Exosomal miR-107 antagonizes profibrotic phenotypes of pericytes by targeting a pathway involving HIF-1α/Notch1/PDGFRß/YAP1/Twist1 axis in vitro.

Microvascular pericytes have been demonstrated as an origin for myofibroblasts that produce excessive extracellular matrix (ECM) proteins such as α-smooth muscle actin (α-SMA) and type I collagen (ColIA1) and contribute to pulmonary fibrosis (PF). However, the signaling mechanism responsible for ECM production within pericytes is poorly understood. In this study, we examined exosomal miR-107 in the fibrotic phenotypes of pericytes and the pathogenesis of PF. Using RT-qPCR, MiR-107 level was compared between clinical or bleomycin-induced PF and normal pulmonary tissues. Exosomes were isolated from cultured microvascular endothelial cells (ECs) derived from either normal or PF tissues, characterized using dynamic light scattering, transmission electron microscopy, flow cytometry, Western blot, and immunofluorescence, and then applied to pericytes. The effects of exosomes or different fibrosis-related signaling molecules were examined by Western blot, and the potential regulations between the signaling molecules were identified using bioinformatic analysis and assessed by electrophoretic mobility shift assay, chromatin immunoprecipitation, luciferase assay, and RNA binding protein immunoprecipitation. MiR-107 was downregulated in clinical or experimental PF tissues and also in exosomes from PF-derived ECs. EC-derived exosomal miR-107 essentially controlled the miR-107 level and inhibited α-SMA and ColIA1 expression in pericytes. The antifibrosis effect of miR-107 was mediated through the suppression of a pathway involving HIF-1α/Notch1/PDGFRß/YAP1/Twist1, where miR-107 directly targeted HIF-1α mRNA, whereas the latter directly activated the transcriptions of both Notch1 and PDGFRß. Functionally, targeting miR-107 promoted and targeting HIF-1α abolished the fibrotic phenotypes of pericytes. Exosomal miR-107 produced by pulmonary vascular ECs may alleviate pericyte-induced fibrosis by inhibiting a signaling pathway involving HIF-1α/Notch1/PDGFRß/YAP1/Twist1.NEW & NOTEWORTHY This work reveals a novel mechanism by which pulmonary vascular endothelial cells, via regulating the transdifferentiation of microvascular pericytes into myofibroblasts, contribute to the pathogenesis of pulmonary fibrosis. Since targeting the formation of myofibroblasts may prevent the development and benefit the treatment of pulmonary fibrosis, this study provides not only mechanistic understanding but also promising therapeutic targets for pulmonary fibrosis.

Modular synthesis of 3-substituted isocoumarins via silver-catalyzed aerobic oxidation/6-endo heterocyclization of ortho-alkynylbenzaldehydes.

A method involving silver-catalyzed aerobic oxidation/6-endo heterocyclization of ortho-alkynylbenzaldehydes to yield 3-substituted isocoumarins is described. The developed protocol allows convenient access to a range of synthetically useful 3-substituted isocoumarins and related fused heterocyclolactones in good to high yields, using silver tetrafluoroborate as the catalyst, and atmospheric oxygen as the terminal oxidant and the source of endocyclic oxygen. Mechanistic studies suggest the involvement of a free-radical pathway.

CT-less electron radiotherapy simulation and planning with a consumer 3D camera.

PURPOSE: Electron radiation therapy dose distributions are affected by irregular body surface contours. This study investigates the feasibility of three-dimensional (3D) cameras to substitute for the treatment planning computerized tomography (CT) scan by capturing the body surfaces to be treated for accurate electron beam dosimetry. METHODS: Dosimetry was compared for six electron beam treatments to the nose, toe, eye, and scalp using full CT scan, CT scan with Hounsfield Unit (HU) overridden to water (mimic 3D camera cases), and flat-phantom techniques. Radiation dose was prescribed to a depth on the central axis per physician's order, and the monitor units (MUs) were calculated. The 3D camera spatial accuracy was evaluated by comparing the 3D surface of a head phantom captured by a 3D camera and that generated with the CT scan in the treatment planning system. A clinical case is presented, and MUs were calculated using the 3D camera body contour with HU overridden to water. RESULTS: Across six cases the average change in MUs between the full CT and the 3Dwater (CT scan with HU overridden to water) calculations was 1.3% with a standard deviation of 1.0%. The corresponding hotspots had a mean difference of 0.4% and a standard deviation of 1.9%. The 3D camera captured surface of a head phantom was found to have a 0.59 mm standard deviation from the surface derived from the CT scan. In-vivo dose measurements (213 ± 8 cGy) agreed with the 3D-camera planned dose of 209 ± 6 cGy, compared to 192 ± 6 cGy for the flat-phantom calculation (same MUs). CONCLUSIONS: Electron beam dosimetry is affected by irregular body surfaces. 3D cameras can capture irregular body contours which allow accurate dosimetry of electron beam treatment as an alternative to costly CT scans with no extra exposure to radiation. Tools and workflow for clinical implementation are provided.

