Temperature impacts fate of antibiotic resistance genes during vermicomposting of domestic excess activated sludge.

Effect of temperature on antibiotic resistance genes (ARGs) during vermicomposting of domestic excess sludge remains poorly understood. Vermicomposting experiment with excess sludge was conducted at three different temperatures (15 °C, 20 °C, and 25 °C) to investigate the fate of ARGs, bacterial community and their relationship in the process. The vermicomposting at 25 °C did not significantly attenuate the targeted ARGs relative to that at 15 °C and 20 °C. The dynamics of qnrA, qnrS, and tetM genes during vermicomposting at 15 °C and 20 °C followed the first-order kinetic model. Temperature remarkably impacted bacterial diversity of the final products with the lowest Shannon index at 25 °C. The presence of the genus (Aeromonas and Chitinophagaceae) at 25 °C may contribute to the rebound of the genes (qnrA, qnrS and tetM). The study indicates that 20 °C is a suitable vermicomposting temperature to simultaneously reach the highest removal efficiency of the ARGs and the good biostability of the final product.

Estrogen-induced transcription at individual alleles is independent of receptor level and active conformation but can be modulated by coactivators activity.

Steroid hormones are pivotal modulators of pathophysiological processes in many organs, where they interact with nuclear receptors to regulate gene transcription. However, our understanding of hormone action at the single cell level remains incomplete. Here, we focused on estrogen stimulation of the well-characterized GREB1 and MYC target genes that revealed large differences in cell-by-cell responses, and, more interestingly, between alleles within the same cell, both over time and hormone concentration. We specifically analyzed the role of receptor level and activity state during allele-by-allele regulation and found that neither receptor level nor activation status are the determinant of maximal hormonal response, indicating that additional pathways are potentially in place to modulate cell- and allele-specific responses. Interestingly, we found that a small molecule inhibitor of the arginine methyltransferases CARM1 and PRMT6 was able to increase, in a gene specific manner, the number of active alleles/cell before and after hormonal stimulation, suggesting that mechanisms do indeed exist to modulate hormone receptor responses at the single cell and allele level.

FOXA1 upregulation promotes enhancer and transcriptional reprogramming in endocrine-resistant breast cancer.

Forkhead box A1 (FOXA1) is a pioneer factor that facilitates chromatin binding and function of lineage-specific and oncogenic transcription factors. Hyperactive FOXA1 signaling due to gene amplification or overexpression has been reported in estrogen receptor-positive (ER+) endocrine-resistant metastatic breast cancer. However, the molecular mechanisms by which FOXA1 up-regulation promotes these processes and the key downstream targets of the FOXA1 oncogenic network remain elusive. Here, we demonstrate that FOXA1 overexpression in ER+ breast cancer cells drives genome-wide enhancer reprogramming to activate prometastatic transcriptional programs. Up-regulated FOXA1 employs superenhancers (SEs) to synchronize transcriptional reprogramming in endocrine-resistant breast cancer cells, reflecting an early embryonic development process. We identify the hypoxia-inducible transcription factor hypoxia-inducible factor-2α (HIF-2α) as the top high FOXA1-induced SE target, mediating the impact of high FOXA1 in activating prometastatic gene sets and pathways associated with poor clinical outcome. Using clinical ER+/HER2- metastatic breast cancer datasets, we show that the aberrant FOXA1/HIF-2α transcriptional axis is largely nonconcurrent with the ESR1 mutations, suggesting different mechanisms of endocrine resistance and treatment strategies. We further demonstrate the selective efficacy of an HIF-2α antagonist, currently in clinical trials for advanced kidney cancer and recurrent glioblastoma, in reducing the clonogenicity, migration, and invasion of endocrine-resistant breast cancer cells expressing high FOXA1. Our study has uncovered high FOXA1-induced enhancer reprogramming and HIF-2α-dependent transcriptional programs as vulnerable targets for treating endocrine-resistant and metastatic breast cancer.

