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.

The invasive arterial blood pressure(ABP)monitoring technique is widely utilized in the management of critically ill patients,providing medical professionals with real-time,continuous,and dynamic blood pressure data that plays a crucial role in guiding patient treatment.However,current traditional methods for arterial catheter blood collection and zero setting and measurement technology for ABP and central venous pressure(CVP)present certain issues such as complex operation procedures,inaccurate zero setting,and the inability to simultaneously monitor both ABP and CVP.Additionally,these methods may increase the risk of bloodstream infection and occupational exposure.Therefore,the department of critical care medicine at Tianjin Medical University General Hospital has developed a vascular access convenient blood collection device which has been granted a National Utility Model Patent(patent number:ZL 202322581247.4).This device includes a connecting tube,a specimen collection structure,a blood suction structure,a multifunctional pressure measurement device with laser emission structure,a pressure measurement conversion structure,and an efficient vascular access blood collection device.By optimizing the blood collection procedure and simplifying the manometry process,this design reduces the risk of bloodstream infection for patients and minimizes occupational exposure for medical staff.The device ensures accurate zero point adjustment of pressure measurements while guaranteeing the authenticity and reliability of collected data.Additionally,it supports synchronous monitoring of ABP and CVP,thereby saving medical consumables and reducing workload for healthcare professionals.This simple yet safe and efficient device meets clinical requirements effectively and is highly recommended for widespread use.

Objective:To explore the role of long noncoding RNA(lncRNA) CCDC18-AS1 in parathyroid carcinoma(PC) diagnosis.Methods:This cross-sectional study included 55 patients with primary hyperparathyroidism treated at Beijing Shijitan Hospital from 2013 to 2024. Of these, 12 patients were diagnosed with PC and 43 with parathyroid adenoma(PA). Tissue samples and clinical data were collected, and lncRNA CCDC18-AS1 expression were measured using real-time quantitative PCR(RT-qPCR).Results:LncRNA CCDC18-AS1 expression was significantly higher in the PC group than that in the PA group( P=0.003). It was identified as an independent risk factor for PC, independent of age, sex, or serum calcium levels. Among patients with hypophosphatemia, no significant differences in lncRNA CCDC18-AS1 expression was observed between the PC and PA groups. However, in patients with normal serum phosphate levels, lncRNA CCDC18-AS1 expression was significantly higher in the PC group( P<0.001) and showed a positive correlation with serum phosphorus concentration( P=0.001). The area under the receiver operating characteristic(ROC) curve(AUC) for lncRNA CCDC18-AS1 in PC diagnosis was 0.758(95% CI 0.620-0.866, P=0.005), comparable to that of lncRNA plasmacytoma variant translocation 1(PVT1). Among patients with normal serum phosphate, the AUC for lncRNA CCDC18-AS1 increased to 0.969(95% CI 0.835-0.999, P<0.001), with 100% sensitivity and 92.31% specificity, suggesting superior diagnostic performance compared to PVT1(0.840, 95% CI 0.653-0.950, P=0.001). Conclusions:LncRNA CCDC18-AS1 may serves as a potential biomarker for PC diagnosis, with greater diagnostic value in patients with normal serum phosphorus levels.

Inflammatory bowel disease (IBD) is a refractory disease characterized by chronic intestinal inflammation. Its typical pathological characteristics are the destruction of intestinal mucosal barrier and the imbalance of immune microenvironment. In severe cases, it can cause intestinal fibrosis and functional failure. Sulfation, a critical post-translational modification, plays an essential role in regulating intestinal homeostasis. Abnormal sulfation metabolism in the intestine of IBD patients can lead to the impairment of intestinal barrier function, immune system disorders and changes in the composition of microbiota. Consequently, targeting the sulfation pathway may be a novel therapeutic strategy for IBD. By supplementing exogenous sulfation substrates, regulating the activity of related key enzymes involved in sulfation or remodeling the microbiota, the level of intestinal sulfation can be effectively restored, thereby repairing the intestinal barrier function and inhibit the inflammatory response. This article systematically summarizes the pathogenic mechanisms of sulfation in IBD, providing a theoretical foundation for developing precision therapeutic strategies targeting the intestinal microenvironment.