Low let-7d exosomes from pulmonary vascular endothelial cells drive lung pericyte fibrosis through the TGFßRI/FoxM1/Smad/ß-catenin pathway.

The pathogenesis of pulmonary fibrosis (PF) was mediated by the progressive deposition of excessive extracellular matrix, but little is known about the regulatory mechanisms of fibrogenesis by lung pericytes. The mouse PF model was established by treatment with bleomycin, followed by isolation of exosomes from mouse broncho-alveolar lavage fluids by the centrifuge method. Relative mRNA/microRNA levels and protein expression were assessed by qRT-PCR and Western blotting, respectively. The binding of let-7d with gene promoter was validated by dual-luciferase reporter assay. Protein interactions were verified via GST pull-down and co-immunoprecipitation. Nuclear retention of Smad3 was analysed by extraction of cytoplasmic and nuclear fraction of pericytes followed by Western blotting. Association of FoxM1 with gene promoter was detected by EMSA and ChIP-PCR methods. FoxM1 expression is significantly elevated in human lung fibroblasts of PF patients and mouse PF model. The expression of let-7d is repressed in exosomes derived from broncho-alveolar lavage fluids of PF mice. Let-7d or FoxM1 knockdown suppressed the expression of FoxM1, Smad3, ß-catenin, Col1A and α-SMA expression in mouse lung pericytes under TGF-ß1 treatment. FoxM1 overexpression elevated above gene expression in mouse lung pericytes under TGF-ß1 treatment. Let-7d directly targets TGFßRI to regulate FoxM1 and downstream gene expression in mouse lung pericytes. FoxM1 directly interacts with Smad3 proteins to promote Smad3 nuclear retention and binds with ß-catenin promoter sequence to promote fibrogenesis. Exosomes with low let-7d from pulmonary vascular endothelial cells drive lung pericyte fibrosis through activating the TGFßRI/FoxM1/Smad/ß-catenin signalling pathway.

[Management of androgenic diseases during the epidemic of COVID-19 pneumonia].

The novel coronavirus (COVID-19) pneumonia has been classified as a category B and dealt with as a category A infectious disease by the National Health Commission of China, and also as a public health emergency of international concern by the World Health Organization. During the epidemic, unnecessary visits to hospitals may increase the risk of infection among patients and clinicians. Therefore, it is particularly important to provide some scientific medical guidance for patients with male diseases, which is also a current imperative for andrology management. And it also deserves the attention of clinical researchers whether COVID-19 pneumonia and its clinical treatments currently used may affect the male reproductive system.

[Clinical characteristics and treatment strategies of prostatic mucinous adenocarcinoma: A report of 10 cases and literature review].

