Conservative management of a rare case of post thyroidectomy tracheal injury with coagulation abnormalities.

Background: Tracheal injury is a rare but potentially serious acute complication of endotracheal intubation. Very few cases of tracheal injury associated with coagulation abnormalities have been reported in the literature. We present a rare case of a patient presenting with tracheal injury in combination with coagulation abnormalities following thyroidectomy. Case presentation: A 58-year-old woman with a history of postoperative chemotherapy for breast cancer, gastric polyps, multiple colonic polyps, esophageal papillary adenomas, and thyroid adenomas presented with dyspnea following 10 ml hemoptysis on the third day after thyroidectomy; she was admitted to the intensive care unit and underwent tracheal intubation for maintaining the airway. Subsequent bronchoscopy revealed a nodular red neoplasm 5-cm from the carina in the trachea obstructing part of the lumen, with a small amount of fresh hemorrhage on the surface. Tracheal injury was considered the preliminary diagnosis. Fiberoptic bronchoscope guided tracheal intubation helped prevent rupture of the tumor, and the cannula was properly inflated to arrest the bleeding while blocking the lower part of the trachea. An emergency surgical evacuation of the cervical hematoma was performed for managing postoperative bleeding. The patient demonstrated persistent pancytopenia despite frequent transfusions. Laboratory examination results revealed abnormal coagulation parameters, anemia, and hepatic dysfunction. Following a multidisciplinary team discussion, pituitrin for hemostasis, tranexamic acid for strengthening hemostasis treatment, and nutritional support and anti-infection treatment were initiated. Endotracheal tube cuff inflation was performed to compress the bleeding site. Complete resolution of the subcutaneous hematoma was observed nine days after the tracheal injury; bronchoscopy revealed residual ecchymosis in the airway hematoma with no evidence of obstruction. Conclusion: Conservative management of tracheal injury limited to the mucosa or submucosa without significant amount of active bleeding using endotracheal intubation is considered a practical and effective approach. Successful management was ensured by appropriate clinical suspicion, early multidisciplinary team discussion, and prompt diagnosis and interventions.

Down-regulating lncRNA KCNQ1OT1 relieves type II alveolar epithelial cell apoptosis during one-lung ventilation via modulating miR-129-5p/HMGB1 axis induced pulmonary endothelial glycocalyx.

OBJECTIVE: Endothelial glycocalyx (EG) maintains vascular homeostasis and is destroyed after one-lung ventilation (OLV)-induced lung injury. Long noncoding RNAs (lncRNAs) are critically involved in various lung injuries. This study aimed to investigate the role and regulatory mechanism of KCNQ1 overlapping transcript 1 (KCNQ1OT1) in OLV-induced lung injury and LPS-induced type II alveolar epithelial cell (AECII) apoptosis. METHODS: The rat OLV model was established, and the effects of KCNQ1OT1 on OLV-induced ALI in vivo were explored. Bax and Caspase-3 expression in rat lung tissues was measured by immunochemistry (IHC). AECIIs were isolated from rat lungs and treated with LPS or normal saline (control) for in vitro analysis. The expression of KCNQ1OT1, miR-129-5p, and HMGB1 was measured by quantitative real-time PCR (qRT-PCR) or Western blot (WB). Cell proliferation and apoptosis were examined by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) and flow cytometry. The downstream targets of KCNQ1OT1 were predicted by bioinformatics, and the binding relationship between KCNQ1OT1 and miR-129-3p was verified by dual-luciferase reporter assays. The potential target of miR-129-5p was further explored on the Targetscan website and revealed to target HMGB1. Enzyme-linked immunosorbent assay (ELISA) or WB was adopted to determine the levels of IL-1ß, TNF-α, MDA, SOD, heparanase (HPA), matrix metalloproteinase 9 (MMP9), heparan sulfate (HS) and syndecan-1 (SDC-1). RESULTS: KCNQ1OT1 and HMGB1 were up-regulated during OLV-induced lung injury, and their expression was positively correlated. KCNQ1OT1 knockdown reduced OLV-induced pulmonary edema and lung epithelial cell apoptosis, increased vascular permeability, reduced IL-1ß, TNF-α, MDA, and SOD levels and glycocalyx markers by targeting miR-129-5p or upregulating HMGB1. Overexpressing KCNQ1OT1 promoted cell apoptosis, reduced cell proliferation, aggravated inflammation and oxidative stress, and up-regulated HMGB1, HPA and MMP9 in LPS-treated AECIIs, while the HMGB1 silencing showed the opposite effects. MiR-129-5p mimics partially eliminated the KCNQ1OT1-induced effects, while recombinant HMGB1 restored the effects of miR-129-5p overexpression on AECIIs. Additionally, KCNQ1OT1 was demonstrated to promote the activation of the p38 MAPK/Akt/ERK signaling pathways in AECIIs via HMGB1. CONCLUSION: KCNQ1OT1 knockdown alleviated AECII apoptosis and EG damage during OLV by targeting miR-129-5p/HMGB1 to inactivate the p38 MAPK/Akt/ERK signaling. The findings of our study might deepen our understanding of the molecular basis in OLV-induced lung injury and provide clues for the targeted disease management.

