Boris knockout eliminates AOM/DSS-induced in situ colorectal cancer by suppressing DNA damage repair and inflammation.

The Brother of Regulator of Imprinted Sites (BORIS, gene symbol CTCFL) has previously been shown to promote colorectal cancer cell proliferation, inhibit cancer cell apoptosis, and resist chemotherapy. However, it is unknown whether Boris plays a role in the progression of in situ colorectal cancer. Here Boris knockout (KO) mice were constructed. The function loss of the cloned Boris mutation that was retained in KO mice was verified by testing its activities in colorectal cell lines compared with the Boris wild-type gene. Boris knockout reduced the incidence and severity of azoxymethane/dextran sulfate-sodium (AOM/DSS)-induced colon cancer. The importance of Boris is emphasized in the progression of in situ colorectal cancer. Boris knockout significantly promoted the phosphorylation of γH2AX and the DNA damage in colorectal cancer tissues and suppressed Wnt and MAPK pathways that are responsible for the callback of DNA damage repair. This indicates the strong inhibition of colorectal cancer in Boris KO mice. By considering that the DSS-promoted inflammation contributes to tumorigenesis, Boris KO mice were also studied in DSS-induced colitis. Our data showed that Boris knockout alleviated DSS-induced colitis and that Boris knockdown inhibited the NF-κB signaling pathway in RAW264.7 cells. Therefore Boris knockout eliminates colorectal cancer generation by inhibiting DNA damage repair in cancer cells and relieving inflammation in macrophages. Our findings demonstrate the importance of Boris in the development of in situ colorectal cancer and provide evidence for the feasibility of colorectal cancer therapy on Boris.

Does the Use of Probe-based Near-infrared Autofluorescence Parathyroid Detection Benefit Parathyroidectomy?: A Randomized Single-center Clinical Trial.

OBJECTIVE: To evaluate the benefits of probe-based near-infrared autofluorescence (NIRAF) parathyroid identification during parathyroidectomy. BACKGROUND: Intraoperative parathyroid gland identification during parathyroidectomy can be challenging, while additionally requiring costly frozen sections. Earlier studies have established NIRAF detection as a reliable intraoperative adjunct for parathyroid identification. METHODS: Patients undergoing parathyroidectomy for primary hyperparathyroidism were prospectively enrolled by a senior surgeon (>20 years experience) and a junior surgeon (<5 years experience), while being randomly allocated to the probe-based NIRAF or control group. Data collected included procedure type, number of parathyroids identified with high confidence by the surgeon and the resident, number of frozen sections performed, parathyroidectomy duration, and number of patients with persistent disease at the first postoperative visit. RESULTS: One hundred sixty patients were randomly enrolled under both surgeons to the probe group (n=80) versus control (n=80). In the probe group, parathyroid identification rate of the senior surgeon improved significantly from 3.2 to 3.6 parathyroids per patient ( P <0.001), while that of the junior surgeon also rose significantly from 2.2 to 2.5 parathyroids per patient ( P =0.001). Parathyroid identification was even more prominent for residents increasing significantly from 0.9 to 2.9 parathyroids per patient ( P <0.001). Furthermore, there was a significant reduction in frozen sections utilized in the probe group versus control (17 vs 47, P =0.005). CONCLUSION: Probe-based NIRAF detection can be a valuable intraoperative adjunct and educational tool for improving confidence in parathyroid gland identification, while potentially reducing the number of frozen sections required.

Eleven-Year Outcomes of Deep Brain Stimulation in Early-Stage Parkinson Disease.

