Distinct from the complementary inhibition mechanism through binding to the target with three-dimensional conformation of small molecule inhibitors, targeted protein degradation technology takes tremendous advantage of endogenous protein degradation pathway inside cells to degrade plenty of “undruggable” target proteins, which provides a novel route for the treatment of many serious diseases, mainly including proteolysis-targeting chimeras, lysosome-targeting chimeras, autophagy-targeting chimeras, antibody-based proteolysis-targeting chimeras, etc. Unlike proteolysis-targeting chimeras first found in 2001, which rely on ubiquitin-proteasome system to mainly degrade intracellular proteins of interest, lysosome-targeting chimeras identified in 2020, which was act as the fastly developing technology, utilize cellular lysosomal pathway through endocytosis mediated by lysosome-targeting receptor to degrade both extracellular and membrane proteins. As an emerging biomedical technology, nucleic acid-driven lysosome-targeting chimeras utilize nucleic acids as certain components of chimera molecule to replace with ligand to lysosome-targeting receptor or protein of interest, exhibiting broad application prospects and potential clinical value in disease treatment and drug development. This review mainly introduced present progress of nucleic acid-driven lysosome-targeting chimeras technology, including its basic composition, its advantages compared with antibody or glycopeptide-based lysosome-targeting chimeras, and focused on its chief application, in terms of the type of lysosome-targeting receptors. Most research about the development of nucleic acid-driven lysosome-targeting chimeras focused on those which utilized cation-independent mannose-6-phosphonate receptor as the lysosome-targeting receptor. Both mannose-6-phosphonate-modified glycopeptide and nucleic aptamer targeting cation-independent mannose-6-phosphonate receptor, even double-stranded DNA molecule moiety can be taken advantage as the ligand to lysosome-targeting receptor. The same as classical lysosome-targeting chimeras, asialoglycoprotein receptor can also be used for advance of nucleic acid-driven lysosome-targeting chimeras. Another new-found lysosome-targeting receptor, scavenger receptor, can bind dendritic DNA molecules to mediate cellular internalization of complex and lysosomal degradation of target protein, suggesting the successful application of scavenger receptor-mediated nucleic acid-driven lysosome-targeting chimeras. In addition, this review briefly overviewed the history of lysosome-targeting chimeras, including first-generation and second-generation lysosome-targeting chimeras through cation-independent mannose-6-phosphonate receptor-mediated and asialoglycoprotein receptor-mediated endocytosis respectively, so that a clear timeline can be presented for the advance of chimera technique. Meantime, current deficiency and challenge of lysosome-targeting chimeras was also mentioned to give some direction for deep progress of lysosome-targeting chimeras. Finally, according to faulty lysosomal degradation efficiency, more cellular mechanism where lysosome-targeting chimeras perform degradation of protein of interest need to be deeply explored. In view of current progress and direction of nucleic acid-driven lysosome-targeting chimeras, we discussed its current challenges and development direction in the future. Stability of natural nucleic acid molecule and optimized chimera construction have a great influence on the biological function of lysosome-targeting chimeras. Discovery of novel lysosome-targeting receptors and nucleic aptamer with higher affinity to the target will greatly facilitate profound advance of chimera technique. In summary, nucleic acid-driven lysosome-targeting chimeras have many superiorities, such as lower immunogenicity, expedient synthesis of chimera molecules and so on, in contrast to classical lysosome-targeting chimeras, making it more valuable. Also, the chimera technology provides new ideas and methods for biomedical research, drug development and clinical treatment, and can be used more widely through further research and optimization.