Embryonic transcription factor SOX9 drives breast cancer endocrine resistance.

The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases. Through the analysis of the ER cistrome in tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2-ER complex that stimulates the transcription of a set of genes, including most notably the stem cell factor SOX9, that promote proliferation and a metastatic phenotype. We show that up-regulation of SOX9 is sufficient to cause relative endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with tamoxifen resistance was validated in a unique set of clinical samples supporting the need for the development of improved ER antagonists.

The oral selective oestrogen receptor degrader (SERD) AZD9496 is comparable to fulvestrant in antagonising ER and circumventing endocrine resistance.

BACKGROUND: The oestrogen receptor (ER) is an important therapeutic target in ER-positive (ER+) breast cancer. The selective ER degrader (SERD), fulvestrant, is effective in patients with metastatic breast cancer, but its intramuscular route of administration and low bioavailability are major clinical limitations. METHODS: Here, we studied the pharmacology of a new oral SERD, AZD9496, in a panel of in vitro and in vivo endocrine-sensitive and -resistant breast cancer models. RESULTS: In endocrine-sensitive models, AZD9496 inhibited cell growth and blocked ER activity in the presence or absence of oestrogen. In vivo, in the presence of oestrogen, short-term AZD9496 treatment, like fulvestrant, resulted in tumour growth inhibition and reduced expression of ER-dependent genes. AZD9496 inhibited cell growth in oestrogen deprivation-resistant and tamoxifen-resistant cell lines and xenograft models that retain ER expression. AZD9496 effectively reduced ER levels and ER-induced transcription. Expression analysis of short-term treated tumours showed that AZD9496 potently inhibited classic oestrogen-induced gene transcription, while simultaneously increasing expression of genes negatively regulated by ER, including genes potentially involved in escape pathways of endocrine resistance. CONCLUSIONS: These data suggest that AZD9496 is a potent anti-oestrogen that antagonises and degrades ER with anti-tumour activity in both endocrine-sensitive and endocrine-resistant models.

Implications of Classification of Os Trigonum: A Study Based on Computed Tomography Three-Dimensional Imaging.

BACKGROUND The os trigonum is an accessory bone that is not fully fused with the talus during secondary ossification, and is one of the risk factors of posterior malleolus impact syndrome. The purpose of this study was to classify the os trigonum and to guide the diagnosis and treatment of related clinical diseases. MATERIAL AND METHODS Ankle computed tomography (CT) scans of 586 Chinese patients between October 2014 and October 2018 were reviewed. CT images of 1011 ankle joints were reconstructed to evaluate the classification of the os trigonum and the measurement of anatomical parameters. RESULTS The incidences of os trigonum in 3 groups were determined as type I (1.9%), type II (10.5%), and type III (14.7%). The macro-axis of type II (0.89±0.31) cm was significantly larger than with type I (0.65±0.24 cm) and type III (0.74±0.23 cm) (p<0.05).The minor axis of similar of type I (0.41±0.23 cm) was significantly shorter than that of type II (0.58±0.32 cm) and type III (0.55±0.16 cm) (p<0.05).The distance from os trigonum to calcaneal tubercle was significantly different than that of type I (1.33±0.52 cm), type II (1.67±0.55 cm), and type III (1.84±0.45 cm) (p<0.05). CONCLUSIONS This study showed that os trigonum has a high incidence. Type I was the least common, the volume of type II was larger, and type III was more common. The anatomical parameters of each type may improve treatment of related diseases and the further development of ankle arthroscopic surgery.

FOXA1 overexpression mediates endocrine resistance by altering the ER transcriptome and IL-8 expression in ER-positive breast cancer.