OBJECTIVE: The deep brain stimulation (DBS) in early-stage Parkinson's disease (PD) pilot clinical trial randomized 30 patients (Hoehn & Yahr II off; medication duration 0.5-4 years; without dyskinesia/motor fluctuations) to optimal drug therapy (ODT) (early ODT) or bilateral subthalamic nucleus (STN) DBS plus ODT (early DBS+ODT). This study aims to report the 11-year outcomes of patients who completed the DBS in early-stage PD pilot clinical trial. MATERIALS AND METHODS: Attempts were made to contact all 29 subjects who completed the two-year trial to participate in an 11-year follow-up study. Mixed-effects models compared overall trend in outcomes for randomization groups (fixed-effects: assigned treatment, year, their interaction; random-effect: subject) to account for repeated measures. RESULTS: Twelve subjects participated in this 11-year follow-up study (n = 8 early ODT, n = 4 early DBS+ODT). Participating subjects were 70.0 ± 4.8 years old with a PD medication duration of 13.7 ± 1.7 years (early DBS duration 11.5 ± 1.3 years, n = 4). Three early ODT subjects received STN-DBS as standard of care (DBS duration 6.5 ± 2.0 years). Early ODT subjects had worse motor complications (Unified Parkinson's Disease Rating Scale [UPDRS]-IV) than early DBS+ODT subjects over the 11-year follow-up period (between-group difference = 3.5 points; pinteraction = 0.03). Early DBS+ODT was well-tolerated after 11 years and showed comparable outcomes to early ODT for other UPDRS domains, Parkinson Disease Questionnaire-39 (PDQ-39), and levodopa equivalent daily dose (LEDD). CONCLUSIONS: Eleven years after randomization, early DBS+ODT subjects had fewer motor complications than early ODT subjects. These results should be interpreted with caution because only 40% of pilot trial subjects participated in this 11-year follow-up study. The Food and Drug Administration has approved the conduct of a pivotal clinical trial evaluating DBS in early-stage PD (IDEG050016). CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT00282152.

Discovery of Highly Potent Daphnane Diterpenoids Uncovers Importin-ß1 as a Druggable Vulnerability in Castration-Resistant Prostate Cancer.

Importins are overexpressed in many cancers and mediate the abnormal nuclear transport of oncogenic factors. The druggable potential of importins still remains unclear, largely because of the lack of potent inhibitors. Herein, the anti-castration-resistant prostate cancer (CRPC) screening of a Euphorbiaceae diterpenoid library followed by target fishing led to the identification of a highly potent importin-ß1 inhibitor, daphnane diterpenoid DD1. DD1 selectively inhibited the growth and survival of CRPC cells at subnanomolar concentrations and completely blocked tumor growth in preclinical models at an extremely low dosage. Mechanistic studies revealed that targeting of importin-ß1 by DD1 significantly reduced the nuclear accumulation of key CRPC drivers, shutting down their downstream oncogenic signaling. Disruption of the predicted binding sites of DD1 on importin-ß1 abolished this anti-CRPC effect. These findings suggest that importin-ß1 is an effective therapeutic target in CRPC and that DD1 as the most potent importin-ß1 inhibitor to date can be developed as therapeutics for treatment of this disease.

Tigliane and rhamnofolane glycosides from Euphorbia wallichii prevent oxidative stress-induced neuronal death in PC-12 cells.

Tigliane and rhamnofolane diterpenoids bearing glycosyl substituents are rarely found in nature. In the current study, seven new tigliane glycosides, euphorwallsides A - G (1-7), and five new rhamnofolane glycosides, euphorwallsides H - L (8-12), were isolated from the whole plants of Euphorbia wallichii. Their structures were elucidated by a combination of spectroscopic, computational, and chemical means. The aglycones of 1-5 represent a rare class of 13-deoxygenated tiglianes, while those of 8-12 represent the first examples of 4-deoxygenated rhamnofolanes. 2, 3, 5, 7, 8, and 12 showed significant neuroprotective effects on sodium nitroprusside (SNP)-induced neuronal death in pheochromocytoma cell line PC-12 at 10 µM, being more active than the clinical drug, edaravone. Mechanistic study revealed that the most active compound, 3, could inhibit reactive oxygen species (ROS) accumulation and restore the mitochondrial membrane potential via modulating the Nrf2 signaling pathway in PC-12 cells.

[function of the patients' male partners].

Objective: To investigate the sexual behavior and sexual function of the male partners of breast cancer patients and their potential relationship with socio-demographic and clinical variables. METHODS: In this cross-sectional study, we conducted an investigation among 196 male partners (aged 23－59 years) of breast cancer patients between May 2020 and October 2020. We completed the Male Sexual Function Questionnaire (BSFI) by online and telephone interview with the subjects and collected relevant socio-demographic and clinical variables. RESULTS: The average age of the interviewees was (46.13 ± 7.75) years old, and the mean duration of the patients' breast cancer was (1.58 ± 0.48) years at the time of the investigation. The incidence rate of sexual dysfunction in the male partners of the patients was dramatically higher after the onset of breast cancer than before it (49.76% vs 9.68%, P < 0.01). Low libido was found to be the main type of sexual dysfunction (38.3%) among the male subjects, with an even high incidence rate among those whose wives received mastectomy (OR = 5.533, P = 0.017, 95% CI: 1.366－22.412) and radiotherapy (OR = 3.439, P < 0.044, 95% CI: 1.058－11.171) and significantly correlated with age (OR = 1.134, P = 0.001, 95% CI: 1.053－1.222). CONCLUSIONS: Breast cancer and its treatment methods may affect the sexual function of the male partners of the patients. It is necessary for doctors to pay attention to the factors affecting the sexual function of the patients and their partners so as to take appropriate intervention measures.

