Objective:To investigate the efficacy of Balanophora involucrata Hook.f.in treatment of hyperuricemia(HUA)based on network pharmacology,molecular docking,and hyperuricemia models in vivo and in vitro,and to clarify the main targets of its active components and related signaling pathway mechanism.Methods:The potential targets of Balanophora involucrata Hook.f.in treatment of HUA were identified by Databases such as the Traditional Chinese Medicine Database in Taiwan,the Chinese Herbal Medicine Identification Database,Professional Chemical Database,TargetNet Database,SwissTargetPrediction Database,GeneCards,Therapeutic Target Database(TTD),DrugBank Database,DisGeNET Database,Online Mendelian Inheritance in Man(OMIM)Database,and Venny Database.STRING Database and Cytoscape software were used to construct the active component-predictive target network and protein-protein interaction(PPI)network for Balanophora involucrata Hook.f.;topological analysis was used to select the main active components and core targets;Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed by R software;AutoDock Vina software was used for molecular docking validation.The NRK-52E cells were divided into blank control group,blank administration group,model group,and different concentrations(2.0,10.0,and 50.0 μmol·L-1)of erythrodiol(EDT)groups.High-performance liquid chromatography culture(HPLC)was used to detect the uric acid(UA)levels in the cell culture supernatants in various groups.The male ICR mice were divided into blank control group,blank administration group,model group,and EDT group;the mice in the last two groups were used to prepare the HUA models;kits were used to detect the levels of UA,creatinine(Cr),and blood urea nitrogen(BUN)in serum of the mice in various groups;the bilateral kidney tissue of the mice was harvested and weighed;the kidney indexes of the mice in various groups were calculated;TUNEL staining was used to observe the apoptosis in kidney tissue of the mice in various groups;Western blotting method was used to detect the expression levels of protein kinase B(AKT),phosphorylated AKT(p-AKT),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and matrix metalloproteinase-9(MMP-9)proteins in kidney tissue of the mice in various groups.Results:Six active components of Balanophora involucrata Hook.f.were identified,involving 116 intersecting targets and 14 core targets.The enrichment analysis yielded 1 828 GO terms and 145 signaling pathways.The molecular docking results showed that EDT had good binding activity with MMP-9.The high uric acid cell experiment results showed that compared with blank control group,the UA level in the cells in model group was significantly increased(P<0.01);compared with model group,the UA levels in the cells in 2.0,10.0,and 50.0 μmol·L-1 EDT groups were significantly decreased(P<0.01).Compared with blank control group,the levels of UA,Cr,and BUN in serum of the mice in model group were increased(P<0.01),and the kidney indexes were significantly increased(P<0.01);compared with model group,the levels of UA,Cr,and BUN in serum of the mice in EDT group were decreased(P<0.05 or P<0.01),and the kidney index was significantly decreased(P<0.05 or P<0.01).Compared with blank control group,the number of apoptotic cells in kidney tissue of the mice in model group was increased;compared with model group,the number of the apoptotic cells in kidney tissue of the mice in EDT group was significantly decreased.Compared with blank control group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in model group were significantly decreased(P<0.05 or P<0.01),while the expression levels of Bax and MMP-9 proteins were significantly increased(P<0.01);compared with model group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in EDT group were significantly increased(P<0.05 or P<0.01),and the expression levels of Bax and MMP-9 proteins were significantly decreased(P<0.01).Conclusion:The active component of Balanophora involucrata Hook.f.,EDT,has a UA-decreasing effect and may inhibit the apoptosis and alleviate the kidney injury by activating the PI3K/AKT signaling pathway.

