BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes ( BRCA ) mutations ( BRCA m) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs . 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs . 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCA m, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCA m, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.
Humans ; Female ; Ovarian Neoplasms/drug therapy* ; Piperazines/therapeutic use* ; Middle Aged ; Retrospective Studies ; Phthalazines/therapeutic use* ; Piperidines/therapeutic use* ; Indazoles/therapeutic use* ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Adult ; Aged ; China ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival

BACKGROUND: Gluconeogenesis is a critical metabolic pathway for maintaining glucose homeostasis, and its dysregulation can lead to glycometabolic disorders. This study aimed to identify hub biomarkers of these disorders to provide a theoretical foundation for enhancing diagnosis and treatment. METHODS: Gene expression profiles from liver tissues of three well-characterized gluconeogenesis mouse models were analyzed to identify commonly differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA), machine learning techniques, and diagnostic tests on transcriptome data from publicly available datasets of type 2 diabetes mellitus (T2DM) patients were employed to assess the clinical relevance of these DEGs. Subsequently, we identified hub biomarkers associated with gluconeogenesis-related glycometabolic disorders, investigated potential correlations with immune cell types, and validated expression using quantitative polymerase chain reaction in the mouse models. RESULTS: Only a few common DEGs were observed in gluconeogenesis-related glycometabolic disorders across different contributing factors. However, these DEGs were consistently associated with cytokine regulation and oxidative stress (OS). Enrichment analysis highlighted significant alterations in terms related to cytokines and OS. Importantly, osteomodulin ( OMD ), apolipoprotein A4 ( APOA4 ), and insulin like growth factor binding protein 6 ( IGFBP6 ) were identified with potential clinical significance in T2DM patients. These genes demonstrated robust diagnostic performance in T2DM cohorts and were positively correlated with resting dendritic cells. CONCLUSIONS Gluconeogenesis-related glycometabolic disorders exhibit considerable heterogeneity, yet changes in cytokine regulation and OS are universally present. OMD , APOA4 , and IGFBP6  may serve as hub biomarkers for gluconeogenesis-related glycometabolic disorders.
Machine Learning ; Humans ; Computational Biology/methods* ; Biomarkers/metabolism* ; Diabetes Mellitus, Type 2/genetics* ; Animals ; Mice ; Gluconeogenesis/physiology* ; Gene Expression Profiling ; Transcriptome/genetics* ; Gene Regulatory Networks/genetics* ; Clinical Relevance

Objective : To explore the factors influencing the efficacy of first-generation EGFR tyrosine kinase inhibitors(EGFR-TKIs) in patients with EGFR-mutated advanced lung adenocarcinoma and to construct and validate a corresponding nomogram prediction model. Methods : A total of 220 patients with EGFR-mutated advanced lung adenocarcinoma treated with icotinib were enrolled and randomly divided into a training group(154 cases) and a validation group(66 cases) in a 7 ∶3 ratio. Cox regression analysis was performed to identify factors affecting the efficacy of first-generation EGFR-TKIs in the training group. A prediction model was constructed, and calibration curves and receiver operating characteristic(ROC) curves were plotted to validate the model′s performance. Results: In the training group, the objective response rate was 35.71%, the disease control rate was 77.27%, the median progression-free survival(PFS) was 12.5 months, the median overall survival was 18 months, the 2-year OS rate was 66.23%, and the PFS rate was 42.21%. Univariate analysis showed that brain metastasis, bone metastasis, TNM stage, differentiation degree, neutrophil-to-lymphocyte ratio(NLR), post-treatment p53 levels, p53 difference(Δp53), post-treatment cancer antigen gene(CAGE) levels, and CAGE difference(ΔCAGE) were associated with PFS(P2=4.429, P=0.351). ROC curve analysis in the training group showed that the nomogram model had a sensitivity of 80.00%, specificity of 77.53%, and AUC of 0.864 for predicting therapeutic efficacy, while the validation group showed a sensitivity of 74.08%, specificity of 71.43%, and AUC of 0.835. Conclusion Changes in lung cancer autoantibodies(Δp53 and ΔCAGE), TNM stage, and NLR are key factors influencing the efficacy of first-generation EGFR-TKIs in EGFR-mutated advanced lung adenocarcinoma. The nomogram prediction model based on p53 and CAGE demonstrates good predictive performance.

