The RET protein encoded by RET proto-oncogene is a receptor tyrosine kinase that serves as a potential therapeutic target in non-small cell lung cancer (NSCLC) . In NSCLC, the incidence of RET fusions variants ranges from 1%-2% and is more common in younger, non-smoking patients. Traditional chemotherapy, immunotherapy, and multitarget kinase inhibitors have shown limited efficacy in treating RET fusion-positive NSCLC patients. However, selective RET inhibitors, such as selpercatinib and pralsetinib, have significantly improved the prognosis of those patients. The treatment strategy following resistance to selective RET inhibitors is a future research direction.

Objective To investigate the mechanism of glycogen synthase kinase-3β（GSK-3β） participating in stroke-induced inflammatory brain injury through endoplasmic reticulum-mitochondria coupling， and to provide a theoretical reference and potential targets for precise treatment. Methods A rat model of middle cerebral artery occlusion was established， and the rats were divided into sham-operation group， model group， and GSK-3β inhibitor（TDZD-8） intervention group. Neurological function score was used to evaluate the degree of brain injury； TTC staining was used to evaluate cerebral infarct area； electron microscopy was used to observe mitochondrial ultrastructure； mitochondrial calcium concentration was measured； ELISA was used to measure the levels of inflammatory factors[tumor necrosis factor-α（TNF-α）and interleukin-1β（IL-1β）]， and Western blot was used to measure the expression levels of related proteins. Results Compared with the sham-operation group， the model group had significant neurological function impairment， an increase in cerebral infarct area， and significant increases in the expression levels of inflammatory factors and GSK-3β，with enhanced endoplasmic reticulum-mitochondria coupling and mitochondrial calcium overload. TDZD-8 significantly improved the above indicators and reduced the levels of inflammatory factors and cerebral infarct area. Conclusion Abnormal activation of GSK-3β damages brain tissue by regulating endoplasmic reticulum-mitochondria coupling and promotes mitochondrial calcium overload and inflammatory response. Inhibiting GSK-3β activity can effectively improve stroke-induced inflammatory brain injury， which provides a new pathway and a molecular target for developing precise treatment strategies.
Stroke

Objective To study the death status of pancreatic cancer among residents in Xuhui district, Shanghai, from 1992 to 2021, and analyze its trends of change, so as to provide evidence for the prevention and treatment of pancreatic cancer. Methods Based on the database of Shanghai death registration system from 1992 to 2021, the crude mortality rate, standardized mortality rate, age-specific mortality rate and other indicators of pancreatic cancer among registered residents in Xuhui district were calculated. The Joinpoint software was used to analyze the trends of average annual percent change (AAPC) of pancreatic cancer mortality rate, and the age-period-cohort model was used to analyze the age effect, period effect and birth cohort effect pairs significant changes in pancreatic cancer mortality. Results In 2021, the mortality rate of pancreatic cancer in Xuhui district, Shanghai, ranked fourth among malignant tumors, and the winning rate and world standard rate of the whole population, males and females were 8.34/100 000 (8.81/100 000, 7.98/100 000) and 7.28/100 000 (7.69/100 000, 6.96/100 000), respectively, with males higher than females. AAPC of crude mortality rate and the standardized (6) mortality rate were higher in males than that in females. The age-specific mortality rate increased with the increase of age, and the highest mortality rate was found in 60-84 years old group. The age-period-cohort model showed that from 1992 to 2021, the annual net shift of pancreatic cancer mortality among the whole population, male and female residents in Xuhui district, Shanghai, was 1.22%, 1.58%, 1.15% (P=0.20, 0.19, 0.45) respectively, and the time trend was not significant. From the perspective of age effect, the risk of death from pancreatic cancer in the whole population and with age deviation in males had an obvious trend with increasing age (P<0.05), while the age effect in females had no obvious trend. From the perspective of period effect, no period deviation was significant in the whole population, males and females (P>0.05). In terms of cohort effects, there were significant differences in the whole population and the male cohort deviations(P<0.05). No significant cohort effect was observed in the female population. Conclusions The mortality rate of pancreatic cancer among registered residents in Xuhui district, Shanghai from 1992 to 2021, was on the rise, especially in the 60-84 years old group and male. The prevention and control of pancreatic cancer needs to develop effective epidemic prevention measures for corresponding populations.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the current nursing practice of nurses specializing in nutritional support in ICUs and analyze their influencing factors in order to improve the training program and promote the development of standardized and precise nursing practice.Methods Convenience sampling method was used to select nutritional support nurses in ICUs in 29 provinces(autonomous regions and municipalities)from October 2023 to March 2025,and the self-developed questionnaire on nursing practice behaviors of nutritional support nurses in ICUs was used to conduct the survey.SPSS 21.0 software was used for descriptive analysis and multiple linear regression analysis.Results A total of 774 questionnaires were distributed,and 766 valid questionnaires were collected,with a recovery rate of 98.97％,and the score of the questionnaire on nursing practice behaviors of nurses specializing in nutritional support in ICU was(90.41±1 1.82).The results of multiple linear regression analysis showed that gender,presence of a nutritional support nursing team in the hospital,a standardized process of nutritional support nursing in the department,clear positional responsibilities of the nutritional support nursing team members,and inclusion of the nutritional support status of the patients in the quality management of the department were the factors influencing the nursing practice behavior scores of the nurses specializing in nutritional support in ICUs(P＜0.05).Conclusion Nurses in the ICUs have a high level of nursing practice behavior,but there is a need for further standardization in parenteral nutrition infusion and monitoring of complications.ICU nursing managers should formulate improvement strategies to address the weaknesses of clinical practice,strengthen nutritional support training,and improve the quality management program,and further improve the practical ability of nurses specializing in nutritional support.

