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

Lipid and glucose metabolism play crucial roles in maintaining energy homeostasis, and their dysregulation can lead to the development of metabolic disorders, such as obesity and diabetes. Studies indicate that the skeleton, involved in lipid and glucose metabolism, functions as an endocrine organ, regulating systemic metabolism through bone-derived molecules. Sclerostin is a protein mainly produced by osteocytes, possessing the ability to inhibit bone formation, and its antibodies have become therapeutic targets for treating osteoporosis. Recent evidence suggests that sclerostin also plays a role in lipid and glucose metabolism disorders. Therefore, through summarizing in vitro and in vivo researches, this article reviews the role of sclerostin in lipid and glucose metabolism, its relationship with obesity and diabetes, and potential role in the treatment of metabolic diseases in the future.

Objective:To investigate the correlation between serum sclerostin and sarcopenia-related indicators in chronic kidney disease (CKD) patients, and to find biomarkers and potential therapeutic targets that can take into account both osteoporosis and sarcopenia.Methods:It was a single-centre cross-sectional study. The clinical data of CKD stage 5 patients undergoing maintenance hemodialysis regularly and CKD stage 1-5 non-dialysis inpatients in the Hemodialysis Centre of Guangzhou Red Cross Hospital from March 2021 to March 2023 were collected retrospectively. The enzyme-linked immunosorbent assay was used to detect the level of serum sclerostin. The anthropometric data such as height, weight, upper arm circumference, upper arm muscle circumference, skinfold thickness, pinch strength and handgrip strength were measured. Body composition analyzer was used to measure the body composition. The patients were divided into CKD stage 1-3 group, CKD stage 4-5 group, and stage 5 hemodialysis group. One-way ANOVA, Kruskal-Wallis H test, and chi-square test were used to compare the differences of demographics and clinical characteristics in different stages of CKD. Spearman correlation analysis and multiple linear stepwise regression analysis were utilized to analyze the correlation between serum sclerostin and sarcopenia-related indicators in CKD patients. Results:The study included 104 patients with CKD stage 5 hemodialysis and 104 patients with CKD stage 1-5 non-dialysis patients, with age of (61.8±13.7) years old and 114 males (54.8%). There were 89 patients (42.8%) with diabetic nephropathy and 67 patients (32.2%) with sarcopenia. As renal injury progressed, serum sclerostin levels were 0.4 (0.3, 0.9) ng/L, 0.5 (0.3, 1.1) ng/L, and 1.1 (0.6, 2.3) ng/L in patients with CKD stage 1-3, stage 4-5, and stage 5 undergoing hemodialysis ( χ2=8.934, P<0.001), and the prevalence of sarcopenia was 16.4% (10/61), 34.9% (15/43), and 40.4% (42/104) ( χ2=10.312, P=0.006), respectively. Spearman correlation analysis showed that serum sclerostin was negatively correlated with estimated glomerular filtration rate ( r=-0.314, P<0.001), pinch strength ( r=-0.229, P=0.007), skinfold thickness ( r=-0.254, P<0.001), appendicular skeletal muscle index ( r=-0.169, P=0.010), body cell mass ( r=-0.174, P=0.020), and phase angle ( r=-0.264, P<0.001), and positively correlated with serum phosphorus ( r=0.227, P=0.002) and intact parathyroid hormone ( r=0.297, P<0.001). Multiple linear stepwise regression analysis showed that lg[appendicular skeletal muscle index] was negatively correlated with male ( β=0.330, t=5.675, P<0.001) and serum sclerostin ( β=-0.125, t=-2.143, P=0.033), and positively correlated with body mass index ( β=0.474, t=8.090, P<0.001). Conclusion:Serum sclerostin can be used as a good index and a potential therapeutic target for sarcopenia in CKD patients.

Objective To investigate the diagnostic potential of low-dose computed tomography angiography(CTA)and global biomimetic three-dimensional model reconstruction technology in patients with arterial erectile dysfunction(ED).Methods A total of 136 patients with ED were selected.Digital subtraction angiography(DSA)was performed on all patients as per their treatment requirements and conditions,following ultrasound and CTA examination,and 75 patients finally completed DSA examination.All patients with International Index for Erectile Function(IIEF5)score ranged from 1 to 20.All patients received immediate ultrasound monitoring after injection of alprostadil 10 μg and underwent CTA examination.DSA was conducted at a minimum interval of 72 h.The global biomimetic three-dimensional model tool was used to reconstruct the CTA data and evaluate the stenosis of the pudendal vessels.The diagnostic efficacy of CTA examination,ultrasound and DSA examination were compared and calculated.Results A total of 1 632 vessels were evaluated in 136 patients,including 155 stenoses.DSA was performed in 75 patients.A total of 900 vessels were evaluated,of which 88 were stenoses.Compared with the results of CTA,ultrasound and DSA,the average stenosis scores of all measured vessels were not statistically significant(P＜0.05).The correlation between CTA and ultrasound(r2=0.939 9,P＜0.000 1)and DSA(r2=0.944 0,P＜0.000 1)in the evaluation of vascular stenosis were good,and the diagnostic consistency was consistent.Conclusion Low-dose CTA and global biomimetic three-dimensional model reconstruction technology can effectively diagnose pudendal artery stenosis,and can perform all-round reconstruction observation,which is worthy of further clinical application.