Prediction models for breast cancer prognosis among Asian women.

BACKGROUND: Robust and reliable prognosis prediction models have not been developed and validated for Asian patients with breast cancer, a rapidly growing yet understudied population in the United States. METHODS: We used longitudinal data from the Shanghai Breast Cancer Survival Study, a population-based prospective cohort study (n = 5042), to develop prediction models for 5- and 10-year disease-free survival (DFS) and overall survival (OS). The initial models considered age at diagnosis, tumor grade, tumor size, number of positive nodes, TNM stage, chemotherapy, tamoxifen therapy, and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status. We then evaluated whether the addition of modifiable lifestyle factors (physical activity, soy isoflavones intake, and postdiagnostic weight change) improved the models. All final models have been validated internally and externally in the National Cancer Database when applicable. RESULTS: Our final models included age at diagnosis, tumor grade, tumor size, number of positive nodes, TNM stage, chemotherapy, tamoxifen therapy, ER status, PR status, 6-month postdiagnostic weight change, interaction between ER status and tamoxifen therapy, and interaction between age and TNM stage. The internal validation yielded C-statistics of 0.76, 0.74, 0.78, and 0.75 for 5-year DFS, 10-year DFS, 5-year OS, and 10-year OS, respectively. The external validation yielded C-statistics of 5- and 10-year OS both at 0.78 for Chinese ethnicity, 0.79 for East Asian ethnicity, and 0.75 and 0.76 for all ethnic groups combined. CONCLUSION: We developed prediction models for breast cancer prognosis from a large prospective study. Our prognostic models performed very well in women from the United States-particularly in Asian American women-and demonstrated high prediction accuracy and generalizability.

Structural Elucidation of Three 9,11-Seco Tetracyclic Triterpenoids Enables the Structural Revision of Euphorol J.

Compounds 1-3, the rare examples of 9,11-seco euphane or lanostane triterpenoids featuring an enol-hemiacetal functionality, were isolated from Euphorbia stracheyi. Their structures were elucidated by a combination of spectroscopic, computational, chemical, and single-crystal X-ray diffraction means, which enables the structure of previously published euphorol J to be revised as 1. 1-3 showed significant cytotoxicities on the breast cancer cell line MDA-MB-468 with IC50 values in the range of 2.9-3.9 µM.

Presegetane diterpenoids from Euphorbia sieboldiana as a new type of anti-liver fibrosis agents that inhibit TGF-ß/Smad signaling pathway.

Seven new diterpenoids, eupholenes A-G (1-7), including two presegetanes (1 and 2), four jatrophanes (3-6), and one paraliane (7), along with 19 known analogues (8-26) were obtained by anti-liver fibrosis bioassay-guided isolation of Euphorbia sieboldiana. Their structures were elucidated by extensive spectroscopic data analyses, chemical methods, ECD calculations, and single-crystal X-ray diffractions. Euphorbesulin A (10), a presegetane diterpenoid (5/9/5 ring system), was identified as a promising anti-liver fibrosis agent that could inhibit the expressions of fibronectin (FN), α-smooth muscle actin (α-SMA), and collagen I in TGF-ß1-stimulated LX-2 cells at a micromolar level. Mechanistic study revealed that 10 suppressed liver fibrosis via inhibition of TGF-ß/Smad signaling pathway, and its potential target was TGF-ß type I receptor. These findings suggested that presegetane diterpenoid could serve as a new type of structural motif in future anti-liver fibrosis drug development.

Salviplenoid A from Salvia plebeia attenuates acute lung inflammation via modulating NF-κB and Nrf2 signaling pathways.