OBJECTIVE: To analyze the clinical and genetic features of a child with Primary ciliary dyskinesia (PCD) due to compound heterozygous variants of the CCDC39 gene and a 22q11.21 deletion, and to explore the potential role of the two types of variants in the formation of complex phenotypes. METHODS: A child presented at the Shanxi Children's Hospital in March 2025 due to multiple congenital anomalies was selected as the study subject. Peripheral blood samples were taken from the child and her parents and subjected to whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Effect of splicing variant was predicted using SpliceAI, and pathogenicity was assessed based on the ACMG guidelines. Copy number variation (CNV) analysis was also performed. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No.: IRB-WZ-2025-019). RESULTS: The patient has exhibited multiple features including severe pneumonia, bronchiectasis, localized pulmonary emphysema, scoliosis, tetralogy of Fallot, and atrial septal defect. Genetic testing revealed that she has harbored compound heterozygous variants of the CCDC39 gene, namely c.1167+1G>A and c.1009A>T, which were inherited from her father and mother, respectively, with the latter being a novel likely pathogenic variant. In addition, a heterozygous deletion of approximately 708 kb at 22q11.21 was detected. CONCLUSION The coexistence of CCDC39 gene variants and a 22q11.21 deletion may underlay the development of complex clinical phenotypes in this child.
Humans ; Female ; Chromosomes, Human, Pair 22/genetics* ; Chromosome Deletion ; DNA Copy Number Variations/genetics* ; Child ; Ciliary Motility Disorders/genetics* ; Exome Sequencing

Objective To investigate the effect of tetrandrine(Tet)on injury of primary human articular chondro-cytes induced by interleukin-1β(IL-1β).Methods Human articular chondrocytes were divided into control group,IL-1β group,hypoxia inducible factor(HIF-1α)inhibitor group[2-methoxyestradiol(2-ME2)group],Tet groups containing low,medium and high concentrations.Each group has six replicated samples.MTT assay was used to de-tect the viability of cells;cell apoptosis was detected by flow cytometry;the level of inflammatory related factors like tumor necrosis factor-α(TNF-α),matrix metalloproteinase 3(MMP-3),inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2)and the activity of antioxidant factors like super oxide dismutase(SOD)and glutathione peroxides(GPx)in cells were detected by ELISA;Western blot was used to detect the expression of HIF-1α and VEGF in cells.Results Compared with the control group,the apoptosis rate,level of TNF-α,MMP-3,iNOS,COX-2 and the protein expression of HIF-1α and VEGF in IL-1β group all increased,the cell survival rate and the activity of SOD and GPx significantly decreased(P＜0.05);compared with IL-1β group,the apoptosis rate,the level of TNF-α,MMP-3,iNOS,COX-2 and the protein expression of HIF-1α and VEGF in 2-ME2 group and Tet groups with low,medium,and high concentration significanthy decreased(P＜0.05).The cell survival rate and the activity of SOD and GPx significantly increased(P＜0.05).Conclusions Tetrandrine attenuates IL-1β-in-duced injury of human articular chondrocytes.