OBJECTIVE: To investigate the clinical characteristics and treatment strategies of prostatic mucinous adenocarcinoma (PMAC). METHODS: We retrospectively analyzed the clinical data on 10 cases of PMAC treated in the First Affiliated Hospital of Nanjing Medical University from January 2014 to June 2018. The patients were aged 51－79 (65 ± 14) years, with a medium PSA level of 89 (14.63－128.05) µg/L and Gleason scores of 3 + 3 in 1 case, 3 + 4 in 2, 4 + 3 in 1 and 8 in 6 cases preoperatively, 1 treated by robot-assisted radical prostatectomy and the other 9 by laparoscopic radical prostatectomy. We conducted pelvic cavity lymph node dissection for all the patients and analyzed their prognosis and survival. RESULTS: Operations were successfully completed in all the cases. Pathological examination revealed 2 cases of mucinous adenocarcinoma with signet ring cell carcinoma in the 10 PMAC patients, 2 at stage ≤T2b, 5 at stage ≥T2c, 3 positive at pelvic lymph node dissection and 5 positive at the incision margin. The patients were followed up for 6－48 (median 26) months. Four of the patients were found with biochemical recurrence within 2 years after operation and treated by androgen-deprivation therapy, radiotherapy and chemotherapy, which reduced the PSA level to <1.0 µg/ml in all the 4 cases. CONCLUSIONS: PMAC has a good prognosis. Radical surgery is recommended for moderate and low-risk PMAC and the patients with postoperative biochemical recurrence can benefit from comprehensive treatment of total androgen blockade.

Vascular injury during primary total knee arthroplasty: A nationwide study.

PURPOSE: To evaluate the incidence, risk factors, mortality, and complications of direct vascular injury (VI) in patients who underwent primary total knee arthroplasty (TKA) using data from a nationwide database. METHODS: Data were collected from the National Health Insurance Research Database of Taiwan. The study group included 111,497 patients who underwent TKA from January 2004 to December 2011. In total, 15 cases of direct VI were reported (VI group). We analyzed the incidence, risk factors, mortality, complications of direct VI and hospital stays between groups (VI group and non-VI group). RESULTS: Average incidence of VI was 13.74 per 100,000 person-years. No patient-dependent risk factors for VI were identified. Surgeons with low surgical volume highly correlated with incidence of VI (P < 0.05). 90-day mortality was significantly higher (33.3% vs. 0.37%) and length of hospital stay was significantly longer (19.43 days vs. 7.26 days) in the VI group than in the control group. In addition, incidence of periprosthetic joint infection, restenosis at the injury site, and limb loss were significantly higher in the VI group than in the control group. CONCLUSION: VI during primary TKA was associated with significantly higher incidence of periprosthetic joint infection, restenosis at the injury site, and limb loss, as well as higher 90-day mortality. Therefore, surgeons should be aware of VI during primary TKA, especially those with low surgical volume.

[Glans-preserving surgery for superficial penile squamous cell carcinoma ≥2 cm in diameter].

OBJECTIVE: To explore the feasibility of glans-preserving surgery (GPS) in the treatment of superficial penile squamous cell carcinoma (PSCC) with the lesion diameter of ≥2 cm. METHODS: We retrospectively analyzed the clinical data on 69 cases of superficial PSCC (≤T1aN0) treated by GPS (n = 36) or radical surgery (total or partial penectomy, n = 33) from July 2007 to July 2017. RESULTS: The mean tumor diameter and depth of invasion were 3.16 (2.0－6.0) cm and 0.89 (0.5－2.0) cm in the GPS group and 3.56 (2.0－6.0) cm and 1.89 (0.6－4.0) cm respectively in the radical surgery group. The patients were followed up for 10－102 (mean 42) months, during which, 5 patients in the GPS group developed local recurrence at 40 days and 2, 4, 7 and 9 months postoperatively, again underwent gansectomy, partial penectomy or GPS, and experienced no more recurrence during the follow-up of 54, 34, 39, 66 and 70 months. No local recurrence was observed in the radical surgery group, and none of the 69 patients experienced lymph node metastasis or died during the follow-up. CONCLUSIONS: GPS is safe and efficient for the treatment of superficial PSCC with the lesion diameter of ≥2 cm.

Effect of nonextraction and extraction orthodontic treatments on smile esthetics for different malocclusions.

