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Background: The high cost, limited availability, and perceived invasiveness of amyloid PET and cerebrospinal fluid biomarkers limit their use for the diagnosis of Alzheimer’s disease. Objective: The present study aimed to assess the associations of mild cognitive impairment (MCI) with circulating amyloid-β (Aβ), methionine circulating metabolites (MCMs), and their downstream products, and to develop a nomogram based on these easily accessible blood indexes for the individualized prediction of MCI risk in older adults. Methods: In this nested case-control study, we recruited 74 MCI patients and, for each, 3 matched controls (n = 222) within the context of the Tianjin Elderly Nutrition and Cognition (TENC) cohort, a population-based prospective study in China. Concentrations of Aβ, MCMs, and their circulating downstream factors (i.e., leukocyte telomere length and inflammatory cytokines) were evaluated in fasting blood sample using standard procedures. We constructed a nomogram for MCI harnessed multivariable logistic models incorporating variables selected in the Lasso regression. Results: Among the many biomarkers examined, the final prediction nomogram retained only 3 factors: Aβ42/Aβ40 ratio, Hcy, and SAM/SAH ratio. The model achieved favorable discrimination, with a C-statistic of 0.75 (95% confidence interval 0.69–0.81) in internal validation after adjustment of optimism. The calibration accuracy was satisfactory; the Brier score of the model was 0.161 in internal validation after adjustment of optimism. Conclusion: his study presents an individualized prediction nomogram incorporating only three blood biomarkers (i.e., Aβ42/Aβ40 ratio, Hcy, and SAM/SAH ratio), which can be conveniently utilized to facilitate early identification and the development of high-risk prevention strategies for MCI in older adults.

Immune checkpoint inhibitors (ICIs) have successfully treated a number of different types of cancer, which is of great significance for cancer treatment. With the widespread use of ICIs in clinical practice, the increasing checkpoint inhibitor pneumonia (CIP) will be a challenge to clinicians. To guide the diagnosis and treatment of CIP, we conducted in-depth discussions based on the latest evidence, forming a consensus among Chinese experts on the multidisciplinary management of CIP.

Targeted protein degradation (TPD), a promising therapeutic strategy in drug discovery, has great potential to regulate the endogenous degradation of undruggable targets with small molecules. As vital resources that provide diverse structural templates for drug discovery, natural products (NPs) are a rising and robust arsenal for the development of therapeutic TPD. The first proof-of-concept study of proteolysis-targeting chimeras (PROTACs) was a natural polyketide ovalicin-derived degrader; since then, NPs have shown great potential to promote TPD technology. The use of NP-inspired targeted protein degraders has been confirmed to be a promising strategy to treat many human conditions, including cancer, inflammation, and nonalcoholic fatty liver disease. Nevertheless, the development of NP-inspired degraders is challenging, and the field is currently in its infancy. In this review, we summarize the bioactivities and mechanisms of NP-inspired degraders and discuss the associated challenges and future opportunities in this field.

DNA nanostructures, with good biosafety, highly programmable assembly, flexible modification, and precise control, are tailored as drug carriers to deliver therapeutic agents for cancer therapy. However, they face considerable challenges regarding their delivery into the brain, mainly due to the blood-brain barrier (BBB). By controlling the acoustic parameters, focused ultrasound combined with microbubbles (FUS/MB) can temporarily, noninvasively, and reproducibly open the BBB in a localized region. We investigated the delivery outcome of pH-responsive DNA octahedra loading Epirubicin (Epr@DNA-Octa) via FUS/MB and its therapeutic efficiency in a mouse model bearing intracranial glioma xenograft. Using FUS/MB to locally disrupt the BBB or the blood-tumor barrier (BTB) and systemic administration of Epr@DNA-Octa (Epr@DNA-Octa + FUS/MB) (2 mg/kg of loaded Epr), we achieved an Epr concentration of 292.3 ± 10.1 ng/g tissue in glioma, a 4.4-fold increase compared to unsonicated animals (p 0.001). The in vitro findings indicated that Epr released from DNA strands accumulated in lysosomes and induced enhanced cytotoxicity compared to free Epr. Further two-photon intravital imaging of spatiotemporal patterns of the DNA-Octa leakage revealed that the FUS/MB treatment enhanced DNA-Octa delivery across several physiological barriers at microscopic level, including the first extravasation across the BBB/BTB and then deep penetration into the glioma center and engulfment of DNA-Octa into the tumor cell body. Longitudinal in vivo bioluminescence imaging and histological analysis indicated that the intracranial glioma progression in nude mice treated with Epr@DNA-Octa + FUS/MB was effectively retarded compared to other groups. The beneficial effect on survival was most significant in the Epr@DNA-Octa + FUS/MB group, with a 50% increase in median survival and a 73% increase in the maximum survival compared to control animals. Our work demonstrates the potential viability of FUS/MB as an alternative strategy for glioma delivery of anticancer drugs using DNA nanostructures as the drug delivery platform for brain cancer therapy.