Based on the theory of 'bi （痹） of both body and viscera'， this paper systematically discussed the pathogenic evolution of rheumatoid arthritis （RA） complicated by sarcopenia from the perspective of traditional Chinese medicine （TCM）. It is proposed that a transformation pathway is muscle bi to spleen bi and then atrophy bi， and the core pathogenesis is diaharmony of ying （营） and wei （卫）. Combining modern molecular biology research， it is suggested that imbalances in skeletal muscle homeostasis mediated by the tumor necrosis factor-like weak inducer of apoptosis-ibroblast growth factor-inducible 14 （TWEAK-Fn14） axis may provide the material basis for the evolution of this disease. Furthermore， this authors proposed TCM treatment strategies， including "regulating and tonifying ying and wei， warming yang and moving bi， nourishing the viscera by supporting the body"， and "promoting the spleen and resolving turbidity， clearing heat and promoting circulation， regulating the organs and calming the body". These strategies emphasize the simultaneous treatment of body and viscera， integrated prevention and treatment， so as to provide TCM theoretical foundation and clinical approaches for preventing and treating RA complicated by sarcopenia.

Objective To investigate the prognosis of patients with triple-negative invasive lobular carcinoma (TN-ILC) undergoing breast-conserving surgery combined with radiotherapy (BCS+RT) versus total mastectomy. Methods A retrospective analysis was performed for 2 386 female patients with TN-ILC who underwent surgery in the SEER database from 2006 to 2018, and the baseline characteristics (age, histological grade, AJCC stage, etc.) were balanced by propensity score matching (PSM, 1∶1, caliper value 0.02), and breast cancer-specific survival (BCSS) and overall survival (OS) were compared by Kaplan-Meier method and COX regression analysis. Results A total of 1 056 pairs of patients were obtained after PSM, and the BCS+RT group had significantly better BCSS and OS than the total mastectomy group (both P<0.001). Stratified analyses showed that BCS+RT had a survival advantage in all subgroups except histologic grade Ⅰ and tumor stage Ⅰ. Multivariate analysis confirmed that BCS+RT was an independent protective factor (BCSS: HR=0.682, OS: HR=0.607, both P<0.001). Conclusions BCS+RT significantly improves survival compared with total mastectomy in patients with TN-ILC, supporting BCS+RT as the preferred treatment strategy for eligible patients.

Objective:To conduct a comparative analysis of the oxygen depletion and oxygen effect of FLASH irradiation and conventional irradiation by direct measurement of oxygen content.Methods:The oxygen content in different tissues and organs of mice was measured using a phosphorescent probe. A subcutaneous xenograft tumor model in mice was established, to receive electron-beam irradiation at different doses and dose rates. The oxygen depletion of tumor and normal tissue was analyzed, and tumor control was evaluated. The oxygen depletion of conventional irradiation and FLASH irradiation was further analyzed using an in vitro model. The survival fraction (SF) of normal cells after conventional irradiation and FLASH irradiation was calculated using colony formation assay under different partial pressures of oxygen, and the data were fitted to the oxygen enhancement ratio (OER) curve. Results:The mean oxygen content of subcutaneous xenograft tumor in mice was 1.28%, suggesting hypoxia. The mean oxygen content of normal tissue ranged from 3.51% to 6.53%, suggesting physioxia. In animal experiments, oxygen depletion was not observed during conventional irradiation. High-dose-rate (20 Gy/s) and ultra-high-dose-rate (FLASH, 40 Gy/s) irradiation produced oxygen depletion. During FLASH irradiation, with the increase of oxygen content, the oxygen depletion was 0.1-0.2 mm Hg/Gy for tumor tissue and 0.19-0.21 mm Hg/Gy for skin tissue, which tended to stabilize. FLASH irradiation maintained equivalent tumor control compared to conventional irradiation. The tumoricidal effect was significantly enhanced with the increase of oxygen content in the tissue ( t=3.46, P<0.01). In in vitro experiments, the mean oxygen depletion rate was about 0.16 mm Hg/Gy for conventional irradiation and 0.16-0.18 mm Hg/Gy for FLASH irradiation, which did not change significantly with the increase of oxygen content. FLASH irradiation was associated with an oxygen effect. When the partial pressure of oxygen decreased from physioxia to hypoxia, the OER value significantly reduced. Conclusions:Normal tissues and organs are in physioxia, which exhibits a lower oxygen content than that in the air. FLASH irradiation can consume a proportion of oxygen, producing an oxygen effect. When oxygen content decreases, the oxygen depletion rate slows down after FLASH irradiation.