Forkhead box protein A1 (FOXA1) is a pioneer factor of estrogen receptor α (ER)-chromatin binding and function, yet its aberration in endocrine-resistant (Endo-R) breast cancer is unknown. Here, we report preclinical evidence for a role of FOXA1 in Endo-R breast cancer as well as evidence for its clinical significance. FOXA1 is gene-amplified and/or overexpressed in Endo-R derivatives of several breast cancer cell line models. Induced FOXA1 triggers oncogenic gene signatures and proteomic profiles highly associated with endocrine resistance. Integrated omics data reveal IL8 as one of the most perturbed genes regulated by FOXA1 and ER transcriptional reprogramming in Endo-R cells. IL-8 knockdown inhibits tamoxifen-resistant cell growth and invasion and partially attenuates the effect of overexpressed FOXA1. Our study highlights a role of FOXA1 via IL-8 signaling as a potential therapeutic target in FOXA1-overexpressing ER-positive tumors.

GPCRs profiling and identification of GPR110 as a potential new target in HER2+ breast cancer.

PURPOSE: G protein-coupled receptors (GPCRs) represent the largest family of druggable targets in human genome. Although several GPCRs can cross-talk with the human epidermal growth factor receptors (HERs), the expression and function of most GPCRs remain unknown in HER2+ breast cancer (BC). In this study, we aimed to evaluate gene expression of GPCRs in tumorigenic or anti-HER2 drug-resistant cells and to understand the potential role of candidate GPCRs in HER2+ BC. METHODS: Gene expression of 352 GPCRs was profiled in Aldeflur+ tumorigenic versus Aldeflur- population and anti-HER2 therapy-resistant derivatives versus parental cells of HER2+ BT474 cells. The GPCR candidates were confirmed in 7 additional HER2+ BC cell line models and publicly available patient dataset. Anchorage-dependent and anchorage-independent cell growth, mammosphere formation, and migration/invasion were evaluated upon GPR110 knockdown by siRNA in BT474 and SKBR3 parental and lapatinib+ trastuzumab-resistant (LTR) cells. RESULTS: Adhesion and class A GPCRs were overexpressed in Aldeflur+ and anti-HER2 therapy-resistant population of BT474 cells, respectively. GPR110 was the only GPCR overexpressed in Aldeflur+ and anti-HER2 therapy-resistant population in BT474, SKBR3, HCC1569, MDA-MB-361, AU565, and/or HCC202 cells and in HER2+ BC subtype in patient tumors. Using BT474 and SKBR3 parental and LTR cells, we found that GPR110 knockdown significantly reduced anchorage-dependent/independent cell growth as well as migration/invasion of parental and LTR cells and mammosphere formation in LTR derivatives and not in parental cells. CONCLUSION: Our data suggest a potential role of GPR110 in tumorigenicity and in tumor cell dissemination in HER2+ BC.

Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast.

Sister chromatid cohesion is normally established in S phase in a process that depends on the cohesion establishment factor Eco1, a conserved acetyltransferase. However, due to the lack of known in vivo substrates, how Eco1 regulates cohesion is not understood. Here we report that yeast Eco1 and its human ortholog, ESCO1, both acetylate Smc3, a component of the cohesin complex that physically holds the sister chromatid together, at two conserved lysine residues. Mutating these lysine residues to a nonacetylatable form leads to increased loss of sister chromatid cohesion and genome instability in both yeast and human. In addition, we clarified that the acetyltransferase activity of Eco1 is essential for its function. Our study thus identified a molecular target for the acetyltransferase Eco1 and revealed that Smc3 acetylation is a conserved mechanism in regulating sister chromatid cohesion.

[The Study on the Characteristics of Organic Pollution in Typical Herbicide Plant Wastewater].