Pathological vascular remodeling and cell proliferation play vital roles in many proliferative vascular diseases. Estrogen can protect the cardiovascular system, but its exact molecular mechanism is unknown. Here we report that 17β-estradiol (E2) suppressed vascular smooth muscle cells (VSMCs) proliferation and inflammation. qRT-PCR and Western blot demonstrated that E2 decreased NF-κB p50 expression and reduced VSMCs proliferation and inflammation. Mechanistically, a dual luciferase reporter assay and chromatin immunoprecipitation suggested that KLF5 promoted NF-κB p50 expression by binding to the NF-κB p50 promoter, whereas E2 reduced the effect of KLF5 binding to the NF-κB p50 promoter and inhibited NF-κB p50 expression. Furthermore, a coimmunoprecipitation assay and immunofluorescence staining showed that the interaction between KLF5 and ERα increased in VSMCs treated with E2, which in turn decreased NF-κB p50 expression levels. Altogether, we reveal that E2 inhibits VSMCs proliferation and inflammation by reducing NF-κB expression induced by an increased interaction between KLF5 and ERα. These data provide further insights into how E2 inhibits vascular proliferation and inflammation.

Most cases of ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) involve small tumors. Although a few guidelines recommend mastectomy, several patients prefer repeat BCS (re-BCS). This study aimed to compare re-BCS and mastectomy in terms of prognosis in patients with IBTR and to identify candidates for re-BCS.The data of patients with small IBTR between 1999 and 2015 were obtained from the Surveillance, Epidemiology, and End Results database. The outcomes of interest were overall survival (OS) and breast cancer-specific survival (BCSS). Multivariable Cox proportional hazards regression models and propensity score matching were applied.Of the 3648 patients with IBTR, 2831 (77.6%) underwent mastectomy and 817 (22.4%) underwent re-BCS. The multivariate Cox model showed that re-BCS was associated with a worse OS (hazard ratio [HR], 1.342; 95% confidence interval [CI], 1.084-1.663) and BCSS (HR, 1.454; 95% CI, 1.004-2.105) compared with mastectomy. The omission of radiation after re-BCS was associated with worse survival overall and especially in patients with estrogen receptor (ER)-negative IBTR (HR, 1.384; 95% CI, 1.110-1.724; and HR, 1.577; 95% CI, 1.075-2.314, respectively). No statistically significant differences were observed in the OS and BCSS between re-BCS with radiation and mastectomy. Subgroup analysis indicated that the surgical approach was not an independent factor for survival in the ER-positive patients with IBTR.Re-BCS should be considered with caution in patients with small IBTR. However, a positive ER status can be an important factor for choosing re-BCS, and radiation therapy may improve oncological safety after re-BCS.Repeat breast-conserving surgery (re-BCS) was investigated to determine if it is safe for patients with small ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS). This population-based cohort study included 2831 patients with small IBTR. Re-BCS was associated with a worse overall survival and breast cancer-specific survival compared with mastectomy. Further analysis found that the IBTR estrogen receptor status was an important basis for choosing re-BCS, and radiation may improve oncological safety after re-BCS.

