Objective: Radical hysterectomy has long been considered as the standard surgical treatment for early-stage cervical cancer (IA2 to IB1 stages), according to the 2009 International Federation of Obstetrics and Gynecology. This study aims to conduct an in-depth evaluation of the effectiveness and safety of non-radical surgery as an alternative treatment for patients with early-stage cervical cancer. Methods: A systematic search of online databases including PubMed, Embase, and the Cochrane Library was conducted to identify relevant literature on surgical treatment options for early-stage cervical cancer. Keywords such as "cervical cancer," "conservative surgery," "early-stage," "less radical surgery," and "simple hysterectomy" were used. Meta-analysis was performed using Stata 15.0 software, which included randomized controlled trials (RCTs) and cohort studies. Results: This meta-analysis included 8 eligible articles covering 9 studies, with 3,950 patients in the simple hysterectomy (SH) surgery group and 6,271 patients in the radical hysterectomy (RH) surgery group. The results indicate that there was no significant difference between the two groups in terms of the Overall Survival (OS) (HR = 1.04, 95% CI: 0.86-1.27, p = 0.671; Heterogeneity: I2 = 33.8%, p = 0.170), Disease Free Survival (DFS) (HR = 1.39, 95% CI: 0.59-3.29, p = 0.456; Heterogeneity: I2 = 0.0%, p = 0.374), Cervical Cancer Specific Survival (CCSS) (HR = 1.11, 95% CI: 0.80-1.54, p = 0.519; Heterogeneity: I2 = 11.9%, p = 0.287) and recurrence rate (RR = 1.16, 95% CI: 0.69-1.97, p = 0.583; Heterogeneity: I = 0.0%, p = 0.488). However, the mortality rate (RR = 1.35, 95% CI: 1.10-1.67, p = 0.006; Heterogeneity: I2 = 35.4%, p = 0.158) and the rate of postoperative adjuvant therapy (RR = 1.59, 95% CI: 1.16-2.19, p = 0.004; Heterogeneity: I2 = 92.7%, p < 0.10) were higher in the SH group compared to those in the RH group. On the other hand, the incidence of surgical complications was lower in the SH group (RR = 0.36, 95% CI: 0.21-0.59, p = 0.004; Heterogeneity: I2 = 0.0%, p = 0.857) than that in the RH group. Subgroup analysis revealed that patients in the IB1 stage SH group had a significantly higher mortality rate compared to those in the RH group (RR = 1.59, 95% CI: 1.23-2.07, p < 0.001; Heterogeneity: I2 = 0.0%, p = 0.332). However, there was no significant difference in mortality rates between the two groups for patients at stage IA2 (RR = 0.84, 95% CI: 0.54-1.30, p = 0.428; Heterogeneity: I2 = 26.8%, p = 0.243). In the subgroups positive for Lymphovascular Space Invasion (LVSI), patients in the SH group had a significantly higher mortality rate than those in the RH group (RR = 1.34, 95% CI: 1.09-1.65, p = 0.005; Heterogeneity: I2 = 41.6%, p = 0.128). However, in the LVSI-negative subgroups, there was no significant difference in mortality rates between the two groups (RR = 0.33, 95% CI: 0.01-8.04, p = 0.499). Conclusion: For patients with early-stage cervical cancer patients at IA2 without LVSI involvement, comparisons between the two groups in terms of OS, DFS, CCSS, recurrence rate, and mortality rates revealed no statistically significant differences, indicating that the choice of surgical approach does not affect long-term survival outcomes for this specific patient group. For patients at IB1 and IA2 stages with LVSI involvement, while there were no significant differences between the two groups in OS, DFS, CSS, and recurrence rate, a significant increase in mortality rates was observed in the SH group. This indicates a potential elevated risk of mortality associated with SH in this subset of patients. Notably, the incidence of surgical complications was significantly lower in the SH group compared to the RH group, highlighting the safety profile of SH in this context. Significantly, among patients in the SH group, an increase in the rate of postoperative adjuvant treatment is associated with a higher occurrence of treatment-related complications. To facilitate more precise patient selection for conservative surgical management, future prospective studies of superior quality are imperative to gain deeper insights into this matter. Systematic review registration: PROSPERO (CRD42023451609: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023451609).