Herbicide wastewater is one of tne industrial wastewater, it has high salt content, poor biodegradability, biodegradable characteristics. Nitrogen-containing organic compounds are dominated in dissolved organic matter and dissolved organic matter of wastewater, BOD: COD = 0.045, C:N:P = 692:426:1. Applying static headspace, purg and trap, solid-phase extraction, solid-phase microextraction and liquid-liquid extraction as pretreatment methods combined with gas chromatography/mass spectrometry (GC/MS), which qualitatively analyzed the organic components of the Atrazine, acetochlor herbicide production wastewater and researched the UV spectrum, three-dimensional fluorescence spectroscopy of the wastewater and its major pollutants. The study of GC/MS indicated that Wastewater contained chlorinated hydrocarbons, BTEX and triazines, amides herbicides etc. 38 kinds of volatile and semi-volatile organic compounds, atrazine and acetochlor herbicides accounted for 87. 99%. Affected monocyclic or heterocyclic substances, the ultraviolet absorption spectrum of the wastewater in 210-230 and 250-270 nm in that the amino group lead to the UV absorption red shift 20 nm. Wastewater generated 5 fluorescence peak in λ(ex)/λ(em) = 200-280/300-400 nm, such as a(225/305 nm), b(265/365 nm), c(275/305 nm), d(285/390 nm), e(320/375 nm). Based on three-dimensional fluorescence results of the different functional groups of the characteristics organic, fluorescent area of unsaturated bond is in λ(ex)/λ(em) = 215-230/290-340 nm, the main contribution of the fluorescent substance in the region were olefins, benzene, heterocyclic in the wastewater; fluorescent area of Phenolic hydroxyl and carbonyl is in λ(ex)/λ(em) = 270/300 nm, the main contribution of the fluorescent substance in the region were phenols, ketones.

Overcoming endocrine resistance due to reduced PTEN levels in estrogen receptor-positive breast cancer by co-targeting mammalian target of rapamycin, protein kinase B, or mitogen-activated protein kinase kinase.

INTRODUCTION: Activation of the phosphatidylinositol 3-kinase (PI3K) pathway in estrogen receptor α (ER)-positive breast cancer is associated with reduced ER expression and activity, luminal B subtype, and poor outcome. Phosphatase and tensin homolog (PTEN), a negative regulator of this pathway, is typically lost in ER-negative breast cancer. We set out to clarify the role of reduced PTEN levels in endocrine resistance, and to explore the combination of newly developed PI3K downstream kinase inhibitors to overcome this resistance. METHODS: Altered cellular signaling, gene expression, and endocrine sensitivity were determined in inducible PTEN-knockdown ER-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer cell and/or xenograft models. Single or two-agent combinations of kinase inhibitors were examined to improve endocrine therapy. RESULTS: Moderate PTEN reduction was sufficient to enhance PI3K signaling, generate a gene signature associated with the luminal B subtype of breast cancer, and cause endocrine resistance in vitro and in vivo. The mammalian target of rapamycin (mTOR), protein kinase B (AKT), or mitogen-activated protein kinase kinase (MEK) inhibitors, alone or in combination, improved endocrine therapy, but the efficacy varied by PTEN levels, type of endocrine therapy, and the specific inhibitor(s). A single-agent AKT inhibitor combined with fulvestrant conferred superior efficacy in overcoming resistance, inducing apoptosis and tumor regression. CONCLUSIONS: Moderate reduction in PTEN, without complete loss, can activate the PI3K pathway to cause endocrine resistance in ER-positive breast cancer, which can be overcome by combining endocrine therapy with inhibitors of the PI3K pathway. Our data suggests that the ER degrader fulvestrant, to block both ligand-dependent and -independent ER signaling, combined with an AKT inhibitor is an effective strategy to test in patients.

Therapeutic potential of the dual EGFR/HER2 inhibitor AZD8931 in circumventing endocrine resistance.