Gene fusions can drive tumor development for multiple types of cancer. Currently, many drugs targeting gene fusions are being approved for clinical application. At present, tyrosine receptor kinase (TRK) inhibitors targeting neurotrophic tyrosine receptor kinase (NTRK) gene fusions are among the first "tumor agnostic" drugs approved for pan-cancer use. Representative TRK inhibitors, including larotrectinib and entrectinib, have shown high efficacy for many types of cancer. At the same time, several second-generation drugs designed to overcome first-generation drug resistance are undergoing clinical development. Due to the rarity of NTRK gene fusions in common cancer types and technical issues regarding the complexity of fusion patterns, effectively screening patients for TRK inhibitor treatment in routine clinical practice is challenging. Different detection methods including immunohistochemistry, fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and (DNA and/or RNA-based) next-generation sequencing have pros and cons. As such, recommending suitable tests for individual patients and ensuring the quality of tests is essential. Moreover, at present, there is a lack of systematic review for the clinical efficacy and development status of first- and second-generation TRK inhibitors. To resolve the above issues, our expert group has reached a consensus regarding the diagnosis and treatment of NTRK gene fusion solid tumors, aiming to standardize clinical practice with the goal of benefiting patients with NTRK gene fusions treated with TRK inhibitors.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is derived from the bacterial innate immune system and engineered as a robust gene-editing tool. Due to the higher specificity and efficiency of CRISPR/Cas9, it has been widely applied to many genetic and non-genetic disease, including cancers, genetic hemolytic diseases, acquired immunodeficiency syndrome, cardiovascular diseases, ocular diseases, and neurodegenerative diseases, and some X-linked diseases. Furthermore, in terms of the therapeutic strategy of cancers, many researchers used the CRISPR/Cas9 technique to cure or alleviate cancers through different approaches, such as gene therapy and immune therapy.Here, we conclude the recent application and clinical trials of CRISPR/Cas9 in non-cancerous diseases and cancers and pointed out some of the problems to be solved.CRISPR/Cas9, derived from the microbial innate immune system, is developed as a robust gene-editing tool and has been applied widely. Due to its high accuracy and efficiency, CRISPR/Cas9 techniques may provide a great chance to treat some gene-related diseases by disrupting, inserting, correcting, replacing, or blocking genes for clinical application with gene therapy.

Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH.Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded.One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]; left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF]; LVEF50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH.PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients.ClinicalTrials.gov, NCT02164526.

Background: Early identification and timely management of septic AKI continue to represent clinical challenges for intensive care. The aim was to evaluate the effect of renal replacement with oXiris filter on clinical outcomes in septic AKI. Methods: This was a single-center randomized controlled trial that enrolled surgical septic shock with AKI patients admitted in the ICU, Renji Hospital, Shanghai Jiao Tong University, School of Medicine from Jan 1, 2021 to Sep 30, 2021, were screened. Results: Sixteen subjects that met the inclusion and exclusion criteria were randomized into CRRT with AN69-oXiris group ( n = 8) and AN69-ST group ( n = 8). The PCT and IL-6 concentration decreased significantly after the first treatment compared to pre-CRRT levels in the oXiris group (PCT: 23.46 [4.18, 84.90] vs 52.79 [9.03, 100.00] µg/L, p = 0.046; IL-6: 3080.15 [527.62, 9806.61] vs 10,457.17 [8150.00, 15,528.87] pg/mL, p = 0.043). The levels of lactate decreased by 1.70 [1.03, 2.83] mmol/L after the first CRRT in the oXiris group ( p = 0.028). The norepinephrine infusion rate was decreased by 0.06 [0, 0.09], 0.05 [0, 0.23] and 0.11 [0, 0.23] μg/kg/min at 4, 6, and 8 h in the oXiris group compared to the ST group ( p = 0.005, 0.038, and 0.017). Conclusion: Using the oXiris filter may improve hemodynamic status during initial CRRT in severe surgical septic shock with AKI. Further large multicenter RCTs are needed to determine the effect of the oXiris filter on patient outcomes. ( http://www.chictr.org.cn/index.aspx (ChiCTR2200055732)).

Genome assembly has been benefited from long-read sequencing technologies with higher accuracy and higher continuity. However, most human genome assembly require large amount of DNAs from homogeneous cell lines without keeping cell heterogeneities, since cell heterogeneity could profoundly affect haplotype assembly results. Herein, using single-cell genome long-read sequencing technology (SMOOTH-seq), we have sequenced K562 and HG002 cells on PacBio HiFi and Oxford Nanopore Technologies (ONT) platforms and conducted de novo genome assembly. For the first time, we have completed the human genome assembly with high continuity (with NG50 of ∼2 Mb using 95 individual K562 cells) at single-cell levels, and explored the impact of different assemblers and sequencing strategies on genome assembly. With sequencing data from 30 diploid individual HG002 cells of relatively high genome coverage (average coverage ∼41.7%) on ONT platform, the NG50 can reach over 1.3 Mb. Furthermore, with the assembled genome from K562 single-cell dataset, more complete and accurate set of insertion events and complex structural variations could be identified. This study opened a new chapter on the practice of single-cell genome de novo assembly.