Objective To evaluate the molluscicidal effects and costs of spraying 20% suspension concentrate of pyricloben-zuron sulphate (SCPS) with drones against Pomacea canaliculata in paddy environments, so as to provide insights into the extensive applications of pyriclobenzuron against P. canaliculata. Methods On July 2022, a paddy field was selected from Nanchang City, Jiangxi Province as the study area, and 72 independent rectangular plots measuring 2 m × 1 m were allocated in the study area, with 1 m interval between each plot, and 20 P. canaliculata snails gently placed in each plot. The activity of 25% wettable powder of pyriclobenzuron sulphate (WPPS) by manual spraying at doses of 0.50, 1.00, 2.00 g/m² and 4.00 g/m² against P. canaliculata was tested in 54 plots, and manual spraying of 50% wettable powder of niclosamide ethanolamine salt (WPNES) at a dose of 0.10 g/m² served as a chemical control, while manual spraying of the same volume of clean water served as a blank control, with 9 plots in each group. The activity of SCPS against P. canaliculata was tested in the remaining 18 plots. Based on the molluscicidal tests of WPPS, the molluscicidal effect of SCPS by manual spraying at doses of 0.20, 0.30, 0.40 g/m² and 0.50 g/m² against P. canaliculata was evaluated, and manual spraying of WPNES at a dose of 0.10 g/m² served as a chemical control, while manual spraying of the same volume of clean water served as a blank control, with three plots in each group. On July 2023, 14 paddy fields with a mean living P. canaliculata density of > 5 snails/m² were selected from Yujiang District, Yingtan City, Jiangxi Province for molluscicidal tests. Based on the molluscicidal effect of pyriclobenzuron against P. canaliculata in plots, the molluscicidal effects of WPPS by manual spraying at doses of 0.25, 0.50 g/m² and 1.00 g/m² and manual applications of WPPS at dose of 0.25, 0.50, 1.00 g/m² and 2.00 g/m² mixed with soil were tested, and manual spraying of 0.10 g/m² WPNES served as a chemical control group, while manual spraying of the same volume of clean water served as a blank control, with one paddy field in each group. Based on the effect of pyriclobenzuron against P. canaliculata in plots, the activity of SCPS sprayed with drones at doses of 0.25 g/m² and 0.50 g/m² mixed in water at 2 kg/667 m² and 4 kg/667 m² was tested against P. canaliculata, and spraying of the same volume of clean water with drones served as a blank control. All P. canaliculata snails were captured 3 days and 7 days following chemical treatment in plots and paddy fields and identified for survival, and the mortality and corrected mortality of P. canaliculata snails were estimated. In addition, the areas of chemical treatment, amount of molluscicide use and labor costs of chemical treatment were estimated in molluscicidal tests in paddy fields, and the costs of chemical treatment for an area covering 667 m² by drones and manual applications were calculated. Results The mortality of P. canaliculata snails was all 100% in plots 3 days and 7 days following spraying WPPS at doses of 0.50, 1.00, 2.00 g/m² and 4.00 g/m², and the mortality rates of P. canaliculata snails were 66.67% to 100.00% 3 days post-treatment with SCPS at various doses (χ² = 277.897, P < 0.05) and 76.67% to 100.00% 7 days post-treatment (χ² = 274.206, P < 0.05). The mortality rates of P. canaliculata snails were 98.19% to 100.00% 3 days post-treatment with WPPS at various doses in paddy fields. There was a significant difference in the mortality of P. canaliculata snails among WPPS treatment groups and controls (χ² = 270.778, P < 0.05), and there were no significant differences between WPPS treatment groups and the chemical control group (all P values > 0.05), while there were significant differences in the mortality of P. canaliculata snails between WPPS treatment groups and the blank control group (all P values < 0.05). The mortality rates of P. canaliculata snails were 89.83% to 95.31% 3 days post-treatment with SCPS at various doses sprayed with drones, and there was a significant difference in the mortality of P. canaliculata snails among SCPS treatment groups and the blank control group (χ² = 1 132.892, P < 0.05). There were no significant differences in the mortality of P. canaliculata snails among SCPS treatment groups or water mixture groups (all P values > 0.05), and there were significant differences in the mortality of P. canaliculata snails between SCPS treatment groups and the blank control group (all P values < 0.05). The mortality rates of P. canaliculata snails were 94.62% to 100.00% 7 days post-treatment with SCPS at various doses sprayed with drones, and there was a significant difference in the mortality of P. canaliculata snails among SCPS treatment groups and the blank control group (χ² = 1 266.932, P < 0.05), with the highest mortality found following spraying 0.50 g/m² SCPS mixed in 2 kg/667 m² water with drones (P < 0.05). The costs of P. canaliculata snail control by drones and manually were 35.85 Yuan/667 m² and 43.33 Yuan/667 m²; however, the snail control efficiency was 6.67 times higher by drones than by manual applications. Conclusions SCPS sprayed with drones is highly active against P. canaliculata snails in paddy fields. SCPS sprayed with drones is highly efficient and low in cost for P. canaliculata snail control in paddy fields, beaches and river courses.