INTRODUCTION: Smile esthetics is a critical factor for evaluating orthodontic treatment outcomes. In this study, we evaluated the differences in esthetic perceptions and smile variables between extraction and nonextraction treatments for different malocclusions. METHODS: Ninety participants were divided into 3 groups according to their pretreatment overjet (group I, 0-4 mm; group II, >4 mm; group III, <0 mm), with 15 extraction participants and 15 nonextraction participants in each group. Posttreatment frontal smiling photographs were evaluated by 30 raters (10 orthodontists, 10 general dentists, 10 laypeople), and 9 smile variables were measured. RESULTS: Smile perception for the group II extraction subjects was higher than for the nonextraction subjects by the orthodontists and general dentists. Regardless of the type of treatment, group III subjects were rated lower than those in groups I and II. The arch form index, maxillary incisor show, and smile arc were greater in the extraction participants. In multiple regression analysis, nonextraction and group III correlated negatively with the esthetic score. Maxillary incisor show, tooth number display, and buccal corridor ratio correlated positively with the esthetic score. CONCLUSIONS: Group II extraction subjects were rated higher than the nonextraction subjects by dental professionals. A smile with greater maxillary incisor show, number of displayed teeth, and buccal corridor ratio was considered more esthetic.

[Biomarkers for predicting the outcome of microdissection testicular sperm extraction for non-obstructive azoospermia patients: A systematic review].

Infertility is a common medical condition which affects nearly 15% of the world population. Non-obstructive azoospermia (NOA) is a most challenging problem inducing male infertility and does not respond to the existing medication. Surgery is the primary method for obtaining sperm from NOA patients, but the outcome of testicular sperm extraction is unpredictable preoperatively. Recently, with the development of detection techniques for male infertility, some new biomarkers have come into notice, which may be of some value in predicting the outcome of microdissection testicular sperm extraction (MTSE) and evaluating male infertility. This article presents an overview of the known biomarkers contributive to the prediction of the outcome of MTSE for NOA patients.

[Outcomes of micro-TESE combined with ICSI for non-obstructive azoospermia].

OBJECTIVE: To investigate the clinicaleffects of micro-dissection of testicular sperm extraction (micro-TESE) and its combination with intracytoplasmic sperm injection (ICSI) in the treatment of non-obstructive azoospermia (NOA). METHODS: We retrospectively analyzed the clinical data on 130 NOA patients treated between December 2015 and December 2017, including36 cases of idiopathic NOA, 22 cases of idiopathic NOA with small testis, 18 cases of Klinefelter syndrome, 46 cases of surgically treated cryptorchidism and 8 cases of AZFc microdeletion.All the patients underwent micro-TESE and 29 of them with sperm received micro-TESE + ICSI. We observed the changes in the postoperative serum T level, analyzed the influences of different types of NOA and testicular pathology on the sperm retrieval rate (SRR) and the outcomes of ICSI. RESULTS: All the micro-TESE operations were successfully completed. The SRR was significantly higher in those surgically treated for cryptorchidism (60.9%) than in the other NOA groups (P<0.05), withstatistically significant differencesnot among the latter groups (P>0.05) but among differenttypes of testicular pathology (P<0.05), the highest in the hypospermatogenesis group (100%), very low in those with Sertoli-cell-only syndrome (11.8%), and the lowest in the cases of spermatogenesis arrest (0). The serum T level was remarkably decreased at 1 and 6 months after operation (P<0.01), but markedly higher at 6 than at 1 month (P<0.01). Of the 52 patients with sperm retrieved at micro-TESE, 29 of their spouses received ICSI, resulting in 17 pregnancies, 6 live births, and 6 spontaneous abortions. CONCLUSIONS: Micro-TESE is an effective method for the treatment of NOA, and its combination with ICSI can help the NOA patients obtain their genetic offspring.

Amelioration of bleomycin-induced pulmonary fibrosis by chlorogenic acid through endoplasmic reticulum stress inhibition.