Anastrozole for the prevention of breast cancer in high-risk postmenopausal women: cost-effectiveness analysis in the UK and the USA.

PURPOSE: The effectiveness of anastrozole for breast cancer prevention has been demonstrated. The objective of this study was to evaluate the cost-effectiveness of anastrozole for the prevention of breast cancer in women with a high risk of breast cancer and to determine whether anastrozole for the primary prevention of breast cancer can improve the quality of life of women and save health-care resources. METHODS: A decision-analytic model was used to assess the costs and effects of anastrozole prevention versus no prevention among women with a high risk of breast cancer. The key parameters of probability were derived from the IBIS-II trial, and the cost and health outcome data were derived from published literature. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for the two strategies,One-way and probabilistic sensitivity analyses were performed. RESULTS: In the base case, the incremental cost per QALY of anastrozole prevention was £125,705.38/QALY in the first 5 years compared with no prevention in the UK, above the threshold of WTP (£3,000/QALY),and in the 12-year period, the ICER was £8,313.45/QALY, less than WTP. For the US third-party payer, ICER was $134,232.13/QALY in the first 5 years and $8,843.30/QALY in the 12 years, both less than the WTP threshold ($150,000/QALY). CONCLUSION: In the UK and US, anastrozole may be a cost-effective strategy for the prevention of breast cancer in high-risk postmenopausal women. Moreover, the longer the cycle of the model, the higher the acceptability. The results of this study may provide a scientific reference for decision-making for clinicians, patients, and national medical and health care government departments.

Is circulating tumor cell count-driven cost-effective for first-line therapy choice in HR+/HER2- metastatic breast cancer in the United States?

BACKGROUND: Circulating tumor cell (CTC) counting may be a useful non-invasive biomarker that helps patients choose first-line treatment options. Nevertheless, the cost of CTC inspection may impose an economic burden on patients, necessitating the simultaneous consideration of both its clinical effectiveness and cost. We evaluated the cost-effectiveness of CTC count-guided chemotherapy and endocrine therapy as first-line therapy for HR+/HER2-metastatic breast cancer (MBC) from the perspective of US payers. METHODS: Based on the STIC CTC trial, a Markov model was constructed for three health states, and health outcomes were measured in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to assess the robustness of the incremental cost per QALY. RESULTS: The base-case analysis revealed that CTC count-driven treatment was associated with improved effectiveness by 0.07 QALYs and increased the overall cost by $9187.05 compared with clinician-driven first-line treatment choices, leading to an ICER of $138 354.15 per QALY. One-way sensitivity analysis indicated that the model was most sensitive to the cost of treatment for neutropenia and the utility for PFS; probability sensitivity analysis indicated that CTC count-driven treatment choices would be considered the cost-effective option at a willingness-to-pay threshold of $150 000 per QALY. CONCLUSIONS: The findings of this cost-effectiveness analysis suggest that, at the current price of CTC enumeration, choosing first-line treatment options based on CTC count is a cost-effectiveness approach for treating patients with HR+/HER2- MBC in the US.