Based on the results of the National Drug Sampling and Inspection Programme,we summarized the history,the standard collection,the production enterprises and the dosage form specifications,the quality standard study,the pharmacological and pharmacodynamic study,and the clinical application study of Wuwei Qingzhuo preparation of Mongolian medicine and Shiliu Jianwei preparation of Zang medicine,to provide the basis for improved quality standards for both preparations.The development of these two preparations was searched and analyzed through literature.The available information shows that there is very little research on the two preparations and insufficient pharmacological experimental and clinical experimental data.The two preparations are basically the same in prescription and efficacy.However,the quality standards are very different,which are not conducive to the quality control of the two and their related dosage forms.And it is suggested that the Chinese Pharmacopoeia should take the situation of this category into comprehensive consideration,and unify the quality standards of the two preparations.

Objective To observe conventional color Doppler ultrasound(CDU)and contrast-enhanced ultrasound(CEUS)manifestations of solitary abdominal mass-forming lymphoma.Methods Thirty-two patients with solitary abdominal mass-forming lymphoma confirmed by pathology who underwent CDU examination were retrospectively included,among them 28 patients also received CEUS.CDU manifestations of lesions were observed,including the size,echogenicity,shape,margin,posterior acoustic features,blood flow,as well as presence of cord-like and reticular high echogenicity and vascular encasement or not.The enhancement distribution,degree and pattern of lesion during CEUS were recorded.Results CDU showed that solitary abdominal mass-forming lymphomas lesions mainly appeared as hypoechoic masses with heterogeneous internal echogenicity(24/32,75.00%),irregular shape(28/32,87.50%),clear margin(26/32,81.25%)and posterior acoustic enhancement(28/32,87.50%),with rich blood flow(Adler gradeⅡ—Ⅲ in 24 of 32,75.00%).Vascular encasement and reticular septation were noticed each in 8 cases(8/32,25.00%).During CEUS,peak intensity of contrast agents appeared rapidly in arterial phase,with common high enhancement(26/28,92.86%),which then washed out quickly after the peak or decreased slowly in arterial phase and low enhancement in venous phase.Diffuse distribution(26/28,92.86%),uniform enhancement pattern(20/28,71.43%)and absence of liquefied necrotic area inside(22/28,78.57%)were common findings.Conclusion CDU and CEUS manifestations of solitary abdominal mass-forming lymphoma had characteristics to a certain degree,which might be helpful to early diagnosis.

Objective:To investigate the predictive value of refeeding syndrome (RFS) and its influencing factors for 30-day intensive care unit (ICU) readmission in critically ill patients.Methods:A prospective cohort study was conducted. Critically ill patients admitted to the department of critical care medicine, department of respiratory and critical care medicine, and department of neurology at Tianjin Medical University General Hospital from January to April in 2025 were enrolled. Patients were assessed for RFS according to the American Society for Parenteral and Enteral Nutrition (ASPEN) criteria. General information within 24 hours of ICU admission was collected via the electronic medical record system. Treatment details and 30-day ICU readmission status were dynamically recorded. Participants were divided into readmission and non-readmission groups based on whether ICU readmission occurred within 30 days. Intergroup comparisons were performed to identify differences. Multivariate Logistic regression was used to analyze the relationship between RFS and its influencing factors with 30-day ICU readmission. Receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive performance of risk factors.Results:A total of 196 critically ill patients were enrolled, among whom 25 (12.76%) were readmitted to ICU within 30 days and 171 (87.24%) were not. Significant differences were observed in the readmission group compared with the non-readmission group, including significantly higher rates of nasogastric decompression, higher acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, a higher incidence of RFS, and a longer duration of nasogastric decompression. Multivariate Logistic regression analysis showed that RFS was an independent risk factor for 30-day ICU readmission [odds ratio ( OR) = 5.756, 95% confidence interval (95% CI) was 1.603-20.670, P = 0.007]. APACHEⅡ score showed a positive correlation trend with 30-day ICU readmission ( OR = 1.057, 95% CI was 0.991-1.127, P = 0.092). ROC curve analysis showed that the combined prediction model incorporating RFS and APACHEⅡ score had an area under the ROC curve (AUC) of 0.766 (95% CI was 0.668-0.864), with a sensitivity of 88.0% and a specificity of 62.0%, which was significantly superior to a single indicator (the AUC of RFS and APACHEⅡ score was 0.639 and 0.624, respectively). Conclusions:RFS significantly increases the risk of 30-day ICU readmission in critically ill patients. A combined model incorporating RFS and APACHEⅡ score demonstrates good predictive efficacy for 30-day ICU readmission in critically ill patients.