To investigate the inhibitory effects of chlorogenic acid on pulmonary fibrosis and the internal mechanisms in vivo and in vitro. 30 male BALB/C mice were randomized into 5 groups: control group, pulmonary fibrosis model group, low, middle and high dose of chlorogenic acid groups. Mice in pulmonary fibrosis model group were administered 5.0 mg/kg bleomycin with intracheal instillation and mice in 3 chlorogenic acid groups were treated with chlorogenic acid every day for 28 days after bleomycin administration. Lung tissue histology was observed using HE staining. Primary pulmonary fibroblasts were isolated and cultured. The expressions of fibrosis related factors (α-SMA and collagen I), as well as ER stress markers (CHOP and GRP78) were determined by both real-time PCR assay and Western blotting, while the expressions of other ER stress signaling pathway factors PERK, IRE-1, ATF-6 and protein levels of caspase-12, caspase-9, caspase-3, PARP were determined by Western blotting. RLE-6TN cell line induced by TGF-ß1 was also used to verify the amelioration effects in vitro study. In both in vivo and in vitro studies, TUNEL staining was used to evaluate cell apoptosis. Expressions of collagen I, α-SMA, GRP78, and CHOP were significantly inhibited by chlorogenic acid in dose-dependent manner. Similarly, decreasing levels of cleaved caspase-12, caspase-9, caspase-3 and increasing level of uncleaved PARP were observed in chlorogenic acid groups compared with those in the fibrosis group both in vivo and in vitro. Chlorogenic acid could also significantly down-regulate the level of phosphorylation of PERK and cleaved ATF-6 in vivo study. Moreover, MTT assay demonstrated chlorogenic acid could enhance proliferation of RLE-6TN cells induced by TGFß1 in vitro. And the apoptosis assays indicated that chlorogenic acid could significantly inhibit cell apoptosis both in vivo and in vitro studies. Chlorogenic acid could inhibit the pulmonary fibrosis through endoplasmic reticulum stress inhibition in vivo and in vitro.

Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling.

Cisplatin is a chemotherapeutic agent widely used in the treatment of various cancers. However, cisplatin can induce nephrotoxicity and neurotoxicity, limiting its dosage and usage. Galangin, a natural flavonol, has been found to exhibit anti-oxidant and anti-inflammatory effects in vivo. Here, we investigated the effects of galangin on cisplatin-induced acute kidney injury (AKI) and its molecular mechanisms in mice. Galangin administration reduced the cisplatin-induced oxidative stress by decreasing renal MDA and 3-NT formations. Galangin administration also increased renal anti-oxidative enzyme activities (SOD, GPx, and CAT) and GSH levels depleted by cisplatin. Furthermore, galangin administration inactivated stress-induced Nrf2 protein and its downstream products, HO-1 and GCLC. In terms of the inflammatory response, galangin administration reduced IκBα phosphorylation, NF-κB phosphorylation and nuclear translocation, and then inhibited cisplatin-induced secretions of pro-inflammatory TNF-α, IL-1ß and IL-6. In addition, cisplatin-induced ERK and p38 phosphorylations were inhibited by galangin administration. In terms of cell death, galangin administration reduced levels of p53, pro-apoptotic Bax and activated caspase-3 to inhibit the cisplatin-induced apoptosis. Galangin administration also reduced the expression levels of RIP1 and RIP3 to inhibit cisplatin-induced RIP1/RIP3-dependent necroptosis. Therefore, galangin administration significantly ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation, and cell death through inhibitions of ERK and NF-κB signaling pathways. Galangin might be a potential adjuvant for clinical cisplatin therapy.

[Adipose-derived stem cells for the treatment of penile erectile dysfunction: An update].

Adipose-derived stem cells (ADSCs) are pluripotent stem cells isolated from the adipose tissue and have the potential for self-renewal and multi-directional differentiation into neurogenic cells, smooth muscle cells, endothelial cells, and so on. Erectile dysfunction (ED) is a common male sexual dysfunction that has a negative impact on the lives of the patients and their partners. Current treatments of ED include surgery and medication, with oral 5-phosphodiesterase inhibitors as the first-line drugs. However, a small number of the patients are not sensitive to these therapies and cannot be improved or cured pathologically. So far, animal experiments and preclinical trials have confirmed the safety and efficacy of ADSCs, which act on ED though paracrine mechanisms. This review summarizes the advances in the recent 5 years in the studies of ADSCs for the treatment of ED.

[Prognostic factors of penis-sparing surgery for early-stage penile cancer].