Acute lung injury (ALI) involves series of inflammatory pathologies and cause high morbidity. Salviplenoid A (SA) was a new sesquiterpenoid from the traditional inflammatory herb Salvia plebeia. In our previous study, SA exhibited antiinflammatory activity in RAW264.7 cells. However, the extensive effects of SA in human cells and in vivo and the active mechanisms are unclear. Thus, in this study, we sought to access its effects in vitro and in vivo and to investigate its mechanisms. SA was proved to inhibit the induction of proinflammatory cytokines in human cell types, including pulmonary epithelial cells and endothetial cells. It also depressed monocyte adhesion. Moreover, SA potently attenuated the acute lung inflammation in the LPS-induced mouse model shown by down-regulation of proinflammatory mediators, inhibition of polymorphonuclear neutrophil infiltration, and alleviation of related symptoms like alveolar congestion and mucus secretion. Further evaluation confirmed that SA regulated NF-κB pathway by inhibiting the IκB-α phosphorylation. And it markedly mediated Nrf2/HO-1 pathway by activating the Nrf2/HO-1 expression and promoting Nrf2 nuclear translocation. Therefore, SA could attenuate acute lung inflammation via suppressing NF-κB and activating Nrf2, which provide a theoretical basis for the potential application of SA in clinic.

Disparities in BRCA counseling across providers in a diverse population of young breast cancer survivors.

PURPOSE: All women diagnosed with breast cancer (BC) ≤age 50 should be referred for genetic counseling (GC) and testing. We sought to compare differences in provider practices and access across a racially and ethnically diverse population of young BC survivors. METHODS: A registry-based sample of women diagnosed with invasive BC ≤age 50 from 2009 to 2012 was recruited through the Florida Cancer Registry, and completed a questionnaire and medical record release. Differences were compared across those tested with or without the involvement of a board-certified or credentialed genetics health professional (GHP) in (1) clinical and demographic variables and (2) pretest GC elements. RESULTS: Of 1622 participants, there were 440 Blacks, 285 Hispanics, and 897 Non-Hispanic Whites. Of 831 participants with medical record verification of testing provider, 170 (20%) had documentation of GHP involvement. Among the 613 who recalled a pretest discussion and had GC elements collected, those with GHP involvement were significantly more likely to recall the seven recognized GC elements. CONCLUSION: GHP involvement was associated with adherence to nationally recommended best practices. With the expanding importance of identifying inherited cancers, it is critical to ensure equitable access to best practices across all populations.

Selective inversion recovery quantitative magnetization transfer imaging: Toward a 3 T clinical application in multiple sclerosis.

BACKGROUND: Assessing the degree of myelin injury in patients with multiple sclerosis (MS) is challenging due to the lack of magnetic resonance imaging (MRI) methods specific to myelin quantity. By measuring distinct tissue parameters from a two-pool model of the magnetization transfer (MT) effect, quantitative magnetization transfer (qMT) may yield these indices. However, due to long scan times, qMT has not been translated clinically. OBJECTIVES: We aim to assess the clinical feasibility of a recently optimized selective inversion recovery (SIR) qMT and to test the hypothesis that SIR-qMT-derived metrics are informative of radiological and clinical disease-related changes in MS. METHODS: A total of 18 MS patients and 9 age- and sex-matched healthy controls (HCs) underwent a 3.0 Tesla (3 T) brain MRI, including clinical scans and an optimized SIR-qMT protocol. Four subjects were re-scanned at a 2-week interval to determine inter-scan variability. RESULTS: SIR-qMT measures differed between lesional and non-lesional tissue (p < 0.0001) and between normal-appearing white matter (NAWM) of patients with more advanced disability and normal white matter (WM) of HCs (p < 0.05). SIR-qMT measures were associated with lesion volumes, disease duration, and disability scores (p ⩽ 0.002). CONCLUSION: SIR-qMT at 3 T is clinically feasible and predicts both radiological and clinical disease severity in MS.

19-nor-, 20-nor-, and tetranor-Halimane-Type Furanoditerpenoids from Croton crassifolius.