The longitudinal association between serum folate concentrations and the risk of cognitive impairment remains unclear in populations with low folate levels. We examined the association between serum folate concentrations and mild cognitive impairment (MCI) in older adults in China, where mandatory fortification of foods with folic acid has not been implemented. We further explored if homocysteine (Hcy) and leukocyte telomere length (LTL) mediate the association between serum folate and MCI.We performed a longitudinal analysis of 3974 participants aged ≥60 years from the Tianjin Elderly Nutrition and Cognition (TENC) cohort study. The associations between serum folate level and the risk of cognitive impairment overall and stratified by apolipoprotein E (APOE) ε4 genotypes were evaluated using multivariable Cox proportional hazards models. The mediating effects of Hcy and LTL on the folate-MCI association were explored via a path analysis approach.Within a 3-year follow-up, we documented 560 incident MCI cases. After multivariable adjustment, higher serum folate concentrations were associated with lower incidence of MCI, with hazard ratios (95% confidence interval) across quartiles of folate (from lowest to highest concentrations) of 1.00 (reference), 0.66 (0.52, 0.83), 0.57 (0.45, 0.73), 0.66 (0.52, 0.84), respectively (p for trendlt;0.001). In mediation analyses, the status of serum folate deficiency and MCI were correlated via two intermediary pathways, Hcy and Hcy-telomere (p lt; 0.05).Lower folate concentrations, independently of APOE genotype, were associated with increased risk of MCI among elderly Chinese people, a population with relatively low folate intake. Our data were compatible with the mediation hypothesis that the association between folate status and MCI was mediated by Hcy and LTL.

Early treatment of oral precancerous lesions is considered as a key strategy for in oral carcinogenesis prevention. Increasing evidence has suggested that the transforming growth factor beta (TGF-β) signaling pathway is tightly involved in the process of oral-carcinogenesis. In this study, we investigated the inhibition effect and potential mechanism of 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) in human oral precancerous cells via TGF-β pathway.Here, the dysplastic oral keratinocyte (DOK) cells were incubated with ALA concentration of 1 mM/mL for 4 h and then irradiated with a Helium-Neon (He-Ne) ion laser at 633 nm (200 mW/cmThe TGF-β signaling could exert in suppressive effects on DOK cells after ALA-PDT. The cell proliferation and migration rate of DOK cells was significantly reduced and apoptosis and ROS generation induced more effectively by ALA-PDT combined with LY2109761. Furthermore, cell cycle analysis revealed that the combined treatment resulted in G0/G1 phase arrest.ALA-PDT suppresses the growth of oral precancerous cells by regulating the TGF-β signaling pathway, and its suppressive effect was enhanced using LY2109761. These results indicate that it could be a promising alternative treatment against oral precancerous lesions.

Objective The objective of this study was to evaluate the influence of ACE I/D gene polymorphisms on diabetic kidney disease (DKD) risk. Methods All eligible investigations were identified, the number of various genotype in the case and control group were reviewed. The pooled analysis was performed using Stata software. Results In overall subjects, 24,321 participants with 12,961 cases and 11,360 controls were included. the pooled analysis showed a significant link between D allele, DD or II genotype and DKD risk (D versus I: OR = 1.316, 95% CI: 1.213–1.427, P = 0.000; DD versus ID + II: OR = 1.414, 95% CI: 1.253–1.595, P = 0.000; II versus DD + ID: OR = 0.750, 95% CI: 0.647–0.869, P = 0.000). The subgroup pooled analysis showed that ACE I/D gene polymorphism was correlated with DKD both in Asian and in Chinese population. In addition, ACE I/D gene polymorphism was correlated with type 2 DKD (D versus I: OR = 1.361, 95% CI: 1.243–1.490, P = 0.000; DD versus ID + II: OR = 1.503, 95% CI: 1.310–1.726, P = 0.000; II versus DD + ID: OR = 0.738, 95% CI: 0.626 –0.870, P = 0.000). However, there was no obvious correlation in Caucasian subjects and type 1 diabetic patients. Conclusion ACE I/D polymorphisms were correlated with DKD in Asian and type 2 diabetic populations. ACE D allele/DD genotype might be a risk factor, while ACE II genotype might be a protective factor for DKD.

