[Objective] To establish a new scoring system to predict the perioperative outcomes (operation time, intraoperative blood loss, and trifecta achievement) in patients undergoing robot-assisted partial nephrectomy (RAPN) by integrating the RENAL and Mayo adhesive probability (MAP) scores. [Methods] Clinical data of 178 patients with renal cell carcinoma who underwent RAPN performed by the same surgeon in our hospital during Jan.2015 and Jan.2022 were retrospectively analyzed.The RENAL and MAP scores of all patients were calculated.Linear regression and logistic regression were used to evaluate the associations between the components of the RENAL and MAP scores (a total of 6 variables) and perioperative outcomes.The factors with significant associations were then included into logistic regression analysis to identify independent predictors for constructing an assessment system for perioperative outcomes, and the receiver operating characteristic (ROC) curve was plotted to calculate the area under the curve (AUC) to predict its efficacy. [Results] Multivariate linear regression analysis showed that tumor size (β=6.14, 95%CI: 1.93—10.34, P=0.004), exophytic rate (β=10.60, 95%CI: 3.44—17.76, P=0.004), and perinephric fat thickness (β=16.48, 95%CI: 8.52—24.45, P<0.001) were significantly associated with operation time.Tumor size (β=10.55 95%CI: 5.60—15.49, P<0.001) was associated with both intraoperative blood loss and trifecta achievement (OR=1.73, 95%CI: 1.26—2.36, P=0.001). Multivariate logistic regression analysis of these 3 factors identified tumor size (OR=9.07, 95% CI: 1.18—69.45, P=0.03) and perinephric fat thickness (OR=2.28, 95%CI: 1.86—6.04, P=0.01) as independent predictors of perioperative outcomes.Based on these findings, the tumor size and perinephric fat thickness (RP) scoring was constructed, which demonstrated better predictive ability than RENAL score or MAP score alone (RP vs.RENAL vs.MAP: 0.766 vs.0.548 vs.0.684). [Conclusion] The RP score includes fewer variables than the RENAL and MAP scores but outperforms them.

Traditional Chinese medicine （TCM） therapy has unique clinical advantages in the treatment of atrial fibrillation， mainly reflected in five aspects， improving quality of life， enabling early diagnosis and treatment， promoting cardiac rehabilitation， making up for the limitations of Western medicine， and improving the success rate of catheter ablation. However， there is insufficient evidence in current clinical research. Based on the current status of TCM research in the treatment of atrial fibrillation， it is suggested that future studies should focus on standardized research on syndrome differentiation and classification. This can be achieved through clinical epidemiological surveys， expert consensus， and other methods to establish a unified syndrome differentiation and classification standard for atrial fibrillation. Clinical efficacy evaluation indicators should be standardized， and core outcome measures for clinical research on TCM treatment of atrial fibrillation should be developed through systematic reviews， patient interviews， and other methods. Additionally， clinical research design， implementation， and data management should be improved. By leveraging modern information technologies such as artificial intelligence， the scientific and standardized nature of TCM intervention research on atrial fibrillation can be enhanced， ultimately improving the quality of research.

Objective:To explore the influencing factors of swallowing function after stroke based on the semi-quantita-tive assessment of the videofluoroscopic dysphagia scale(VDS),to provide a basis for clinical screening and treatment.Method:A retrospective survey method was conducted on 120 stroke patients who met the inclusion criteria.Clinical characteristics were collected,including gender,age,type of stroke,lesion location,disease duration,food consistency,nasogastric tube placement,tracheostomy,and comorbidities.All patients underwent a video-fluoroscopic swallowing study(VFSS),and swallowing function was assessed using the videofluoroscopic dys-phagia scale(VDS).Univariate and multivariate linear regression analyses were conducted to examine the ef-fects of clinical characteristics on oral phase,pharyngeal phase,and global swallowing function.Result:Univariate analysis revealed that subcortical lesions in the middle cerebral artery(MCA)region(ex-cluding the basal ganglia)(P＜0.001),basal ganglia lesions(P=0.040),and medullary lesions(P＜0.001)were significantly associated with global swallowing function after stroke.Multivariate linear regression analysis indi-cated that medullary lesions(P＜0.001),subcortical lesions in the MCA region(excluding the basal ganglia)(P＜0.001),and MCA(including basal ganglia)lesions(P=0.019)were risk factors for global swallowing function after stroke.Regarding food consistency,consumption of thickened liquids(P=0.018)and pureed foods(P=0.006)were protective factors for global swallowing function.Subgroup analysis of global swallow-ing function revealed that MCA(including basal ganglia)lesions(P=0.003),female gender(P＜0.001)and tra-cheotomy(P＜0.001)were risk factors for oral phase swallowing function after stroke.Compared with patients without a gastrostomy tube,those with a gastrostomy tubes(P=0.034)had less effect on swallowing function in the oral phase.Compared with hemorrhagic stroke,ischemic stroke(P＜0.001)had a less impact on the oral phase swallowing function.Medullary lesions(P＜0.001)and subcortical lesions in the MCA region(ex-cluding the basal ganglia)(P＜0.001)were risk factors for pharyngeal phase swallowing function.For food con-sistency,the consumption of thickened liquids(P=0.005)and pureed foods(P=0.002)were protective factors for pharyngeal phase swallowing function after stroke.Conclusion:Identifying clinical characteristics in the assessment of swallowing function in stroke patients helps to determine the type of dysphagia and the key points of treatment.This approach may facilitate the de-velopment and implementation of more targeted rehabilitation treatment plans,and accelerate the recovery of swallowing function and feeding ability in stroke patients.

