Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans ; Peptides/pharmacology* ; Animals ; Neoplasms/drug therapy* ; Drug Discovery ; Neurodegenerative Diseases/drug therapy* ; Diabetes Mellitus/drug therapy*

This paper systematically summarizes the practical experience of the 2025 Dingri earthquake emergency medical rescue in Tibet. It analyzes the requirements for earthquake medical rescue under conditions of high-altitude hypoxia, low temperature, and low air pressure. The paper provides a detailed discussion on the strategic layout of earthquake medical rescue at the national level, local government level, and through social participation. It covers the construction of rescue organizational systems, technical systems, material support systems, and information systems. The importance of building rescue teams is emphasized. In high-altitude and cold conditions, rapid response, scientific decision-making, and multi-party collaboration are identified as key elements to enhance rescue efficiency. By optimizing rescue organizational structures, strengthening the development of new equipment, and promoting telemedicine technologies, the precision and effectiveness of medical rescue can be significantly improved, providing important references for future similar disaster rescues.

Objective To improve and refine the relevant regulations and guiding principles of warnings on drug instructions and labels in China.Methods This paper sorted out the drug instructions of small molecule anti-tumor drugs listed by the U.S.Food and Drug Administration(FDA)from 2005 to 2022,included the drugs mentioned in the QT interval prolongation risk,analyzed the clinical research and QT research results,and sorted out the identification and warning rules of the instructions.Results A total of 35 drugs were included,4 drugs wrote the risk of QT interval prolongation in the black box warning,21 drugs were wrote in the warning and precautions position,6 drugs were wrote in the adverse reaction section,and 2 drugs were only described under clinical pharmacology section.According to the severity of the QT interval prolongation caused by the drug and whether there were serious clinical consequences,they were displayed in the warnings(black box warnings),precautions(warnings and precautions)and adverse reactions in the instructions.Conclusion The aim of this article is to provide a reference for the writing of QT risk warning information of the instructions of domestic drug production enterprises and regulatory departments.It is recommended to clarify the severity of drug safety and the location of the instructions in clinical research,and continue to carry out safety monitoring and update the instructions in time after listing.

AIM To investigate the effects of Yunpi Tongchang Formula on intestinal mucosal barrier damage in rats with opioid-induced constipation(OIC)of Spleen-Kidney Yang Deficiency Syndrome.METHODS In contrast to the 10 rats of the blank group,the 50 rats of the modeling group were induced into models of OIC of Spleen-Kidney Yang Deficiency Pattern by 7 days consecutive administration of both subcutaneous loperamide injection and alternating gavage of activated carbon ice water and vinegar.Following successful modeling,rats were randomly allocated into the model group,the mosapride citrate tablet group(1.35 mg/kg),and the high-dose,medium-dose,and low-dose Yunpi Tongchang Formula groups(15.12,7.56,3.78 g/kg),with 8 mice in each group.Upon the completion of the 14 days treatment,the rats had their TCM Syndrome scores assessed;their fecal water content,initial black stool excretion time,and small intestine propulsion rate measured;their colon tissue morphology observed by HE staining;their serum levels of IL-6,TNF-α,and IL-1β detected by ELISA;their expressions of occludin and zonula occludens-1(ZO-1)in colon tissues detected by immunohistochemistry;their mRNA expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by RT-qPCR;and their protein expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by Western blot.RESULTS Compared to the blank group,the model group had higher TCM Syndrome scores(P＜0.01);lower fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);longer initial black stool excretion time(P＜0.01);more mucosal edema in colon tissue,obvious inflammatory infiltration,and glandular disorder;increased serum levels of IL-6,TNF-α and IL-1 β(P＜0.05);decreased colon expressions of ZO-1 and occludin(P＜0.01);and increased mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.01).Compared to the model group,both the medium-dose Yunpi Tongchang Formula group and the mosapride citrate tablet group demonstrated effectively reduced TCM syndrome scores(P＜0.01);increased fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);and shorter initial black stool excretion time(P＜0.01);improved colon mucosal edema and inflammatory infiltration;decreased serum levels of IL-6,TNF-α and IL-1β(P＜0.01);upregulated protein expressions of ZO-1 and occludin(P＜0.01);and downregulated mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.05,P＜0.01).CONCLUSION Yunpi Tongchang Formula significantly ameliorates constipation symptoms in OIC rat models of Spleen-Kidney Yang Deficiency Syndrome because of its efficacy in attenuating intestinal inflammation and preserving the integrity of intestinal epithelial barrier structure,with its mechanistic action in downregulating TLR4/MyD88/NF-κB signaling pathway activation.