Can a non-invasive embryo transfer strategy provide a reference for embryo selection to be established?Chromosome sequencing of 345 paired blastocyst culture medium and whole blastocyst samples was carried out and a non-invasive embryo grading system was developed based on the random forest machine learning algorithm to predict blastocyst ploidy. The system was validated in 266 patients, and a blinded prospective observational study was conducted to investigate clinical outcomes between machine learning-guided and traditional non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) analyses. Embryos were graded as A, B or C according to their euploidy probability levels predicted by non-invasive chromosomal screening (NICS).Higher live birth rate was observed in A- versus C-grade embryos (50.4% versus 27.1%, P = 0.006) and B- versus C-grade embryos (45.3% versus 27.1%, P = 0.022) and lower miscarriage rate in A- versus C-grade embryos (15.9% versus 33.3%, P = 0.026) and B- versus C-grade embryos (14.3% versus 33.3%, P = 0.021). The embryo utilization rate was significantly higher through the machine learning strategy than the conventional dichotomic judgment of euploidy or aneuploidy in the niPGT-A analysis (78.8% versus 57.9%, P0.001). Better outcomes were observed in A- and B-grade embryos versus C-grade embryos and higher embryo utilization rates through the machine learning strategy compared with traditional niPGT-A analysis.A machine learning guided embryo grading system can be used to optimize embryo selection and avoid wastage of potential embryos.

Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) has recently been employed as a novel treatment for gastric outlet obstruction (GOO). The aim of this study was to evaluate the safety and efficacy of EUS-GE for GOO at different sites.Consecutive hospitalized patients who underwent EUS-GE for GOO at the Department of Gastroenterology, Nanjing Drum Tower Hospital from March 2017 to April 2020 were recruited in this retrospective study. Patients were divided into three groups depending on the obstruction site. The primary outcomes included technical success and clinical success. The secondary outcomes were operation time, post-procedure length of stay (LOS), hospitalization cost, and complications such as peritonitis, bleeding, pneumoperitoneum, abdominal pain, and infection.A total of 51 patients were included. Technical success achieved in 100% patients with proximal GOO and in 88.9% with distal GOO (P = 0.176). Clinical success declined from the oral side to the anal side (P = 0.510). Operation time, hospitalization costs, and post-procedural LOS were similar among groups (P = 0.532, 0.520, and 0.144, respectively). Complications were observed in 28 (54.9%) patients. In approaching the mature phase of the endosopist, clinical success improved, while the secondary outcomes showed no statistically significant difference compared with the initial phase.EUS-GE may be challenging for distal GOO; however, it is safe and effective when carried out by experienced endoscopists. A complete preoperative evaluation to assess the difficulty of the procedure is necessary. Prospective studies with large sample size are needed to further validate our findings.

Context Nephropathy is a severe complication of type 1 diabetes (T1DM). However, the interaction between the PDHA1-regulated mechanism and CD4+ T cells in the early stage of kidney tubular injury remains unknown. Objective To evaluate the role of PDHA1 in the regulation of tubular cells and CD4+ T cells and further to study its interaction in tubular cell injury in T1DM. Methods Plasma and total RNA were collected from T cells of T1DM patients (n = 35) and healthy donors (n = 33) and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, PDHA1, and biomarkers of CD4+ T cells including T helper 1 cells (Th1) and regulatory T cells (Treg) markers. HK-2 cells cocultured with CD4+ T cells from T1DM patients or healthy donors (HDs) to evaluate the interaction with CD4+ T cells. Results Increased PDHA1 gene expression levels in CD4+ T cells were positively associated with the plasma level of NGAL in T1DM patients and HDs. Our data demonstrated that the Th1/Treg subsets skewed Th1 in T1DM. Knockdown of PDHA1 in kidney tubular cells decreased ATP/ROS production, NAD/NADH ratio, mitochondrial respiration, and cell apoptosis. Furthermore, PDHA1 depletion induced impaired autophagic flux. Coculture of tubular cells and T1DM T cells showed impaired CPT1A, upregulated FASN, and induced kidney injury. Conclusion Our findings indicate that Th1 cells induced tubular cell injury through dysregulated metabolic reprogramming and autophagy, thereby indicating a new therapeutic approach for kidney tubular injury in T1DM.