Investigated the mechanisms by which baicalein regulates nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)to ameliorate lipopolysaccharide(LPS)-induced sepsis-asso-ciated acute kidney injury(AKI)in mice.Sixty male C57BL/6 mice were randomly divided into six groups:control,model,low-dose baicalein(50 mg/kg),medium-dose baicalein(100 mg/kg),high-dose baicalein(200 mg/kg),and high-dose baicalein+brusatol(4 mg/kg).Baicalein was adminis-tered orally for 7 days as a preventative measure.Sepsis was induced via intraperitoneal injection of LPS.Murine sepsis score(MSS)was assessed within 12 hours post-induction.Serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an automatic biochemical analyzer and enzyme-linked immunosorbent assays(ELISA),respectively.Histopathological changes in kidney tissues were ob-served via hematoxylin-eosin(HE)staining.Western blot analysis was employed to determine the protein expression levels of Nrf2,HO-1,caspase-8,TNF-α,IL-1β,and IL-6 in kidney tissues.Additionally,total superoxide dismutase(SOD)activity in kidney tissues was assessed using com-mercially available kits.Compared to the model group,baicalein treatment significantly improved renal histopathological changes,alleviated cellular damage,and reduced the levels of inflammatory cytokines(TNF-α,IL-1βand IL-6)(P＜0.01)and kidney injury markers(Scr and BUN)(P＜0.01).Moreover,baicalein treatment significantly increased the protein expression levels of Nrf2 and HO-1(P＜0.01)and enhanced antioxidant enzyme activity.In conclusion,baicalein may pro-tect against LPS-induced sepsis-associated AK1 in mice by modulating the Nrf2/HO-1 signaling pathway,thereby attenuating oxidative stress,reducing inflammation,and disrupting the vicious cycle between inflammation and oxidative stress.

Objective:To evaluate the safety and clinical efficacy of enteral nutrition (EN) initiated within 24 h after heart transplantation in pediatric patients.Methods:A retrospective cohort study was conducted. Clinical data from 16 pediatric heart transplant recipients at the Seventh Medical Center of the Chinese People′s Liberation Army General Hospital between October 2022 and October 2024 were collected, including demographics, anthropometric measurements, biochemical markers, cytokine levels, and clinical outcomes. Based on the timing of EN initiation, the patients were divided into EN-initiated within 24 h and EN-initiated after 24 h 2 groups. Demographic data, preoperative extracorporeal membrane oxygenation (ECMO) support, physical examination indicators, laboratory parameters, and cytokine levels were compared between groups using independent samples t-test, Mann-Whitney U test, Fisher′s exact probability test. Results:The cohort comprised 16 patients (10 males and 6 females) with an age of (12.5±1.9) years. The EN-initiated within 24 h group comprised 6 cases, and the EN-initiated after 24 h group comprised 10 cases. No significant difference was observed between the two groups in age, preoperative body mass index Z-score, preoperative ECMO support, physical examination indicators, laboratory parameters (total protein, albumin, hemoglobin), or cytokine levels (all P>0.05). Compared to the EN-initiated after 24 h group, the EN-initiated within 24 h group exhibited a shorter intensive care unit stay ( t=2.65, P<0.05) and shorter mechanical ventilation duration ( t=2.23, P<0.05) than EN-initiated after 24 h group. Total hospitalization length had no significant difference ( P>0.05). At 72 h post-transplant, the EN-initiated within 24 h group had a lower interleukin-12 P70 ( t=2.46, P<0.05) and interferon-γ levels ( t=2.55, P<0.05) than EN-initiated after 24 h group. Prior to discharge, the EN-initiated within 24 h group has a lower mean skinfold thickness ( t=2.49, P<0.05) and lower mid-upper arm circumference ( t=2.36, P<0.05) compared with the EN-initiated after 24 h group. Conclusions:Initiating EN within 24 h postoperatively is safe and feasible in pediatric heart transplant recipients. Early EN may shorten the length of intensive care unit stay and mechanical ventilation while attenuating postoperative release of inflammatory cytokine.