Inflammatory bowel disease (IBD) is a refractory disease characterized by chronic intestinal inflammation. Its typical pathological characteristics are the destruction of intestinal mucosal barrier and the imbalance of immune microenvironment. In severe cases, it can cause intestinal fibrosis and functional failure. Sulfation, a critical post-translational modification, plays an essential role in regulating intestinal homeostasis. Abnormal sulfation metabolism in the intestine of IBD patients can lead to the impairment of intestinal barrier function, immune system disorders and changes in the composition of microbiota. Consequently, targeting the sulfation pathway may be a novel therapeutic strategy for IBD. By supplementing exogenous sulfation substrates, regulating the activity of related key enzymes involved in sulfation or remodeling the microbiota, the level of intestinal sulfation can be effectively restored, thereby repairing the intestinal barrier function and inhibit the inflammatory response. This article systematically summarizes the pathogenic mechanisms of sulfation in IBD, providing a theoretical foundation for developing precision therapeutic strategies targeting the intestinal microenvironment.

Based on the results of the National Drug Sampling and Inspection Programme,we summarized the history,the standard collection,the production enterprises and the dosage form specifications,the quality standard study,the pharmacological and pharmacodynamic study,and the clinical application study of Wuwei Qingzhuo preparation of Mongolian medicine and Shiliu Jianwei preparation of Zang medicine,to provide the basis for improved quality standards for both preparations.The development of these two preparations was searched and analyzed through literature.The available information shows that there is very little research on the two preparations and insufficient pharmacological experimental and clinical experimental data.The two preparations are basically the same in prescription and efficacy.However,the quality standards are very different,which are not conducive to the quality control of the two and their related dosage forms.And it is suggested that the Chinese Pharmacopoeia should take the situation of this category into comprehensive consideration,and unify the quality standards of the two preparations.

Objective To observe conventional color Doppler ultrasound(CDU)and contrast-enhanced ultrasound(CEUS)manifestations of solitary abdominal mass-forming lymphoma.Methods Thirty-two patients with solitary abdominal mass-forming lymphoma confirmed by pathology who underwent CDU examination were retrospectively included,among them 28 patients also received CEUS.CDU manifestations of lesions were observed,including the size,echogenicity,shape,margin,posterior acoustic features,blood flow,as well as presence of cord-like and reticular high echogenicity and vascular encasement or not.The enhancement distribution,degree and pattern of lesion during CEUS were recorded.Results CDU showed that solitary abdominal mass-forming lymphomas lesions mainly appeared as hypoechoic masses with heterogeneous internal echogenicity(24/32,75.00%),irregular shape(28/32,87.50%),clear margin(26/32,81.25%)and posterior acoustic enhancement(28/32,87.50%),with rich blood flow(Adler gradeⅡ—Ⅲ in 24 of 32,75.00%).Vascular encasement and reticular septation were noticed each in 8 cases(8/32,25.00%).During CEUS,peak intensity of contrast agents appeared rapidly in arterial phase,with common high enhancement(26/28,92.86%),which then washed out quickly after the peak or decreased slowly in arterial phase and low enhancement in venous phase.Diffuse distribution(26/28,92.86%),uniform enhancement pattern(20/28,71.43%)and absence of liquefied necrotic area inside(22/28,78.57%)were common findings.Conclusion CDU and CEUS manifestations of solitary abdominal mass-forming lymphoma had characteristics to a certain degree,which might be helpful to early diagnosis.