OBJECTIVE: To investigate the factors influencing the prognosis of penis-sparing surgery (PSS) for early-stage penile cancer. METHODS: We retrospectively studied the clinical data about 45 cases of early-stage penile cancer treated by PSS from January 2007 to December 2014. We calculated the rate of local recurrence-free survival by the Kaplan-Meier method, and conducted univariate and multivariate COX regression analyses on the relevant factors including the patient's age, marital status, tumor location, tumor size, postoperative sexual life, histological grade, and TNM stage. RESULTS: One-year and three-year local recurrence-free survival rates were 95.5% and 52.2%, respectively. Multivariate analysis demonstrated that the histological grade (P = 0.039) and postoperative sexual life (P = 0.049) were independent factors for the prognosis of PSS. Logistic regression showed the patients age to be significantly associated with histological grade (P = 0.014). CONCLUSION: Histological grade and postoperative sexual life are important independent prognostic factors of PSS for early-stage penile cancer, and the patients age is associated with the prognosis of PSS through its influence on the tumor grade.

[Corporoplasty using autologous tunica vaginalis graft for Peyronie's disease].

OBJECTIVE: To assess the effect of corporoplasty with autologous tunica vaginalis graft in the treatment of Peyronie's disease. METHODS: Ten patients with Peyronie's disease underwent plaque excision and corporoplasty with autologous tunica vaginalis graft. We obtained and compared IIEF-5 scores of the patients before and at 1 and 5 years after operation. RESULTS: After surgery, penile curvature was obviously relieved and all the patients achieved normal penile erection and satisfactory sexual intercourse without erection-related pain or recurrent erectile dysfunction. The mean IIEF-5 score was significantly improved at 1 year (22.40±1.08) and 5 years postoperatively (23.00±1.14) as compared with the baseline, (19.20±2.28) (P<0.05 or 0.01). CONCLUSIONS: Corporoplasty with autologous tunica vaginalis graft is a safe, simple and effective option for the treatment of Peyronie's disease, though its definite efficiency is to be further supported by large-sample clinical studies.

A novel BLAST-Based Relative Distance (BBRD) method can effectively group members of protein arginine methyltransferases and suggest their evolutionary relationship.

We developed a novel BLAST-Based Relative Distance (BBRD) method by Pearson's correlation coefficient to avoid the problems of tedious multiple sequence alignment and complicated outgroup selection. We showed its application on reconstructing reliable phylogeny for nucleotide and protein sequences as exemplified by the fmr-1 gene and dihydrolipoamide dehydrogenase, respectively. We then used BBRD to resolve 124 protein arginine methyltransferases (PRMTs) that are homologues of nine mammalian PRMTs. The tree placed the uncharacterized PRMT9 with PRMT7 in the same clade, outside of all the Type I PRMTs including PRMT1 and its vertebrate paralogue PRMT8, PRMT3, PRMT6, PRMT2 and PRMT4. The PRMT7/9 branch then connects with the type II PRMT5. Some non-vertebrates contain different PRMTs without high sequence homology with the mammalian PRMTs. For example, in the case of Drosophila arginine methyltransferase (DART) and Trypanosoma brucei methyltransferases (TbPRMTs) in the analyses, the BBRD program grouped them with specific clades and thus suggested their evolutionary relationships. The BBRD method thus provided a great tool to construct a reliable tree for members of protein families through evolution.

Volume overload correlates with cardiovascular risk factors in patients with chronic kidney disease.

Volume overload is a predictor of mortality in dialysis patients. However, the fluid status of patients with chronic kidney disease (CKD) but not yet on dialysis has not been accurately characterized. We used the Body Composition Monitor, a multifrequency bioimpedance device, to measure the level of overhydration in CKD patients, focusing on the association between overhydration and cardiovascular disease risk factors. Overhydration was the difference between the amount of extracellular water measured by the Body Composition Monitor and the amount of water predicted under healthy euvolemic conditions. Volume overload was defined as an overhydration value at and above the 90th percentile for the normal population. Of the 338 patients with stages 3-5 CKD, only 48% were euvolemic. Patients with volume overload were found to use significantly more antihypertensive medications and diuretics but had higher systolic blood pressures and an increased arterial stiffness than patients without volume overload. In a multivariate analysis, male sex, diabetes, pre-existing cardiovascular disease, systolic blood pressure, serum albumin, TNF-α, and proteinuria were independently all associated with overhydration. Thus, volume overload is strongly associated with both traditional and novel risk factors for cardiovascular disease. Bioimpedance devices may aid in clinical assessment by helping to identify a high-risk group with volume overload among stages 3-5 CKD patients.