Modest up-regulation of either HER-ligands or receptors has been implicated in acquired endocrine resistance. AZD8931, a dual tyrosine kinase inhibitor (TKI) of epithelial growth factor receptor (EGFR)/HER2, has been shown to more effectively block ligand-dependent HER signaling than the HER TKIs lapatinib or gefitinib. We therefore examined the effect of AZD8931 in ER-positive/HER2-negative breast cancer cells with acquired resistance to tamoxifen, where there is ligand up-regulation associated with HER pathway activation. RNA-seq ligand profiling and levels of HER receptors and signaling by western blotting were conducted in ER+ MCF7 and T47D parental cells and their Tam-resistant derivatives (TamRes). In vitro cell growth and apoptosis and HER ligand-stimulated signaling were measured in response to endocrine and HER TKIs. For studies in vivo, transplantable MCF7/TamRes xenografts were treated with tamoxifen or fulvestrant, either alone or in combination with AZD8931. AZD8931 only minimally enhanced endocrine sensitivity in MCF7 parental cells, but showed a greater effect in the T47D parental model. AZD8931 combined with either tamoxifen or fulvestrant inhibited cell growth more than lapatinib in T47D TamRes cells, and was also significantly, though modestly, more potent in MCF7 TamRes cells. In both TamRes models, AZD8931 significantly inhibited cell proliferation and induced apoptosis. Under ligand-stimulated conditions, AZD8931 more potently inhibited HER signaling than lapatinib or gefitinib. AZD8931 also significantly delayed the growth of MCF7 TamRes xenografts in the presence of tamoxifen or fulvestrant. The strongest inhibition was achieved with a fulvestrant and AZD8931 combination, though no tumor regression was observed. This study provides evidence that AZD8931 has greater inhibitory efficacy in tamoxifen-resistant settings than in an endocrine therapy naïve setting. The absence of tumor regression, however, suggests that additional escape pathways contribute to resistant growth and will need to be targeted to fully circumvent tamoxifen resistance.

Fiber-optic catheter-based polarization-sensitive OCT for radio-frequency ablation monitoring.

An all-fiber optic catheter-based polarization-sensitive optical coherence tomography system is demonstrated. A novel multiplexing method was used to illuminate the sample, splitting the light from a 58.5 kHz Fourier-domain mode-locked laser such that two different polarization states, alternated in time, are generated by two semiconductor optical amplifiers. A 2.3 mm forward-view cone-scanning catheter probe was designed, fabricated, and used to acquire sample scattering intensity and phase retardation images. The system was first verified with a quarter-wave plate and then by obtaining intensity and phase retardation images of high-birefringence plastic, human skin in vivo, and untreated and thermally ablated porcine myocardium ex vivo. The system can potentially in vivo image of the cardiac wall to aid radio-frequency ablation therapy for cardiac arrhythmias.

The pINDUCER lentiviral toolkit for inducible RNA interference in vitro and in vivo.

The discovery of RNAi has revolutionized loss-of-function genetic studies in mammalian systems. However, significant challenges still remain to fully exploit RNAi for mammalian genetics. For instance, genetic screens and in vivo studies could be broadly improved by methods that allow inducible and uniform gene expression control. To achieve this, we built the lentiviral pINDUCER series of expression vehicles for inducible RNAi in vivo. Using a multicistronic design, pINDUCER vehicles enable tracking of viral transduction and shRNA or cDNA induction in a broad spectrum of mammalian cell types in vivo. They achieve this uniform temporal, dose-dependent, and reversible control of gene expression across heterogenous cell populations via fluorescence-based quantification of reverse tet-transactivator expression. This feature allows isolation of cell populations that exhibit a potent, inducible target knockdown in vitro and in vivo that can be used in human xenotransplantation models to examine cancer drug targets.

RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53 stability in response to DNA damage.

