventilation is the primary treatment for ARDS, and the small tidal volume, appropriate level of positive end-expiratory pressure based lung protective ventilation strategy can effectively reduce the incidence of ventilator-induced lung injury (VILI). However, in the process of clinical treatment, it is sometimes necessary to briefly disconnect the connection between the artificial airway and the ventilator circuit, which will not only cause the residual aerosol in the respiratory system to spill out and pollute the surrounding environment, increase the risk of nosocomial infection including medical staff, but also interfere with the implementation of lung protective ventilation strategy and aggravate ventilator-induced lung injury. In addition, studies have shown that a lot of medical staff have nosocomial infections, especially staff involved in tracheal intubation, extubation and other airway related operations. In addition to enhancing personal protective measures, it is crucial to safeguard healthcare workers from aerosol contamination and minimize associated risks during airway management. At present, there are few researches on the temporary sealing of airway lines and ventilator system, and there is a lack of clear guidance. This review summarizes the research status in related fields to provide a reference for corresponding solutions and programs.
Humans ; Respiratory Distress Syndrome/etiology* ; Respiration, Artificial ; Ventilator-Induced Lung Injury/prevention & control* ; Severe Acute Respiratory Syndrome ; COVID-19 ; Clinical Relevance

Objective·To develope an auditory brainstem implant(ABI)vocoder based on cochlear implant(CI)vocoder characteristics and ABI electrode array topology,and to verify its reliability.Methods·An"n-of-m"coding strategy CI/ABI vocoder was constructed based on MATLAB.Within each frame,only the envelopes of the n channels with the highest energy were selected.The interaction coefficient(IC)(range:1?3),channel numbers(range:5?22),and electrode array topology(CI/ABI)were adjustable parameters,allowing for the synthesis of simulated speech.Psychoacoustic evaluation was employed,recruiting normal hearing subjects to perform closed-set simulated phoneme perception.The phoneme recognition accuracy(20 vowel questions/condition,11 consonant questions/condition)was compared with the corresponding conditions of CI and ABI from reference literature to determine the IC value of the vocoder and verify its reliability.Results·The vocoder successfully synthesized all test stimuli.In the closed-set CI-simulated speech recognition,the simulated vowel and consonant recognition accuracy for IC2 and IC3 conditions showed no significant difference compared to the accuracy reported in the CI reference literature(P＞0.05).The difference in vowel and consonant accuracy between IC2 and the literature was smaller than that between IC3 and the literature(vowel|d|=1.6%vs.20%,consonant|d|=8.4%vs.9.9%),thus determining the optimal interaction coefficient of this model as 2.Subsequently,when modifying the electrode array topology to ABI,it was found that the simulated phoneme recognition accuracy for a 16-channel ABI was significantly lower than that for the 16-channel CI group,consistent with the reported literature.The simulated vowel and consonant accuracy within the 5?8 channel range for ABI showed no significant difference(P＞0.05),also aligning with the trend reported in the literature.Conclusion·A CI/ABI vocoder based on"n-of-m"coding strategy is established and the optimal IC is determined.The established ABI encoder has been evaluated for high reliability through psychoacoustic experiments.It provides suitable technical means for validating ABI-specific coding strategies.

