In recent years， significant progress has been made in the standardized diagnosis and treatment of pancreatic cancer in China. From the lack of treatment options and poor drug efficacy at the beginning to the current comprehensive treatment modality integrating surgery， chemotherapy， radiotherapy， immunotherapy， and targeted therapy under multidisciplinary decision-making， the diagnosis and treatment of pancreatic cancer has gradually achieved higher levels of individualization， refinement， and precision. With reference to the latest evidence-based medical data， this article discusses the hot topics in the diagnosis and treatment of pancreatic cancer and explores the future development directions of this field.

The Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation is one of the most prevalent activating alterations in cancer. It indicates a poor overall prognosis due to its highly invasive nature. Although several KRAS inhibitors have been developed in recent years, a significant clinical challenge has emerged as a substantial proportion of patients eventually develop resistance to these therapies. Therefore, identifying determinants of drug resistance is critical for guiding treatment strategies. This review provides a comprehensive overview of the mutation landscape and molecular mechanisms of KRAS activity in various cancers. Meanwhile, it summaries the progress and prospects of small molecule KRAS inhibitors undergoing clinical trials. Furthemore, this review explores potential strategies to overcome drug resistance, with the ultimate goal of steering toward patient-centric precision oncology in the foreseeable future.
Humans ; Drug Resistance, Neoplasm/drug effects* ; Proto-Oncogene Proteins p21(ras)/metabolism* ; Mutation/genetics* ; Neoplasms/genetics* ; Antineoplastic Agents/therapeutic use*

Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Pancreatic surgery is characterized by great trauma, difficult operation, high risk and high complication rate. Minimally invasive, refined and standardized pancreatic surgery is the future trend. With its advantages of high precision, high safety, and more realistic and clear operating field, robotic pancreatic surgery has gradually become the preferred method of pancreatic surgery worldwide. In the past 10 years, more than a dozen large pancreas centers in China have matured to carry out robotic pancreatic surgery, including pancreaticoduodenectomy, pancreaticocaudectomy, pancreatic tumor enucleation, middle pancreatectomy, total pancreatectomy, pancreaticodectomy with duodenum preserved and other pancreatic surgery methods. However, there are still some problems in robotic pancreatic surgery, such as complex system construction, lack of force feedback, inadequate imaging fusion, and immature remote operation. Pancreatic surgeons should continue to carry out high-quality clinical studies on robotic pancreatic surgery to verify its safety and effectiveness, and standardize robotic pancreatic surgery with the accumulation of experience.

OBJECTIVE: To analyze the clinical phenotype and results of genetic testing in three children with Cornelia de Lange syndrome (CdLS). METHODS: Clinical data of the children and their parents were collected. Peripheral blood samples of the pedigrees were collected for next generation sequencing analysis. RESULTS: The main clinical manifestations of the three children have included growth delay, mental retardation, peculiar facies and other accompanying symptoms. Based on the criteria proposed by the International Diagnostic Consensus, all three children were suspected for CdLS. As revealed by whole exome sequencing, child 1 has harbored NIPBL gene c.5567_5569delGAA insTAT missense variant, child 2 has harbored SMC1A gene c.607A>G missense variant, and child 3 has harbored HDAC8 gene c.628+1G>A splicing variant. All of the variants were de novo in origin. CONCLUSION All of the children were diagnosed with CdLS due to pathogenic variants of the associated genes, among which the variants of NIPBL and HDAC8 genes were unreported previously. Above finding has enriched the spectrum of pathogenic variants underlying CdLS.
Humans ; Cell Cycle Proteins/genetics* ; De Lange Syndrome/diagnosis* ; Genotype ; Phenotype ; Genetic Testing ; Histone Deacetylases/genetics* ; Repressor Proteins/genetics*

Pancreatic cystic neoplasm (PCN) is characterized by cystic degeneration with a low incidence. With the development of imaging technology and the popularization of screening, the detection rate of this disease has been increasing in recent years, especially in the elderly population. Due to the multiple subtypes of PCN, difficult differential diagnosis, and the potential risk of malig-nant transformation, the formulation of reasonable diagnosis and treatment strategy is the key to treat PCN. Although many clinical guidelines have been released, the diagnosis and treatment strategies of PCN are still controversial. Elderly patients are generally weak, some with serious comorbidities, and have poor tolerance to surgery. In the process of diagnosis and treatment, clinicians need to pay special attention, carefully evaluate and weigh the advantages and disadvantages, so as to make the best plan for treatment. Based on the current guidelines and clinical experience, the authors summarize the diagnosis, surgical indications, and the whole-course management strategies of elderly patients with PCN, in order to provide suggestions for the diagnosis and treatment of this disease.

OBJECTIVE: To explore the genetic etiology of a child with Pitt-Hopkins syndrome. METHODS: A child who had presented at the Medical Genetics Center of Gansu Provincial Maternal and Child Health Care Hospital on February 24, 2021 and his parents were selected as the study subjects. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing. Karyotype analysis was also carried out for the child, and her mother was subjected to ultra-deep sequencing and prenatal diagnosis upon her subsequent pregnancy. RESULTS: The clinical manifestations of the proband included facial dysmorphism, Simian crease, and mental retardation. Genetic testing revealed that he has carried a heterozygous c.1762C>T (p.Arg588Cys) variant of the TCF4 gene, for which both parents had a wild-type. The variant was unreported previously and was rated as likely pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (ACMG). Ultra-deep sequencing indicated that the variant has a proportion of 2.63% in the mother, suggesting the presence of low percentage mosaicism. Prenatal diagnosis of amniotic fluid sample suggested that the fetus did not carry the same variant. CONCLUSION The heterozygous c.1762C>T variant of the TCF4 gene probably underlay the disease in this child and has derived from the low percentage mosaicism in his mother.
Child ; Female ; Humans ; Male ; Pregnancy ; Intellectual Disability/genetics* ; Mosaicism ; Mothers ; Mutation ; Parents ; Transcription Factor 4/genetics*

With the progress of imaging technology and the popularization of healthy examination, the detection rate of pancreatic cystic neoplasm(PCN) has increased significantly. PCN has complex disease spectrum, strong heterogeneity, and diverse surgical treatment strategies. Surgical timing and methods directly affect patients′ prognosis. Therefore, how to identify malignant tumors and formulate reasonable treatment strategies are the keys to treat PCN. Many guidelines for clinical diagnosis and treatment of PCN have been released, but there are still many disputes about its surgical indications. Hence, fully assessing the surgical indications is of great significance to improve the PCN patients′ prognosis. This paper deeply discusses on the surgical indications of PCN by reviewing the current clinical diagnosis, treatment and research progress of PCN, in order to standardize the diagnosis and treatment of PCN.

With the progress of imaging technology and the popularization of healthy examination, the detection rate of pancreatic cystic neoplasm(PCN) has increased significantly. PCN has complex disease spectrum, strong heterogeneity, and diverse surgical treatment strategies. Surgical timing and methods directly affect patients′ prognosis. Therefore, how to identify malignant tumors and formulate reasonable treatment strategies are the keys to treat PCN. Many guidelines for clinical diagnosis and treatment of PCN have been released, but there are still many disputes about its surgical indications. Hence, fully assessing the surgical indications is of great significance to improve the PCN patients′ prognosis. This paper deeply discusses on the surgical indications of PCN by reviewing the current clinical diagnosis, treatment and research progress of PCN, in order to standardize the diagnosis and treatment of PCN.