[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.

ObjectiveTo evaluate the pharmacological effect of Buzhong Yiqitang on brain development in offspring of rats with subclinical hypothyroidism （SCH） during pregnancy and explore its potential mechanism. MethodsForty-eight SPF female SD rats were divided into sham operation group （n=8） and model group （n=40）. The rat model of subclinical hypothyroidism （SCH） was constructed by total thyroidectomy combined with postoperative subcutaneous injection of levothyroxine （L-T₄）. The modeled rats were randomly allocated into model， low-， medium-， and high-dose （5.58， 11.16， 22.32 g∙kg^-1， respectively） Buzhong Yiqitang， and euthyrox （4.5×10^-6 g∙kg^-1） groups， with 8 rats in each group. These rats were co-housed with normal male rats for mating. Drug administration started 2 weeks before pregnancy and continued until delivery. Hematoxylin-eosin staining and Golgi-cox staining were used to observe pathological changes in the hippocampal tissue of offspring rats. Western blot was employed to detect the effects of Buzhong Yiqitang on the protein levels of cytochrome C oxidase subunitⅠ （COX）Ⅰ and COXⅣ in the hippocampal tissue of offspring rats. A colorimetric method was used to measure the mitochondrial adenosine triphosphate （ATP） content in the hippocampal tissue of offspring rats. For in vitro experiments， a hydrogen peroxide （H₂O₂）-induced oxidative damage model was established with rat pheochromocytoma cells （PC12）. Interventions included the DNA methyltransferase inhibitor （SGI-1027）， Buzhong Yiqitang-medicated serum， and euthyrox-medicated serum. The cell counting kit-8 （CCK-8） assay was used to examine the effect of Buzhong Yiqitang on cell proliferation. Immunofluorescence staining was performed to evaluate the effect on tubulin beta 3 class Ⅲ （TUBB3） in PC12 cells. Western blot was employed to assess the effects on the protein levels of DNA methyltransferases （TETs and DNMTs） in PC12 cells. The fluorescent probe 2′，7′-dichlorodihydrofluorescein diacetate （DCFH-DA）， luciferase assay， and JC-1 staining were employed to assess the effects of Buzhong Yiqitang on the levels of reactive oxygen species （ROS） and ATP and the mitochondrial membrane potential in PC12 cells. ResultsCompared with the sham group， the model group showed a reduction in the number of hippocampal neurons， incomplete pyramidal cell bodies， loose arrangement， shortened average dendrite length， decreased dendritic complexity and dendritic spine density， and reduced expression levels of COXⅠ and COXⅣ and content of ATP in the brain tissue （P<0.05， P<0.01）. Compared with the model group， after administration of Buzhong Yiqitang and euthyrox， hippocampal neurons exhibited regular arrangement， complete morphology， extended dendrite， increased dendritic complexity and dendritic spine density， and restored expression levels of COXⅠ and COXⅣ and content of ATP （P<0.05， P<0.01）， with the medium-dose Buzhong Yiqitang group showing the best therapeutic effect. In the PC12 cell model of oxidative damage， Buzhong Yiqitang increased the cell viability （P<0.01）， enhanced neuronal differentiation， down-regulated the expression levels of DNMTs （P<0.05）， up-regulated the expression levels of TETs （P<0.05）， decreased the ROS content （P<0.01）， and restored the ATP content and mitochondrial membrane potential （P<0.01）. ConclusionBuzhong Yiqitang protects brain development in offspring of pregnant rats with SCH. It mainly acts on the oxidative stress and mitochondrial dysfunction resulted from abnormal mtDNA methylation， with DNMTs and TETs as the key proteins for its effects.

This study employs ultra-performance liquid chromatography(UPLC) to analyze the differences in alkaloid content of Commelina communis from various geographical origins, exploring its feasibility as a quality evaluation indicator. A total of 57 batches of C. communis samples from 23 provinces, autonomous regions, and municipalities in China were selected. The MicroPulite HSS T3(2.1 mm×50 mm, 1.8 μm)column was used with a mobile phase of acetonitrile-0.2% phosphoric acid aqueous solution(20∶80), detection wavelength at 254 nm, and a flow rate of 0.3 mL·min~(-1) to measure the content of 1-deoxynojirimycin(DNJ) and deoxymannojirimycin(DMJ). The MicroPulite XP tC_(18)(2.1 mm×100 mm, 1.7 μm)column was employed with a mobile phase of acetonitrile-0.2% phosphoric acid aqueous solution(4∶96), detection wavelength at 254 nm, and a flow rate of 0.4 mL·min~(-1) to measure the content of norharmine(NHM) and harmanme(HM). Chemometric methods were applied to study the relationships and differences among the 57 batches of C. communis. Significant differences in alkaloid content were observed among C. communis from different regions, with the average total content decreasing in the order of North China, Northeast China, Northwest China, East China, Southwest China, Central China, and South China. Cluster analysis(CA) and principal component analysis(PCA) further revealed the quality differences of C. communis from various origins, and partial least squares discriminant analysis(PLS-DA) identified DNJ as a marker compound to distinguish the quality differences between different geographical sources of C. communis. It is recommended that the content limit of DNJ be set at no less than 0.055 9%, providing a reference for the quality evaluation and clinical application of C. communis medicinal materials.
Alkaloids/analysis* ; Drugs, Chinese Herbal/chemistry* ; China ; Chromatography, High Pressure Liquid ; Chemometrics/methods* ; Quality Control

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in "cold" tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.

Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To investigate the role of solute carrier family 7 member 11(SLC7A11)in the pathogenesis and progression of clear cell renal cell carcinoma(ccRCC)and its prognostic significance.Methods Mendelian randomization analysis was employed to identify genes causally associated with the risk of ccRCC.The expression patterns and prognostic relevance of SLC7A11 were assessed using RNA sequencing data and clinical information obtained from the UCSC Xcna pan-cancer cohort.Gene set enrichment analysis(GSEA)was conducted using data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma(TCGA-KIRC)dataset(training set).A prognostic model based on SLC7A11 was then developed using stepwise Cox regression and validated externally in the E-MTAB-1980 cohort(validation set).Results Elevated level of SLC7A11 was associated with an increased risk of ccRCC(HR=1.27,95％CI:1.15-1.40,P＜0.001).SLC7A11 was overexpressed in various tumors and correlated with higher T stage and poorer survival(P＜0.05).GSEA demonstrated that SLC7A11 was enriched in pathways related to proliferation and metastasis,including E2F and epithelial-to-mesenchymal transition signaling pathways.Moreover,the SLC7A11 prognostic model exhibited robust predictive performance in both the training set(1-,3-,and 5-year AUC=0.78,0.73,0.71,respectively)and the external validation set(1-,3-,and 5-year AUC=0.70,0.71,0.72,respectively).Conclusion SLC7A11 can be a potential biomarker and therapeutic target for ccRCC,offering novel perspectives for precision medicine.

Objective To explore the characteristics of blood pressure in the elderly patients with hypertensive cerebral small vessel disease(CSVD)and their correlation with traditional Chinese medicine(TCM)syndrome types.Methods A retrospective analysis was conducted in 189 elderly patients with essential hypertension.With reference to the presence or absence of CSVD,the patients were divided into CSVD group(87 cases)and non-CSVD group(102 cases).The blood pressure related parameters and clinical data obtained by four diagnostic methods of TCM in the two groups were collected,and then the characteristics of blood pressure and their correlation with TCM syndromes were analyzed with statistical methods.Results(1)CSVD group had higher values than non-CSVD group in the ambulatory blood pressure parameters of 24-hour systolic blood pressure(24hSBP),24-hour diastolic blood pressure(24hDBP),daytime systolic blood pressure(DSBP),daytime diastolic blood pressure(DDBP),nighttime systolic blood pressure(NSBP),nighttime diastolic blood pressure(NDBP),24-hour pulse pressure(24hPP),daytime pulse pressure(DPP),nighttime pulse pressure(NPP),maximum SBP,morning SBP,daytime SBP load and nighttime SBP load(P＜0.01).(2)The analysis of blood pressure variability showed that the mean value of nighttime SBP standard deviation(NSSD)in CSVD group was higher than that in the non-CSVD group(P＜0.01).(3)The analysis of circadian rhythm of blood pressure showed that there was significant difference in the comparison of circadian rhythm of ambulatory blood pressure between the two groups(P＜0.05):non-CSVD group was predominated by non-dipper type blood pressure(50 cases,49.02%)and dipper type blood pressure(31 cases,30.39%),and CSVD group was predominated by non-dipper type blood pressure(38 cases,43.68%)and super-dipper type blood pressure(31 cases,35.63%).(4)Logistic regression analysis showed that 24hSBP(OR=1.296,95%CI:1.112-1.511),maximum SBP(OR=1.074,95%CI:1.006-1.146),morning SBP(OR=1.064,95%CI:1.013-1.118),abnormal circadian rhythm of blood pressure(OR=3.736,95%CI:1.663-8.390)were the influence factors of CSVD(P＜0.05 or P＜0.01).(5)The analysis of the distribution of TCM syndrome types showed that non-CSVD group was dominated by accumulation of excess phlegm-damp syndrome(58.82%)and yin deficiency and yang hyperactivity syndrome(21.57%),and CSVD group was dominated by yin deficiency and yang hyperactivity syndrome(51.72%)and accumulation of excess phlegm-damp syndrome(21.84%).(6)The analysis of blood pressure in patients with various syndrome types showed that the DPP of patients with accumulation of excess phlegm-damp syndrome in the CSVD group was significantly higher than that in the non-CSVD group(P＜0.01),and the 24hDBP and NDBP of patients with yin deficiency and yang hyperactivity syndrome in the CSVD group were significantly higher than those in the non-CSVD group(P＜0.01).Conclusion It is indicated that 24hSBP,maximum SBP,elevated morning SBP,and abnormal blood pressure circadian rhythms may be the important risk factors for the hypertensive CSVD in the elderly.Elderly hypertensive patients with accumulation of excess phlegm-damp syndrome should pay more attention to the mean daytime pulse pressure,and elderly hypertensive patients with yin deficiency and yang hyperactivity syndrome should pay more attention to monitoring DBP.The dynamic observation and early control of the blood pressure is helpful for the prevention and treatment of CSVD in the elderly patients with hypertension.