AIM To establish an HPLC method for the simultaneous content determination of 5-hydroxymethylfurfural,chlorogenic acid,caffeic acid,strychnine,paeoniflorin,ferulic acid,paeoniflorin Ⅰ,epimedium glycoside,psoralen,isopsoralen and glycyrrhetinic acid in Bunao Soft Capsules.METHODS The analysis was performed on a 35 ℃ thermostatic Waters Symmetry C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1％phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 230,280 nm.RESULTS Eleven constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 98.47％-103.30％with RSDs of 1.13％-2.80％.CONCLUSION This simple and reliable method can be used for the quality control of Bunao Soft Capsules.

Objective To investigate the value of prone-position MRI of lumbar spine for diagnosing pediatric occult tethered cord syndrome(OTCS).Methods A total of 67 children with suspected tethered cord syndrome(TCS)and confirmed OTCS by surgery were prospectively enrolled as OTCS group,while 73 healthy subjects were recruited as control group.Supine-and prone-position lumbar MR examinations were performed in both groups.The position of filum terminale on prone axial T2WI and the presence or absence of"sunset sign"(i.e.filum terminale located within the dorsal 1/2 of spinal canal on prone axial T2WI)were observed,spinal cord conus mobility was calculated.The efficacy of"sunset sign"for diagnosing OTCS in children was calculated through comparison between groups.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the diagnostic efficacy of spinal cord conus mobility.Results On prone-position axial T2WI,"sunset sign"was found in 58 cases(58/67,86.57％)but not in 9 cases(9/67,13.43％)in OTCS group,which was not even observed in control group.The sensitivity of"sunset sign"for diagnosing pediatric OTCS was 86.57％(58/67),with specificity of 100％(73/73),positive predictive value of 100％(58/58)and negative predictive value of 89.02％(73/82).The spinal cord conus mobility was(19.30±5.89)％in OTCS group and(31.71±6.58)％in control group,being statistically different between groups(t=-11.722,P＜0.001).The sensitivity,specificity and AUC of spinal cord conus mobility for diagnosing pediatric OTCS was 80.60％,90.41％and 0.920,respectively.Conclusion Prone-position MRI of lumbar spine could be used in diagnosing pediatric OTCS.

Objective:To compare the efficacy of laminoplasty via the intermuscular approach or posterior midline approach for treating spinal cord injury without radiographic abnormality (SCIWORA).Methods:A multi-center retrospective cohort study was conducted to analyze the clinical data of 135 patients with SCIWORA admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University School of Medicine, Xi'an No.5 Hospital, Henan Provincial People's Hospital, Zhengzhou Orthopedic Hospital, Xuanwu Hospital of Capital Medical University from February 2021 to June 2023, including 75 males and 60 females, aged 35-78 years [(55.3±8.1)years]. The injury segments involved C 3-C 6. All the patients underwent posterior cervical open-door laminoplasty, among whom 70 patients were treated via the intermuscular approach (intermuscular group) and 65 via the posterior midline approach (posterior midline group). The operation duration, intraoperative blood loss, postoperative drainage volume, and length of hospital stay were recorded. The visual analogue scale (VAS) score, Japanese Orthopedic Association (JOA) score, neck disability index (NDI), Barthel index, cervical Cobb angle, and cervical range of motion (ROM) were measured preoperatively, at 3, 6, 12 months postoperatively and at the final follow-up. The American Spinal Injury Association (ASIA) scale was evaluated preoperatively, at 3, 12 months postoperatively and at the final follow-up. The postoperative complication rate was recorded as well. Results:All the patients were followed up for 15-19 months [(16.3±1.6)months]. The operation duration, intraoperative blood loss, postoperative drainage and length of hospital stay were (125.0±23.0)minutes, (210.4±34.8)ml, and (165.3±23.7)ml, and (5.3±0.1)days in the intermuscular group, which were significantly shorter or less than (168.0±27.6)minutes, (260.2±45.3)ml, (196.4±31.6)ml, and (6.4±0.2)days in the posterior midline group ( P<0.01). The