Is Alpelisib Plus Fulvestrant Cost-Effective for Treating PIK3CA-Mutation, HR+/HER2- Advanced Breast Cancer in the USA?

BACKGROUND AND OBJECTIVE: There is a considerable survival benefit of alpelisib in patients with PIK3CA-mutated, hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC), yet the financial burden may limit its use. Therefore, this study evaluated the cost-effectiveness of alpelisib plus fulvestrant in patients with PIK3CA-mutated, HR+/HER2- ABC in the USA. METHODS: A Markov model was constructed to simulate the progression of PIK3CA-mutated, HR+/HER2- ABC. Efficacy and safety data were derived from the SOLAR-1 trial. A parametric survival model was used to explore the long-term effect. From a US payer perspective, only direct medical costs were considered. The cost data were estimated based on local pricing and relevant literature. The health outcomes were expressed in quality-adjusted life years (QALYs). Model stability was assessed using one-way sensitivity analysis and probability sensitivity analysis. Subgroup analyses were performed to explore cost-effectiveness outcomes for patients with different clinical characteristics. RESULTS: The QALY increased by 0.28 with alpelisib plus fulvestrant with an additional cost of $94,345.87 compared with placebo plus fulvestrant, leading to an incremental cost-effectiveness ratio (ICER) of $340,153.30/QALY gained. Sensitivity analyses suggested that the model is most sensitive to the price of alpelisib. At a willingness-to-pay (WTP) threshold of $150,000/QALY, alpelisib plus fulvestrant was cost effective when the cost of alpelisib was less than $71 per 300 mg (36.5 % of the original price), whereas this cost would be less than $168 per 300 mg (86.5 % of the original price) at a WTP threshold of $300,000/QALY. In addition, alpelisib + fulvestrant was not cost effective in all subgroups compared with placebo + fulvestrant at the WTP threshold of $150,000/QALY. In contrast, at the WTP threshold of $300,000/QALY, alpelisib + fulvestrant was cost effective in nearly all subgroups except for endocrine-sensitive patients. CONCLUSION: At current drug prices, alpelisib plus fulvestrant is not cost effective for patients with PIK3CA-mutated, HR+/HER2- ABC from a US payer perspective. Given the considerable progression-free survival (PFS) and overall survival (OS) benefits observed with alpelisib in this setting, further discussion and negotiation of the price of alpelisib are warranted to provide more favorable economic outcomes and thereby increase the value of the alpelisib plus fulvestrant regimen in patients.

Correlation between serum lipid levels and endocrine resistance in patients with ER-positive breast cancer.

Lipid metabolism may be involved in the development of endocrine drug resistance in ER-positive (ER+) breast cancer (BC). This study aimed to investigate the relationship between serum lipid levels, risk stratification of dyslipidemia, and endocrine resistance. We collected the data from 166 ER + breast cancer patients who received endocrine therapy (ET). 73 of 166 patients (44.0%)developed endocrine resistance. Univariate and multivariate COX regression were conducted to explore the potential factors affecting endocrine resistance in BC. The clinical T stage, mean serum lipid levels in ET progression-free-survival (total cholesterol, triglycerides, low-density lipoprotein cholesterol, apolipoprotein A, and triglycerides/high-density lipoprotein cholesterol) were correlated with endocrine resistance (R = 0.214, P = .006; R = 0.268, P < .001; R = 0.182, P = .019;R = 0.197, P = .011; R = 0.211, P = .006; R = 0.159, P < .041). Clinical stage, triglycerides (TG) in endocrine therapy progression-free-survival (ePFS) and low-density lipoprotein cholesterol (LDL-C) in ePFS were independent predictors of endocrine resistance (P < .05; OR = 1.406, CI 1.108-1.783, P < .05; OR = 1.309, CI 1.026-1.669, P < .05, respectively). Moreover, in clinical stage III, the ePFS was worse in patients with in the high-risk and extremely high-risk group the median ePFS time was 8.0 months (95% CI: 1.140-14.860, P < .05). Clinical stage, TG in ePFS and LDL-C in ePFS may act as a new predictive biomarker for endocrine resistance in BC. The lipid levels of BC patients should be closely monitored throughout the treatment process, and patients with dyslipidemia should receive treatment immediately.