Thymic lymphoepithelioma-like carcinoma (LELC) is a rare primary malignant neoplasm originating from the thymus. Thymic LELC diagnosis is often terminal when diagnosed, some patients have lost the opportunity for surgery. Platinum- and anthracycline-based systemic chemotherapy are the first-line treatment plan; however, there is no clear consensus on therapy when first-line treatment fails because of the lack of cases of advanced thymic LELC. Here was a rare case of advanced thymic LELC with bone marrow metastasis at relapse, which is reported in a patient who responded well to toripalimab combined with anlotinib therapy. The treatment showed tolerable toxicity with good antitumor activity in the patient. As far as we know, this is the first case that the combination of toripalimab with anlotinib is effective in controlling advanced thymic LELC with bone marrow metastasis. The case reports represent an essential means by which an effective therapy for advanced thymic LELC may not be practical given the low frequency of a thymic LELC with multiple metastases.

Endoscopic papillectomy (EP) is an effective treatment for ampullary lesions but technically challenging because of anatomical specificities concerning the high rate of adverse events. Bleeding is one of the most feared complications and can be potentially life-threatening.To study the risk factors for bleeding after EP are presented with the goal of establishing preventive measures.A total of 173 consecutive patients with ampullary lesions undergone EP from January 2006 to October 2020 were enrolled in this study. They were divided into a bleeding group and a non-bleeding group depending on whether postoperative bleeding occurred. Related factors were analyzed by univariate and multivariate logistics regression.Postoperative bleeding was experienced in 33 patients (19.07%). Multivariate analysis also identified intraoperative bleeding (OR: 4.38, 95% CI: 1.87-11.15,This retrospective evaluation found that endoscopic closure was associated with reduced risk and intraoperative bleeding with increased risk of bleeding after EP. Lesion size may indirectly influence the risk of postoperative bleeding by increasing the risk of intraoperative bleeding.

Recently, electroencephalography (EEG) signals have shown great potential for emotion recognition. Nevertheless, multichannel EEG recordings lead to redundant data, computational burden, and hardware complexity. Hence, efficient channel selection, especially single-channel selection, is vital. For this purpose, a technique termed brain rhythm sequencing (BRS) that interprets EEG based on a dominant brain rhythm having the maximum instantaneous power at each 0.2 s timestamp has been proposed. Then, dynamic time warping (DTW) is used for rhythm sequence classification through the similarity measure. After evaluating the rhythm sequences for the emotion recognition task, the representative channel that produces impressive accuracy can be found, which realizes single-channel selection accordingly. In addition, the appropriate time segment for emotion recognition is estimated during the assessments. The results from the music emotion recognition (MER) experiment and three emotional datasets (SEED, DEAP, and MAHNOB) indicate that the classification accuracies achieve 70-82% by single-channel data with a 10 s time length. Such performances are remarkable when considering minimum data sources as the primary concerns. Furthermore, the individual characteristics in emotion recognition are investigated based on the channels and times found. Therefore, this study provides a novel method to solve single-channel selection for emotion recognition.

BACKGROUND Atherosclerosis and vascular inflammatory response have been considered as risk factors for non-typhoidal Salmonella (NTS) vascular infection. The study aims to assess the risk of vascular infection by measuring atherosclerosis severity, NTS vascular infection (NTSVI) score, and serum levels of inflammatory markers in people with NTS bacteremia. METHODS A prospective observational study was conducted in two medical centers and two regional hospitals. Adults aged ≥50 years with NTS bacteremia who underwent computed tomography (CT) scan for revealing vascular infections were enrolled. The degree of atherosclerosis was scaled by a calcium score determined by a CT scan. Serum concentrations of inflammatory biomarkers were determined in the patients enrolled in a medical center. RESULTS Fourteen (20.3%) of 69 patients with NTS bacteremia had vascular infections. Calcium scores over the thoracic (12,540 vs. 3,261, P = 0.0005) and abdominal (9755 vs. 3,461, P = 0.0006) aorta of those with vascular infections were higher than those without vascular infection. All vascular infections were present in the high-risk group (NTSVI score ≥1), yielding a sensitivity of 100% and specificity of 30.9%. Among 17 low-risk patients (NTSVI score