In unstressed cells, the tumor suppressor p53 is maintained at low levels by ubiquitin-mediated proteolysis mainly through Mdm2. In response to DNA damage, p53 is stabilized and becomes activated to turn on transcriptional programs that are essential for cell cycle arrest and apoptosis. Activation of p53 leads to accumulation of Mdm2 protein, a direct transcriptional target of p53. It is not understood how p53 is protected from degradation when Mdm2 is up-regulated. Here we report that p53 stabilization in the late phase after ionizing radiation correlates with active ubiquitination. We found that an E3 ubiquitin ligase RFWD3 (RNF201/FLJ10520) forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and is required to stabilize p53 in the late response to DNA damage. This process is regulated by the DNA damage checkpoint, because RFWD3 is phosphorylated by ATM/ATR kinases and the phosphorylation mutant fails to stimulate p53 ubiquitination. In vitro experiments suggest that RFWD3 is a p53 E3 ubiquitin ligase and that RFWD3-Mdm2 complex restricts the polyubiquitination of p53 by Mdm2. Our study identifies RFWD3 as a positive regulator of p53 stability when the G(1) cell cycle checkpoint is activated and provides an explanation for how p53 is protected from degradation in the presence of high levels of Mdm2.

High FOXA1 levels induce ER transcriptional reprogramming, a pro-metastatic secretome, and metastasis in endocrine-resistant breast cancer.

Aberrant activation of the forkhead protein FOXA1 is observed in advanced hormone-related cancers. However, the key mediators of high FOXA1 signaling remain elusive. We demonstrate that ectopic high FOXA1 (H-FOXA1) expression promotes estrogen receptor-positive (ER+) breast cancer (BC) metastasis in a xenograft mouse model. Mechanistically, H-FOXA1 reprograms ER-chromatin binding to elicit a core gene signature (CGS) enriched in ER+ endocrine-resistant (EndoR) cells. We identify Secretome14, a CGS subset encoding ER-dependent cancer secretory proteins, as a strong predictor for poor outcomes of ER+ BC. It is elevated in ER+ metastases vs. primary tumors, irrespective of ESR1 mutations. Genomic ER binding near Secretome14 genes is also increased in mutant ER-expressing or mitogen-treated ER+ BC cells and in ER+ metastatic vs. primary tumors, suggesting a convergent pathway including high growth factor receptor signaling in activating pro-metastatic secretome genes. Our findings uncover H-FOXA1-induced ER reprogramming that drives EndoR and metastasis partly via an H-FOXA1/ER-dependent secretome.

SGK3 is associated with estrogen receptor expression in breast cancer.

While breast cancer mortality rate has seen a steady decline in the last few decades, advances in better treatment and diagnostic tools remain important as we come into the age of personalized therapy. In this report, we describe our studies of SGK3's role in breast cancer. SGK3 (also known as CISK) is a member of the AGC family of kinases. Our previous work indicates that SGK3 functions downstream of the PI 3-kinase cascade and shares molecular and biochemical similarities with Akt. Here, we show that SGK3 expression is linked to estrogen receptor (ER) both in breast caner cell lines and in primary tumor samples. Our analysis also indicated a positive correlation between SGK3 expression and tumor prognosis. Importantly, our immunochemistry analysis of human tumor samples established a clinical link between SGK3 expression and ER+ tumors. These findings implicate SGK3 as an additional component to a complex and heterogeneous disease, and point to the potential benefits of incorporating SGK3 into the process of breast cancer diagnosis and treatment.

Interferon Signaling in Estrogen Receptor-positive Breast Cancer: A Revitalized Topic.

Cancer immunology is the most rapidly expanding field in cancer research, with the importance of immunity in cancer pathogenesis now well accepted including in the endocrine-related cancers. The immune system plays an essential role in the development of ductal and luminal epithelial differentiation in the mammary gland. Originally identified as evolutionarily conserved antipathogen cytokines, interferons (IFNs) have shown important immune-modulatory and antineoplastic properties when administered to patients with various types of cancer, including breast cancer. Recent studies have drawn attention to the role of tumor- and stromal-infiltrating lymphocytes in dictating therapy response and outcome of breast cancer patients, which, however, is highly dependent on the breast cancer subtype. The emerging role of tumor cell-inherent IFN signaling in the subtype-defined tumor microenvironment could influence therapy response with protumor activities in breast cancer. Here we review evidence with new insights into tumor cell-intrinsic and tumor microenvironment-derived IFN signaling, and the crosstalk of IFN signaling with key signaling pathways in estrogen receptor-positive (ER+) breast cancer. We also discuss clinical implications and opportunities exploiting IFN signaling to treat advanced ER+ breast cancer.