OBJECTIVES: To explore the active components that mediate the therapeutic effect of Centella asiatica on psoriasis and their therapeutic mechanisms. METHODS: TCMSP, TCMIP, PharmMapper, Swiss Target Prediction, GeneCards, OMIM and TTD databases were searched for the compounds in Centella asiatica and their targets and the disease targets of psoriasis. A drug-active component-target network and the protein-protein interaction network were constructed, and DAVID database was used for pathway enrichment analysis. In a RAW264.7 macrophage model of LPS-induced inflammation, the anti-inflammatory effect of 7.5, 15, 30, and 60 μmol/L quercetin, asiaticoside, and asiatic acid, which were identified as the main active components in Centella asiatica, were tested by measuring cellular production of NO, TNF‑α and IL-6 using Griess method and ELISA and by detecting mRNA expressions of IL-23, IL-17A, TNF-α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727) with RT-qPCR and Western blotting. RESULTS: A total of 139 targets of Centella asiatica and 4604 targets of psoriasis were obtained, and among them CASP3, EGFR, PTGS2, and ESR1 were identified as the core targets. KEGG analysis suggested that quercetin, asiaticoside, and asiatic acid in Centella asiatica were involved in cancer and IL-17 and MAPK signaling pathways. In the RAW264.7 macrophage model of inflammation, treatment with quercetin significantly reduced cellular production of NO, TNF‑α and IL-6, and lowered mRNA expressions of IL-23, IL-17A, TNF‑α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727). CONCLUSIONS Quercetin, asiaticoside and asiatic acid are the main active components in Centella asiatica to mediate the therapeutic effect against psoriasis, and quercetin in particular is capable of suppressing cellular production of NO, TNF‑α and IL-6 and regulating the IL-23/IL-17A inflammatory axis by mediating STAT3 phosphorylation to inhibit inflammatory response.
Quercetin/pharmacology* ; Psoriasis/metabolism* ; STAT3 Transcription Factor/metabolism* ; Mice ; Animals ; Centella/chemistry* ; Triterpenes/pharmacology* ; Phosphorylation ; Interleukin-17/metabolism* ; Interleukin-23/metabolism* ; RAW 264.7 Cells ; Pentacyclic Triterpenes/pharmacology* ; Macrophages/drug effects* ; Signal Transduction ; Plant Extracts

CD20 is a surface marker protein of B-cell lymphoma, and its extracellular region is the target of specific antibodies and drugs. To obtain a cheap and easily modified specific preparation targeting CD20, we optimized the gene of CD20 extracellular region according to codon degeneracy to facilitate its expression in Escherichia coli. The optimized gene was cloned into pGEX-4T-1 vector, and the recombinant vector was transformed into E. coli BL21(DE3) for expression. The purified protein was identified by SDS-PAGE and Western blotting. Systematic evolution of ligands by exponential enrichment (SELEX) was employed to screen the ssDNA aptamer that specifically binds to the fusion protein, and the affinity of the aptamer to CD20 was detected by flow cytometry. Then, the cytotoxicity test was carried out to examine the inhibitory effect of the aptamer on B lymphoma cells. In this study, we established the prokaryotic expression method of CD20 and obtained the aptamer specifically binding to the extracellular region of CD20, which laid a foundation for the development of therapeutic drugs targeting CD20.
Humans ; Escherichia coli/metabolism* ; SELEX Aptamer Technique/methods* ; Aptamers, Nucleotide/genetics* ; Antigens, CD20/metabolism* ; Ligands