preoperative VAS score, JOA score, NDI and Barthel index showed no significant differences between the two groups ( P>0.05). The VAS score and JOA score also showed no significant differences between the two groups at 3, 6, 12 months postoperatively or at the final follow-up ( P>0.05). The NDI and Barthel index also showed no significant differences between the two groups at 3 months postoperatively ( P>0.05). At 6, 12 months postoperatively and at the final follow-up, the NDI were (15.4±2.5)points, (11.8±2.1)points and (8.6±1.5)points in the intermuscular group, significantly lower than (19.1±3.4)points, (14.3±2.4)points and (11.9±1.4)points in the posterior midline group ( P<0.01). At 6, 12 months postoperatively and at the final follow-up, the Barthel index were (71.4±6.2)points, (83.4±5.8)points and (89.2±7.1)points in the intermuscular group, significantly higher than (59.6±4.7)points, (74.2±3.9)points and (78.8±6.2)points in the posterior midline group ( P<0.01). Both groups showed significant improvements in VAS score, JOA score, NDI and Barthel index at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P<0.05). Among them, the VAS score, NDI and Barthel index were further improved over time ( P<0.05). Simultaneously, the JOA score was significantly improved at 6, 12 months postoperatively and at the last follow-up when compared to that at 3 months postoperatively ( P<0.05), with no significant difference at later time points between the two groups ( P>0.05). The preoperative cervical Cobb angle and ROM showed no significant differences between the two groups ( P>0.05). There was no significant difference in the Cobb angle between the two groups at 3, 6 or 12 months postoperatively ( P>0.05), while it was (13.6±2.4)° in the intermuscular group at the final follow-up, significantly larger than (10.4±2.8)° in the posterior midline group ( P<0.01). At 3, 6, 12 months postoperatively and at the final follow-up, the cervical ROM were (34.1±6.4)°, (32.6±7.3)°, (31.8±9.1)° and (29.6±8.7)° in the intermuscular group, significantly larger than (23.7±8.3)°, (22.3±7.8)°, (22.5±8.1)° and (20.6±9.3)° in the posterior midline group ( P<0.01). In the intermuscular group, the cervical Cobb angle showed no significant changes at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P>0.05). In the posterior midline group, the Cobb angles were significantly reduced at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P<0.05), showing significant decrease at 12 months postoperatively and at the final follow-up from those at 3, 6 months postoperatively ( P<0.05), no significant difference at 6 months postoperatively from that at 3 months postoperatively ( P>0.05), and significant decrease at the final follow-up from that at 12 months postoperatively ( P>0.05). In the intermuscular group, the cervical ROM were significantly improved at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively and showed further improvement over time ( P<0.05). In the posterior midline group, the cervical ROM were significantly improved at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P<0.05), showing significant decreases at 6, 12 months postoperatively and at the final follow-up from that at 3 months postoperatively ( P<0.05), significant decreases at the final follow-up from those at 6, 12 months postoperatively ( P<0.05), and no significant difference at 12 months postoperatively from that at 6 months postoperatively ( P>0.05). The ASIA grades showed no significant difference between the two groups preoperatively, at 3, 12 months postoperatively and at the final follow-up ( P>0.05) , but were gradually improved over time in both groups ( P<0.05). The postoperative complication rate was 9%(6/70) in the intermuscular group, significantly lower than 48%(31/65) in the posterior midline group ( P<0.01). Conclusion:Compared to the posterior midline approach, the intermuscular approach for laminoplasty in patients with SCIWORA possesses advantages, including shorter operative time and length of hospital stay, reduced intraoperative blood loss and postoperative drainage, less postoperative neck disability, higher daily life quality, better long-term preservation of cervical lordosis and motion, and a lower complication rate.

