Intraoperative Radiotherapy as a Tumour-Bed Boost Combined with Whole Breast Irradiation Versus Conventional Radiotherapy in Patients with Early-Stage Breast Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: There is no definitive answer regarding the efficacy of intraoperative radiotherapy (IORT) as a tumour bed boost for patients with early-stage breast cancer. The purpose of this meta-analysis was to summarise the available evidence and explore the efficacy and safety of IORT combined with whole breast irradiation (WBI) versus conventional radiotherapy in women with early-stage breast cancer who underwent breast-conserving surgery. METHODS: The PUBMED, MEDLINE, EMBASE, Web of Science, and Cochrane Library databases were searched from inception to December 31, 2022. We collected studies on the efficacy, cosmetic outcome, and safety of IORT boost combined with WBI compared with those of conventional radiotherapy in patients with early-stage breast cancer after breast-conserving surgery. Two authors independently performed the literature selection and data extraction. The quality of the randomised, controlled trials (RCTs) was assessed according to the PEDro scale. The quality of non-RCTs was assessed according to the Methodological Index for Non-Randomised Studies. Risk ratios (RRs) for the local recurrence rate (LRR), distant metastasis rate (DMR), disease-free survival (DFS), cosmetic outcome, and toxicity were pooled using fixed or random effects models. Meta-analysis of the included studies was performed by using RevMan 5.3 software. RESULTS: Nine studies, including one RCT and eight non-RCTs, with a total of 3219 patients were included. In terms of LRR, there was no significant benefit of IORT boost+WBI over conventional radiotherapy (with or without the tumour bed boost) (RR = 0.77, 95% confidence interval (CI): 0.54-1.09, P = 0.14), but a trend towards benefit could be identified. There was a significant reduction in DMR in the IORT boost+WBI group (RR = 0.63, 95% CI: 0.46-0.85, P = 0.003) and a significant improvement in DFS (RR = 0.40, 95% CI: 0.25-0.65, P = 0.0002). Exploratory subgroup analysis showed that the DMR and DFS of the electron boost group were significantly better than those of conventional radiotherapy group, and there was a tendency for LRR to improve in the electron boost group. However, the LRR, DMR, and DFS did not effectively improve in the x-ray boost group. In terms of appearance and toxicity, there were no significant differences in cosmetic outcome, fibrosis, and hyperpigmentation between the two groups (RR = 0.99, 95% CI: 0.91-1.07, P = 0.78; RR = 1.02, 95% CI: 0.41-2.56, P = 0.96; RR = 0.42, 95% CI: 0.10-1.72, P = 0.23), but the incidence of oedema was significantly reduced in the IORT boost+WBI group (RR = 0.27, 95% CI: 0.13-0.59, P = 0.0009). CONCLUSIONS: IORT boost+WBI is more effective than conventional radiotherapy after breast-conserving surgery in patients with early-stage breast cancer, and electron boost exhibits better efficacy than x-ray boost. In addition, the cosmetic and safety profiles of IORT boost+WBI are not inferior to those of conventional radiotherapy.

A novel incision technique of a totally implanted venous access port in the upper arm for patients with breast cancer.

BACKGROUND: A totally implanted venous access port (TIVAP) in the upper arm is a safe and cost-effective vascular access device and is widely used in breast cancer patients. Traditional tunnelling technique increases the operation time and has an unsatisfied cosmetic effect, so we explored the feasibility, cosmetic effect and complications of an upper arm port with a novel incision in this retrospective study. METHODS: We reviewed 489 cases of totally implantable venous access port implantation in the upper arm with two types of incisions in our centre from 1 January 2018 to 30 January 2022. The patients were divided into two different incision groups including the puncture site incision group (n = 282) and the conventional tunnelling group (n = 207). The comparison of the results was collected between the two groups, and contributing factors were analyzed for major complications. RESULTS: A total of 489 patients were successfully implanted with arm ports using the puncture site incision technique (n = 282, 57.7%) and conventional tunnelling technique (n = 207, 42.3%). The average operation time of the two types of incisions was 36.5 ± 15 min in the puncture site incision group and 55 ± 18.1 min in the tunnel needle group (P < 0.05). In terms of complications, 33 catheter-related complications occurred (6.4%), including 9 cases of infection, 15 cases of catheter-related thrombosis and 7 cases of skin exposure. Fourteen patients in the puncture site incision group developed complications compared with 17 in the traditional incision group. There were no significant differences between the two groups in terms of overall complication events (5.0% and 8.2%, P = 0.145) while the same result was found in each complication event. Weight, total cholesterol and diabetes were found to be associated with device-related infections in the univariate Cox proportional hazard regression models. Diabetes was found to be associated with device-related infections in multivariate analysis while hypertension was associated with thrombosis. CONCLUSIONS: The puncture site incision method is a novel technique with a better cosmetic appearance and less operation time than the traditional tunnelling technique, providing a comparable overall rate of complications. It offers a preferable choice for clinicians when dealing with different situations of patients. It is worthy of being used and promoted for patients requiring the totally implanted venous access port in the upper arm.