OBJECTIVE: To evaluate the efficacy and safety of mirvetuximab soravtansine in treating recurrent ovarian cancer with folate receptor alpha (FRa) expression. METHODS: A comprehensive search was conducted on online databases, including PubMed, Cochrane Library, and EMBASE, to identify relevant literature about the efficacy and safety of mirvetuximab soravtansine in recurrent ovarian cancer with FRa-positive expression. The keywords were the following: recurrent ovarian cancer, mirvetuximab soravtansine, FRa, and antibody-drug conjugate. Furthermore, studies that satisfied the necessary qualifications were carefully evaluated for further meta-analysis. RESULTS: This meta-analysis involved the examination of seven trials with a total of 631 patients. According to the pooled data, the objective response rate (ORR) was 36% (95%CI: 27%-45%). Similarly, the disease control rate (DCR) was 88% (95% CI: 84-91%). Furthermore, the median progression-free survival (PFS) was determined to be 6.1 months (95% CI: 4.27-7.47). The overall response rate and PFS for platinum-resistant ovarian cancer were found to be 29% (95% CI: 25-32%) and 6.26 months (95% CI: 4.67-7.85), respectively. The most often observed adverse events (AEs) in patients with recurrent ovarian cancer (OC) receiving mirvetuximab soravtansine were blurred vision (all grades: 45%, Grade III: 2%), nausea (all grades: 42%, Grade III: 1%), and diarrhea (all grades: 42%, Grade III: 2%). These AEs were specifically associated with the safety profile of mirvetuximab soravtansine in this patient population. CONCLUSION: The efficacy of mirvetuximab soravtansine in treating recurrent ovarian cancer with FRa-positive expression is satisfactory, and the safety is tolerable.
Antibodies, Monoclonal, Humanized , Immunoconjugates , Maytansine , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/drug therapy , Drug Resistance, Neoplasm , Carcinoma, Ovarian Epithelial/drug therapy , Immunoconjugates/adverse effects , Maytansine/analogs & derivatives
This paper presents comprehensive research of the advantages and applicability of various concrete carbonation detection methods. Employing a combination of Phenolphthalein indicator (PI), Thermogravimetric analysis (TGA), X-ray phase analysis (XRD), Fourier transform infrared spectroscopy (FTIR), and Quantitative calcium carbonate analysis (CA), a detailed comparison to determine the carbonation depth in the partial carbonation zone of concrete specimens is conducted. Among the quantitative analysis methods, CA measures CaCO3 content based on chemical reactions, while TGA obtains the concentration distribution of Ca(OH)2 and CaCO3. Among qualitative analysis methods, XRD tested the intensity distribution of Ca(OH)2 and CaCO3, while FTIR traced the characteristic peaks of C-O functional groups in a specific spectral range to determine the depth of carbonation of concrete. Results indicate that the depth of carbonation values measured by CA, TGA, XRDA, and FTIR are 2-3 times higher than those measured by PI. This research may provide valuable insights for the design of carbonation detection in concrete.
Objective: To explore the efficacy and safety of PD-1/PD-L1 inhibitors in treating recurrent/refractory ovarian cancer (OC). Methods: The online databases, including PubMed, Embase and Cochrane Library, were searched for relevant literatures on exploring the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of recurrent/refractory OC. The keywords are as follows: Ovarian neoplasms, programmed death receptor, PD-1, PD-L1, immunotherapy, and immune checkpoint inhibitor. Furthermore, qualified studies were screened for further meta-analysis. Results: In this study, 11 studies (990 patients) were analyzed to evaluate the efficacy of PD-1/PD-L1 inhibitors in the treatment of recurrent/refractory OC. The combined results proved that the objective response rate (ORR) was 6.7%, 95% CI (4.6%,9.2%), disease control rate (DCR) was 37.9%, 95% CI (33.0%, 42.8%), median overall survival (OS) was 10.70 months, 95% CI (9.23, 12.17), and median progression free survival (PFS) was 2.24 months, 95% CI (2.05, 2.43). In addition, in terms of the safety of patients suffering from recurrent/refractory OC and receiving PD-1/PD-L1 inhibitors, the combined treatment related adverse events (TRAEs) were 70.9% (61.7%-80.2%), and the combined immune related adverse events (iAEs) were 29%, 95% CI (14.7%, 43.3%). Conclusion: In patients with recurrent/refractory OC, PD-1/PD-L1 inhibitors were used alone and there was no obvious evidence of improved efficacy and survival. As for safety, the incidences of TRAEs and iAEs are high, so PD1/PD-L1 inhibitors should be applied according to individual conditions. Clinical Trial Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367525, identifier CRD42022367525.