Effects of Press Needling combined with general anesthesia on postoperative analgesia in thoracoscopic pulmonary resection for lung cancer: A randomized, single-blind, controlled trial.

OBJECTIVES: To investigate the effects of press needle therapy on postoperative analgesia and other relevant complications in patients undergoing thoracoscopic pulmonary resection. DESIGN: randomized, single-blind, controlled trial SETTING: Teaching hospitals affiliated with universities. INTERVENTIONS: Eighty-six patients were randomized into: the Acu group (press-needle group) and the control group MAIN OUTCOME MEASURES: Pain levels 24, 48, and three months after surgery were measured using the numeric rating scale (NRS). Perioperative hemodynamics, total and effective pressing numbers of patient-controlled intravenous analgesia (PCIA), and incidence of postoperative pulmonary complications were recorded. Peripheral blood samples were collected to measure the levels of inflammatory mediators RESULTS: Acu group had significantly lower NRS scores at 24 and 48 h after operation (NRS scores on movement at 24 h after surgery: Acu vs. Control, 3 (2,3) vs. 3 (3,5), Z = -3.393, P < 0.01 and NRS scores on movement at 48 h after surgery: 2 (1,3) vs. 3 (2,5), Z = -3.641, P < 0.01), lower number of PCIA attempts and effective rates (mean total pressing numbers: 4(2,8) vs. 6(3,19), Z = -1.994, P = 0.046 and mean effective pressing numbers: 3(2,8) vs. 6(3,16), Z = -2.116, P = 0.034). The Acu group had significantly reduced IL-1 (14.52 ± 3.84 vs. 16.36 ± 3.30, mean difference (MD): - 1.85, 95% confidence interval (CI): - 3.46, - 0.23, P = 0.026), HIF-1α (10.15 ± 1.71 vs. 10.96 ± 1.73, MD: -0.81, 95% CI: -1.59, -0.04, P = 0.040) and the incidence of pulmonary complications after surgery. CONCLUSION: Press needles are a non-invasive and feasible adjunctive intervention for postoperative analgesic management in patients undergoing thoracoscopic pulmonary resection.

The effect of ferroptosis - related proteins and histone deacetylases1 on neoadjuvant chemotherapy in breast cancer.

Ferroptosis may improve the efficacy of tumor treatment, according to recent evidences. This study is to explore value of histone deacetylases 1 (HDAC1), ATP binding cassette subfamily B member 1 and ferroptosis-related proteins as potential predictive biomarkers. Eighty-two women who received neoadjuvant chemotherapy (NAC) confirmed breast cancer was included. Immunohistochemistry staining of HDAC1, ATP binding cassette subfamily B member 1 and ferroptosis-related proteins was performed in core needle biopsy and tumor resection tissue. Univariate and multivariate logistic regression were conducted to explore the potential biomarkers for breast cancer undergoing NAC. There was a weak positive correlation of HDAC1 level before and after NAC with imaging outcome (R = 0.390, P < .001). The expression of HDAC1 and glutathione peroxidase 4 before NAC was an independent predictor of imaging efficacy (OR = 7.633, CI 1.831-31.821, P < .001; OR = 0.700, CI 0.505-0.971, P < .05, respectively). HDAC1 and Glutathione peroxidase 4 may act as a new predictive biomarker for NAC in breast cancer. And personalized treatment can be provided based on them.

Is Lidocaine Patch Beneficial for Postoperative Pain?: A Meta-analysis of Randomized Clinical Trials.