Methods: From September 3, 2018, to March 23, 2024, participants with essential hypertension (receiving antihypertensive medication treatment, hypertension group) and normal blood pressure (control group) were recruited from the Cardiology Department of Shanghai Hospital of Traditional Chinese Medicine, the Coronary Care Unit of Shanghai Tenth People's Hospital, the Physical Examination Center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, and the Gaohang Community Health Service Center. This study employed the propensity score matching (PSM) method to reduce study participants selection bias. Spectral information in the facial visible light spectrum of the subjects was collected using a flame spectrometer, and the spectral chromaticity values were calculated using the equal-interval wavelength method. The study analyzed the differences in spectral reflectance across various facial regions, including the entire face, forehead, glabella, nose, jaw, left and right zygomatic regions, left and right cheek regions as well as differences in parameters within the Lab color space between the two subject groups. Feature selection was conducted using least absolute shrinkage and selection operator (LASSO) regression, followed by the application of various machine learning algorithms, including logistic regression (LR), support vector machine (SVM), random forest (RF), Naïve Bayes (NB), and eXtreme Gradient Boosting (XGB). The reduced-dimensional dataset was split in a 7 : 3 ratio to establish a classification and assessment model for facial coloration related to primary hypertension. Additionally, model fusion techniques were applied to enhance the predictive power. The performance of the models was evaluated using metrics including the area under the curve (AUC) and accuracy. Shapley Additive exPlanations (SHAP) was used to interpret the outcomes of the models. Results: A total of 114 participants were included in both hypertension and control groups. Reflectance analysis across the entire face and eight predefined areas revealed that the hypertensive group exhibited significantly higher reflectance of corresponding color light in the blue-violet region (P < 0.05) and a lower reflectance in the red region (P < 0.05) compared with control group. Analysis of Lab color space parameters across the entire face and eight predefined areas showed that hypertensive group had significantly lower a and b values than control group (P < 0.05). LASSO regression analysis identified a total of 18 facial color features that were highly correlated with hypertension, including the a values of the chin and the right cheek, the reflectance at 380 nm and at 780 nm of the forehead. The results of the multi-model classification showed that the RF classification model was the most effective, with an AUC of 0.74 and an accuracy of 0.77. The combined model of RF + LR + SVM outperformed a single model in their classification performance, achieving an AUC of 0.80 and an accuracy of 0.76. SHAP model visualization results indicated that the top three contributors to ideal prediction results based on the characteristics from the facial spectrum were the reflectance at 380 nm across the entire face and of the nose as well as the a value of the chin. Conclusion Within the same age group, patients with essential hypertension exhibited significant and regular changes in facial color and facial spectral reflectance parameters after the administration of antihypertensive drugs. Furthermore, facial reflectance indicators, such as the overall reflectance at 380 nm and the a value of the chin, could offer valuable references for clinically assessing the drug efficacy and health status of patients with essential hypertension.