Objective: The selection of minimally invasive surgery (MIS) or open laparotomy for ovarian cancer (OC) after neoadjuvant chemotherapy still remains controversial. This study aimed to assess the efficacy and safety of MIS versus open laparotomy following neoadjuvant chemotherapy for advanced OC, so as to provide another option to select optimal surgical procedures for patients with OC. Methods: Relevant literature studies about the risks of progression or mortality between women receiving MIS and open laparotomy for interval debulking surgery (IDS) were searched in the online databases, including PubMed, Embase, and the Cochrane Library with the following keywords: "ovarian neoplasms", "minimally invasive surgical procedures", "laparotomy", and "neoadjuvant therapy". Eligible studies were screened out for further meta-analysis. Results: Six eligible literature studies, with 643 patients in the MIS group and 2,885 patients in the open laparotomy group, were included in this meta-analysis. No significant differences were detected in the overall survival (OS) of patients with OC who were treated with MIS or open laparotomy [hazard ratio (HR) = 0.85; 95% confidence interval (CI) = 0.59-1.23; heterogeneity: P = 0.051, I2 = 57.6%]. However, the progression-free survival (PFS) was significantly higher in patients with OC treated with MIS than those treated with laparotomy (HR = 0.73; 95% CI = 0.57 to 0.92; heterogeneity: P = 0.276, I2 = 22.4%). The completeness of debulking removal (R0 rate) in the open laparotomy group was not statistically higher compared with the control group (RR = 1.07; 95% CI = 0.93 to 1.23; heterogeneity: P = 0.098, I2 = 52.3%), and no significant differences in residual disease of ≤1 cm (R1) (RR = 1.08; 95% CI = 0.91 to 1.28; heterogeneity: P = 0.330, I2 = 12.6%) and postoperative complications were found between the two groups (RR = 0.72; 95% CI = 0.34 to 1.54; heterogeneity: P = 0.055, I2 = 60.6%). Furthermore, the length of stays in hospital was significantly shorter in patients with OC treated with MIS than those treated with open laparotomy (Standard Mean Difference (SMD) = -1.21; 95% CI = -1.78 to -0.64; heterogeneity: P < 0.001, I2 = 92.7%]. Conclusions: For IDS after NACT in patients with advanced OC, complete cytoreductive surgery with MIS is another feasible and effective choice. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022298519, identifier CRD42022298519.
The effects of reinforcement corrosion and sustained axial load on mechanical performance of reinforced concrete (RC) columns were investigated in the present study. Three different degrees of reinforcement corrosion were achieved by controlling the durations of accelerated corrosion test (i.e., 16 days, 31 days, and 63 days). Three levels of sustained axial load (i.e., 0%, 30%, and 60% of the ultimate bearing capacity) were concentrically applied on column specimens. The impressing current and the sustained load were applied on column specimens simultaneously, mimicking the degradation of RC columns in real structures. Results indicated that transverse stirrups yielded higher corrosion degree than that of the longitudinal rebar under identical duration of accelerated corrosion test. The application of sustained axial load improved the performance of corroded RC columns in terms of the reinforcement corrosion, the ultimate axial load, as well as the stiffness. Additionally, more longitudinal cracks along the main rebar were exhibited for column specimens subjected to sustained axial load. For both loaded and unloaded column specimens, corrosion of reinforcing steels exacerbated the mechanical deterioration of RC columns, lowering the ultimate load carrying capacity and the axial deformation compared to the uncorroded columns.
