CRISPR/Cas9-based therapeutics face significant challenges in penetrating the dense microenvironment of solid tumors, resulting in insufficient gene editing and compromised treatment efficacy. Current nanostrategies, which mainly focus on the paracellular pathway attempted to improve gene editing performance, whereas their efficiency remains uneven in the heterogenous extracellular matrix. Here, the nanoCRISPR system is prepared with self-cascading mechanisms for gene editing-mediated robust apoptosis and transcellular penetration. NanoCRISPR unlocks its self-cascade capability within the matrix metallopeptidase 2-enriched tumor microenvironment, initiating the transcellular penetration. By facilitating cellular uptake, nanoCRISPR triggers robust apoptosis in edited malignancies, promoting further transcellular penetration and amplifying gene editing in neighboring tumor cells. Benefiting from self-cascade between robust apoptosis and transcellular penetration, nanoCRISPR demonstrates continuous gene transfection/tumor killing performance (transfection/apoptosis efficiency: 1st round: 85%/84.2%; 2nd round: 48%/27%) and homogeneous penetration. In xenograft tumor-bearing mice, nanoCRISPR treatment achieves remarkable anti-tumor efficacy (∼83%) and significant survival benefits with minimal toxicity. This strategy presents a promising paradigm emphasizing transcellular penetration to enhance the effectiveness of CRISPR-based antitumor therapeutics.

Ulcerative colitis （UC）， which is characterized by a complex and multifactorial etiology， remains one of the challenging disorders in the international field of digestive system diseases. In recent years， rectal administration preparations have made rapid progress in UC therapeutic applications. This study systematically reviews the dosage forms， mechanisms of action， and clinical applications of rectally-administered preparations for the treatment of UC. It is found that suppositories are the most commonly used dosage forms for rectal administration. The newer suppositories have the advantages of high bioavailability and good stability. Enemas can retain the drug in the intestine as much as possible to achieve the effects of diluting intestinal toxins， cleansing the bowel， and reducing inflammation. Gels can achieve a drug-sustained-release effect and effectively improve intestinal mucosal damage. The mechanism of action of this type of preparation is mainly to inhibit inflammatory cell infiltration， regulate intestinal microbial homeostasis， and increase the expression of tight-junction proteins， so as to play anti-inflammatory， regulate the intestinal bacterial flora， repair the intestinal mucosa， and other efficacies. The diversity of rectal administration forms provides a wide range of choices for the clinical treatment of UC， such as Mesalazine suppositories， Lianshao enemas， and temperature- sensitive gels loaded with drugs for UC.

Objective:To explore the chain mediating role of general self-efficacy and humanistic care competence between oncology nurses' empathy and medical narrative competence, with a view to informing the development of targeted medical narrative competence enhancement strategies.Methods:Convenience sampling was used to select 1 104 oncology nurses from 17 ClassⅢ Grade A hospitals in Yunnan Province from May to August 2023 for the study. The General Information Questionnaire, Narrative Competence Scale, Chinese version of the Jefferson Scale of Empathy, Caring Ability Inventory, and General Self-Efficacy Scale were used to survey oncology nurses. Pearson correlation was used to analyze the correlation among oncology nurses' general self-efficacy, empathy, humanistic care competence, and medical narrative competence. Mediating effects were analyzed using Model 6 in the SPSS macro program PROCESS 4.0 plug-in. Bootstrap method was used to repeat the sampling 5 000 times for the chained mediating effect test.Results:A total of 1 104 questionnaires were distributed and the number of valid questionnaires recovered was 931, with a valid recovery rate of 84.33% (931/1 104). Among 931 oncology nurses, the scores of Narrative Competence Scale, Caring Ability Inventory, Chinese version of Jefferson Scale of Empathy, and General Self-Efficacy Scale were (151.52±17.61), (191.68±18.80), (95.31±13.96), and (27.59±6.02), respectively. There was a positive two-by-two correlation among oncology nurses' medical narrative competence, empathy, humanistic care competence, and general self-efficacy ( P<0.01). General self-efficacy and humanistic care competence acted as chain mediators between oncology nurses' empathy and medical narrative competence, with the mediating effect accounting for 43.13% of the total effect. Conclusions:General self-efficacy and humanistic care are mediating variables between oncology nurses' empathy and medical narrative competence. Nursing managers should focus on the cultivation of nurses' empathy, stimulate nurses' self-efficacy, and promote the practice of nursing humanistic care, which in turn improves oncology nurses' medical narrative competence and the quality of nursing services.

