Objective To evaluate the value of postoperative radiotherapy (PORT) in patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy. Methods Patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy were chosen from the SEER Research Plus Database [17 Registries, November 2012 Submission (2000-2019)]. The patients were divided into a PORT group and a non-PORT group according to whether the PORT was used. To balance baseline characteristics between non-PORT and PORT groups, R software was used to conduct a propensity score matching (PSM) with a ratio of 1 : 1 and a matching tolerance of 0.01. Both the Cox regression analysis and Kaplan-Meier survival analysis were conducted to evaluate the value of PORT in terms of overall survival (OS) and disease-specific survival (DSS). Results In total, 2468 patients with stage ⅢA-N2 non-small cell lung cancer were enrolled, including 1078 males and 1390 females with a median age of 65 (58-71) years. There were 1336 patients in the PORT group, and 1132 patients in the non-PORT group. Cox regression analysis showed that PORT was not significantly associated with OS (multivariate analysis: HR=1.051, 95%CI 0.949-1.164, P=0.338) and DSS (multivariate analysis: HR=1.094, 95%CI 0.976-1.225, P=0.123). No statistical difference was found in the OS or DSS between non-PORT group and PORT group after PSM analysis (P＞0.05). Conclusion PORT does not have a survival benefit for patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy.

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

The chemical components of Carthami Flos were investigated by using macroporous resin, silica gel column chromatography, reversed-phase octadecylsilane(ODS) column chromatography, Sephadex LH-20, and semi-preparative high-performance liquid chromatography(HPLC). The planar structures of the compounds were established based on their physicochemical properties and ultraviolet-visible(UV-Vis), infrared(IR), high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), and nuclear magnetic resonance(NMR) spectroscopic technology. The absolute configurations were determined by comparing the calculated and experimental electronic circular dichroism(ECD). Six flavonoid C-glycosides were isolated from the 30% ethanol elution fraction of macroporous resin obtained from the 95% ethanol extract of Carthami Flos, and identified as saffloquinoside F(1), 5-hydroxysaffloneoside(2), iso-5-hydroxysaffloneoside(3), isosafflomin C(4), safflomin C(5), and vicenin 2(6). Among these, the compounds 1 to 3 were new chalcone C-glycosides. The compounds 1, 2, 4, and 5 could significantly increase the viability of H9c2 cardiomyocytes damaged by oxygen-glucose deprivation/reoxygenation(OGD/R) at a concentration of 50 μmol·L~(-1), showing their good cardioprotective activity.
Glycosides/pharmacology* ; Flowers/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Carthamus tinctorius/chemistry* ; Chalcones/pharmacology* ; Animals

PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors

OBJECTIVE: To study the clinical effects of pomalidomide-based regimen in the treatment of relapsed and refractory multiple myeloma (RRMM). METHODS: 60 patients with RRMM in hematology department of the First Affiliated Hospital of Xinxiang Medical University from November 2020 to January 2023 were selected. Among them, 15 cases were treated with PDD regimen (pomalidomide + daratumumab + dexamethasone), and 45 cases were treated with PCD regimen (pomalidomide + cyclophosphamide + dexamethasone). The clinical effects were evaluated. RESULTS: The median number of treatment cycles for the entire cohort was 5 (2-11), with an overall response rate (ORR) of 75.0%. The ORR of patients treated with PDD regimen was 73.3%, while the ORR of patients treated with PCD regimen was 75.6%. The ORR of 46 patients with non high-risk cytogenetic abnormalities (non-HRCA) was 86.9%, significantly higher than the 35.7% of 14 patients with HRCA (χ² =15.031, P < 0.05). The median PFS for all patients was 8.0(95%CI : 6.8-9.1) months and the median OS was 14.0 (95%CI : 11.3-16.7) months. Among patients treated with PDD regimen, the PFS and OS of patients with non-HRCA were significantly higher than those of patients with HRCA [PFS: 7.0(95%CI : 4.6-9.3) months vs 4.0(95%CI : 3.1-4.8) months, χ² =5.120, P < 0.05; OS: not reached vs 6.0(95%CI : 1.1-10.9) months, χ² =9.870, P < 0.05]. Among patients treated with PCD regimen, the PFS and OS of patients with non-HRCA were significantly higher than those of patients with HRCA [PFS: 9.0(95%CI : 6.2-11.8) months vs 6.0(95%CI : 5.4-6.6) months, χ²=14.396, P < 0.05; OS: not reached vs 11.0(95%CI : 6.4-15.6) months, χ² =7.471, P < 0.05]. CONCLUSION The pomalidomide-based regimen has a good clinical effect and safety in the treatment of RRMM.
Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/administration & dosage* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Male ; Middle Aged ; Recurrence ; Aged ; Cyclophosphamide/therapeutic use* ; Treatment Outcome ; Antibodies, Monoclonal

