Boron-Containing MOF Nanoparticles with Stable Metabolism in U87-MG Cells Combining Microdosimetry To Evaluate Relative Biological Effectiveness of Boron Neutron Capture Therapy.

Accurate prediction of the relative biological effectiveness (RBE) of boron neutron capture therapy (BNCT) is challenging. The therapy is different from other radiotherapy; the dynamic distribution of boron-containing compounds in tumor cells affects the therapeutic outcome considerably and hampers accurate measurement of the neutron-absorbed dose. Herein, we used boron-containing metal-organic framework nanoparticles (BMOFs) with high boron content to target U87-MG cells and maintain the concentration of the 10B isotope in cells. The content of boron in the cells could maintain 90% (60 ppm) within 20 min compared with that at the beginning; therefore, the accurate RBE of BNCT can be acquired. The effects of BNCT upon cells after neutron irradiation were observed, and the neutron-absorbed dose was obtained by Monte Carlo simulations. The RBE of BMOFs was 6.78, which was 4.1-fold higher than that of a small-molecule boron-containing agent (boric acid). The energy spectrum of various particles was analyzed by Monte Carlo simulations, and the RBE was verified theoretically. Our results suggested that the use of nanoparticle-based boron carriers in BNCT may have many advantages and that maintaining a stable boron distribution within cells may significantly improve the efficiency of BNCT.

Association of mismatch repair deficiency in endometrial cancer with 18F-FDG PET/CT and clinicopathological features and their prognostic value.

PURPOSE: Identification of the mismatch repair (MMR) deficiency in endometrial cancer (EC) may aid in the screening of patients who may benefit from immunotherapy. Our goal was to investigate the relationship between MMR status and 18F-FDG PET/CT metabolic parameters and clinicopathological features in patients with EC, as well as to explore their prognostic value. METHODS: This retrospective study included 106 EC patients who were classified as MMR deficient (dMMR) or MMR proficient (pMMR) group based on MMR protein expression status evaluated by immunohistochemistry. Clinicopathological characteristics and PET metabolic parameters were compared between the dMMR and pMMR groups, and their relationships with MMR status and prognosis were evaluated. RESULTS: Of 106 EC patients, 30 patients (28.1%) had dMMR, while 76 (71.7%) had pMMR. Compared with the pMMR group, the dMMR group showed a lower prevalence of overweight (BMI ≥ 25) (17.2% vs. 43.9%, P = 0.019) and more lymph vascular space invasion (43.3% vs. 21.1%, P = 0.029). Although no relationship between glucometabolism parameters and MMR status was observed in all enrolled patients, higher SUVmax was observed in the endometrioid type of EC with MMR deficiency (P = 0.047). Additionally, SUVmax related to MMR status was found in EC patients with advanced FIGO stage (P = 0.026) or deep myometrial invasion (P = 0.026). Multivariate Cox regression analysis revealed that lymph node metastasis was independently predictive of PFS, while advanced FIGO stage was an independent predictor of OS. No significant association between MMR status and prognosis was found in EC. CONCLUSION: Higher SUVmax was associated with MMR deficiency in EC patients with endometrioid type, advanced stage, or deep myometrial invasion, which may be useful for predicting the MMR status and thus aiding in determination of immunotherapy for patients with EC.

RNF43 Suppressed Triple-Negative Breast Cancer Progression by Inhibiting Wnt/beta-Catenin Pathway.