OBJECTIVES: The aim of this meta-analysis was to evaluate whether a lidocaine patch is beneficial for postoperative pain as an option for multimodal analgesia. METHODS: Information was obtained from PubMed, Embase, and the Cochrane Central Register of Controlled Trials for clinical randomized controlled trials of lidocaine patches for postoperative pain (as of March 2022). Two researchers independently completed study screening, risk bias assessment, and data extraction. Review Manager (version 5.4, Cochrane Collaboration) was used to conduct the meta-analysis. The evaluation metrics were postoperative pain scores, opioid consumption, and patient satisfaction. RESULTS: Sixteen randomized controlled trials were included, and data from 918 patients were available. Pain scores differed between the 2 groups at 12, 24, and 48 hours postoperatively, and the pain scores of the lidocaine patch group were significantly lower (mean difference [MD]=-1.32 [95% CI, -1.96 to -0.68], P <0.0001; I2 =92%) at 12 hours after the operation; (MD=-1.23 [95% CI, -1.72 to -0.75], P <0.00001; I2 =92%) at 24 hours after the operation; and (MD=-0.25 [95% CI,-0.29 to -0.21], P <0.00001; I2 =98%) at 48 hours after the operation. In addition, the lidocaine patch group had decreased opioid requirements (MD=-3.57 [95% CI, -5.06 to -2.09], P <0.00001; I2 =96%). The lidocaine patch group seemed to be more satisfied, but there was no statistically significant difference (risk ratio, 1.50 [95% CI, 0.74 to 3.05], P =0.26) between the groups. DISCUSSION: Lidocaine patches are beneficial for postoperative pain and can be used in multimodal analgesia to reduce opioid use, but there is no significant increase in patient satisfaction with pain control. More data are needed to support this conclusion due to the large heterogeneity in the present study.

Cost-effectiveness of olaparib, a PARP inhibitor, for patients with metastatic castration-resistant prostate cancer in China and United States.

Background: Metastatic prostate cancer is initially sensitive to androgen receptor inhibition, but eventually becomes metastatic castration-resistant prostate cancer (mCRPC). Olaparib has longer progression-free survival and better measures of response and patient-reported end points than either enzalutamide or abiraterone. In the present study, 2 Markov models were established to analyze the cost utility of olaparib in treating mCRPC from the perspectives of health services in China and the United States. Methods: Markov models were established to simulate the progress of mCRPC in China and the United States. The state transition probabilities and clinical data were extracted from the PROfound trial. The cost data were estimated from local pricing, the relevant literature and expert consultancy. The health outcomes are expressed by quality-adjusted life years (QALYs). All costs and incremental cost-effectiveness ratios (ICERs) are presented in US dollars. One-way deterministic sensitivity analysis and probabilistic sensitivity analysis were performed to assess the uncertainty of the models. Results: Based on the Chinese Markov model, the base case ICER for olaparib versus the control group was ¥392,727.87, with incremental costs of ¥93,673.23 and an incremental QALY of 0.23, indicating that it was not cost effective from the aspect of the Chinese healthcare system. However, as shown by the American Markov model, olaparib was dominant versus the control group, with a cost saving of $69,675.20 and a gain of 0.23 QALYs. One-way deterministic sensitivity analysis and probabilistic sensitivity analyses showed that the modeling results were not significantly affected by the model parameters. Conclusions: Olaparib treatment in patients with mCRPC is not cost effective in China, but it is cost saving in the United States.

NUDT15 genetic testing-guided 6-mercaptopurine dosing in children with ALL likely to be cost-saving in China.

OBJECTIVE: The cost-effectiveness of NUDT15 genetic testing-guided initial 6-mercaptopurine (6-MP) dosing in children with acute lymphoblastic leukemia (ALL) was evaluated. METHODS: A decision tree model was used to evaluate the cost to China's medical system per quality-adjusted life-year (QALY) gained and cost per case of severe leukopenia avoided of NUDT15 genetic testing using public clinical data. RESULTS: Genetic testing-guided initial 6-MP dosing reduced overall costs by $518.61, and prevented 0.221 cases of Grade III-IV leukopenia and increased QALY by 0.00136 per patient. Results were robust in one-way analyses and probabilistic sensitivity analyses. CONCLUSION: NUDT15 genetic testing prior to the initial administration of 6-MP in pediatric ALL patients in China is less expensive than standard dosing without genetic testing.

Long non-coding RNA H19 mediates N-acetyltransferase 1 gene methylation in the development of tamoxifen resistance in breast cancer.