MiR-490-3p inhibits autophagy via targeting ATG7 in hepatocellular carcinoma.

The miR-490-3p was transfected into HepG2 cells to explore the correlation between miR-490-3p and hepatocellular carcinoma cell proliferation, apoptosis, and autophagy and its downstream target gene ATG7. Then we could possibly provide a mechanism for the treatment of hepatocellular carcinoma. MiR-490-3p was screened out by fold change > 4 and P < 0.01 using gene microarray data. The expression level of miR-490-3p was tested by qRT-PCR and the prognosis analysis was achieved by using TCGA data. The cell proliferation was tested via colony formation assay and CCK-8 after the miR-490-3p mimics were transfected into HepG2 cells; the variations of cell cycle and apoptosis was examined by flow cytometry assay; the number of autophagosome was observed by electron microscopy and the changes of autophagy-relative protein LC-II and LC-I as well as their ratio was tested by western blot. MiR-490-3p is low expressed in hepatocellular carcinoma cell lines and tissues. The results of TCGA showed that miR-490-3p high expression indicated better prognosis. After HepG2 cells were transfected with miR-490-3p mimics, cell viability was increased, cell proliferation was enhanced, cell cycle was blocked in G0/G1 phase, cell apoptosis rate was increased, the number of autophagosomes was reduced, autophagy-associated protein LC-II was decreased, and LC-I was increased and their ratio was decreased. After 3-MA was added, cell proliferation was declined, cell apoptosis rate was increased. Besides, the autophagy was inhibited by knocking down the ATG7, which promoted the cell apoptosis. MiR-490-3p could suppress cell proliferation, retard cell cycle and upgrade cell apoptosis by inhibiting autophagy in HCC cells via targeting ATG7. © 2018 IUBMB Life, 70(6):468-478, 2018.

Maternal Bisphenol A exposure impaired endochondral ossification in craniofacial cartilage of rare minnow (Gobiocypris rarus) offspring.

Bisphenol A (BPA), an endocrine disrupting compound, is present in the aquatic environment. BPA can mimic estrogen and cause adverse effects on development and reproduction in different organisms. As epigenetic modifications due to BPA exposure have been reported, the interest on the effects of this chemical has increased. To assess the potential effects of maternal BPA exposure on offspring bone development, adult Gobiocypris rarus (G. rarus) females were exposed to 15 µg L-1 and 225 µg L-1 BPA for 21 days. Eggs were collected after artificial spawning and fertilized with the fresh milt of non-exposed male fish. The offspring were raised in clean water and randomly selected for examination at different development stages. Our results showed that specific effects including poor quality of the embryos, increased malformation (bent spine and tail), and delayed craniofacial cartilage ossification of the larvae. Additionally, the transcripts of ossification related genes were significantly downregulated in offspring, and the lysyloxidase activity decreased. The present study demonstrated the maternal-mediated skeleton toxicity of BPA and its adverse effects on G. rarus.

A survey of breastfeeding among women with previous surgery for benign breast disease: a descriptive exploratory study.