Objective:To investigate the clinical effects of combined tissue flap transplantation in repairing giant chest wall defects.Methods:This study was a retrospective observational study. From August 2013 to December 2020, 31 patients with chest wall tumor or radiation ulcer after radical resection of chest wall tumor and conformed to the inclusion criteria were admitted to the Department of Breast Oncoplastic Surgery of Hunan Cancer Hospital, including 12 males and 19 females, aged 25-71 years. After resection of tumor or ulcer and wound debridement, the area of secondary chest wall defect was 300-600 cm 2 with length of 16-35 cm and width of 16-32 cm. According to the actual situation of the patients and the preoperative design, the chest wall defects were repaired with the flexible combination of perforator flaps and myocutaneous flaps from different donor sites, and the area of the combined tissue flap was 260-540 cm 2 with length of 20-30 cm and width of 13-20 cm. Free posteromedial thigh perforator flap+free anterolateral thigh myocutaneous flap were used in 2 patients, free deep inferior epigastric artery perforator flap+free anterolateral thigh myocutaneous flap were used in 5 patients, free deep inferior epigastric artery perforator flap+pedicled rectus abdominis myocutaneous flap+free anterolateral thigh myocutaneous flap were used in 7 patients, free deep inferior epigastric artery perforator flap+pedicled rectus abdominis myocutaneous flap+pedicled latissimus dorsi myocutaneous flap were used in 2 patients, and bilateral free anterolateral thigh myocutaneous flaps were used in 15 patients. For the remaining small area of superficial tissue defect after being repaired by combined tissue flaps, skin graft was used to repair or delayed local flap transfering was performed after the tissue flaps survived and edema subsided. The appropriate blood vessels in the donor and recipient sites were selected for anastomosis to reconstruct the blood supply of tissue flaps. The wounds in the donor sites of tissue flaps that can be directly sutured were sutured directly; for those that cannot be sutured directly, the skin grafting or delayed suture was performed. The anastomosis of blood vessels in the recipient sites, operation length, and postoperative hospital stay were recorded. The survivals of tissue flaps and skin grafts, the shape and texture of reconstructed chest wall, the wound healing, scar formation, and function of donor sites of tissue flaps, and the scar formation of the donor sites of skin grafts were observed after operation. Tumor recurrence and death of recurrent patients were followed up after operation. Results:The blood vessels in the recipient sites were anastomosed as follows: proximal internal thoracic vessels for 24 times, distal internal thoracic vessels for 12 times, trunk of thoracodorsal vessels for 4 times, anterior serratus branches of thoracodorsal vessels for 8 times, and thoracoacromial vessels for 12 times. The operation length was 6.0 to 8.5 hours, and the postoperative hospital stay was 9 to 21 days. Necrosis at the edge of partial tissue flaps occurred in 4 patients after operation, which healed after dressing change, and the tissue flaps and skin grafts of the other patients survived completely. The shape and texture of the reconstructed chest wall were good. Four patients had poor wound healing in the donor sites of abdominal tissue flaps, which healed after dressing change and local drainage. Only linear scar was left in the donor sites of all tissue flaps, and there was no obvious dysfunction in the donor sites of tissue flaps. Mild hypertrophic scar was left in the donor sites of skin grafts. During follow-up of 9 to 36 months after operation, 6 patients had tumor recurrence, and the recurrence time was 5 to 20 months after operation. After comprehensive treatment for patients with tumor recurrence, 3 patients died.Conclusions:Transplantation of combined tissue flaps in repairing the giant chest wall defects can shorten the time of total operation and hospital stay, and avoid multiple operations. After operation, patients had good chest wall appearance, with reduced tumor recurrence in patients with chest wall tumor.

Malignant tumors are major diseases that seriously threaten human health.Although the integration of traditional Chinese and Western medicine has become an expert consensus on treatment of malignant tumors in China,a mature treatment mode of integrat-ed traditional Chinese and Western medicine has not yet been formed.This paper explores the construction of integrated traditional Chi-nese and Western medicine treatment mode for malignant tumors,namely synergistic therapy,palliative therapy,and preventive thera-py,covering different stages of malignant tumors,in order to give full play to the advantages and characteristics of integrated traditional Chinese and Western medicine treatment in the treatment of malignant tumors.

Objective:To explore the correlation between clinical classification and genotype and prognosis among Chinese children with Very-long chain acyl-CoA dehydrogenase deficiency (VLCADD).Methods:A Chinese pedigree affected with VLCADD admitted at the First People′s Hospital of Yunnan Province in February 2019 was selected as the study subject. The characteristics of disease onset, diagnosis and treatment and prognosis were retrospectively analyzed. Relevant literature was also systematically searched and reviewed.Results:The proband, a 1-year-old boy, had the clinical manifestations of frequently vomiting, hypoglycemia, abnormal liver function and myocardial enzymes. Tandem mass spectrometry screening showed significantly elevated C14, C14: 1, C16: 1, C16: 2, C18 and C14/C8. Genetic testing revealed that he has harbored compound heterozygous variants of the ACADVL gene, namely c. 664G>A (p.G222R) and c. 1345G>A (p.E449K), which were respectively derived from his father and mother. The child was diagnosed with VLCADD cardiomyopathy type and deceased 2 weeks later. Literature review has identified 60 Chinese children with VLCADD. The clinical classifications were mainly cardiomyopathy type and liver disease type, which accounted for 73.3% (43/60). The combination of ACADVL gene variants were correlated with the clinical classifications of VLCAD. Children with one or two loss-of-function (LOF) mutations showed more severe clinical manifestation and a higher mortality. Cardiomyopathy type had the poorest prognosis, with a mortality rate of 76.9% (20/26). C14: 1 may be used as an indicator for the diagnosis of VLCADD, but cannot be used for clinical subtyping and prognosis evaluation. The c. 1349G>A (p.R450H) variant had the highest frequency among the Chinese patients, accounting for 10.8% (13/120). Conclusion:The clinical classifications of VLCADD are strongly correlated with the prognosis, and LOF mutations are more common in those with severe clinical manifestations. c. 1349G>A (p.R450H) may be the most common variant among the Chinese patients, and early screening and diagnosis can greatly improve the prognosis of patients.