Objective:To investigate the impact of sarcopenia on mortality in maintenance hemodialysis (MHD) patients.Methods:It was a retrospective cohort study. MHD patients admitted to the blood purification center of Guangzhou Red Cross Hospital in March 2021 were recruited. Demographic data and laboratory indicators, grip strength, and bioelectrical impedance analysis indexes were collected. The patients were divided into sarcopenia group and non-sarcopenia group based on whether they had sarcopenia or not. By following up for 18 months, the survival status of the patients was documented. Kaplan-Meier method, multivariate Cox regression model, and Fine-Gray competing risk model were used to assess the relationship between sarcopenia and all-cause mortality, cardio-cerebrovascular disease mortality, and infection-related disease mortality.Results:A total of 143 MHD patients were enrolled in this study, with age of 65 (58,74) years old and 89 males (62.24%). The prevalence of sarcopenia was 25.17% (36/143). The sarcopenia group had older age ( Z=3.486, P<0.001), higher single-pool Kt/V ( Z=3.634, P<0.001), interleukin-6 ( Z=3.434, P<0.001) and extracellular water/intracellular water ratio ( Z=2.477, P=0.013), and lower body mass index ( Z=-3.210, P=0.001), serum phosphorus ( t=2.475, P=0.015), serum creatinine ( t=3.319, P=0.001), serum albumin ( t=2.851, P=0.005), serum prealbumin ( t=3.384, P<0.001), extracellular water ( Z=-5.124, P<0.001), intracellular water ( Z=-5.417, P<0.001), grip strength ( Z=-3.796, P<0.001) and appendicular skeletal muscle mass index ( t=3.862, P<0.001) than those in the non-sarcopenia group. Kaplan-Meier survival curves showed that the overall survival rate in the sarcopenia group was lower than that in the non-sarcopenia group (Log-rank test χ2=15.99, P<0.001). Multivariable Cox regression analysis demonstrated that sarcopenia was independently correlated with all-cause mortality in MHD patients after adjusting for confounding factors ( HR=2.75, 95% CI 1.07-7.10, P=0.036). Fine-Gray competing risk model result showed that there was no statistically significant difference in cardio-cerebrovascular disease mortality between sarcopenia group and non-sarcopenia group ( SHR=4.99, 95% CI 0.94-26.85, P=0.069); the risk of infection-related disease mortality in sarcopenia group was 5.76 folds than that in non-sarcopenia group ( SHR=5.76, 95% CI 1.15-28.96, P=0.034). Conclusions:There is prevalent sarcopenia in MHD patients. Moreover, sarcopenia is an independent risk factor of all-cause mortality and infection-related disease mortality in MHD patients.