Background: Increasing evidence indicates that an imbalance in oncogenes is implicated in cancer chemotherapy resistance. Methyl-CpG binding protein 2 (MeCP2), which acts as a major epigenetic regulator of the expression of various genes, is involved in the carcinogenesis and progression of gastric cancer. However, is it not known whether the role of MeCP2 is vital in acquired cisplatin resistance in gastric cancer. Objective: This study aimed to determine whether inhibition of MeCP2 expression could sensitize DDP-resistant GC cells to DDP and elucidate the underlying molecular mechanism. Methods: qRT-PCR and western blotting were used to evaluate MeCP2 expression in DDP-resistant GC cells. Subsequently, cell viability, colony formation, cell cycle, apoptosis, and tumorigenicity assays were performed to explore the in vitro and in vivo roles of MeCP2. Chromatin immunoprecipitation- qPCR and luciferase reporter assays were used to identify whether 3-phosphoinositide-dependent protein kinase 1 (PDK-1) was a direct target gene of MeCP2. Results: MeCP2 was upregulated in malignant DDP-resistant cells compared to non-DDP-resistant GC cells or normal gastric epithelial cells. MeCP2 knockdown increased the sensitivity of DDP-resistant GC cells to DDP, resulting in reduced cell growth, G0/G1 phase arrest, and increased apoptosis, whereas MeCP2 overexpression attenuated DDP sensitivity of DDP-resistant GC cells. In addition, MeCP2 knockdown enhanced DDP sensitivity in vivo. MeCP2 elevated PDK-1 expression by binding to CpG sites in promoter regions, and inhibition of PDK-1 reversed the inductive effect of MeCP2 overexpression on DDP resistance in GC cells. Conclusion: These findings indicate that silencing of MeCP2 may potentiate DDP-induced cell death, thereby providing a promising therapeutic strategy for GC.

The pathophysiology of autistic spectrum disorder (ASD) is not fully understood and there are no diagnostic or predictive biomarkers. Extracellular vesicles (EVs) are cell-derived nano-sized vesicles, carrying nucleic acids, proteins, lipids, and other bioactive substances. As reported, serum neural cell adhesion molecule L1 (L1CAM)-captured EVs (LCEVs) can provide reliable biomarkers for neurological diseases; however, little is known about the LCEVs in children with ASD. The study enrolled 100 children with ASD (2.5-6 years of age; 90 males) and 60 age-matched TD children (54 males) as control. The serum sample was collected and pooled into five ASD subgroups and three TD subgroups (n = 20). LCEVs were isolated and characterized meticulously. Whole-transcriptome of LCEVs was analyzed by lncRNA microarray and RNA-sequencing. All raw data was submitted on GEO Profiles, and GEO accession numbers is GSE186493. RNAs expressed differently in LCEVs from ASD sera vs. TD sera were screened, analyzed, and further validated. A total of 1418 mRNAs, 1745 lncRNAs, and 11 miRNAs were differentially expressed, and most of them were downregulated in ASD. Most RNAs were involved in neuron- and glycan-related networks implicated in ASD. The levels of EDNRA, SLC17A6, HTR3A, OSTC, TMEM165, PC-5p-139289_26, and hsa-miR-193a-5p were validated in at least 15 ASD and 15 TD individual serum samples, which were consistent with the results of transcriptome analysis. In conclusion, whole-transcriptome analysis of serum LCEVs reveals neural and glycosylation changes in ASD, which may help detect predictive biomarkers and molecular mechanisms of ASD, and provide reference for diagnoses and therapeutic management of the disease.

Circular RNAs (circRNAs) are linked with the occurrence and progression of renal cell carcinoma (RCC). However, circRNAs' mechanism in developing resistance to RCC has not been clarified. This research assessed the role and mechanism of circular RNA circ Eps15-homology domain-containing protein 2 (EHD2) in the resistance of sunitinib (SU) to RCC. ACHN, 786-O, 769P, and HEK-293 T cells and RCC tissue samples were used for the investigations. The circEHD2 expression in RCC cells and tissues was determined through RT-qPCR. Association of circEHD2 with RCC histological grade of RCC was done through Chi-square. MiR-4731-5p, ABCF2, and circEHD2 were transfected into RCC cell lines. A dual-luciferase reporter assay was used to determine the interaction between miR-4731-5p, circEHD2, and ABCF2. MTT assay was used to analyze cell viability, while apoptosis was studied using flow cytometry. Colony-formation and transwell experiments were used to assess migration and invasion. The ATP Binding Cassette Subfamily F Member 2 (ABCF2) expression was analyzed through western blot. The results showed increased circEHD2 in SU-resistant RCC tissues and cell lines and implicated in RCC histological grade and SU resistance. Knock-down of circEHD2 down-regulated the resistance of RCC to SU

Alcoholic liver disease (ALD), with its increasing morbidity and mortality, has seriously and extensively affected the health of people worldwide. Caffeic Acid Dimethyl Ether (CADE) significantly inhibits alcohol-induced hepatic steatosis