Long non-coding RNA (lncRNA) H19 is associated with proliferation, invasion and metastasis in numerous types of cancer. H19 lncRNA has been demonstrated to be an estrogen-inducible gene, the expression of which is significantly increased in tamoxifen (TAM)-resistant MCF-7 breast cancer cells. The aim of the present study was to investigate the role and molecular mechanism of lncRNA H19 in the development of TAM resistance. TAM-resistant MCF-7 (MCF-7R) cells were developed by the treatment of wild-type MCF-7 cells with 4-hydroxytamoxifen. Analysis of H19 expression in the cells indicated that upregulation of H19 contributed to the resistance of the MCF-7R cell line. Furthermore, when H19 was knocked down in the MCF-7R cells, the sensitivity to 4-hydroxytamoxifen was markedly restored. The results further demonstrated that N-acetyltransferase 1 (NAT1) may serve an important role in TAM-resistant cells, as NAT1 expression was notably downregulated in the MCF-7R cells but significantly elevated following the knockdown of H19. In addition, lower expression of NAT1 and higher expression of H19 were indicated to be associated with poor prognosis in patients with breast cancer treated with TAM. The results of bisulfite genomic sequencing PCR analysis indicated that the methylation rate of NAT1 in MCF-7R cells was significantly higher compared with that in MCF-7 cells, while the methylation rate of NAT1 in TAM-resistant cells transfected with small interfering RNA against H19 was significantly lower than that in the corresponding untransfected cells. Therefore, the present study suggests that the H19 gene regulates NAT1 expression in TAM-resistant cells via the mediation of NAT1 promoter methylation.

Efficacy of Laparoscopic Hepatectomy versus Open Surgery for Hepatocellular Carcinoma With Cirrhosis: A Meta-analysis of Case-Matched Studies.

BACKGROUND: The role of laparoscopic hepatectomy (LH) in hepatocellular carcinoma (HCC) with cirrhosis remains controversial and needs to be further assessed. The present meta-analysis aimed to compare the surgical and oncological outcomes of LH with those of open hepatectomy (OH) for HCC with cirrhosis. METHODS: The PubMed, Embase, and Cochrane Library databases were searched for studies comparing LH and OH until Mar 2021. Weighted mean differences (WMDs), odds ratios (ORs), and hazard ratios (HRs) were calculated for continuous, dichotomous, and long-term variables, respectively, with 95% confidence intervals (CIs). Subgroup analysis was performed according to different resection types: major resection and minor resection. The meta-analysis was performed using the STATA 12.0. RESULTS: A total of 16 case-matched studies (784 patients in the LH group and 1,191 patients in the OH group.) were included in this meta-analysis. In terms of primary outcomes, LH was associated with decreased overall complication rate (OR 0.57; 95% CI 0.46 to 0.71; P <0.01), major complication rate (OR 0.52; 95% CI 0.33 to 0.82; P < 0.01), postoperative mortality (OR 0.27; 95% CI 0.11 to 0.66; P <0.01), 1-y overall survival (OS) rate (HR 0.48; 95% CI 0.31 to 0.73; P <0.01), 2-y OS (HR 0.61; 95% CI 0.45 to 0.83; P < 0.01), and 5-y OS (0.67; 95% CI 0.53 to 0.85; P < 0.01). With respect to secondary outcomes, blood loss (WMD -69.16; 95% CI -101.72 to -36.61; P < 0.01), length of hospitalization (LOH) (WMD -2.65; 95% CI -3.41 to -1.89; P < 0.01), minor complication rate (OR 0.70; 95% CI 0.53 to 0.94; P = 0.02), postoperative liver failure (OR 0.60; 95% CI 0.38 to 0.95; P = 0.03), and postoperative ascites (OR 0.44; 95% CI 0.28 to 0.72; P < 0.01) was lower in LH than in OH. No significant differences in operation time (P = 0.07), transfusion rate (P = 0.05), 1-, 2-, and 5-year DFS rate (1-year, P = 0.08; 2-year, P = 0.08; 5-year, P = 0.23) were noted between LH and OH. Subgroup analysis based on minor resection revealed that LH had similar favored outcomes in comparison with those in the overall pooled analysis. However, LH had a longer operation time than OH in the setting of major resection (P < 0.01). CONCLUSION: LH is technically feasible and safe for selected HCC patients with cirrhosis. LH can achieve favored short-term and long-term oncological outcomes in minor liver resection. Laparoscopic major hepatectomy (LMH) seems to offer some advantages over the open approach; however concerns about surgical and oncological safety remain. More evidence on LMH is warranted before expanding its indication to patients with cirrhosis.

