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.

This article summarized Professor Rao Xiangrong's experience in the diagnosis and treatment of obesity-related nephropathy.According to Rao,this disease belongs to congenital deficiency and acquired malnutrition,and diet,labor and leisure are out of proportion,resulting in dryness and heat in the middle energizer,excess of yang-ming or concomitant deficiency of the shao-yin,or blood stasis and phlegm obstruction,and blood circulation is out of proportion.In the later stage,turbidity,toxicity,phlegm,and blood stasis coexist.The syndrome belongs to the same disease of middle and lower energizer.Treatment should clear away heat and dryness in the middle energizer,clear phlegm and dampness,remove blood stasis and eliminate turbidity.The prescriptions of modified Yunü Decoction,Dahuang Huanglian Xiexin Decoction,Qingzhong Decoction should be used,with good efficacy.

OBJECTIVE To explore the clinical characteristics of the neonates with early-onset sepsis caused by Listeria monocytogenes and analyze the risk factors for adverse treatment outcomes.METHODS A total of 16 neo-nates with early-onset sepsis caused by L.monocytogenes who were treated in neonatology department of the Affili-ated Suzhou Hospital of Nanjing Medical University from Jan.2012 to Dec.2023 were recruited as the research subjects.The clinical data and the results of laboratory test and drug susceptibility testing were collected from the neonates,and the risk factors for the adverse prognosis were analyzed.RESULTS Totally 14 neonates were born in the hospital,and the incidence rate was 6.7/100,000;13 cases were preterm infants,accounting for 81.25％.The peak of the onset ranged between May and November.Most of the 16 neonates showed clinical symptoms instantly after the birth,and the major manifestations included gasping and moaning(12 cases),hypotonia(11 cases),pale skin(10 cases)and poor response(9 cases).Totally 14 neonates showed the rise of C-reactive protein(CRP)in varying degree within 6 hours after the birth.In terms of the treatment outcomes,9 cases were cured and dis-charged,2 cases were improved and discharged,and 4 cases died.One of another cases was improved and died due to poor prognosis after against-advice discharge.There were significant differences in the decline of base excess,septic shock,use of sensitive antibiotics in early stage,invasive mechanical ventilation and peak value of CRP be-tween the survival group and the death group(P＜0.05).All of the L.monocytogenes were tested resistant to ce-foxitin,6 to ampicillin,6 to vancomycin,8 to linezolid.CONCLUSIONS The early-onset sepsis caused by L.mono-cytogenes is common among the preterm neonates and is prevalent in summer and autumn.Most of the cases show the symptoms instantly after the birth,the clinical manifestations are usually severe,and the mortality rate is high.The pregnant women who are suspected for L.monocytogenes infection before the delivery can be treated with penicillin,the neonates can be treated with the first choice of penicillin or ampicillin,and the severe cases can be treated with combination of vancomycin and linezolid.

Objective:To observe the effects of 12.5% carbohydrate (CHO) solution and medium chain triglycerides (MCT) solutions at various concentrations on gastric emptying, in order to determine the optimal MCT-CHO combination for enhanced recovery after surgery.Methods:This study was a prospective study. Ten healthy volunteers were selected to ingest 400 ml of the following 5 solutions every day: water, 12.5% CHO, 1% MCT, 2% MCT and 4% MCT. According to the above results, the optimal concentration of MCT solution was 2% MCT, showing comparable gastric emptying rate compared with 12.5% CHO solution. On this basis, combinations of MCT and CHO solutions were determined to be 30 energy % (EN%) MCT+70 EN% CHO and 20 EN% MCT+80 EN% CHO according to the energy distribution ratio. Then the volunteers were given 400 ml of the following 4 solutions every day: 12.5% CHO, 2% MCT, 30 EN% MCT+70 EN% CHO (equivalent to 2% MCT+8% CHO), and 20 EN% MCT+80 EN% CHO (equivalent to 4.4% MCT+10% CHO). Gastric emptying during fasting (T m) and immediately (T 1), 30 min (T 2), 60 min (T 3), 90 min (T 4) and 120 min after ingestion (T 5) were observed by antral ultrasonography. The degree of thirst, hunger, and anxiety was assessed by Visual Analogue Scale, and the taste was rated. Results:The gastric emptying rate in descending order was 20%EN MCT+80%EN CHO group>30%EN MCT+70%EN CHO group≈2％MCT group≈12.5%CHO group. There was no significant difference in gastric emptying rate between 30 EN% MCT+70 EN% CHO group and 12.5% CHO group ( P>0.05). The scores of thirst, hunger and anxiety in 30 EN% MCT+70 EN% CHO group at T 1 to T 5 were significantly lower than those at T m ( P<0.05). 30 EN% MCT+70 EN% CHO group showed the highest taste score. Conclusion:30 EN% MCT+70 EN% CHO solution has similar gastric emptying rate compared with 12.5% CHO solution. It can relieve thirst, hunger, anxiety and other subjective feelings caused by fasting, with tastes better than 12.5% CHO solution.