Objective:To explore the mechanism of Tripterygium wilfordii in treating renal cell carcinoma using network pharmacology and experimental validation. Methods:The traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform was utilized to screen the active ingredients of T. wilfordii and predict the targets using the Swiss database. Renal cell carcinoma related targets were collected from DisGeNET, GeneCards, and OMIM databases, and intersecting targets were obtained through Venny 2.1.0. Protein-protein interaction (PPI) networks were mapped using the STRING database and Cytoscape software, and gene ontology (GO) and kyoto encyclopedia of genes and genomics (KEGG) enrichment analyses were performed. Component-target-pathway networks were constructed using Cytoscape software. To induce the subcutaneous transplantation tumor model of renal cell carcinoma, nude mice were randomly divided into a control group and a treatment group, with 5 mice in each group. In the treatment group, mice were gastrically instilled with 615 mg/ml of T. wilfordii solution (1 845 mg T. wilfordii granules dissolved into 3 ml water) 2.46 g/kg, 10 μl/time, once daily for 21 d. In the control group, mice were gastrically instilled with an equal amount of saline. Tumor volume was measured once every 5 days, and the expression of serine/threonine protein kinase 1 (AKT1), signal transduction and transcription activator 3 (STAT3), tumor necrosis factor (TNF), tumor protein p53 (TP53), JUN, mitogen-activated protein kinase 8 (MAPK8), and MAPK14 was detected by enzyme-linked immunoassay. Results:Twenty-eight active pharmaceutical ingredients and 117 potential targets of T. wilfordii were screened; 13 425 related disease targets were identified; and finally, 113 drug-disease intersecting targets were obtained. In the PPI network, AKT1, STAT3, TNF, TP53, JUN, MAPK8, and MAPK14 were the core targets. GO analysis showed that BP mainly included nuclear receptor activity, ligand-activated transcription factor activity, RNA polymerase-specific DNA-binding transcription factor binding, nuclear steroid receptor activity, and adrenergic receptor activity, etc. CC mainly included the response to hormones, the cellular response to lipids, the positive regulation of cell migration, the response to TNF, the inflammatory response, the cellular response to hormonal stimulation, the response to hypoxia, the response to metal ions, etc. MF involves membrane rafts, membrane microregions, the outer side of the plasma membrane, the lateral side of the membrane, plasma membrane rafts, presynaptic membranes, vesicles, transcriptional regulatory complexes, post-synaptic membranes, synaptic membranes, etc. KEGG analysis showed that T. wilfordii treatment of RCC involves signaling pathways such as lipid and atherosclerosis, advanced glycosylation end product-receptor for advanced glycosylation end products (AGE-RAGE), TNF, Toll-like receptor, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt), and MAPK. The experimental validation results showed that the tumor volume was reduced after treatment with tretinoin ( P < 0.05), the expression of TP53 protein was increased ( P < 0.001), and the expression of AKT1, STAT3, TNF, JUN, MAPK8, and MAPK14 proteins were all reduced (all P < 0.001). Conclusions:In this study, the target and signaling pathways of T. wilfordii treatment of renal cell carcinoma were initially predicted, providing a reference basis for further research on its protective mechanism and clinical application.

Objective:To investigate the expression of maternal embryonic leucine zipper kinase (MELK) in renal clear cell carcinoma and its relationship with clinical and pathological characteristics of the patients with renal clear cell carcinoma, and to evaluate its effect on the proliferation of renal clear cell carcinoma.Methods:The expression of MELK in renal clear cell carcinoma and its relationship with the overall survival of patients was analyzed using the gene expression profiling interactive analysis (GEPIA) online database. Cancer tissue samples from 77 patients with renal clear cell carcinoma treated at Xinxiang Central Hospital were collected, all of which have been confirmed as renal clear cell carcinoma through immunohistochemistry experiments. The relationship between the expression of MELK in renal clear cell carcinoma tissue and the clinical and pathological characteristics of the patients was analyzed. The effect of MELK on the proliferation of renal clear cell carcinoma cells was explored through cloning experiments and CCK-8 assay.Results:Information from the GEPIA database revealed that the expression level of the MELK gene was upregulated in renal clear cell carcinoma compared with normal tissues. The clinicopathological analysis results showed that MELK expression was significantly correlated with tumor size and diameter of renal clear cell carcinoma ( P < 0.05), and had no statistically significant correlation with patient age, gender, or tumor differentiation. The results of the clonogenic assay and the CCK-8 assay showed that MELK expression promoted the proliferation of renal clear cell carcinoma cells (all P < 0.05). Conclusions:MELK promotes the proliferation of kidney cancer cells, which may provide a new therapeutic strategy for the treatment of renal clear cell carcinoma.

Mesh-related visceral complications caused by mesh erosion after tension-free inguinal hernia repair are one kind of rare long-term complications, but they are easily neglected. Interval time from initial hernia repair to mesh-related visceral complications by preperitoneal and laparoscopic repair is short. Rutkow and transabdominal preperitoneal repair have the highest reported rate. Lichtenstein has the longest interval time and the lowest reported rate. The most frequently eroded organs are sigmoid colon, bladder and small intestine. The common clinical manifestations of sigmoid colon erosion are hematochezia, abdominal wall fistula and colitis, hematuria and recurrent urinary tract infection in bladder erosion cases, intestinal obstruction and abdominal wall fistula in intestinal erosion case, sigmoid-bladder fistula and intestinal-bladder fistula in multiple organ erosion cases. Resection or repair of corresponding organs with mesh removal have good efficacies in most patients. The authors summarize and analyze researches on mesh-related visceral complications after tension-free inguinal hernia repair from 1994 to 2021, review their advances, in order to raise awareness of such complications in clinicians.