Objective To explore the correlation of red cell distribution width/albumin ratio(RAR)and fibrinogen/albumin ratio(FAR)with severity of coronary artery disease(CAD)in patients with coronary heart disease(CHD),and to further explore the relationship of RAR and FAR with CAD severity in different glucose metabolic states.Methods A total of 577 CHD patients undergoing coronary angiography(CAG)in Department of Cardiology of Tianjin People's Hospital from January 2021 to December 2022 were enrolled,and according to the results of CAG,412 patients were diagnosed with multi-vessel CAD and the other 165 patients with single-vessel CAD.Their baseline data and results of laboratory tests were collected,and RAR and FAR values were calculated.Univariate and multivariate logistic regression analyses were performed with RAR and FAR as independent variables,and ROC curve was plotted to evaluate the predic-tive values of the 2 indicators for the severity of CAD.Spearman correlation analysis was applied to analyze the occurrence of major adverse cardiovascular events(MACEs)in the patients.Results Logistic regression analysis showed that RAR and FAR were independent risk factors for CAD(OR=1.974,95％CI:1.348-2.593,P=0.000;OR=1.737,95％CI:1.486-2.377,P=0.000).Un-der different glucose metabolic states,RAR had the highest correlation with the risk of CAD in diabetic patients(OR=2.828,95％CI:1.157-7.145),while FAR was associated with a relatively low risk of CAD in diabetic patients(OR=2.217,95％CI:1.533-5.570).ROC curve analysis showed that RAR(AUC=0.776,95％CI:0.731-0.821,P=0.000)and FAR(AUC=0.725,95％CI:0.676-0.774,P=0.000)had predictive value for the severity of CAD in CHD patients.Spearman correlation analysis indicated that RAR and FAR were positively correlated with occur-rence of MACEs in CHD patients(P＜0.001).Conclusion RAR and FAR are independent pre-dictors for CHD patients.RAR has a stronger predictive value for lesion severity in CHD patients with concomitant abnormal glucose metabolism.

Objective To investigate the protective effect and mechanism of magnesium isoglycyrrhizinate(MgIG)on cisplatin(CDDP)-induced myocardial injury in rats.Methods Twenty-four Wistar rats were randomly divided into the normal control group,the cisplatin model group(CDDP group),the cisplatin+magnesium isoglycyrrhizinate low-dose group(MgIG-L group)and the cisplatin+magnesium isoglycyrrhizinate high-dose group(MgIG-H group),with 6 rats in each group.Changes of body mass of rats were monitored daily.At the end of drug administration,cardiac function indexes including left ventricular ejection fraction(LVEF),left ventricular short-axis narrowing rate(LVFS),left ventricular end-systolic internal diameter(LVESD)and left ventricular end-diastolic internal diameter(LVEDD)were detected by echocardiography.The morphology of myocardial tissue was observed by HE staining.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of creatine kinase isoenzyme MB(CK-MB)and troponin I(cTnI).Levels of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione synthase(GSH),reactive oxygen species(ROS)and ferrous ion(Fe2+)in homogenates of myocardial tissue were measured biochemically.The protein expressions of nuclear factor E2-associated factor 2(Nrf2),long-chain fatty acyl coenzyme A synthase 4(ACSL4),glutathione peroxidase 4(GPX4)and ferritin heavy chain 1(FTH1)protein were detected by Western blot assay.Results The body mass of rats in the control group showed an increasing trend during feeding,and the body mass of rats in the CDDP group showed a decreasing trend.Compared with the CDDP group,the body mass of rats in the MgIG-L group and the MgIG-H group increased after 5 d,9 d and 13 d of treatment(P＜0.05).Compared with the control group,the CDDP group showed decreased LVEF and LVFS,increased LVESD and LVEDD,disturbed myocardial fiber alignment,myocardial fiber degeneration and fracture,increased serum CK-MB and cTnI levels,increased levels of MDA,Fe2+and ROS in myocardial tissue,decreased levels of SOD and GSH,and decreased levels of Nrf2,GPX4,and decreased FTH1 protein expression levels and increased ACSL4 protein expression levels in myocardial tissue(P＜0.05).Compared with the CDDP group,the above indicators and myocardial histopathological changes were significantly improved in the MgIG-L group and the MgIG-H group.Conclusion Magnesium isoglycyrrhizinate can ameliorate cisplatin-induced myocardial injury by regulating myocardial oxidative stress and inhibiting cardiomyocyte iron death in rats.

Since 2004, Beijing Children's Hospital affiliated to Capital Medical University has applied objective structured clinical examination (OSCE) to comprehensively assess the post competency of pediatric residents during standardized training. While exploring a hierarchical and progressive training model for standardized residency training, according to the competency requirements for residents of different grades, our hospital has studied annual assessment strategies based on OSCE stations, and designed targeted annual assessment content and corresponding training courses, providing a reference for further improving the quality of training of pediatric residents.