Lack of association between COX-2 8473T>C polymorphism and breast cancer risk: a meta-analysis.

AIM OF THE STUDY: Results of recent published studies on the association between the COX-2 8473T>C polymorphism and the risk of breast cancer have often been conflicting. To make a more precise estimation of the potential relationship, a meta-analysis was performed. MATERIAL AND METHODS: A total of seven case-control studies with 7,033 cases and 9,350 controls were included in the current meta-analysis through searching the databases of PubMed, Embase, and Cochrane Library (up to March 1(st), 2013). The odds ratio (OR) and 95% confidence interval (95% CI) were calculated to assess the strength of the association. The meta-analysis was conducted in a fixed/random effect model. RESULTS: We found no significant associations for all genetic models after all studies were pooled into the meta-analysis (for C vs. T: OR = 0.974, 95% CI: 0.906-1.047, p = 0.471; for CC vs. TT: OR = 0.957, 95% CI: 0.803-1.140, p = 0.62; for TC vs. TT: OR = 0.964, 95% CI: 0.881-1.055, p = 0.421; for CC + TC vs. TT: OR = 0.963, 95% CI: 0.880-1.053, p = 0.406; for CC vs. TT + TC: OR = 0.978, 95% CI: 0.831-1.15, p = 0.788). We also observed no obvious associations in the subgroup analyses by ethnicity (Caucasian) and source of controls (population based, PB) for all genetic models. CONCLUSIONS: Current evidence suggests that the COX-2 8473T>C polymorphism is not associated with breast cancer risk.

Access to New Clinic Appointments for Patients With Cancer.

Importance: Racial and ethnic disparities have been observed in the outpatient visit rates for specialist care, including cancer care; however, little is known about patients' experience at the critical step of attempting to access new clinic appointments for cancer care. Objective: To determine simulated English-speaking, Spanish-speaking, and Mandarin-speaking patient callers' ability to access new clinic appointments for 3 cancer types (colon, lung, and thyroid cancer) that disproportionately impact Hispanic and Asian populations. Design, Setting, and Participants: This cross-sectional audit study was conducted between November 2021 and March 2023 using 479 clinic telephone numbers that were provided by the hospital general information personnel at 143 hospitals located across 12 US states. Using standardized scripts, trained research personnel assigned to the roles of English-speaking, Spanish-speaking, and Mandarin-speaking patients called the telephone number for a clinic that treats colon, lung, or thyroid cancer to inquire about a new clinic appointment. Data analysis was conducted from June to September 2023. Main Outcomes and Measures: The primary outcome was whether the simulated patient caller was able to access cancer care (binary variable, yes or no), which was defined to include being provided with a clinic appointment date or scheduling information. Multivariable logistic regression analysis was performed to determine factors independently associated with simulated patient callers being able to access cancer care. Results: Of 985 total calls (399 English calls; 302 Spanish calls; 284 Mandarin calls), simulated patient callers accessed cancer care in 409 calls (41.5%). Differences were observed based on language type, with simulated English-speaking patient callers significantly more likely to access cancer care compared with simulated Spanish-speaking and Mandarin-speaking patient callers (English, 245 calls [61.4%]; Spanish, 110 calls [36.4%]; Mandarin, 54 calls [19.0%]; P < .001). A substantial number of calls ended due to linguistic barriers (291 of 586 Spanish or Mandarin calls [49.7%]) and workflow barriers (239 of 985 calls [24.3%]). Compared with English-speaking simulated patient callers, the odds of accessing cancer care were lower for Spanish-speaking simulated patient callers (adjusted odds ratio [aOR], 0.34; 95% CI, 0.25-0.46) and Mandarin-speaking simulated patient callers (aOR, 0.13; 95% CI, 0.09-0.19). Compared with contacting clinics affiliated with teaching hospitals, callers had lower odds of accessing cancer care when contacting clinics that were affiliated with nonteaching hospitals (aOR, 0.53; 95% CI, 0.40-0.70). Conclusions and Relevance: In this cross-sectional audit study, simulated patient callers encountered substantial barriers when attempting to access clinic appointments for cancer care. These findings suggest that interventions focused on mitigating these barriers are necessary to increase access to cancer care for all patients.