Objective:To observe the effects of 12.5% carbohydrate (CHO) solution and medium chain triglycerides (MCT) solutions at various concentrations on gastric emptying, in order to determine the optimal MCT-CHO combination for enhanced recovery after surgery.Methods:This study was a prospective study. Ten healthy volunteers were selected to ingest 400 ml of the following 5 solutions every day: water, 12.5% CHO, 1% MCT, 2% MCT and 4% MCT. According to the above results, the optimal concentration of MCT solution was 2% MCT, showing comparable gastric emptying rate compared with 12.5% CHO solution. On this basis, combinations of MCT and CHO solutions were determined to be 30 energy % (EN%) MCT+70 EN% CHO and 20 EN% MCT+80 EN% CHO according to the energy distribution ratio. Then the volunteers were given 400 ml of the following 4 solutions every day: 12.5% CHO, 2% MCT, 30 EN% MCT+70 EN% CHO (equivalent to 2% MCT+8% CHO), and 20 EN% MCT+80 EN% CHO (equivalent to 4.4% MCT+10% CHO). Gastric emptying during fasting (T m) and immediately (T 1), 30 min (T 2), 60 min (T 3), 90 min (T 4) and 120 min after ingestion (T 5) were observed by antral ultrasonography. The degree of thirst, hunger, and anxiety was assessed by Visual Analogue Scale, and the taste was rated. Results:The gastric emptying rate in descending order was 20%EN MCT+80%EN CHO group>30%EN MCT+70%EN CHO group≈2％MCT group≈12.5%CHO group. There was no significant difference in gastric emptying rate between 30 EN% MCT+70 EN% CHO group and 12.5% CHO group ( P>0.05). The scores of thirst, hunger and anxiety in 30 EN% MCT+70 EN% CHO group at T 1 to T 5 were significantly lower than those at T m ( P<0.05). 30 EN% MCT+70 EN% CHO group showed the highest taste score. Conclusion:30 EN% MCT+70 EN% CHO solution has similar gastric emptying rate compared with 12.5% CHO solution. It can relieve thirst, hunger, anxiety and other subjective feelings caused by fasting, with tastes better than 12.5% CHO solution.

OBJECTIVE To explore the clinical characteristics of the neonates with early-onset sepsis caused by Listeria monocytogenes and analyze the risk factors for adverse treatment outcomes.METHODS A total of 16 neo-nates with early-onset sepsis caused by L.monocytogenes who were treated in neonatology department of the Affili-ated Suzhou Hospital of Nanjing Medical University from Jan.2012 to Dec.2023 were recruited as the research subjects.The clinical data and the results of laboratory test and drug susceptibility testing were collected from the neonates,and the risk factors for the adverse prognosis were analyzed.RESULTS Totally 14 neonates were born in the hospital,and the incidence rate was 6.7/100,000;13 cases were preterm infants,accounting for 81.25％.The peak of the onset ranged between May and November.Most of the 16 neonates showed clinical symptoms instantly after the birth,and the major manifestations included gasping and moaning(12 cases),hypotonia(11 cases),pale skin(10 cases)and poor response(9 cases).Totally 14 neonates showed the rise of C-reactive protein(CRP)in varying degree within 6 hours after the birth.In terms of the treatment outcomes,9 cases were cured and dis-charged,2 cases were improved and discharged,and 4 cases died.One of another cases was improved and died due to poor prognosis after against-advice discharge.There were significant differences in the decline of base excess,septic shock,use of sensitive antibiotics in early stage,invasive mechanical ventilation and peak value of CRP be-tween the survival group and the death group(P＜0.05).All of the L.monocytogenes were tested resistant to ce-foxitin,6 to ampicillin,6 to vancomycin,8 to linezolid.CONCLUSIONS The early-onset sepsis caused by L.mono-cytogenes is common among the preterm neonates and is prevalent in summer and autumn.Most of the cases show the symptoms instantly after the birth,the clinical manifestations are usually severe,and the mortality rate is high.The pregnant women who are suspected for L.monocytogenes infection before the delivery can be treated with penicillin,the neonates can be treated with the first choice of penicillin or ampicillin,and the severe cases can be treated with combination of vancomycin and linezolid.

This article summarized Professor Rao Xiangrong's experience in the diagnosis and treatment of obesity-related nephropathy.According to Rao,this disease belongs to congenital deficiency and acquired malnutrition,and diet,labor and leisure are out of proportion,resulting in dryness and heat in the middle energizer,excess of yang-ming or concomitant deficiency of the shao-yin,or blood stasis and phlegm obstruction,and blood circulation is out of proportion.In the later stage,turbidity,toxicity,phlegm,and blood stasis coexist.The syndrome belongs to the same disease of middle and lower energizer.Treatment should clear away heat and dryness in the middle energizer,clear phlegm and dampness,remove blood stasis and eliminate turbidity.The prescriptions of modified Yunü Decoction,Dahuang Huanglian Xiexin Decoction,Qingzhong Decoction should be used,with good efficacy.