Objective:To explore the prognostic factors associated with clear cell adenocarcinoma (CCAC) of the uterine cervix based on data in the Surveillance, Epidemiology and End Results (SEER) database.Methods:Clinical data were collected from 431 patients with confirmed CCAC in the SEER database from 1976 to 2017. Survival analysis was performed using the Kaplan-Meier method with log-rank test for comparison between subgroups. Cox proportional hazards model was used to analyze the influencing factors of overall survival (OS).Results:The median age [ M ( Q1, Q3)] of 431 patients was 54 years old (40 years old, 71 years old); there were 333 cases (77.3%) of whit. The median OS time of 431 patients was 93 months (95% CI: 47-148 months), and the 1-, 2-, and 5-year OS rates were 80.1%, 65.8% and 54.2%, respectively. The median OS time was not reached in patients with American Joint Committee on Cancer (AJCC) stage Ⅰ, 83 months (95% CI: 21-144 months) for stage Ⅱ, 32 months (95% CI: 16-47 months) for stage Ⅲ, and 9 months (95% CI: 5-13 months) for stage Ⅳ ( P < 0.001). Median OS time was not reached in patients with SEER stage of localized lesions, 46 months (95% CI: 8-83 months) for regional lesions stage, and 9 months (95% CI: 5-12 months) for distant metastases stage ( P < 0.001). Of the patients with clear AJCC staging and some with unspecified AJCC staging, 118 received surgical treatment alone and 119 received postoperative radiotherapy, the median OS time of the two groups was 443 months (95% CI: 162-723 months) and 102 months (95% CI: 75-129 months), and the difference in OS between the two groups was statistically significant ( P < 0.001). Among the patients with AJCC stage Ⅰ, the 5-year OS rates in surgery-only group and postoperative radiotherapy group were 82.5% and 78.5%, the stage Ⅱ were 80.0% and 52.3%, and the stage Ⅲ were 27.8% and 63.3%, respectively; the differences in OS between different stages were not statistically significant (all P>0.05). Among the patients with SEER localized lesions stage, the 5-year OS rates in surgery-only group and postoperative radiotherapy group were 88.9% and 73.1%, and the difference was statistically significant ( P = 0.012); the regional lesions stage were 45.5% and 60.0%, and the difference was not statistically significant ( P = 0.568). The results of multivariate Cox regression analysis showed that AJCC staging (stage Ⅰ vs. stage Ⅳ, HR = 0.281, 95% CI: 0.178-0.543, P < 0.001; stage Ⅱ vs. stage Ⅳ, HR = 0.347, 95% CI: 0.113-0.439, P < 0.001; stage Ⅲ vs. stage Ⅳ, HR = 0.399, 95% CI: 0.030-0.145, P < 0.001), SEER staging (localized lesions stage vs. distant metastases stage, HR = 0.104, 95% CI: 0.059-0.182, P < 0.001; regional lesions stage vs. distant metastases stage, HR = 0.301, 95% CI: 0.195-0.463, P < 0.001) and whether or not receive surgery (yes vs. no, HR = 0.359, 95% CI: 0.241-0.535, P < 0.001) were independent influencing factors of OS in CCAC patients. Conclusions:AJCC staging, SEER staging and surgery are independent influence factors for OS in patients with CCAC, and postoperative radiotherapy may not provide more survival benefit.

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.

To investigate the role of the nucleotide-binding domain and leucine-rich-repeat-contai-ning family member X1(NLRX1)in the replication of Newcastle disease virus(NDV),the ex-pression level of NLRX1 was examined following infection of 10-day-old specific pathogen-free(SPF)chicks and HD11 cells with the NDV NA-1 strain.Additionally,the proliferation of NDV,the expression of pro-inflammatory cytokines in HD11 cells,and the oxidative stress status were e-valuated in the presence of either overexpressed or underexpressed NLRX1.The results demonstra-ted that NA-1 infection led to an increase in NLRX1 expression both in vivo and in vitro.Further-more,overexpression of NLRX1 inhibited viral proliferation,enhanced the expression of cellularIL-1β,IL-6,and IFN-β,without affecting levels of autophagy or apoptotic cells.However,NLRX1 elevation resulted in elevated mRNA levels of iNOS,Keap1,Nrf2,NQO1,and HO-1 within 24 h.In conclusion,NLRX1 suppresses NDV proliferation by promoting early ROS production.