OBJECTIVE: Triple-negative breast cancer (TNBC) is a subtype with high invasiveness. Due to lacking specific and effective therapies, it is necessary to explore the mechanism of TNBC progression and search for new therapeutic targets. METHODS: Data from the GEPIA2 database was analyzed to explore RNF43 expression in each subtype of breast cancer. RNF43 expression in TNBC tissue and cell lines was determined by RT-qPCR. In vitro biological function analyses including MTT assay, colony formation assay, wound-healing assay and Transwell assay were conducted to explore the role of RNF43 in TNBC. In addition, the markers of epithelial-mesenchymal transition (EMT) were detected by western blot. The expression of ß-Catenin and its downstream effectors were also detected. RESULTS: Data from the GEPIA2 database indicated that RNF43 expression was lower in tumor tissue compared to paired adjacent tissue in TNBC. In addition, RNF43 expression in TNBC was lower than in other subtypes of breast cancer. Consistently, down-regulation of RNF43 expression in TNBC tissue and cell lines was observed. Overexpressing RNF43 attenuated the proliferation and migration of TNBC cells. Depletion of RNF43 showed the opposite effect, confirming that RNF43 played an anti-oncogenic role in TNBC. In addition, RNF43 suppressed several markers of EMT. Furthermore, RNF43 restrained the expression of ß-Catenin and its downstream effectors, implying RNF43 exerted the suppressive role in TNBC by inhibiting the ß-Catenin pathway. CONCLUSIONS: This study demonstrated that the RNF43-ß-Catenin axis attenuated TNBC progression, which might provide novel therapeutic targets for TNBC.

Hsa_circ_0000851 promotes PDK1/p-AKT-mediated cell proliferation and migration by regulating miR-1183 in triple-negative breast cancer.

Breast cancer (BC) is the most common cause of cancer-related mortality in women worldwide. Circular RNAs (circRNAs), a type of non-coding RNA, have garnered interest because of their unique looped structure. In recent years, circRNAs have been shown to be involved in various diseases, including carcinogenesis, and to serve as biomarkers for early risk assessment and survival prediction of different tumour types. This study aimed to identify a novel circRNA, hsa_circ_0000851, generated from the sixth intron of the oncogene TCF4, reported to be involved in BC pathogenesis. Our study showed that hsa_circ_0000851 was mainly located in the cytoplasm of BC cells and upregulated in BC cell lines and tissue samples. Higher hsa_circ_0000851 expression levels resulted in increased proliferation of BC cells both in vitro and in vivo, while treatment of BC cells with hsa_circ_0000851 siRNA decreased their proliferation. We found that hsa_circ_0000851 bound directly to miR-1183, accelerating the expression of its target gene PDK1, which facilities BC cell proliferation and migration through PDK1/p-AKT.

Research on Elastic-Plastic Contact Behavior of Hemisphere Flattened by a Rigid Flat.

The contact behavior of a hemisphere pressed by a rigid plane is of great significance to the study of friction, wear, and conduction between two rough surfaces. A flattening contact behavior of an elastic-perfectly plastic hemisphere pressed by a rigid flat is researched by using the finite element method in this paper. This behavior, influenced by different elastic moduli, Poisson's ratios, and yield strengths, is compared and analyzed in a large range of interference values, which have not been considered by previous models. The boundaries of purely elastic, elastic-plastic, and fully plastic deformation regions are given according to the interference, maximum mean contact pressure, Poisson's ratio, and elastic modulus to yield strength ratio. Then, a new elastic-plastic constitutive model is proposed to predict the contact area and load in the elastic-plastic range. Compared with previous models and experiments, the rationality of the present model is verified. The study can be applied directly to the contact between a single sphere and a plane. In addition, the sphere contact can also be used to simulate the contact of single asperity on rough surfaces, so the present proposed model can be used to further study the contact characteristics of rough surfaces.

Diffuse biliary peritonitis secondary to rupture of metastatic liver adenocarcinomas after drug-eluting bead transcatheter arterial chemoembolization: a case report.