Objective:To determine whether spinal cord injury (SCI) triggers secondary neuroinflammation and neuronal injury in remote brain regions by impairing the drainage function of the meningeal lymphatic vessels (MLVs).Methods:Fifty-two female C57BL/6 mice were assigned with the random number table into four groups ( n=13 per group): sham group, SCI group, adeno-associated virus negative control group (negative control group), and adeno-associated virus overexpressing VEGF-C group (VEGF-C group). The sham group underwent laminectomy without spinal cord injury. In the SCI group, negative control group and VEGF-C group, T 9 contusion was made to establish the SCI models using a modified Allen′s impactor. At 4 weeks before SCI modeling, the negative control group and VEGF-C group were injected via the cisterna magna with 3 μl adeno-associated virus for negative control or adeno-associated virus for VEGF-C overexpression. At 56 days after injury, Alexa Fluor? 647 ovalbumin conjugate (OVA-647) was injected via the cisterna magna as a tracer. Two hours later, the proportion of OVA-647 in the deep cervical lymph nodes (dCLN) was detected. Immunofluorescence was performed to assess the proportion of MLVs marker lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and expression levels of microglial marker ionized calcium-binding adaptor molecule 1 (Iba1) in the cerebral cortex, hippocampus, midbrain, and thalamus across the experimental groups. ELISA was employed to quantify the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and Nissl staining was used to assess neuronal counts in these regions. Results:At 56 days after injury, the OVA-647 proportion in the dCLN was higher in the sham group than that in the SCI group and negative control group ( P<0.01), whereas the SCI group and negative control group showed a lower OVA-647 proportion in the dCLN than the VEGF-C group ( P<0.05). At 56 days after injury, the dural LYVE-1 proportion was higher in the sham group than that in the SCI group and negative control group ( P<0.01), whereas it was lower in the SCI group and negative control group than that in the VEGF-C group ( P<0.05). At 56 days after injury, the count of Iba1-positive microglia across all the above-mentioned regions was increased in the SCI group and negative control group ( P<0.01), compared with that in the sham group, whereas it was reduced in these regions in the VEGF-C group, compared with that in the SCI group and negative control group ( P<0.01). At 56 days after injury, TNF-α and IL-1β levels in these regions were both elevated in the SCI group and negative control group when compared with those in the sham group ( P<0.05), whereas they were reduced in the VEGF-C group, compared with those in the SCI group and negative control group ( P<0.05). At 56 days after injury, neuronal survival in the regions was decreased in the SCI group and negative control group, compared with that in the sham group ( P<0.05), whereas it was increased in the VEGF-C group, compared with that in the SCI group and negative control group ( P<0.05). Conclusion:SCI can induce secondary neuroinflammation and neuronal damage in remote brain regions by impairing the drainage function of MLVs.

Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Drug-induced liver injury(DILI)is a common adverse drug reaction in clinical practice,which can lead to acute liver failure and even death in severe cases.In recent years,with the continuous introduction of new drugs and the expansion of their usage,the incidence and mortality rates of DILI have shown an upward trend,posing significant challenges to public health and clinical treatment.Macrophages,as a crucial component of the innate immune system,exhibit high plasticity and heterogeneity.They can polarize into pro-inflammatory M1 type or anti-inflammatory M2 type in response to microenvironmental signals.Research has demonstrated that macrophage polarization plays a central regulatory role in the occurrence and progression of DILI by influencing various processes such as inflammatory responses,cell apoptosis,and tissue repair.This review focuses on elucidating the regulatory mechanisms and roles of macrophage polarization in DILI,providing a theoretical framework for developing precise immunotherapeutic strategies.