Objective:To analyze the effectiveness and safety of the second course radiotherapy for unresectable colorectal cancer liver metastases.Methods:We retrospectively collected the data of 28 patients with unresectable colorectal cancer liver metastases who received the second course radiotherapy at Peking University Cancer Hospital and Institute from 2017 to 2023, to analyze the feasibility of re-irradiation.Results:For the 28 patients, the median follow-up time after re-irradiation was 20.2 months. The median time interval between the first- and second-course radiotherapy was 11.1 months. The median biologically effective doses of the first- and second-course radiotherapy were 100 Gy and 96 Gy, respectively. Stereotactic body radiotherapy was administered to 25 patients (89.3%) during the first course and 24 patients (85.7%) during the second course of radiotherapy. The mean equivalent dose in 2 Gy fractions to the normal liver was 10.1 Gy in the first-course radiotherapy and 7.9 Gy in the second-course radiotherapy. The complete response rate, partial response rate, and objective response rate after re-irradiation were 54.5%, 18.2%, and 72.7%, respectively. After re-irradiation, the 2-year cumulative local failure rate was 17.0% when calculated based on patients and 15.1% when calculated based on lesions, the 1-year progression-free survival rate was 27.4%, and the 3-year overall survival rate was 46.7%. The second-course radiotherapy was well tolerated, with most patients (75.0%) experiencing grade 1-2 acute adverse reactions and only one case (3.6%) experiencing grade 3 acute adverse events.Conclusions:Second course radiotherapy is an effective and safe treatment approach for selected patients with unresectable colorectal cancer liver metastases.

Background: Arctic-like (AL) lineages of rabies viruses (RABVs) remains endemic in some Arctic and Asia countries. However, their evolutionary dynamics are largely unappreciated. Objectives: We attempted to estimate the evolutionary history, geographic origin and spread of the Arctic-related RABVs. Methods: Full length or partial sequences of the N and G genes were used to infer the evolutionary aspects of AL RABVs by Bayesian evolutionary analysis. Results: The most recent common ancestor (tMRCA) of the current Arctic and AL RABVs emerged in the 1830s and evolved independently after diversification. Population demographic analysis indicated that the viruses experienced gradual growth followed by a sudden decrease in its population size from the mid-1980s to approximately 2000.Genetic flow patterns among the regions reveal a high geographic correlation in AL RABVs transmission. Discrete phylogeography suggests that the geographic origin of the AL RABVs was in east Russia in approximately the 1830s. The ancestral AL RABV then diversified and immigrated to the countries in Northeast Asia, while the viruses in South Asia were dispersed to the neighboring regions from India. The N and G genes of RABVs in both clades sustained high levels of purifying selection, and the positive selection sites were mainly found on the C-terminus of the G gene. Conclusions The current AL RABVs circulating in South and North Asia evolved and dispersed independently.

Objective:To translate the Cardiac Symptom Survey and analyze its reliability and validity in the post-valvular heart replacement survey and to provide the basis for the clinical application of this scale.Methods:The symptoms of 233 patients after heart valve replacement were investigated in Suining Central Hospital by Chinese version of the Cardiac Symptom Survey. The reliability of the scale was evaluated by Cronbach'α coefficient and the split half coefficient, the validity of the scale was evaluated by exploratory factor analysis and content validity index.Results:The internal consistency coefficient of the Chinese version of the Cardiac Symptom Survey ranged from 0.875 to 0.968, both above 0.870.The split half coefficient was 0.699,which demonstrated better internal consistency.The content validity index of the Chinese version of the Cardiac Symptom Survey ranged from 0.84 to 1.00.Factor analysis got five factors, which explained 68.133% of the total variance.Conclusions:The Chinese version of the Cardiac Symptom Survey has good reliability and validity in the investigation of the symptoms of patients after heart valve replacement, and can be used for the investigation and management of the symptoms of patients after heart valve replacement.