Transcatheter arterial chemoembolization (TACE) has become one of the first-line standard treatments for intermediate-advanced hepatocellular carcinoma, as well as an effective treatment for metastatic hepatic carcinoma. The majority of TACE-related complications are mild and acceptable to patients. Compared with conventional (C)-TACE, drug-eluting bead (DEB)-TACE allows permanent embolization of blood vessels, a slow continuous release of anti-tumour drugs in a locally targeted manner, and reduction of the systemic release of anti-tumour drugs, so that their adverse effects are significantly reduced. The general consensus is that DEB-TACE is safer and better tolerated by patients than C-TACE because serious complications after DEB-TACE are rarely reported. This current case report describes a rare case of diffuse biliary peritonitis secondary to rupture of a hepatic tumour after DEB-TACE. After the procedure, the patient presented with progressively worsening upper abdominal pain. As conventional management methods for the suspected tumour rupture failed, an emergency laparotomy was performed to remove the metastatic mass of differentiated hepatic adenocarcinoma. The patient remains under surveillance with no further complications. In our opinion, although DEB-TACE is safe and rarely has serious complications, caution should be exercised when this method is used to treat tumours that are located close to the liver surface.

Efficacy and safety of mycophenolate mofetil for IgA nephropathy: An updated meta-analysis of randomized controlled trials.

The efficacy and safety of mycophenolate mofetil (MMF) for immunoglobulin A nephropathy (IgAN) remains debatable. Therefore, the present meta-analysis was conducted with randomized controlled trials (RCTs). PubMed/MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were analyzed to identify eligible trials. The pooled risk ratio (RR) with 95% confidence interval (CI) was estimated for all the dichotomous outcome measures. A total of eight RCTs with nine publications (n=510 patients) were included. No significant difference was noted between therapeutic regimens with and without MMF for renal remission and end stage renal disease (ESRD) of patients with IgAN (seven trials; RR, 1.250; 95% CI, 0.993-1.574; P=0.057; and four trials; RR, 0.728; 95% CI, 0.164-3.236; P=0.676). To further define the effects of MMF for renal remission, subgroup analysis was performed, demonstrating that MMF was significantly more effective compared with the placebo (three trials; RR, 2.152; 95% CI, 1.198-3.867; P=0.010), although the immunosuppressive regimens with MMF had no significantly different effects compared with those without MMF (four trials; RR, 1.140; 95% CI, 0.955-1.361; P=0.146), indicating that MMF was superior to placebo and had a similar efficacy to other immunosuppressants for renal remission. In addition, subgroup analysis for ESRD revealed no significant differences between MMF and placebo and between the immunosuppressive regimens with and without MMF (three trials; RR, 0.957; 95% CI, 0.160-5.726; P=0.962; and one trial; RR, 0.205; 95% CI, 0.010-4.200; P=0.303). Furthermore, there were no significant differences between the therapeutic regimens with and without MMF in terms of the risk of adverse events. The present meta-analysis demonstrated that MMF was more effective compared with the placebo, may have similar efficacy to other immunosuppressants in terms of inducing renal remission of IgAN and may not increase the risk of adverse events. The long-term effects of MMF on the prognosis of patients with IgAN require verification in further studies.

Treatment of an incarcerated inguinal hernia associated with abdominal tuberculosis in an adult patient.

The incidence of tuberculosis is increasing worldwide, especially in developing countries. The prevalence of abdominal tuberculosis has been found to be as high as 12% in people with extrapulmonary tuberculosis. Peritoneal thickening and intestinal adhesions can occur in patients with abdominal tuberculosis. Inguinal hernias are extremely rare in people with abdominal tuberculosis; only 11 cases have been reported in the English-language literature, half of which involved pediatric patients. No definitive guideline on the management of such cases is available. In this report, we describe the unusual finding of an incarcerated inguinal hernia in an adult with abdominal tuberculosis and propose a therapy to treat this complicated disease based on our successful experience.

Development and assessment of a predictive nomogram for the progression of IgA nephropathy.