Objective:To investigate the current status of peripherally inserted central catheter (PICC) -associated thrombosis prevention nursing practices among surgical nurses, and to provide a scientific basis for targeted future interventions.Methods:A convenience sampling method was used to select 3 151 surgical nurses from tertiary hospitals in 11 provinces and municipalities who attended the Surgical Nursing Academic Symposium of the Chinese Nursing Association between April and May 2023. The survey utilized a standardized questionnaire assessing current practices in PICC-associated thrombosis prevention among clinical nurses.Results:A total of 3 151 questionnaires were distributed, and 2 341 valid responses were collected, yielding a valid response rate of 74.29% (2 341/3 151) . Among the respondents, the training rate on PICC-associated thrombosis prevention was only 62.45% (1 462/2 341) , and just 1.28% (30/2 341) had received full-time (off-duty) training. The usage rate of standardized procedures for PICC-related thrombosis prevention was 92.40% (2 163/2 341) , and the risk assessment rate was 79.79% (1 868/2 341) . Compared to urology and cardiothoracic surgery departments, breast surgery departments had significantly higher rates of thrombosis risk assessment ( P<0.05) . Additionally, 56.69% (1 327/2 341) of surgical nurses used risk assessment tools specific to PICC-associated thrombosis. Among non-pharmacological prevention measures, the implementation rate of encouraging patients to perform grip strength exercises was only 68.26% (1 598/2 341) . Conclusions:The current level of PICC-associated thrombosis prevention nursing among surgical nurses needs further improvement. Efforts should be strengthened in professional training, implementation of standardized protocols, risk assessment, and non-pharmacological interventions.

Objective:To evaluate the safety and efficacy of early precise lower limb weight-bearing functional rehabilitation after open reduction and internal fixation of ankle fractures.Methods:A restropective multi-center study was conducted to enroll the eligible 120 patients with malleolar fracture who received the same surgical treatment from March 2023 to December 2023 at the trauma centers in 7 tertiary hospitals according to the inclusion criteria. They were assigned into a study group ( n=60) for precise lower limb weight-bearing functional rehabilitation with the assistance of intelligent lower limb walking rehabilitation crutches and a control group ( n=60) for conventional weight-bearing functional rehabilitation which was gradually increased according to their own feelings under the protection of a walking boot. All the 60 patients in the study group completed their final follow-ups. They were 25 males and 35 females, with an age of (43.8±16.6) years and a body mass index of (25.3±2.3) kg/m 2. Only 51 patients in the control group completed their final follow-ups. They were 27 males and 24 females, with an age of (45.1±16.4) years and a body mass index of (24.7±2.3) kg/m 2. When their incisions healed and their sutures were removed 2 weeks after operation, the patients were guided to start lower limb weight-bearing functional rehabilitation, and exercises for foot and ankle joint mobility and lower limb muscles. The end point of follow-up was 12 weeks after operation. The 2 groups were compared in terms of the crutch-off rates, thigh circumferences, calf circumferences, dorsiflexions, plantarflexions, ankle swellings, American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores, and visual analog scale (VAS) pain scores at 6 and 12 weeks after operation. The complications were also recorded in the 2 groups. Results:No statistically significant differences were observed in the baseline characteristics between the 2 groups, indicating comparability ( P>0.05). At 6 and 12 weeks after operation, the crutch-off rates [41.7% (25/60) and 100.0% (60/60)], dorsiflexions (69.3%±21.6% and 82.9%±26.3%) and AOFAS ankle-hindfoot scores [(68.5±7.6) points and (96.9±3.7) points] in the study group were significantly better than those in the control group [13.7% (7/51) and 39.2% (20/51), 61.5%±16.5% and 72.0%±14.3%, (61.9±9.3) points and (90.1±7.2) points] ( P<0.05). At 6 weeks after operation, the thigh circumference (97.4%±1.9%), calf circumference (97.3%±1.9%), and plantarflexion (76.6%±19.8%) in the study group were significantly higher than those in the control group (95.9%±2.5%, 94.6%±3.2%, and 63.9%±16.9%) ( P<0.05). There were no significant differences between the 2 groups in ankle swelling at 6 or 12 weeks after operation, or thigh or calf circumference, plantarflexion, or VAS pain score at 12 weeks after operation ( P>0.05). No wound complications, secondary fracture displacement, or loosening of internal fixation occurred in either group during the follow-up period. There were no cases of nonunion or delayed union. Conclusions:Early lower limb weight-bearing functional rehabilitation after open reduction and internal fixation of ankle fractures demonstrates good safety. Precise weight-bearing rehabilitation accelerates functional recovery of the ankle, enabling earlier return to normal daily activities.