Objective To design a digital intelligence-driven critical treatment platform to implement integrated treatment procedure inside and outside the hospital and intelligent whole-course managment from pre-hospital emergency care to discharge for critically ill patients.Methods The platform was designed with 5G,IoT,big data and aritificial intelligence techniques and developed with Java language,which adopted Oracle database-based data management and front-end and back-end separation mode,with the front end realized by Vue.js framework and the back end by microservice architecture.There were five functional modules for pre-hospital emergency care,multidisciplinary joint diagnosis and treatment,critical care,quality control management and post-discharge follow-up involved in the platform.Results The platform developed simplified the treatment procedure,enhanced the timeliness of emergency care,decreased the workload of nursing staffs and improved medical service efficiency and working efficiency effectively.Conclusion The platform increases first aid quality and treatment efficiency and provides critically ill patients with high-quality medical experience.[Chinese Medical Equipment Journal,2025,46(1):38-43]

OBJECTIVE: To investigate whether Buyang Huanwu Decoction (BYHWD) had a good curative effect on the neuroprotection of red nucleus neurons after spinal cord injury (SCI) and the possible molecular mechanism. METHODS: Ninety male Sprague-Dawley rats were divided into 5 groups (n=18 per group) according to a random number table, including the control, model, low- (12.78 g/kg, BL group), medium- (25.65 g/kg, BM group), and high-dose BYHWD groups (51.30 g/kg, BH group). A rubrospinal tract transection model in rats was established, and different doses of BYHWD were intragastrically administrated for 4 weeks. The forelimb locomotor function was recorded using the spontaneous vertical exploration test. Cyclic adenosine monophosphate (cAMP) level in red nucleus was detected through an enzyme-linked immunosorbent assay. The morphology and number of red nucleus neurons were observed using Nissl's staining and axonal retrograde tracing by Fluoro-Gold (FG). The expression of cAMP-dependent protein kinase A (PKA), nuclear factor kappa-B (NF-κB) p65, and brain-derived neurotrophic factor (BDNF) in red nucleus were detected using immunohistochemistry and quantitative real-time polymerase chain reaction. RESULTS: Compared with the control group, the utilization rate of bilateral forelimbs, unilateral right forelimbs, proportion of FG-labeled positive neurons, cAMP level, protein expressions of PKA and BDNF, and BDNF mRNA expression were significantly decreased in the model group (P<0.01), while NF-κB p65 was increased in the model group (P<0.01). Compared with the model group, the utilization rate of bilateral forelimbs and unilateral right forelimbs were significantly higher in the BL, BM and BH groups (P<0.01), the proportion of FG-labeled positive neurons, cAMP level, protein expressions of PKA and BDNF and BDNF mRNA expression in all BYHWD groups were increased (P<0.05 or P<0.01), while NF-κB p65 were decreased in all BYHWD groups (P<0.05 or P<0.01). CONCLUSIONS BYHWD possesses a sound neuroprotective effect on red nucleus neurons after SCI, and the efficacy was dose-related. The mechanism may be related to regulating the cAMP/PKA/NF-κ B p65 signaling pathway, finally promoting expression of BDNF.
Animals ; Spinal Cord Injuries/pathology* ; Drugs, Chinese Herbal/therapeutic use* ; Rats, Sprague-Dawley ; Male ; Cyclic AMP/metabolism* ; Transcription Factor RelA/metabolism* ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Signal Transduction/drug effects* ; Brain-Derived Neurotrophic Factor/genetics* ; Red Nucleus/metabolism* ; Recovery of Function/drug effects* ; Neurons/metabolism* ; Rats