NAT1 is a critical prognostic biomarker and inhibits proliferation of colorectal cancer through modulation of PI3K/Akt/mTOR.

The aim of this study was to analyze the correlations between NAT1 and clinicopathological features of and prognosis in colorectal cancer (CRC). RNA sequencing data and clinical information were retrieved from The Cancer Genome Atlas database. Wilcoxon test, logistic regression and Kaplan-Meier method were used to estimate the association between NAT1 and prognosis in CRC. In vitro experiments were conducted to confirm the role of NAT1. NAT1 is significantly less expressed in CRC and independently associated with poor prognosis in CRC patients. The authors further confirmed that expression of NAT1 was significantly lower in SW116 colon cancer cells than in NCM460 cells. Overexpressed NAT1 obviously inhibited the growth of CRC cells by downregulating phosphorylation of the PI3K/Akt/mTOR signaling pathway. NAT1 may be a potential therapeutic target for CRC.

Lay abstract Colorectal cancer (CRC) is a common malignancy worldwide. Because of the limited understanding of the pathogenesis and prognostic factors associated with CRC, the treatment effect in CRC remains poor. In the present study, the authors demonstrate that NAT1 is significantly less expressed in CRC and independently associated with poor prognosis in CRC patients. NAT1 may exert antitumor activity by inhibiting phosphorylation of the PI3K/Akt/mTOR signaling pathway. These results suggest that NAT1 may be a prognostic factor in and therapeutic target for CRC.

Curcumin attenuates lncRNA H19­induced epithelial­mesenchymal transition in tamoxifen­resistant breast cancer cells.

The H19 long non­coding RNA is involved in the development of tamoxifen resistance in breast cancer. However, the relationship between H19 and the metastatic potential and treatment options for tamoxifen­resistant (TAMR) breast cancer is not completely understood. Curcumin inhibits cellular proliferation, migration and invasiveness in several cancer types, including pancreatic cancer, breast cancer and chronic myeloid leukemia. The present study aimed to investigate the role of H19 in MCF­7/TAMR cell epithelial­mesenchymal transition (EMT), migration and invasiveness, and to assess the ability of curcumin to inhibit H19­mediated effects. Reverse transcription­quantitative PCR and western blot analysis were conducted to detect the gene or protein expression. Cell Counting Kit­8, wound healing and Transwell invasion assays were performed to estimate the capabilities of cell viability, invasion and migration. H19 overexpression enhanced MCF­7/TAMR cell EMT, invasion and migration by upregulating Snail. Furthermore, curcumin notably decreased the expression levels of epithelial marker E­cadherin and markedly increased the expression levels of mesenchymal marker N­cadherin in MCF­7/TAMR cells compared with the control group. In addition, following treatment with curcumin for 48 h, H19 expression was decreased in a dose­dependent manner. Moreover, curcumin treatment for 48 h significantly attenuated H19­induced alterations in N­cadherin and E­cadherin expression levels. Curcumin also prevented H19­induced invasion and migration. The present study indicated that H19 may serve as a promoting factor of EMT, invasion and migration in MCF­7/TAMR cells, suggesting that curcumin may prevent H19­associated metastasis. Therefore, curcumin may serve as a promising therapeutic drug for patients with TAMR breast cancer.

The Roles of Inflammation in Keloid and Hypertrophic Scars.

The underlying mechanisms of wound healing are complex but inflammation is one of the determining factors. Besides its traditional role in combating against infection upon injury, the characteristics and magnitude of inflammation have dramatic impacts on the pathogenesis of scar. Keloids and hypertrophic scars are pathological scars that result from aberrant wound healing. They are characterized by continuous local inflammation and excessive collagen deposition. In this review, we aim at discussing how dysregulated inflammation contributes to the pathogenesis of scar formation. Immune cells, soluble inflammatory mediators, and the related intracellular signal transduction pathways are our three subtopics encompassing the events occurring in inflammation associated with scar formation. In the end, we enumerate the current and potential medicines and therapeutics for suppressing inflammation and limiting progression to scar. Understanding the initiation, progression, and resolution of inflammation will provide insights into the mechanisms of scar formation and is useful for developing effective treatments.