Objective:To explore the chain mediating role of general self-efficacy and humanistic care competence between oncology nurses' empathy and medical narrative competence, with a view to informing the development of targeted medical narrative competence enhancement strategies.Methods:Convenience sampling was used to select 1 104 oncology nurses from 17 ClassⅢ Grade A hospitals in Yunnan Province from May to August 2023 for the study. The General Information Questionnaire, Narrative Competence Scale, Chinese version of the Jefferson Scale of Empathy, Caring Ability Inventory, and General Self-Efficacy Scale were used to survey oncology nurses. Pearson correlation was used to analyze the correlation among oncology nurses' general self-efficacy, empathy, humanistic care competence, and medical narrative competence. Mediating effects were analyzed using Model 6 in the SPSS macro program PROCESS 4.0 plug-in. Bootstrap method was used to repeat the sampling 5 000 times for the chained mediating effect test.Results:A total of 1 104 questionnaires were distributed and the number of valid questionnaires recovered was 931, with a valid recovery rate of 84.33% (931/1 104). Among 931 oncology nurses, the scores of Narrative Competence Scale, Caring Ability Inventory, Chinese version of Jefferson Scale of Empathy, and General Self-Efficacy Scale were (151.52±17.61), (191.68±18.80), (95.31±13.96), and (27.59±6.02), respectively. There was a positive two-by-two correlation among oncology nurses' medical narrative competence, empathy, humanistic care competence, and general self-efficacy ( P<0.01). General self-efficacy and humanistic care competence acted as chain mediators between oncology nurses' empathy and medical narrative competence, with the mediating effect accounting for 43.13% of the total effect. Conclusions:General self-efficacy and humanistic care are mediating variables between oncology nurses' empathy and medical narrative competence. Nursing managers should focus on the cultivation of nurses' empathy, stimulate nurses' self-efficacy, and promote the practice of nursing humanistic care, which in turn improves oncology nurses' medical narrative competence and the quality of nursing services.

Objective:To evaluate the efficacy and safety of radiotherapy as a combined mode with in-situ vaccine for patients with advanced soft tissue sarcoma(STS).Methods:The clinical data of 12 patients with advanced STS who received combination therapy mode at the Cancer Center of Gulou Hospital Affiliated to the School of Medicine of Nanjing University between December 2020 and September 2024 were retrospectively analyzed.All 12 patients received combined therapy.The main radiotherapeutic approach was hypofractionated radiotherapy.The targeted therapy mainly involved Anlotinib(in 10 cases)or Apatinib(in 2 cases).Immunotherapy mainly involved PD-1 antibodies.The primary endpoint was disease control rate(DCR),and the secondary endpoints were objective response rate(ORR)and safety.Results:Among the 12 STS patients who received combined treatment,0 cases achieved CR,4 cases achieved PR;7 cases had SD,and 1 case had PD.The ORR was 33%,and the DCR was 91.7%,among which the DCR of the target lesions was 100%.Among the 12 patients,9 patients experienced grade Ⅰ to grade Ⅱ adverse reactions.The most frequently occurring hematological adverse reactions were anemia(6 cases)and abnormal results of liver function tests(3 cases).The most frequently occurring non-hematological adverse reactions were proteinuria(5 cases),hypertension(4 cases),abnormal thyroid function(3 cases),anorexia(3 cases),and nausea and vomiting(2 cases).Only 2 cases had grade Ⅲ hematological toxicity,and 1 case had grade Ⅲpneumothorax.Conclusion:Radiotherapy as a combined therapy mode with in situ vaccine can achieve a higher DCR in advanced soft tissue sarcomas without serious adverse reactions.This combined treatment modality demonstrates good efficacy and safety.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