BACKGROUND: Surgery is the primary treatment for benign breast disease and causes some disruption to the normal physiology of the breast, even when this disruption is localised, it remains unclear whether it affects women's ability to breastfeed. There are only a few studies describing the experience of breastfeeding in women who have undergone benign breast disease (BBD) surgery. METHODS: We retrospectively analysed data from patients aged 20-40 years in Guangdong, China, who underwent breast lumpectomy for BBD in our department between 01 January 2013 and 30 June 2019, with a follow-up date of 01 February 2022. Patients were included who had a history of childbirth between the time of surgery and the follow-up date. By collecting general information about this group of patients and information about breastfeeding after surgery, we described the breastfeeding outcomes of women of a fertile age who had previously undergone surgery for benign breast disease. RESULTS: With a median follow-up of 5.9 years, a total of 333 patients met the inclusion criteria. From the breastfeeding data of the first child born postoperatively, the mean duration of 'exclusive breastfeeding' was 5.1 months, and the mean duration of 'any breastfeeding' was 8.8 months. The rate of 'ever breastfeeding' is 91.0%, which is lower than the national average of 93.7%, while the exclusive breastfeeding rate at six months was 40.8%, was higher than the 29.2% national average. The any breastfeeding rate at 12 months was 30.0%, which was well below the 66.5% national average. The common reason for early breastfeeding cessation was insufficient breast milk. A total of 29.0% of patients who had ever breastfed after surgery voluntarily reduced the frequency and duration of breastfeeding on the operated breast because of the surgery. CONCLUSIONS: There are some impacts of BBD surgery on breastfeeding and some may be psychological. Institutions should provide more facilities for mothers who have undergone breast surgery to help them breastfeed, such as conducting community education on breastfeeding after breast surgery, training professional postoperative lactation consultants in hospitals, and extending maternity leave. Families should encourage mothers to breastfeed with both breasts instead of only the non-operated breast.

Influence of obesity on in-hospital and postoperative outcomes of hepatic resection for malignancy: a 10-year retrospective analysis from the US National Inpatient Sample.

OBJECTIVES: The influence of obesity on the outcomes of curative liver resection for malignancies remains controversial. We aimed to compare the in-hospital outcomes of liver resection for malignancy between obese and non-obese patients. DESIGN: This was a population-based, retrospective, observational study using data from the Nationwide Inpatient Sample (NIS), the largest all-payer US inpatient care database. SETTING: Hospitalisations of adults ≥18 years old with diagnoses of primary hepatobiliary malignancy or secondary malignant neoplasms of liver in the USA were identified from the NIS database between 2005 and 2014. PARTICIPANTS: Data of 18 398 patients ≥18 years old and underwent liver resection without pancreatic resection in the NIS were extracted. All included subjects had primary hepatobiliary malignancy or secondary malignant neoplasms of the liver. Patients were divided into obese and non-obese groups. These groups were compared with respect to postoperative complications, length of hospital stay and hospital cost according to surgical extent and approach. INTERVENTIONS: Patients were undergoing lobectomy of liver or partial hepatectomy. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoints of this study were postoperative complications, length of hospital stay and hospital cost. RESULTS: After adjustment, obese patients were significantly more likely to experience postoperative complications than were non-obese patients (adjusted OR 1.25, 95% CI 1.10 to 1.42), regardless of whether lobectomy or partial hepatectomy was performed. Furthermore, obesity was significantly associated with increased risk of postoperative complications in patients who underwent open liver resection, but not laparoscopic resection. No significant difference was observed in length of hospital stay or total hospital costs between obese and non-obese patients. CONCLUSIONS: After adjustment for preoperative comorbidities and other potential confounders, obesity is significantly associated with greater risk of complications in patients undergoing open liver resection for malignancy, but not laparoscopic resection.

Bisphenol A disturbed the lipid metabolism mediated by sterol regulatory element binding protein 1 in rare minnow Gobiocypris rarus.

Bisphenol A (BPA), a representative endocrine disrupting compound, exists ubiquitously in the aquatic environment. Several studies on fish have validated the role of BPA in the lipid metabolism. However, the action mechanisms of BPA on lipid metabolism have been little studied. To clarify how BPA regulates lipid metabolism, Gobiocypris rarus were exposed to 15 µg/L BPA for 3 and 6 weeks. Results showed that BPA altered lipid content by regulating some metabolism-related genes. The BPA's inhibiting effect on fatty acid ß-oxidation might be stronger than on lipid synthesis. BPA disturbed the expression of acaca (acetyl-CoA carboxylase), fasn (fatty acid synthase) and cpt1α (carnitine palmitoyltransferase 1α) by altering the sterol regulatory element binding protein 1 (SREBP-1) binding to their sterol regulatory elements (SREs). Our result also revealed that DNA methylation in the 5' flanking regions of cpt1α could perturb the SREBP-1 binding adjacent to its SRE in females under BPA exposure. Besides, BPA exposure led to gender-specific effect on fatty acid ß-oxidation in G. rarus. This will contribute to our understanding of the regulation mechanisms of BPA on lipid metabolism in fish.