BACKGROUND: Previous studies provided inconsistent results regarding the association between inflammatory bowel disease (IBD) and risk of abnormalities of uterine cervix. The study aimed to make a meta-analysis to evaluate the association between IBD and risk of abnormalities of uterine cervix. METHODS: Articles published until April 2021 and regarding the association between IBD and risk of abnormalities of uterine cervix were searched in the following databases: PubMed, Web of Science, EMBASE, Medline, and Google Scholar. Odds ratios (ORs) from case-control studies and relative risks (RRs) from cohort studies with their 95% confidence intervals (CIs) were computed to generate a pooled effect size and 95% CI using STATA 12.0 software. RESULTS: The present study finally included seven cohort studies (including 94 144 IBD patients and 53 661 004 HC) and four case-control studies (including 20 267 cases and 60 034 matched controls). The meta-analysis indicated a positive association between IBD and risk of abnormalities of uterine cervix with a random-effects model (OR/RR = 2.46, 95% CI 1.55-3.91, I2 = 91.8%, p < 0.001). However, no significant association between IBD and risk of cervical cancer was showed in the study with a random-effects model (OR/RR = 1.54, 95% CI 0.83-2.85, I2 = 82.2%, p < 0.001). CONCLUSION: In conclusion, IBD is associated with a 146% higher risk of abnormalities of uterine cervix. However, the study demonstrated no significant association between IBD and risk of cervical cancer. Thus, a conventional screening for abnormalities of uterine cervix is essential for IBD patients.
Inflammatory Bowel Diseases , Uterine Cervical Neoplasms , Cohort Studies , Female , Humans , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/epidemiology , Odds Ratio , Risk , Uterine Cervical Neoplasms/epidemiology
BACKGROUND: Ovarian cancer (OC) is a gynecological malignancy with the highest mortality rate. Cisplatin (DDP) based chemotherapy is a standard strategy for ovarian cancer. Despite good response rates for initial chemotherapy, almost 80% of the patients treated with DDP based chemotherapy will experience recurrence due to drug-resistant, which will ultimately result in fatality. The aim of the present study was to examine the pathogenesis and potential molecular markers of cisplatin-resistant OC by studying the differential expression of mRNAs and miRNAs between cisplatin resistant OC cell lines and normal cell lines. METHODS: Two mRNA datasets (GSE58470 and GSE45553) and two miRNA sequence datasets (GSE58469 and GSE148251) were downloaded from the Gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were screened by the NetworkAnalyst. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to analyze the biological functions of DEGs. The protein-protein interaction network was constructed using STRING and Cytoscape software to identify the molecular mechanisms of key signaling pathways and cellular activities. FunRich and MiRNATip databases were used to identify the target genes of the DEMs. RESULTS: A total of 380 DEGs, and 5 DEMs were identified. Protein-protein interaction (PPI) network of DEGs containing 379 nodes and 1049 edges was constructed, and 4 key modules and 24 hub genes related to cisplatin-resistant OC were screened. Two hundred ninety-nine target genes of the 5 DEMs were found out. Subsequently, one of these 299 target genes (UBB) belonging to the hub genes of GSE58470 and GSE45553 was identified by MCODE and CytoHubba,which was regulated by one miRNA (mir-454). CONCLUSIONS: One miRNA-mRNA regulatory pairs (mir-454-UBB) was established. Taken together, our study provided evidence concerning the alteration genes involved in cisplatin-resistant OC, which will help to unravel the mechanisms underlying drug resistant.
Drug Resistance, Neoplasm/genetics , MicroRNAs/genetics , Ovarian Neoplasms/genetics , Protein Interaction Maps/genetics , Ubiquitin/genetics , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Cisplatin/therapeutic use , Computational Biology , Databases, Genetic , Female , Gene Ontology , Humans , MicroRNAs/analysis , Microarray Analysis , Neoplasm Recurrence, Local/genetics , Ovarian Neoplasms/drug therapy , RNA, Messenger/analysis , RNA, Messenger/genetics , Signal Transduction , Software
Based on the fractal geometry, a quantitative index describing the development degree of the internal corrosion expansion of reinforced concrete was proposed. This approach could describe the similarity and complexity of the development of corrosion-induced cracks in concrete simultaneously. Based on this approach, the influence of cracking pattern and coarse aggregate distribution on crack distribution was investigated. This study obtained the crack distribution of reinforced concrete by using the half-soaking galvanic accelerated corrosion method. The results showed that the cracking pattern was the main factor affecting the complexity of crack distribution. For cracks with the simplest cracking pattern, the presence of coarse aggregate and its surface irregularity greatly affected their development trend.