The solute carrier family 12(SLC12)of cation-chloride cotransporters(CCCs)comprises potassium chlo-ride cotransporters(KCCs,e.g.KCC1,KCC2,KCC3,and KCC4)-mediated Cl-extrusion,and sodium po-tassium chloride cotransporters(N[K]CCs,NKCC1,NKCC2,and NCC)-mediated Cl-loading.The CCCs play vital roles in cell volume regulation and ion homeostasis.Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues.In recent years,there have been considerable ad-vances in our understanding of CCCs'control mechanisms in cell volume regulations,with many tech-niques developed in studying the functions and activities of CCCs.Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs.These techniques include the ammonium pulse technique,radioactive or nonradioactive rubidium ion uptake-assay,and thallium ion-uptake assay.CCCs'activity can also be indirectly observed by measuring y-aminobutyric acid(GABA)activity with patch-clamp electrophysiology and intracellular chloride con-centration with sensitive microelectrodes,radiotracer 36Cl-,and fluorescent dyes.Other techniques include directly looking at kinase regulatory sites phosphorylation,flame photometry,22Na+uptake assay,structural biology,molecular modeling,and high-throughput drug screening.This review sum-marizes the role of CCCs in genetic disorders and cell volume regulation,current methods applied in studying CCCs biology,and compounds developed that directly or indirectly target the CCCs for disease treatments.

Objective:To summarize the characteristics of clinical, muscle pathology and gene mutation of late-onset reducing body myopathy caused by FHL1 gene mutation, in order to improve clinicians′ understanding of this disorder. Methods:The clinical, muscle pathology and muscle magnetic resonance imaging data of the proband from a family diagnosed as reducing body myopathy in Jiaozuo People′s Hospital in December 2021 were collected. Genetic tests and pedigree verification were conducted on the proband and her son.Results:The proband was a 59-year-old female with progressive, asymmetrical limb weakness and muscular atrophy. Her mother, sister and brother had similar symptoms. Electromyography showed myogenic and neurogenic damage. Muscle magnetic resonance imaging indicated that the lesion mainly involved the posterior muscles of the thigh and calf, as well as the gluteus maximus. The muscle pathology showed eosinophilic granular inclusion bodies and rimmed vacuoles in the muscle fibers of the lesion. The structure of myofibrils was disordered and abnormal protein deposition was observed. The gene sequencing showed the FHL1 gene p.C150S heterozygous variation. Conclusions:Late-onset reducing body myopathy is characterized by progressive asymmetric proximal limb muscle weakness, partially involving distal limb muscles and gluteus maximus. Muscle pathology shows the characteristic pathological changes of many kinds of myofibrillar myopathies. FHL1 gene mutation is an important basis for diagnosis.

Objective:In this study, the liver, spleen, and hepatic portal vein in the portal venous phase images of abdominal enhanced computed tomography (CT) are artificially segmented and annotated, and the radiomics features are extracted from them. A model for predicting portal pressure in patients with hepatitis B virus (HBV) related cirrhosis is constructed by combining radiomics features with clinical indicators.Methods:A total of 171 patients who had abdominal enhancement CT examination and trans-jugular hepatic venous pressure gradient (HVPG) measurement at the same time were enrolled from January 2016 to May 2020 in the Zhongshan Hospital Affiliated to Fudan University. The liver, spleen, and hepatic portal vein in the portal venous phase images of the CT were manually labeled by using ITK-SNAP 3.8 software. The radiomics features of these three sites were extracted using Python programming, and an HVPG prediction model was established.Results:A total of 171 patients was included in the study. The average age was (51.1±10.3)years, of which 134(78.4%) were males, and the average HVPG was 16.87±5.695. A total of 2 553 radiomics features were extracted from three sites of the portal venous phase images of abdominal enhanced CT in each patient. The 2 553 features extracted were screened using LASSO, and by combing with clinical features and radiomics features, the predictive model of HVPG was obtained: m_HVPG=31.622+ 0.028 8T×total bile acids-6.31(portal venous wavelet-LHH_glcm_ClusterShade)=0.253(portal venous wavelet-LHL_glszm_LargeAreaLowGrayLevelEmphasis)-20.9(spleen wavelet-LLH_glcm_Correlation)-0.000 127(liver original_shape_SurfaceArea)+ 2.79(liver wavelet-LLH_glcm_ClusterShade). The coefficient of determination R2 was 0.345. Conclusions:The study suggests that radiomics features of the liver, spleen, and portal venous combined with clinical features may be used as a non-invasive method to assess the portal pressure in patients with HBV-related cirrhosis.