Objective:To explore the research hotspots and emerging trends in the field of breast cancer-associated lymphedema, as reflected in the domestic and international literatures.Methods:The bibliometric method was used to retrieve literatures related to breast cancer-associated lymphedema from the Wanfang Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and the core collection of Web of Science, covering the time range from January 1, 2014, to December 31, 2023. CiteSpace 6.3.R3 software was employed for analysis, which involved statistical assessment of the publication volume, authors, countries, and institutions, as well as the identification of highly cited papers. A co-occurrence analysis of keywords was performed, followed by burst analysis and cluster analysis based on the results.Results:A total of 4 419 Chinese-language articles were retrieved from the three Chinese databases, of which 2 888 were included after duplicate removal. The Web of Science Core Collection yielded 2 142 English-language articles. Among the domestic authors, the top three with the highest publication counts were Zhang Lijuan (25 papers), Jia Jie (22 papers), and Zhong Qiaoling (21 papers). In the English-language literatures, the top three authors with the highest number of publications were Singhal D (32 papers), Devoogdt N (27 papers), and Boyages J (27 papers). A total of 76 countries worldwide had conducted research on breast cancer-associated lymphedema, with the United States contributing the most publications (748 papers), followed by China (227 papers). In total, 642 institutions worldwide had publications on this topic, with 385 domestic institutions. The leading domestic institution was Jiangxi Provincial Cancer Hospital (31 papers), while the top foreign institution was Harvard University (118 papers). The Top 10 most cited papers focused on key research areas in breast cancer-associated lymphedema. A total of 359 Chinese keywords and 513 English keywords were included for co-occurrence analysis. The five most frequent Chinese keywords were quality of life, nursing, complications, upper limb function, and risk factors. In the English literatures, the top five most frequent keywords were quality of life, women, survivors, risk factors, and surgery. Cluster analysis of the keywords revealed 16 clusters in the Chinese literatures, with the largest cluster "functional exercise", while 17 clusters were identified in the English literatures, with the largest cluster "lymph node transfer". The five most consistent clusters in Chinese literatures were lymphatic drainage, rehabilitation, functional impairment, evidence-based nursing, and circumferential lymphatics. In recent years, emerging topics in Chinese literatures included lymphatic drainage, breast reconstruction, and pathophysiology. In English literatures, the consistent top clusters were transplantation, node biopsy, morbidity, identification, and randomized trials, with recent emerging topics including obesity, adipose tissue, healing approaches, lymphatic microsurgical preventive healing approach, and anastomosis.Conclusion:The research on breast cancer-related lymphedema both domestically and internationally shows similarities and differences in direction and focus. Common research hotspots across both domestic and international studies include lymphatic drainage, functional exercise, health behaviors, and lymph node transfer. Recent emerging topics in Chinese literatures include lymphatic drainage, breast reconstruction, and pathophysiology. In contrast, English literatures focus more on the areas such as obesity, adipose tissue, healing methods, and lymphatic anastomosis.

Objective:To explore the efficacy and safety of intravascular lithotripsy (IVL) for the treatment of calcified lesions in lower limb peripheral artery disease (PAD).Methods:A literature search was conducted on PubMed, Web of Science, Cochrane Library, and Embase, including studies related to IVL for calcified lesions in PAD published from January 2016 to December 2024. Data on patient baseline characteristics, lesion information, IVL procedural parameters, changes in vascular stenosis, and complication occurrence were extracted and included. The Methodological Index for Non-Randomized Studies (MINORS) was used to assess the quality of the included studies. The meta-analysis was performed using STATA 15.1 software. The heterogeneity of different studies was evaluated using Cochran′s Q test. The publication bias was assessed through funnel plots and Egger test.Results:A total of nine studies were included (1 983 patients, 2 387 lesions). The meta-analysis demonstrated that regarding efficacy, after IVL treatment, the average reduction in vascular stenosis was 52.1% (95% CI 45.3%-58.9%). Regarding safety, the incidence of flow-limiting dissection was only 0.6% (95% CI 0.1%-1.4%), and the perforation rate was 0.4%-0.5%, with no events of severe amputation or death. In combined treatments, the usage rate of drug-coated balloons reached 51.2%, and the stent implantation rate was 20.4%. Conclusions:IVL can effectively reduce the degree of vascular stenosis in calcified lesions and has a high safety profile. Combined treatment with drug-coated balloons can reduce the dependence on stents.