Objective:To investigate the effect of tidal volume (Vt DI) on pulse pressure variation (ΔPP DI) during deep inspiration maneuvers in spontaneously breathing patients with sepsis and to test if adjusting ΔPP DI by Vt DI can further improve its ability in predicting fluid responsiveness (FR). Methods:Spontaneously breathing, nonintubated sepsis or septic shock patients who were admitted to the Intensive Care Unit of the Characteristic Medical Center of Chinese People's Armed Police Force and Nanjing Gaochun People's Hospital were prospectively enrolled from October 2017 to October 2019. Volume expansion (VE) was performed by infusing 500 mL saline over 20 min. Prior to VE, measurements including pulse pressure variation and tidal volume were obtained during quiet spontaneous breathing (ΔPP TB and Vt TB, respectively) and during the deep inspiration maneuver (ΔPP DI and Vt DI, respectively). Patients were classified as responders if stroke volume (SV) increased ≥ 15% after VE, otherwise non-responders. Multiple linear regression analysis was conducted to investigate the correlation of ΔPP DI with Vt DI and VE-induced percentage changes in SV (ΔSV). Receiver operating characteristic (ROC) curve analysis and the gray zone approach were used to assess the ability of each index to predict FR. Changes in gray zone limits according to the cost ratio (R = cost[false positive (FP)]/cost[false negative (FN)]) were also evaluated. Results:Of the included 31 patients, 17 were responders. There was no significant difference in ΔPP TB between fluid responders and non-responders ( P>0.05), whereas ΔPP DI was significantly higher in responders than in non-responders [(19.1±7.4)% vs (11.2±4.5)%; P=0.001]. The area under the ROC curve (AUC) of ΔPP DI predicted FR was 0.832, sensitivity of 76.47% and specificity of 71.43%, which was significantly higher than ΔPP TB (AUC=0.580, sensitivity of 47.06% and specificity of 71.43%; P<0.05). Multiple linear regression analysis showed that both Vt DI and ΔSV were independently associated with ΔPP DI ( P<0.01), the AUC of ΔPP DI adjusted by Vt DI was signigicantly higher than that of ΔPP DI alone ( P=0.03). Among the ΔPP TB, ΔPP DI and ΔPP DI/Vt DI, ΔPP DI/Vt DI had the narrowest gray zone (12.7-14.5) for the normal fluid policy (R=1), which only included 19% of the patients. When applying "restrictive" fluid management (R=2), the gray zone for ΔPP DI/Vt DI was 12.8-14.5 and included only 2 patients (6.5%). Conclusions:In spontaneously breathing, nonintubated patients with sepsis or septic shock, the ΔPP value obtained during the deep inspiration maneuver predicts FR with moderate accuracy. Given the close correlation between Vt DI and ΔPP DI, ΔPP DI adjusted by Vt DI performs better than ΔPP DI alone in predicting FR.

Objective:To compare the therapeutic effect of polysaccharide iron complex capsule and Shengxuening tablet on renal anemia in maintenance hemodialysis (MHD) patients.Methods:Patients who received MHD treatment from April to June 2016 in our dialysis center and met the criteria for iron deficiency anemia were block-randomly divided into two groups: the polysaccharide-iron complex group and the Shengxuening group. Blood routine, iron metabolism biomarkers and biochemical exams were measured before treatment and at the 1st, 2nd and 3rd months after treatment, and the incidence of adverse reactions were recorded. The compliance rate of the two groups was observed and compared, and the block-randomized-statistical methods were used to compare the clinical data of the two groups before and after treatment, and cost-benefit analysis was also conducted.Results:Thirty patients in each group completed follow-up. After three months of treatment, the blood routine and iron metabolism indicators of the two groups were improved. Compared with the Shengxuening group, the polysaccharide iron complex group had higher therapeutic efficiency, and the levels of hemoglobin, transferrin saturation and serum ferritin were higher, and lower use of recombinant human erythropoietin ( P<0.05). The other indexes such as red blood cell (RBC), hematocrit (HCT) levels and the effective rate of anemia correction, the effective rate of iron therapy, the effective rate of iron therapy between the two groups were similar. Cost-benefit analysis suggested that the use of polysaccharide iron complexes to treat anemia has lower costs and higher benefits ( P<0.05). Conclusions:Polysaccharide iron complex capsule can better correct anemia and improve iron metabolism, and has low cost-effectiveness, which can effectively reduce medical insurance expenditure. It is a good iron supplementing method in addition to intravenous iron supplement.