The present study is to establish a nomogram for predicting the prognosis of IgA nephropathy (IgAN). Of the 869 IgAN patients, four-fifths were randomly assigned to the development cohort and one-fifth to the validation cohort. The primary outcome was a composite event of either a ≥ 50% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease or death. The mean follow-up time was 44 months. The Cox regression model identified urinary protein excretion (1-3.5 g/d, HR 11.639, 95% CI 3.601-37.625; ≥ 3.5 g/d, HR 32.435, 95% CI 10.079-104.380), eGFR (G2, HR 5.293, 95% CI 2.011-13.932; G3, HR 15.797, 95% CI 6.584-37.905; G4, HR 34.619, 95% CI 13.887-86.301; G5, HR 217.651, 95% CI 83.807-565.248), hyperuricaemia (HR 7.031, 95% CI 4.126-11.980), mesangial proliferation (HR 36.667, 95% CI 5.098-263.711), segmental glomerulosclerosis (HR 5.122, 95% CI 3.114-8.425), tubular atrophy/interstitial fibrosis (T1, HR 33.351, 95% CI 7.831-142.044; T2, HR 213.888, 95% CI 51.048-896.182), crescents (C1, HR 3.123, 95% CI 1.771-5.510; C2, HR 7.353, 95% CI 3.590-15.062) and glomerulosclerosis (25-49%, HR 3.123, 95% CI 1.771-5.510; ≥ 50%, HR 14.384, 95% CI 8.813-23.479) for developing the nomogram. The C-index was 0.945 (95% CI 0.914-0.976) in both the development and validation cohorts, showing good agreement between the nomogram-predicted probability and actual free-of-progression probability. Thus, our nomogram could accurately predict the progression of IgAN patients.

Efficacy and Safety of Tacrolimus Versus Cyclophosphamide for Primary Membranous Nephropathy: A Meta-Analysis.

OBJECTIVE: The objective of this systematic review was to compare the efficacy and safety of tacrolimus with cyclophosphamide in primary membranous nephropathy (PMN) patients. DATA SOURCES AND STUDY ELIGIBILITY CRITERIA: We conducted a literature search in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CCRCT). Any study that compared the efficacy or safety between tacrolimus and cyclophosphamide in the adult PMN patients was included. RESULTS: We included four randomized controlled trials and two prospective cohort studies with 389 PMN patients. The pooled results using the Dersimonian and Laird method showed that renal remission rates at the longest follow-up periods were not significantly different between the tacrolimus and cyclophosphamide groups (overall remission, six trials, n = 389, relative risk [RR] 0.994 [95% confidence interval [CI] 0.768-1.286); complete remission, six trials, n = 389, RR 1.256 [95% CI 0.733-2.150]). Further analyses found that tacrolimus was comparable with cyclophosphamide for inducing renal remission within 1 year but inferior to cyclophosphamide after 1-year follow-up. It should be noted that only two studies reported the outcomes after 1-year follow-up, which might be considered as weak evidence. The rates of relapse and the drop-outs due to adverse effects were not significantly different (relapse, six trials, n = 389, RR 2.244 [95% CI 0.892-5.644]; drop-outs, six trials, n = 389, RR 1.330 [95% CI 0.412-4.291]). However, the cyclophosphamide group had a significantly higher risk of leukopenia than the tacrolimus group (four trials, n = 216, RR 0.203 [95% CI 0.045-0.916]), whereas the rates of tremor were significantly higher in the tacrolimus group than in the cyclophosphamide group (three trials, n = 202, RR 8.939 [95% CI 1.694-47.173]). LIMITATIONS: The quality and short follow-up durations of the studies limited the reliability of our conclusions. CONCLUSIONS: Tacrolimus was comparable with cyclophosphamide for inducing renal remission of PMN patients within 1 year, but the long-term effects need to be investigated. The cyclophosphamide group had a significantly higher risk of leukopenia, whereas the tacrolimus group had significantly higher rates of tremor. These conclusions need to be further verified.