For cementitious materials, electrical resistivity is often used in the study of the cement hydration process at early age, as one of the few indicators that can be continuously and non-destructively monitored. Variation characteristics of resistivity are widely reported to interact with the early-age performance of cement paste, such as hydration kinetics parameters and setting time. However, there is no reasonable mathematical model to predict the resistivity at early ages, especially within the first 24 h, due to significant changes in the porosity and degree of saturation. In this work, a mathematical model was developed by considering the partially saturated state and density change of C-S-H (calcium silicate hydrate). To verify the model, two experimental methods were chosen, including the non-contact electrical resistivity test and isothermal calorimetry test. The hydration heat and resistivity of cement paste with a water-cement ratio of 0.35 and 0.45 were continuously monitored for 3 days. In the resistivity test, embedded temperature sensors were used to monitor the internal temperature and temperature correction was treated carefully in order to obtain accurate data. The test results prove that the mathematical model can accurately predict electrical resistivity and describe the saturation state of early-age cement pastes under sealed curing.
In this work, the failure process of non-corroded and corroded reinforced concrete (RC) columns under eccentric compressive loading is studied using the acoustic emission (AE) technique. The results show that reinforcement corrosion considerably affects the mechanical failure process of RC columns. The corrosion of reinforcement in RC columns leads to highly active AE signals at the initial stage of loading, in comparison to the non-corroded counterparts. Also, a continuous AE hit pattern with a higher number of cumulative hits is observed for corroded RC columns. The spatial distribution and evolution of AE events indicate that the reinforcement corrosion noticeably accelerates the initiation and propagation of cracking in the RC columns during compressive loading. The AE characteristics of corroded RC columns are in agreement with the macroscopic failure behaviors observed during the damage and failure process. A damage evolution model of corroded RC columns based on the AE parameters is proposed.
In this work, the non-uniform corrosion characteristics of steel bars in stressed reinforced concrete beams after accelerated depassivation and seven-year outdoor natural corrosion is analyzed using fractal theory. 3D laser scanning and 3D reconstruction technology are applied to collect the cross-sectional area along the steel bars and obtain the corrosion curves. The non-uniformity of corrosion is analyzed by fractal dimensions which is calculated by variation method. The results indicate that the initial loading level and loading zone have some influence on non-uniform characteristics of steel bars. For an ordinary concrete beam, the increase of load can cause a reduction of fractal dimension of corrosion curves by 5%, which indicates the non-uniformity of corrosion will increase with the increase of load level. The fractal dimension in the bending zone is lower than that in the tension-shear zone, which indicates that corrosion is more non-uniform in bending zone. However, the loading level and loading zone have a slight influence on corrosion level, and the maximum difference of corrosion level caused by load is merely 0.23%. Furthermore, the corrosion level increases with the decrease of fractal dimension, suggesting that the non-uniformity of corrosion increases with the growth of corrosion level. The incorporation of slag powder can help reduce the non-uniformity of corrosion, but the influence on reduction of the corrosion level is about 0.25%. For concrete structures under marine environment, application of slag powder is a good method to slow down the corrosion and reduce the non-uniformity of corrosion.
Previous studies indicated the potential of styrene maleic acid copolymer (SMA)-conjugated pirarubicin (4'-O-tetrahydropyranyldoxorubicin [THP]) for targeted anticancer therapy based on the enhanced permeability and retention effect. In this study, to achieve further improved therapeutic efficacy, a pH-responsive SMA-conjugated THP-containing hydrazone bond (SMA-hyd-THP) was synthesized and evaluated in vitro and ex vivo using human ovarian cancer cells and tissues. SMA-hyd-THP showed good water solubility, forming micelles with a mean particle size of 48.0 nm, which is applicable for enhanced permeability and retention-based tumor accumulation. The THP loading in this preparation was 15% (wt/wt), and release rate of free THP from SMA-hyd-THP at physiological pH (7.4) was approximately 10% in 72 h. However, it increased rapidly at pH 6.5 (42%) and 5.5 (83%), which indicates that tumor environment of weak acidic condition (pH 6.5-6.9) is favorable for release of THP. This notion was partly proved by incubating SMA-hyd-THP with tumor tissues from ovarian cancer patients. In addition, release of THP was not affected by serum, suggesting that SMA-hyd-THP is relatively stable in circulation. Finally, SMA-hyd-THP showed much increased cytotoxicity against various ovarian cancer cells at acidic tumor pH (6.5). These findings may provide an option for targeted therapy against ovarian cancer.