The phytochemical investigation of the roots of Croton crassifolius led to the isolation of 16 new halimane furanoditerpenoids, crohalifuranes A-P (1-16), along with 15 known analogues, 17-31. The new structures including their absolute configurations were elucidated by NMR and MS data analysis, comparison of experimental and calculated electronic circular dichroism data, single-crystal X-ray diffraction data, and chemical methods. Crohalifuranes A (1) and B (2) are tetranor- and 19-nor-halimane diterpenoids featuring a rare decahydroacenaphthene core, respectively, which might be derived from the accompanying crassifoliusin A by loss of the furan ring or the C-19 substituent. Crohalifurane C (3) represents the first example of a 20-nor-halimane diterpenoid, and crohalifurane D (4) is characterized by an unusual 6,20-δ-lactone moiety. All compounds were examined for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide in RAW264.7 cells, and 2 and 23 exhibited moderate inhibition on NO production with IC50 values of 17.2 ± 1.3 and 23.7 ± 1.4 µM, respectively.

Euphoresulanes A-M, structurally diverse jatrophane diterpenoids from Euphorbia esula.

Thirteen new jatrophane diterpenoids, euphoresulanes A-M (1-13), and seven known analogues (14-20) were isolated from the whole plants of Euphorbia esula. Their structures were elucidated by extensive spectroscopic analysis, and the absolute configurations of 1, 6, and 10 were confirmed by single crystal X-ray diffraction. Compounds 1-20 were screened for the multidrug resistance (MDR) reversal activity on P-glycoprotein (Pgp)-dependent cancer cell line HepG2/ADR, and 1, 2, 4, 6, and 8 exhibited comparable activity to the positive drugs. Euphoresulane H (8), the most active MDR modulator, could enhance the efficacy of anticancer drug adriamycin to ca. 33 folds at 5 µM. The structure-activity relationship (SAR) study revealed that the acyloxy substitution at C-9 is essential to the activity and presence of H-2 was favorable.

Ingol diterpenoids as P-glycoprotein-dependent multidrug resistance (MDR) reversal agents from Euphorbia marginata.

Twenty new ingol diterpenoids, euphornans A-T (1-20), representing a rare class of C-19-oxidated and H-2, H-3 ß-oriented ingols, were isolated from the seeds of Euphorbia marginata. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis, ECD analysis, and single crystal X-ray diffraction. Compounds 1-20 were screened for the multidrug resistance (MDR) reversal activity on P-glycoprotein (Pgp)-dependent MDR cancer cell line HepG2/ADR, and 11, 14, and 18 were identified as potent MDR modulators that could enhance the efficacy of anticancer drug adriamycin to ca. 20 folds at 5 µM. The Pgp inhibition mechanism and brief structure-activity relationships (SARs) of these compounds were also discussed.

Two highly oxygenated nor-clerodane diterpenoids from Croton caudatus.

Two highly oxygenated nor-clerodane diterpenoids, crocleropenes A and B (1 and 2), together with four known compounds (3-6) were isolated from the leaves and twigs of Croton caudatus. Their structures were elucidated by combination of extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. 1 and 2 represent the first examples of nor-clerodane-3,5(10)-diene diterpenoids. Compounds 1 and 2 exhibited weak cytotoxicity in vitro against MCF-7 cancer cells with IC50 values of 35.8 and 40.2 µM, respectively. [Formula: see text].

Physical therapy versus natural history in outcomes of rotator cuff tears: the Rotator Cuff Outcomes Workgroup (ROW) cohort study.

BACKGROUND: We compared the outcomes of patients who performed physical therapy versus those who did not in a longitudinal cohort of patients undergoing nonoperative treatment of rotator cuff tears. We also assessed whether there was a dose effect in which the pain and functional outcomes in patients performing physical therapy plateaued. METHODS: From February 2011 to June 2015, a multicenter cohort of patients with rotator cuff tears undergoing nonoperative treatment completed a detailed health and demographic questionnaire and the Shoulder Pain and Disability Index (SPADI) at baseline and 3, 6, 12, and 18 months. Longitudinal mixed models were used to assess whether physical therapy in the first 3 months predicted SPADI scores and dose effect. RESULTS: Among the 55 patients in our cohort, the performance of physical therapy within the first 3 months predicted better SPADI scores versus nonperformance of physical therapy at 3 months (P = .02). Scores were similar between groups at 6, 12, and 18 months. A threshold of 16 physical therapy sessions was observed for pain and functional improvement during follow-up, after which significant improvement was not seen. CONCLUSIONS: Patients who performed physical therapy within the first 3 months had statistically significant improvements in pain and function as measured by the SPADI score at 3 months compared with patients who did not report performing physical therapy. Depending on the minimal clinically important difference used for the SPADI score, our results could be interpreted as meeting the minimal clinically important difference threshold or not. Improvement in outcomes was observed up to 16 sessions of physical therapy, after which outcomes plateaued.