Objective To explore the clinical and genetic characteristics of children with holocarboxylase synthetase(HLCS)deficiency.Methods A retrospective analysis was conducted on the clinical data of 3 children with HLCS deficiency who were admitted to Children's Hospital Affiliated to Zhengzhou University from December 2014 to January 2024.Relevant literature indexed in CNKI,Wanfang Data,PubMed and other databases was reviewed to summarize the clinical characteristics and HLCS gene mutations of children with HLCS deficiency.Results All 3 children were male,with onset age of 4-6 months.The main clinical manifestations included shortness of breath,vomiting,diarrhea,and poor mental state,and partial cases were complicated by growth retardation and neurological symptoms.Laboratory tests showed metabolic acidosis in all cases,blood amino acid and acylcarnitine profiles as well as urinary organic acid analysis suggested multiple carboxylase deficiency.Genetic testing revealed compound heterozygous mutation in the HLCS gene of all 3 children,among which the c.1892delT(p.L631X)mutation was previously unreported.According to the guidelines of the American College of Medical Genetics and Genomics(ACMG),the c.1892delT(p.L631X)mutation was rated as pathogenic mutation(PVS1+PM2_supporting+PM3).Biotin supplementation was effective in all cases.Literature review included 27 English literatures and 29 Chinese literatures,reporting a total of 133 children with HLCS deficiency caused by HLCS gene mutation.Common clinical manifestations included metabolic acidosis,skin lesions,vomiting,feeding difficulties,dyspnea,diarrhea,and neurological symptoms,etc.Conclusions Blood amino acid and acylcarnitine profiles,urine organic acid analysis,and gene testing are helpful for the diagnosis of HLCS deficiency.Timely biotin supplementation leads to a good prognosis.The mutation of HLCS gene is considered as the genetic etiology of HLCS deficiency in 3 children,among which the c.1892delT(p.L631X)mutation is a newly discovered mutation.

In analytical techniques such as ion mobility spectrometry(IMS)and mass spectrometry(MS),the ionization efficiency of target analytes is primarily constrained by the type of ionization source and factors such as the species and number density of the reactant ions.Systematic investigation into the reactivity differences of various reactant ions under varying conditions can not only significantly enhance the detection sensitivity of target compound product ions but also provide a theoretical foundation for establishing efficient detection methods based on ion-molecule reaction mechanisms.In this study,the pressure of a pressure-tunable photoionization tandem ion mobility spectrometry(PI-tandem-IMS)was reduced from ambient pressure(100 kPa)to low pressure(20 kPa)to systematically examine the reactivity differences between two negative reactant ions,CO3-and CO4-,and methyl salicylate(MeSA)under varying pressures.When the pressure decreased,the increased relative signal intensity of CO4-significantly influenced the detection sensitivity of the characteristic product ion[MeSA·O2]-.Based on differences in ion mobility(k0),the delay time for the opening of TPG2 was adjusted to selectively inject CO-3 and CO-4 in the drift region 2.Independent characterization of the reactivity of these reactant ions with MeSA in the reaction region confirmed that CO4-exhibited superior reactivity toward MeSA.The theoretical model revealed an Arrhenius plot for the ion-molecule reaction between CO4-and MeSA,showing a positive correlation between the reaction rate coefficient(k)and temperature,the activation energy Ea was 62.45 kJ/mol.Furthermore,controlling parameters such as pressure or temperature significantly influenced the progression of this ion-molecule reaction,demonstrating the technical advantages of PI-tandem-IMS in mechanistic studies and regulation of ion-molecule reactions.

The resolving power and sensitivity are critical for on-site detection of hazardous chemicals using stand-alone ion mobility spectrometry(IMS).However,improving the sensitivity and resolving power of IMS has long been a prominent research hot spot.In the commonly used IMS based on the Bradbury-Nielsen gate(BNG),the gating voltage difference(GVD)applied between the two sets of grid wires affects the electric field distribution in the ionization region and the drift region.This,in turn,influences the spatial distribution and temporal width of the injected ion swarm,and has an impact on the ion mobility discrimination,sensitivity,and resolving power of the instrument.This study showed that increasing the GVD could induce an ion converging effect,boosting the ion number density in front of the BNG by nearly 300％.To simultaneously utilize temporal compression and ion converging effects,a novel BNG controlling mode was proposed by adding a chopping state to the conventional controlling mode.This chopping state reduced the mobility discrimination effects between ions with mobility differences up to about 0.90 cm2/(V·s)to 1/22 of their original value.When analyzing hazardous chemical mixtures using the novel BNG controlling mode,compared with conventional mode,the signal intensity of low-mobility methyl salicylate ions(MS·O2)-increased by 18-fold while the resolving power maintained around 100,and the detection limit for MS was improved from 3.75 μg/L to 97 ng/L.This novel BNG controlling mode only added a potential wave to the low voltage wires,with no requirement of changing the structure of the drift tube,and was easy to apply to existing commercial instruments.