Objective To explore the prevalence of depressive symptoms in postoperative patients with ovarian cancer and to analyze its influencing factors from multiple dimensions, including clinical characteristics, psychological factors, and laboratory indicators. Methods A cross-sectional study was conducted, which enrolled 235 postoperative patients with ovarian cancer. Depressive status was assessed using the patient health questionnaire, and the demographic, pathological, and medical record data of the patients were collected using the generalized anxiety disorder scale, Pittsburgh sleep quality index, European organization for research and treatment of cancer quality of life questionnaire core 30, and ECOG performance status score. Peripheral blood tumor marker (CA125), routine blood test, lymphocyte subsets, and serum cytokine levels were measured. Univariate and multivariate binary logistic regression analysis were used for statistical analysis. Results The prevalence of depression in postoperative patients with ovarian cancer was 39.15% (92/235). Univariate analysis showed that ECOG score ≥ 2 points, pain, anxiety, poor sleep quality, low quality of life, low life satisfaction, tumor recurrence, six or more cycles of chemotherapy, as well as higher levels of CA125, NLR, and NAR, and lower hemoglobin levels were significantly associated with depression (all P<0.05). Multivariate binary Logistic regression analysis showed that anxiety (OR=1.975, 95%CI: 1.231-3.170), sleep efficiency (OR=4.181, 95%CI: 1.211-14.43), sleep latency (OR=34.806, 95%CI: 4.258-284.542), ECOG performance status score, cognitive function (OR=0.918, 95%CI: 0.868-0.97), and life satisfaction were independent risk factors for depression (all P<0.05). Laboratory indicators were not independent influencing factors in the multivariate Logistic regression model. Conclusion Depression in postoperative patients with ovarian cancer is influenced by physiological, psychological, and social factors. Clinical management should focus on patients with anxiety, sleep disorders, poor physical condition, and low life satisfaction, and a comprehensive prevention and treatment strategy centered on psychological intervention and taking into account symptom management and social support should be implemented.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To establish a survival prediction model based on the independent prognostic factors of long-term prognosis after laparoscopic liver resection(LLR) for intrahepatic cholangiocarcinoma(ICC). Methods: The clinical and pathological data of 351 consecutive patients with ICC who received radical LLR in 13 Chinese medical centers from August 2010 to May 2021 were collected retrospectively. There were 190 males and 161 females,aged(M(IQR)) 61(14)years(range:23 to 93 years). The total cohort was randomly divided into a training dataset(264 cases) and a validation dataset(87 cases). The patients were followed up by outpatient service or telephone,and the deadline for follow-up was October 2021. Based on the training dataset,the multivariate Cox proportional hazards regression model was used to screen the independent influencing factors of long-term prognosis to construct a Nomogram model. The Nomogram model's discrimination,calibration,and clinical benefit were evaluated through internal and external validation,and an assessment of the overall value of two groups was made through the use of a receiver operating characteristic(ROC) curve. Results: There was no significant difference in clinical and pathological characteristics and long-term survival results between the training and validation datasets(all P>0.05). The multivariate Cox analysis showed that CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis were independent prognostic factors for ICC patients after LLR(all P<0.05). The survival Nomogram was established based on the independent prognostic factors obtained from the above screening. The ROC curve showed that the area under the curve of 1, 3 and 5-year overall survival rates of patients in the training dataset were 0.794(95%CI:0.721 to 0.867),0.728(95%CI:0.618 to 0.839) and 0.799(95%CI:0.670 to 0.928),and those in the validation dataset were 0.787(95%CI:0.660 to 0.915),0.831(95%CI:0.678 to 0.983) and 0.810(95%CI:0.639 to 0.982). Internal and external validation proved that the model exhibited a certain discrimination,calibration,and clinical applicability. Conclusion: The survival Nomogram model based on the independent influencing factors of long-term prognosis after LLR for ICC(including CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis) exhibites a certain differentiation,calibration,and clinical practicability.
Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; CA-19-9 Antigen ; Cholangiocarcinoma/diagnosis* ; Female ; Humans ; Laparoscopy ; Lymphatic Metastasis ; Male ; Nomograms ; Prognosis ; Retrospective Studies

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ² test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.
Colectomy ; Colonic Neoplasms/surgery* ; Female ; Humans ; Laparoscopy ; Male ; Prognosis ; Propensity Score ; Retrospective Studies ; Robotic Surgical Procedures ; Treatment Outcome