Objective To explore the potential categories and influencing factors of the fear of progression in patients with inflammatory bowel diseases(IBD).Methods IBD patients who received inpatient treatment in a tertiary hospital in Nanjing from July 2022 to July 2023 were selected as the study subjects by convenience sampling method.The General Demographic Information Questionnaire,the Chinese version of the Fear of Progression Questionnaire-Short Form(FoP-Q-SF),the Chinese version of Inflammatory Bowel Disease Self-efficacy Scale(IBD-SES),and Social Support Rating Scale(SSRS)were administered to the participants.We applied one-way ANOVA and Logistic regression analysis to identify the factors associated with the potential categories of the fear of progression.Results A total of 303 retumed questionnaires(out of the 310)were valid,resulting an effective response rate of 97.74％.According to the results of latent profile analysis,we classified the respondents into 3 categories by the fear of progression,namely"low risk fear of disease adaptation group"(n=127,41.91％),"medium risk fear of illness distress group"(n=139,45.88％),"high risk fear of dysfunction group"(n=37,12.21％).3 groups showed statistically significant differences in permanent address,self-rated financial pressure,current disease status and self-efficacy(P＜0.05).Conclusion Patients with IBD had obvious differences in characteristics on the fear of progression.Nursing personnel should formulate personalized intervention strategies based on the classification characteristics of the fear of progression of IBD patients.Moreover,nurses should focus on improving patients'self-efficacy and promoting patients to treat medical care,stress and emotion management correctly.

Objective:To investigate the prognosis of marginal donor heart in heart transplantation.Methods:The clinical data of consecutive heart transplant recipients and donors in Zhengzhou 7th. People’s Hospital from April 2018 to November 2022 were retrospectively included. According to the definition of marginal donor hearts, the patients were divided into conventional donor hearts group (117 cases) and marginal donor hearts group ( 62 cases), the data before and after heart transplantation of the two groups were analyzed.Results:The main reason for the formation of marginal donor hearts was the cold ischemia time of donor hearts >6 h; it was easier to receive marginal donor hearts with ECMO and MV before operation; the use of marginal donor hearts in heart transplantation increased postoperative mechanical ventilation time, surgical post-intensive care unit length of stay; patients with marginal donors had lower survival than conventional donors, but did not produce a significant difference in survival after heart transplantation.Conclusion:The application of marginal donor heart in heart transplantation is an effective method to solve the shortage of heart organs and reduce the death of transplant waiting persons.

Objective To evaluate the molluscicidal effect of spraying different formulations of niclosamide ethanolamine salt with drones against Oncomelania hupensis in ditches. Methods A semi-dry and semi-wet ditch with O. hupensis snails was selected in the second branch field of Jiangbei Farm, Jiangling County, Hubei Province in May 2023, and divided into 4 experimental areas, named groups A1, A2, B1 and B2. Environmental cleaning was performed in groups A1 and B2, and was not conducted in groups A2 or B2. Then, 50% wettable powder of niclosamide ethanolamine salt was sprayed with drones at an effective dose of 2 g/m² in groups A1 and A2, and 5% niclosamide ethanolamine salt granule was sprayed with drones at an effective dose of 2 g/m² in groups B1 and B2. O. hupensis snails were surveyed using the systematic sampling method 1, 3, 5, 7, 14 days after spraying, and the natural mortality and corrected mortality of O. hupensis snails were calculated. Results The occurrence of frames with living snails, mean density of living snails and natural mortality of snails were 97.50% (117/120), 6.30 snails/0.1 m² and 1.18% (9/765) in the test ditch before spraying, respectively. There were significant differences in the mortality of snails among four groups 1, 3, 5, 7 and 14 days after spraying niclosamide formulations with drones (χ² = 17.230, 51.707, 65.184, 204.050 and 34.435, all P values < 0.01). The overall mortality rates of snails were 94.51% (1 051/1 112), 79.44% (908/1 143), 96.54% (977/1 012) and 88.55% (1 021/1 153) in groups A1, A2, B1 and B2 (χ² = 207.773, P < 0.05), respectively. In addition, there was no significant difference in the overall snail mortality between groups A1 and B1 (P > 0.05), and the snail mortality in groups A1 and B1 were both statistically different from that in groups A2 and B2 (all P values < 0.05). Conclusion Both 50% wettlable powder of niclosamide ethanolamine salt and 5% niclosamide ethanolamine salt granule sprayed with drones are active against O. hupensis snails in ditches, and environmental cleaning may improve the molluscicidal effect.