Cost-effectiveness Analysis of CYP2D6*10 Pharmacogenetic Testing to Guide the Adjuvant Endocrine Therapy for Postmenopausal Women with Estrogen Receptor Positive Early Breast Cancer in China.

BACKGROUND: A CYP2D6 gene polymorphism is related to the effect of tamoxifen treatment in patient with estrogen-receptor positive (ER) positive breast cancer and CYP2D6*10 T/T can lead to a poor prognosis in Asian patients. Although one-off pharmacogenetic testing may optimize adjuvant endocrine therapy, testing prior to tamoxifen initiation incurs additional costs. AIM: We conducted a study to assess the cost-effectiveness of CYP2D6*10 pharmacogenetic testing to guide the adjuvant endocrine therapy compared with tamoxifen without CYP2D6*10 testing in China. METHODS: A semi-Markov model was developed to evaluate costs and health outcomes represented as quality adjusted life year (QALY) gained. Input data were obtained from the public literature. The results were expressed as incremental cost per QALY gained. A one-way deterministic sensitivity analysis explored the impact of uncertainty in the model parameters on results, and probabilistic uncertainty was assessed through a Monte Carlo probabilistic sensitivity analysis. RESULTS: In the base-case analysis, in the CYP2D6*10 testing and alternative adjuvant endocrine therapy group, the incremental total cost was US$17,966.95 and the incremental QALY was 3.582. Thus, the incremental cost-effectiveness ratio was US$5015.693 per QALY gained. Compared with a willingness-to-pay threshold of US$26,508/QALY in China, the CYP2D6*10 testing is the dominant strategy in postmenopausal women with ER-positive breast cancer in China, and the increased cost of genetic testing was completely worthwhile. The sensitivity analyses showed that the model we built was quite stable. CONCLUSION: From the perspective of the Chinese healthcare system, CYP2D6*10 pharmacogenetic testing was cost effective for postmenopausal women with ER-positive early breast cancer.

A Modified Technique Using Levator Aponeurosis-Müller Muscle-Reinforced Plication for Blepharoptosis Correction.

BACKGROUND: Blepharoptosis is a common and challenging clinical problem for oculoplastic surgeons, and various surgical techniques have been used to correct ptosis. The aims of this study were to present the clinical results of a modified technique using levator aponeurosis-Müller muscle-reinforced plication for blepharoptosis correction and to demonstrate its advantages over conventional advancement or plication methods. METHODS: This study was conducted in the Plastic Surgery Department of Sir Run Run Shaw Hospital between April 2017 and September 2018. By using this modified technique, the levator-Müller complex was reinforced with a plication suture that pierced under and through the levator-Müller complex, and the posterior and lower part of the levator-Müller complex was advanced to the tarsus, which provided permanent, reliable adhesion. The primary outcome was marginal reflex distance 1 preoperatively and postoperatively. Secondary outcomes were the cosmetic outcome, complications, and operative time. RESULTS: Eighty-six patients (169 eyelids) underwent this modified surgery. Patients' average age was 26 ± 7.6 years, and the median follow-up was 14 months. The preoperative and postoperative mean marginal reflex distance 1 values were 1.72 ± 0.32 and 3.69 ± 0.28 mm, respectively. The amount of plication ranged from 4 to 15 mm. The overall surgical success rate was 88.17%. Some complications were observed including undercorrection (5.92%), asymmetry (4.73%), lagophthalmos (0.59%), and conjunctival prolapse (0.59%). CONCLUSIONS: The modified technique provided good functional and cosmetic outcomes for blepharoptosis correction by avoiding unpredicted adhesion, and it has its advantages including simplicity, easy adjustment of the eyelid height intraoperatively, minimal edema formation, and high success rate.