Enhancing anaerobic digestion of dairy and swine wastewater by adding trace elements: evaluation in batch and continuous experiments.

Trace elements play a critical role for microbial activity in anaerobic digestion (AD) but their effects were probably overestimated in batch tests and should be comparably evaluated in continuous systems. In this study, Fe2+, Co2+, Ni2+, Cu2+ and Zn2+ were added in different concentrations to manure wastewater, and the effects were compared in both batch and continuous systems. The results were used to demonstrate suitable trace element compositions for AD of dairy and swine wastewater, and to compare the outcomes from batch and continuous systems. Fe2+ and Zn2+ were identified as being the most efficient stimulant of dairy and swine wastewater respectively. The addition of 5 mg/L Fe2+ and 0.4 mg/L Zn2+ increased the batch specific methane yield by 62% and 126% for dairy and swine wastewater, respectively. Nevertheless, a lower increment of 2% and 21%, for dairy and swine wastewater was obtained in the 120-day continuously-fed experiments. The 16S rRNA gene sequencing results indicated a relationship between the methanogens population, specific methanogenic activities, propionate, and dissolved hydrogen. Conclusively, the addition of a low dosage of Fe2+ and Zn2+ is a feasible strategy to enhance the methanogenic metabolism of the AD of dairy and swine wastewater respectively.

Directed solutions to address differences in access to liver transplantation.

The United Network for Organ Sharing recently altered current liver allocation with the goal of decreasing Model for End-Stage Liver Disease (MELD) variance at transplant. Concerns over these and further planned revisions to policy include predicted decrease in total transplants, increased flying and logistical complexity, adverse impact on areas with poor quality health care, and minimal effect on high MELD donor service areas. To address these issues, we describe general approaches to equalize critical transplant metrics among regions and determine how they alter MELD variance at transplant and organ supply to underserved communities. We show an allocation system that increases minimum MELD for local allocation or preferentially directs organs into areas of need decreases MELD variance. Both models have minimal adverse effects on flying and total transplants, and do not disproportionately disadvantage already underserved communities. When combined together, these approaches decrease MELD variance by 28%, more than the recently adopted proposal. These models can be adapted for any measure of variance, can be combined with other proposals, and can be configured to automatically adjust to changes in disease incidence as is occurring with hepatitis C and nonalcoholic fatty liver disease.

Presence and molecular characteristics of oxazolidinone resistance in staphylococci from household animals in rural China.

Objectives: To investigate the presence and molecular characteristics of oxazolidinone resistance genes cfr and optrA in staphylococci from household animals in rural China. Methods: Various samples were collected from household animals in 12 rural villages. Staphylococcal isolates showing florfenicol MICs ≥10 mg/L were identified and screened for the presence of cfr and/or optrA. PCR-positive isolates were characterized by antimicrobial susceptibility testing, S1 nuclease PFGE and Southern blotting. WGS data were analysed to identify the core-genome phylogenetic profile of each isolate as well as the genetic environment of cfr and/or optrA. Results: Nine optrA-positive (seven Staphylococcus sciuri and two Staphylococcus simulans) and 10 cfr-positive staphylococci were identified from eight and five villages, respectively. The gene optrA was chromosomally encoded in all nine isolates, whereas cfr was located on a plasmid in one S. sciuri and three Staphylococcus saprophyticus and in the chromosomal DNA of single Staphylococcus cohnii and Staphylococcus lentus isolates and two S. sciuri isolates. The remaining two cfr-carrying Staphylococcus haemolyticus isolates were indistinguishable by PFGE. Most optrA- or cfr-carrying staphylococci also harboured phenicol, tetracycline and/or macrolide-lincosamide-streptogramin B resistance genes. Genetic environment analysis showed that, for the first time, optrA was associated with transposon Tn6261, while cfr was adjacent to both a tnp (transposase) gene and a Tn558 transposon. Conclusions: The current study reveals for the first time the wide distribution of oxazolidinone resistance genes optrA and cfr in household animals in rural areas of China and is the first identification of optrA in S. simulans isolates.