A distal ileum malignant peripheral nerve sheath tumor causing intussusception in a patient in China: a case report.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) arise from a peripheral nerve or display nerve sheath differentiation. Most MPNSTs typically originate on the trunk, extremities, head, neck, and paravertebral regions. Gastrointestinal MPNSTs are rare entities with only 10 cases reported worldwide in the literatures. CASE PRESENTATION: Here, we report the first Chinese case of a malignant peripheral nerve sheath tumor of the distal ileum presenting as intussusception. A 53-year-old female patient without pathological antecedent for neurofibromatosis was admitted with pain in the right lower abdomen and multiple episodes of vomiting for 1 week. Preoperative diagnosis was intussusception with a contrast-enhanced computed tomography scan (CECT) of the abdomen showing characteristic target sign. Due to difficulty reducing the ileum-colon intussusception, right hemicolectomy with ileocolostomy was performed. Histopathology was suggestive of low-grade MPNST. The patient received postoperative care and was followed up for 9 months. There is no sign of tumor recurrence and metastatic disease. CONCLUSIONS: This case is unique in terms of a rare tumor presenting with unusual complication.

[Dynamic renal scintigraphy versus dual-plasma sample clearance for determining glomerular filtration rates in patients with nonfunctioning kidneys shown by intravenous pyelography].

OBJECTIVE: To study the actual glomerular filtration rates (GFR) in patients with nonfunctioning kidneys as shown by intravenous pyelography (IVP) using single photon emission computed tomography (SPECT) dynamic renal scintigraphy and dual-plasma sample clearance method. METHODS: We retrospectively analyzed 107 patients with nonfunctioning kidneys shown by IVP who underwent renal dynamic 99Tcm-DTPA SPECT imaging. GFR was measured by Gates' methods (GFRGates') and dual-plasma sample clearance method (GFRdual-plasma). Based on the dynamic functional images and GFRdual-plasma measurements, the patients were categorized into mild renal impairment (GFRdual-plasma≥30 mL/min), moderate renal impairment group (GFRdual-plasma of 20-30 mL/min), severe renal impairment group (GFRdual-plasma of 10 to 20 mL/min), and nonfunctioning kidney group (GFRdual-plasma≤10 mL/min), and GFRGates' were compared among the groups. RESULTS: According to GFRdual-plasma, the numbers of patients having mild, moderate, and severe renal impairment and nonfunctioning kidneys were 12(11.2%), 33(30.8%), 41(38.3%), and 21(19.6%), respectively. GFRdual-plasma and GFRGates' were not significantly different in mild and moderate renal impairment groups, but in patients with severe renal impairment, GFRdual-plasma was significantly lower than GFRGates' (13.9∓6.2 vs 18.8∓4.2 mL/min; t=-2.73, P=0.03), which was also the case with patients with nonfunctinging kidneys (4.5∓2.1 vs 7.2∓3.2 mL/min; t=-3.81, P=0.005). CONCLUSION: Of the patients with nonfunctinging kidneys shown by IVP, only 58% of them actually have severe renal impairment or worse, and further SPECT dynamic renal scintigraphy is necessary to assess the actual risk of renal function impairment before operation.

[Correlation of examination couch position and height with image registration accuracy in an effective field of vision of SPECT/CT].

OBJECTIVE: To explore the correlation of the position and height of the examination couch with the accuracy of image registration in an exact effective field of vision (FOV) of single photon emission computed tomography/computed tomography (SPECT/CT) and determine the optimal position of the examination couch for best image registration. METHODS: The tests were performed on a SPECT/CT with 6 radioactive (153)Gd sources in 3 groups (two in each group with energy peak of 40.9 Kev, 41.54 Kev, and 103.18 Kev) in an assorted standard pattern. Thirteen groups of slice data were obtained by changing the position and height of the bed but keeping the tomograpy slice constant. The bias of the accuracy of image registration was acquired using ALIGNMENT software and compared for different examination couch positions and heights. RESULTS: The position of the examination couch at 0 cm in the Z axis and -4 cm in the Y axis showed the least error of image registration. CONCLUSION: To achieve optimal SPECT and CT image fusion, quality control must be implemented and calibration of image registration accuracy should be done when necessary.