BCL2L10/BECN1 modulates hepatoma cells autophagy by regulating PI3K/AKT signaling pathway.

The aim of this study was to investigate BCL2L10 and BECN1 expression and their effect on autophagy in hepatocellular carcinoma (HCC). We found that BCL2L10 expression was low in hepatoma tissues and cells. Overexpression of BCL2L10 decreased the activity of hepatoma cells. To analyze autophagic flux, we monitored the formation of autophagic vesicles by fluorescence protein method. Autophagy-related protein LC3B-II was accumulated and P62 was decreased, which indicated that autophagy was induced by BECN1, while BCL2L10 could suppress this trend. Immunofluorescence assay showed that BCL2L10 and Beclin 1 were co-located in hepatoma cells. Immunoprecipitation showed that BCL2L10 could inhibit the autophagy of hepatoma cells by combining with Beclin 1. ELISA and co-immunoprecipitation suggested that the combination between BCL2L10 and Beclin 1 reduced the bond between Beclin 1 and PI3KC3. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the PI3K/AKT signaling pathway was significantly upregulated in HCC. In conclusions, BCL2L10 had a low expression in HCC tissues and cells, which could release BECN1 to induce autophagy of hepatoma cells by downregulating PI3K/AKT signaling pathway.

Steroidal and phenolic endocrine disrupting chemicals (EDCs) in surface water of Bahe River, China: Distribution, bioaccumulation, risk assessment and estrogenic effect on Hemiculter leucisculus.

This study investigated selected steroidal and phenolic endocrine disrupting compounds (EDCs) in the surface water of the Bahe River (China) using gas chromatography mass spectrometry (GC-MS). Their effect on the wild sharpbelly Hemiculter leucisculus was investigated. The concentrations of 4-t-octylphenol, nonylphenol, bisphenol-A, estrone, 17 ß-estradiol, 17 α-Ethinylestradiol, and estriol were up to 126.0, 634.8, 1573.1, 55.9, 23.9, 31.5, and 5.2 ng L-1 in the surface water, and up to 26.4, 103.5, 146.9, 14.2, 9.3, 13.8, and 1.3 ng g-1 in the fish muscle tissue, respectively. High estrogen equivalent levels and hazard quotients were found in the middle and lower reaches of the river, and the pollution in these regions caused enhanced growth conditions, inhibition of gonad growth, and suppression of spermatogenesis in H. leucisculus. The up-regulation of Vitellogenin mRNA expression in male fish, collected from relatively heavily EDCs contaminated areas, indicates a potential estrogenic effect. The differential expression profiles of genes related to steroidogenesis at all sampling sites suggests that these endpoints may play an important role for the pollution monitoring of estrogenic EDCs in the Bahe River.

Occurrence and distribution of antibiotics and antibiotic resistance genes in Ba River, China.

The riverine system is usually considered as a natural reservoir of antibiotic resistance genes (ARGs) and more susceptible to anthropogenic activities. In this study, the occurrence and distribution of 14 antibiotics belonging to 7 categories together with 23 corresponding ARGs in Ba River of Xi'an China were investigated in March and July 2017. Sulfonamides, quinolones, macrolides and tetracyclines were detected in high frequencies ranged from 85.7% to 100%. Tetracyclines were detected with high concentrations in water samples (up to 8.54 × 102 ng L-1) and sediment samples (up to 2.08 × 103 µg kg-1), respectively. The total concentrations of antibiotics were much higher in July in comparison with March. The sul1, tetA, tetC, tetZ, gyrA, ermF, cmlA and blaTEM were the predominant ARGs in terms of absolute abundance. For both water and sediment samples in March compared with July, the relative abundance of ARGs had no significant difference except for sul3. The tetracyclines had positive correlation with tet genes, whereas the remaining antibiotics had no significant correlations with their corresponding ARGs, suggesting that environmental factors and cross-selection may significantly influenced the distribution of ARGs. Redundancy analysis was performed to further predict the influences of environmental factors on antibiotics and ARG abundance. The findings suggest that anthropogenic activities contribute significantly to the persistence of antibiotics pollution.