Objective To investigate the predictive value of combined plasma gluconic acid(GA),fumaric acid(FA),and pseudouridine levels at admission for acute kidney injury(AKI)in elderly patients with acute myocardial infarction(AMI).Methods A total of 78 elderly AMI patients transferred from Emergency Department to Coronary Care Unit in Fuwai Hospital during Decem-ber 2021 and July 2022 were enrolled in this prospective study.They were divided into AKI group(40 cases)and non-AKI group(38 cases)according to whether they developed AKI during hospi-talization.Plasma levels of GA,FA and pseudouridine were quantitatively detected with liquid chromatography-tandem mass spectrometry.ROC curve was plotted to assess the predictive value of these three plasma metabolites for AKI in AMI patients.Multivariate logistic regression analy-sis was applied to analyze the clinical risk factors for AKI.Results There were no statistical differences in the plasma levels of GA,FA and pseudouridine between the AKI group and the non-AKI group(P＞0.05).ROC curve analysis revealed that the plasma levels of the three indicators had no predictive value for the development of AKI in elderly AMI patients(AUC=0.576,95％CI:0.449-0.704,P=0.246;AUC=0.595,95％CI:0.467--0.721,P=0.154;AUC=0.563,95％CI:0.435-0.692,P=0.337).Multivariate logistic regression analysis revealed that left ventricu-lar ejection fraction(LVEF)was an independent predictor for AKI development in elderly AMI patients(OR=0.923,95％CI:0.870-0.978,P=0.007).Conclusion Plasma GA,FA and pseud-ouridine cannot predict the development of AKI in elderly AMI patients,while,LVEF is an inde-pendent predictor for the development.

Objective:To analyze and evaluate the safety and efficacy of a Chinese domestically manufactured Heart Con-type implantable third-generation magnetic and hydrodynamic levitation left ventricular assist device(LVAD) for the treatment of end-stage heart failure(ESHF), by reporting the results of eleven-center clinical trial on 50 cases.Methods:This study was a multicenter clinical trial, designed by means of prospective, multicenter and single-group target value. 50 subjects with ESHF were competitively enrolled and treated with HeartCon as the LVAD in eleven centers. The primary efficacy measure was survival, defined as either the subjects experiencing the transition to heart transplantation(HT) or myocardial recovery assisted by the device within 90 days, or as successfully assisted by the LVAD for full 90 days after implantation. The target survival rate was 60%, other observations included implantation success rate, mortality, pump failure needing replacement or emergency heart transplantation.Results:All enrolled 50 patients received LVAD implantation successfully, 46 survived with the pump for 90 days, 1 patient transitioned to heart transplantation, and 3 patients experienced pump thrombosis, within which 2 patients underwent pump replacement and continued to live with the pump for 90 days, and the other one received emergency heart transplantation. There were no dropout subjects. The survival rate at full 90 days after HeartCon implantation was 100%. The survival rates with pump in the full set analysis and the protocol set analysis were 96.00% and 95.92% respectively, which were higher than the target value of 60%. The differences were both statistically significant( P<0.05). Conclusion:The results of the multicenter clinical trial with the largest sample size in China using domestically manufactured third-generation LVAD has demonstrated that, HeartCon is a safe and effective LVAD to treat ESHF patients.

Objective:To investigate the effects of TYRO protein tyrosine-binding protein(TYROBP)on neuroinflammation and autophagy via the PI3K/AKT signaling pathway in a transgenic APP/ PS1 mouse model of AD. Methods:C57BL/6J, TYROBP-/- and APP/ PS1 transgenic male mice aged 15-month-old were randomly divided into 3 group: the C57BL/6J group, the TYROBP-/- group and the APP/ PS1 group, with 19 in each group.The eight-arm maze test and novel object recognition test were conducted to assess the learning and memory ability of mice.The activation of microglia and NLRP3 inflammasomes were assessed by immunofluorescence.The mRNA levels of TNF-α, IL-6 and IL-1β were measured by real-time PCR, and the protein expression levels of NLRP3, cleaved caspase-1, SQSTM1, LC3B, TYROBP, p-PI3K, PI3K, p-AKT and AKT were assayed by Western blot. Results:Compared with the C57BL/6J group, the learning and memory abilities were significantly decreased(all P<0.05), activated microglia and NLRP3 inflammasomes were increased(all P<0.05), the mRNA and protein expression levels of TNF-α, IL-6, and IL-1β were increased(all P<0.05)and the protein expression levels of LC3B-Ⅱ, SQSTM1, TYROBP, p-PI3K, p-AKT were increased(all P<0.05)in the APP/ PS1 group.Compared with C57BL/6J group, the protein expression levels of TNF-α, IL-6, IL-1β, LC3B Ⅱ, SQSTM1, p-PI3K and p-AKT were decreased(all P<0.05). Conclusions:TYROBP promotes the inflammatory response and inhibits autophagy possibly by activating the PI3K/AKT signaling pathway, thus participating in the occurrence and development of AD.