AIM:To investigate the effect of CUDC-907, a dual histone deacetylase (HDAC) and phosphatidylinositol 3-kinase (PI3K) inhibitor, on the DNA damage, cell cycle distribution and autophagy in human glioma U251cells.METHODS:U251 cells were treated with CUDC-907 of different concentrations, and the cell viability was detected by MTT assay.The quantitativeγ-H2AX foci were determined by laser scanning confocal microscopy.The cell cycle distribution of U251 cells was examined by flow cytometry.The protein expression was determined by Western blot analysis.RESULTS:CUDC-907 inhibited the cell viability and the phosphorylation of Akt and p70 ribosomal protein S6 kinase (p70s6K) in the U251 cells (P<0.05).In CUDC-907-treated cells, the number ofγ-H2AX foci and protein expression ofγ-H2AX were increased significantly (P<0.05).CUDC-907 also induced cell arrest in theM phase by up-regulating the expression of p21, and inhibiting the protein level of cyclin B1 and the phosphorylation of cell division cycle protein2 (Cdc2).In addition, CUDC-907 triggered cell autophagy, and inhibition of autophagy increased CUDC-907-induced DNA damage of U251 cells.CONCLUSION:CUDC-907 significantly inhibits PI3K/Akt signaling pathway, induces DNA damage and arrests cell cycle inM phase.Blockage of autophagy promotes CUDC-907-induced DNA damage of U251cells.

OBJECTIVETo investigate the antiinflammatory activities of aqueous extract of Occimum gratissmium (OGE) with emphasis on expression of proinflammatory cytokines in Lipopolysaccharide (LPS)-stimulated epithelial cell BEAS-2B.

METHODSEffects of OGE on cell viability were determined by MTT assay. mRNA expression were analyzed by and reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time PCR. Activation of kinase cascades was investigated by immunoblot. Intracellular reactive oxygen species (ROS) was analyzed by flow cytometry.

RESULTSOGE (<200 μg/mL) treatment or pretreatment and following LPS exposure slightly affected viability of BEAS-2B cells. Increase of interleukin (IL)-6 and IL-8 and the elevated level of intracellular ROS in LPS-stimulated BEAS-2B cells were diminished by OGE pretreatment in a dose-dependent manner. OGE suppressed inflammatory response-associated mitogen-activated protein kinases (MAPKs) and Akt activation. Additionally, OGE pretreatment increased level of cellular inhibitor of κBα (IκBα) and inhibited nuclear translocation of nuclear factor kappa B (NF-κB).

CONCLUSIONThese findings indicate that significant suppression of IL-6 and IL-8 expressions in LPS-stimulated BEAS-2B cells by OGE may be attributed to inhibiting activation of MAPKs and Akt and consequently suppressing nuclear translocation of NF-κB.

Cell Nucleus ; drug effects ; metabolism ; Cell Survival ; drug effects ; Cytosol ; drug effects ; metabolism ; Epithelial Cells ; drug effects ; enzymology ; metabolism ; Gene Expression Regulation ; drug effects ; Humans ; I-kappa B Proteins ; metabolism ; Interleukin-6 ; genetics ; metabolism ; Interleukin-8 ; genetics ; metabolism ; Intracellular Space ; drug effects ; metabolism ; Lipopolysaccharides ; pharmacology ; Mitogen-Activated Protein Kinases ; metabolism ; NF-KappaB Inhibitor alpha ; NF-kappa B ; metabolism ; Ocimum ; chemistry ; Phosphorylation ; drug effects ; Plant Extracts ; pharmacology ; Protein Transport ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Reactive Oxygen Species ; metabolism ; Respiratory System ; cytology ; Water

The acquisition of metastasis potential is a critical point for malignant tumors. Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) is a potential tumor suppress gene and frequently down-regulated in malignant tumors. It has been implicated that overexpression of MDA-7 led to proliferation inhibition in many types of human tumor. Invasion is an important process which is potential to promote tumor metastasis. However, the role and potential molecular mechanism of mda-7/IL-24 to inhibit the invasion of human melanoma cancer is not fully clear. In this report, we identified a solid role for mda-7/IL-24 in invasion inhibition of human melanoma cancer LiBr cells, including decreasing of adhesion and invasion in vitro, blocking cell cycle, down-regulating the expression of ICAM-1, MMP-2/9, CDK1, the phosphorylation of ERK and Akt, NF-kappaB and AP-1 transcription activity. Meanwhile, there was an increased expression of PTEN in mda-7/IL-24 over-expression LiBr cells. Our results demonstrated that mda-7/IL-24 is a potential invasion suppress gene, which inhibits the invasion of LiBr cells by the down-regulation of ICAM-1, MMP-2/9, PTEN, and CDK1 expression. The molecular pathways involved were the MAPK/ERK, PI3K-Akt, NF-kappaB, and AP-1. These findings suggest that mda-7/IL-24 may be used as a possible therapeutic strategy for human melanoma cancer.
CDC2 Protein Kinase/genetics/metabolism ; Cell Line, Tumor ; Cell Movement ; Down-Regulation ; G2 Phase Cell Cycle Checkpoints ; Humans ; Intercellular Adhesion Molecule-1/genetics/metabolism ; Interleukins/genetics/*metabolism ; M Phase Cell Cycle Checkpoints ; Matrix Metalloproteinase 2/genetics/metabolism ; Matrix Metalloproteinase 9/genetics/metabolism ; Melanoma/metabolism/pathology ; NF-kappa B/genetics/metabolism ; PTEN Phosphohydrolase/genetics/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/genetics/metabolism ; Transcription Factor AP-1/genetics/metabolism ; Up-Regulation