[Minimally invasive osteotomy with absorbable screws in treating hallux valgus deformity].

OBJECTIVE: To evaluate clnical effect of minimally invasive osteotomy with absorbable screws in treating hallux valgus deformity. METHODS: Clnical data of 31 patients with hallux valgus deformity were retrospective analyzed from January 2019 to December 2020, and divided into absorbable screws group (17 patients) and titanium cannulated screw group (14 patients). In absorbable screws group, there were 1 male and 16 females aged from 32 to 72 years old with an average of (54.53±12.12) years old;6 patients on the left side, 5 on bilateral and 6 on the right side;1 patient was mild, 11 moderate and 5 severe;treated with minimally invasive osteotomy and fixation of absorbable screws. In titanium cannulated screw group, there were 2 males and 12 females aged from 18 to 71 years old with an average of (47.57±15.68) years old;4 patients on the left side, 4 on bilateral and 6 on the right side;1 patient was mild, 9 moderate and 4severe;treated with minimally invasive osteotomy and fixation of titanium cannulated screw. Complications between two groups were observed, changes of hallux valgus angle (HVA)and intermetatarsal angle (IMA)were detected and compared before and after operation at 12 months, American Orthopedic Foot and Ankle Society(AOFAS) and visual analogue scale(VAS) before and after operation at 12 months were also compared. RESULTS: All 31 patients were followed up from 13 to 20 months with an average of (16.61±2.47) months. Patients in absorbable screws group were followed up from 14 to 20 months with an average of (16.88±2.80) months, while patients in titanium cannulated screw group were followed up from 13 to 19 months with an average of (16.29±2.05) months;there was no difference between two groups(P>0.05). One patient in absorbable screws group occurred numbness around incision, 3 patients in titanium cannulated screw group occurred complications, including numbness around incision in 1 patient, skin irritation due to internal fixation in 1 patient, and recurrence in 1 case;there was no statistic difference between two groups (χ2=1.651, P=0.199). There were no statistic difference in HVA and IMA between two groups before and after operation at 12 months(P>0.05). There were no statistic difference between two groups in AOFAS and VAS before and after operation at 12 months(P>0.05). CONCLUSION: Compare with mainstream fixation with titanium hollow screw after minmally invasive osteotomy, fixation with absorbable screw could achieve comparable clinical outcome on the basis of images and function evaluation.

Parental exposure 3-methylcholanthrene disturbed the enterohepatic circulation in F1 generation of mice.

3-methylcholanthrene (3 MC) is an environmental compound belonging to the PAHs and is reportedly thought to be a risk factor for the prevalence of hepatic function disorder. Here, a dose of 0.5 mg/kg of 3 MC was given to 4-week-old male and female mice (F0) in their diet for 6 weeks. After exposure, then the mice were mated between different groups. The first filial (F1) generation offspring of exposed or unexposed parental mice were sacrificed at the age of 5 weeks (F1-5 W), and the potential effects on the F0 and F1 offspring were evaluated. The results showed that the total bile acids (TBAs) in the serum and feces in F0 females and female F1-5 W individuals born from female mice exposed to 3 MC decreased, while the TBAs in the liver increased. The transcriptional levels of major genes participating in synthesis, regulation, transportation and apical uptake was also altered correspondingly. In addition, the transcription of some genes related to inflammation was enhanced in these mice. Further investigation revealed that in addition to distinct changes in the mucus secretion, tight junction proteins and ion transport were induced, and antimicrobial peptides were also disrupted in the intestine of F0 mice and F1-5 W female offspring of maternal mice exposed to 3 MC. Our results suggested that exposure to 3 MC, but not male exposure, had the potential to interfere with BAs metabolism, affecting gut barrier function. Females were more seriously affected than males.