Objective:To investigate the expression and clinical significance of oxidized low density lipoprotein receptor 1 (OLR1) in gastric cancer.Methods:In gastric cancer tissues and adjacent tissues, the relationship between the expression of OLR1 and the stage and clinical prognosis of gastric cancer was analyzed from the Gene Expression Profiling Interactive Analysis (GEPIA) database and Kaplan-Meier Plotter online database. We collected 6 case of fresh gastric cancer tissues and adjacent tissues of patients undergoing radical gastrectomy in our hospital from October 2018 to December 2018, The extracted RNA were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) to verify the expression in gastric cancer and adjacent tissues. From January 2012 to January 2014, 36 patients with pathological biopsy specimens of radical gastrectomy in our hospital were examined. Immunohistochemistry was used to confirm the correlation between protein expression level of OLR1 in gastric cancer and paracancerous tissues and clinical pathological stage and prognosis.Results:GEPIA database and Kaplan-Meier Plotter online database analysis showed that OLR1 mRNA was highly expressed in various cancer tissues and significantly higher in gastric cancer tissues than normal tissues ( P<0.05). High expression of OLR1 mRNA is associated with clinical stage and poor prognosis of gastric cancer; qRT-PCR results showed that OLR1 mRNA was highly expressed in gastric cancer tissues; the results of immunohistochemistry showed that the staining score of OLR1 in gastric cancer tissues was significantly higher than that in adjacent tissues ( P<0.001), and its expression level was correlated with depth of tumor invasion and clinical tumor node metastasis (TNM) stage (both P<0.05). Kaplan-Meier survival analysis showed that the expression level of OLR1 was associated with poor prognosis in patients. The median survival time was 18 months in OLR1 high expression group and 30 months in OLR1 low expression group, with statistically significant difference ( P=0.016). Conclusions:OLR1 is highly expressed in gastric cancer tissues, and its expression level is associated with tumor progression and poor prognosis.

Objective:To report a pediatric organ donor with brain death due to wild mushroom poisoning to examine whether or not brain death caused by mushroom poisoning might become a potential organ donor and how to evaluate donated organs.Methods:Strict clinical observations, laboratory tests and biopsy were performed for potential donor.Results:This donor's clinical changes were consistent with toxic hepatitis. Gross morphology, laboratory examinations and pathological biopsy of two kidneys were generally normal during organ acquisition. Two kidneys were assigned to two adult recipients and liver was discarded. After a follow-up period of 6 months, one recipient recovered well while another gradually recovered after delayed graft function.Conclusions:This extraordinary case provides some references for selecting potential donors of mushroom poisoning. When the donor's relevant laboratory tests are normal, there is no pathological contraindication, sufficient time is available for estimating the type of mushroom poisoning, observing the trends of organ damage and waiting for the toxin clearance, donor with brain death from wild mushroom poisoning may donate organ.

Objective:To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer.Methods:A prospective single arm phase Ⅱ trial developed at Department of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute was preliminarily analyzed. Subjects were enrolled from August 2016 to January 2019. Low-risk rectal cancer with following MRI features were recruited: mid-low tumor, mrT2-3b, MRF (-), EMVI (-), CRM (-), differentiation grade 1-3. Patients received intensity-modulated radiotherapy (IMRT) 50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR confirmed by physical examination, rectal MRI, endoscopy, and serum CEA were recommended for watch & wait approach or local excision (LE). The main study outcomes were 2-year organ preservation rate (OPR) and sphincter preservation rate (SPR).Results:Thirty-eight patients were eligible for analysis, including 24 males and 14 females with median age of 56 years; 9 cases of mrT2 (23.7%), 14 cases of mrT3a (36.8%) and 15 cases of mrT3b (39.5%); 5 cases of well differentiated adenocarcinoma (13.2%), 32 cases of moderately differentiated adenocarcinoma (84.2%) and 1 case of mucinous adenocarcinoma (2.6%). Carcinoemobryonic antigen (CEA) was elevated before treatment in 1 case. One case (2.6%) of grade 3 radiation dermatitis occurred during IMRT; 18 cases (47.4%) occurred grade 3 to 4 adverse events during consolidation chemotherapy. After total neoadjuvant treatment, the cCR and near-cCR rates were 42.1% (16/38) and 23.7% (9/38), respectively, while non-cCR rate was 34.2% (13/38). Twenty patients (20/38, 52.6%) of cCR or near-cCR underwent watch & wait approach, with a local regrowth rate of 20% (4/20). Four patients received LE, including one salvage LE. Thirteen patients (4 were ypCR) received radical resection, including 10 cases of initial low anterior resections (LAR), 1 cases of initial abdominal perineal resection (APR) and 2 cases of salvage LAR, four patients refused operation. The median follow-up time was 23.5 (8.5-38.3) months. At the last interview of follow-up, the OPR and SPR were 52.6% (20/38) and 84.2% (32/38), respectively. Only one patient developed lung metastasis and no local recurrence occurred after radical resection or LE.Conclusion:Total neoadjuvant treatment for low-risk rectal cancer achieves high cCR/near-cCR rate, with increased probability of receiving watch and wait approach and organ preservation in this subgroup.