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

Objective : To explore the polymorphism of endothelial nitric oxide synthase(eNOS) gene in umbilical cord blood of preterm infants and its relationship with major complications in preterm infants. Methods : A total of 254 preterm infants(<37 weeks) who were hospitalized were selected as the study subjects. Umbilical cord blood was collected at delivery to determine the genotypes and alleles of eNOS gene at three loci: rs61722009, rs2070744,and rs1799983. Clinical data of the preterm infants were recorded, and the relationship between eNOS gene polymorphism and major complications in preterm infants was analyzed. Results: (1) The TC+CC genotype at locus rs2070744 was an independent risk factor for bronchopulmonary dysplasia(BPD) in preterm infants, with an OR(95%CI) of 1.266(1.017-1.577).(2) The GT+TT genotype at locus rs1799983 was an independent risk factor for retinopathy prematurity(ROP), with an OR(95%CI) of 1.184(1.008-1.391).(3) The AB+AA genotype at locus rs61722009 was also an independent risk factor for ROP,with an OR(95%CI) of 1.335(1.033-1. 726).(4) There was no significant relationship between gene polymorphism and the occurrence of respiratory distress syndrome( RDS) and periventricular-intraventricular hemorrhage( PIVH). Conclusion eNOS gene polymorphism is associated with the occurrence of BPD and ROP in preterm infants. The evaluation of e NOS gene polymorphism by umbilical cord blood measurement is helpful for the prevention and correct management of some serious complications.

Abstract: To explore the relationship between the replication-associated bromodomain protein 4 ( BRD4)and human papillomavirus (HPV) 16(HPV16) viral load in cervical squamous cell carcinoma and CIN Ⅰ tissues , confirm the effects of BRD4 degradation agent MZ1 on viral load . Methods : Thirty HPV16-positive cervi- cal cancer specimens and 30 non-cervical cancer specimens were collected , and the viral load of the samples was detected by real-time fluorescence quantitative PCR , and the expression of BRD4 was analyzed by immunohisto- chemistry and Western blot. Results : The viral load was higher in the samples of cervical cancer group than in the samples of non-cancer group , the difference is statistically significant ( P < 0. 01) . Immunohistochemistry results showed that the expression of BRD4 were significantly higher in cervical cancer specimens than in noncancerous specimens , the difference is statistically significant (P < 0. 05) . BRD4 expression was significantly and positively correlated with high viral loads , the difference is statistically significant (P < 0. 001) . the BRD4 degradation agent MZ1 significantly reduced the viral load , the difference is statistically significant (P < 0. 01) . Conclusion BRD4 may be involved in the replication of HPV16 virus , and BRD4 degradation agent MZ1 can inhibit the replication of HPV16 virus .

Objective : To explore the utility of a nomogram integrating contrast-enhanced CT radiomics with clinical features in the preoperative prediction of WHO/ISUP grade for clear cell renal cell carcinoma(ccRCC). Methods: A total of 214 patients with pathologically proven ccRCC who underwent enhanced CT scan before surgery were retrospectively included. According to the WHO/ISUP grade system, the cases were classified into low-grade(grades Ⅰ-Ⅱ) and high-grade(grades Ⅲ-Ⅳ), and then randomly divided into training and test set with a ratio of 4 ∶1. Regions of interest were segmented from both unenhanced and three-phase enhanced images, and radiomic features were extracted. Feature selection and dimensionality reduction were performed using Spearman rank correlation coefficients and LASSO regression, followed by the construction of the radiomic model with the KNN algorithm. Clinical and semantic imaging features were selected through univariate and multivariate analyses, and a clinical model was developed using the KNN algorithm. The clinical and radiomics signatures were used to construct a combined model and a nomogram was developed. The ROC curve and delong test were used to evaluate the diagnostic performance of the model, while calibration and decision curve analyses assessed its accuracy and clinical applicability. Results: 8 clinical features and 11 radiomic features were selected. The combined model, integrating these clinical and radiomics signatures, exhibited robust predictive performance with AUC values of 0.887 in the training set and 0.800 in the test set. The calibration curve demonstrated good consistency between the nomogram model and actual outcomes, while decision curve analysis indicated a favorable net benefit for the nomogram. Conclusion The nomogram constructed by combining radiomics and clinical signatures can provide evidence for preoperative prediction of ccRCC grade and guide clinical decision-making.