Matrine exhibits anti-tumor effect on the proliferation and invasion of colorectal cancer (CRC) cells by reducing the activity of the p38 signaling pathway. However, these studies were limited because the underlying mechanism by which matrine inhibited CRC progression remained unclear. In this study, we provided for the first time that endoplasmic reticulum lipid raft associated protein 1 (Erlin1) is a novel target of matrine. Erlin1 was significantly upregulated in tumors and its knockdown suppressed the proliferation and migration of CRC cells, while its overexpression promoted CRC cell growth and migration. Furthermore, Erlin1 overexpression promoted inhibited apoptosis. Importantly, matrine treatment could reverse the oncogenic function of Erlin1 on CRC cell proliferation and migration. When Erlin1 was knocked down, matrine exhibited a more obvious anti-tumor effect in CRC cells. Partly due to this, matrine functions as an important anti-tumor drug and the results discovered here may clarify the mechanisms of matrine application for CRC treatment. CRC patients with low expression of Erlin1 might be more suitable for the treatment of matrine. This study could promote the application of matrine to be a promising therapeutic strategy for CRC patients.

The pathological roles of long non-coding RNAs (lncRNAs) in colorectal carcinoma (CRC) have been corroborated. To date, the pathological contributions of LINC01315 in the epithelial-mesenchymal transition (EMT) property of CRC are still ambiguous. By silencing LINC01315, we disclosed that LINC01315 promoted the growth, metastatic characteristics, and the EMT of CRC cells

Background parenchymal enhancement (BPE) of breast fibroglandular tissue (FGT) in dynamic contrast-enhanced breast magnetic resonance imaging (MRI) has shown an association with response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. Fully automated segmentation of FGT for BPE calculation is a challenge when image artifacts are present. Low spatial frequency intensity nonuniformity due to coil sensitivity variations is known as bias or inhomogeneity and can affect FGT segmentation and subsequent BPE measurement. In this study, we utilized the N4ITK algorithm for bias correction over a restricted bilateral breast volume and compared the contralateral FGT segmentations based on uncorrected and bias-corrected images in three MRI examinations at pre-treatment, early treatment and inter-regimen timepoints during NAC. A retrospective analysis of 2 cohorts was performed: one with 735 patients enrolled in the multi-center I-SPY 2 TRIAL and the sub-cohort of 340 patients meeting a high-quality benchmark for segmentation. Bias correction substantially increased the FGT segmentation quality for 6.3–8.0% of examinations, while it substantially decreased the quality for no examination. Our results showed improvement in segmentation quality and a small but statistically significant increase in the resulting BPE measurement after bias correction at all timepoints in both cohorts. Continuing studies are examining the effects on pCR prediction.

Mitochondrial DNA (mtDNA) mutations have been identified in various human cancers, including thyroid cancer. However, the relationship between mtDNA and thyroid cancer remains unclear. Previous studies by others and us strongly suggested that mtDNA mutations in complex I may participate in thyroid cancer processes according to sequencing results of thyroid cancer tissue, although the associated pathogenic processes remain unknown. Here, to investigate whether mtDNA mutations contribute to thyroid cancer, we reanalyzed our sequencing results and characterized thyroid cancer-associated mutations in the mitochondrial complex. The results identified the highest mutation frequencies in nicotinamide adenine dinucleotide hydride (NADH) dehydrogenase subunit 4 gene (ND4) and cytochrome c oxidase subunit 1 gene (COI), which also harbored the highest rates of G > A substitutions, with most of the mutations resulting in changes in the polarity of amino acids. We then established cybrids containing the G3842A mutation identified in papillary thyroid carcinoma, which revealed it as a mutation in NADH dehydrogenase subunit 1 gene (ND1) and is previously reported in follicular thyroid carcinoma, thereby suggesting a possibly pathogenic role in thyroid carcinoma. Additionally, we found that the G3842A mutation accelerates tumorigenicity and decreases the abundance and activity of mitochondrial complex I, the oxygen consumption rate, and adenosine triphosphate levels. By contrast, the levels of reactive oxygen species (ROS) were increased to activate extracellular signal-regulated kinase (ERK1/2) signaling, which contributed to tumorigenicity. These findings suggest for the first time that mtDNA mutations help drive tumor development and that G3842A may represent a new risk factor for thyroid cancer. Furthermore, our findings indicate that drugs targeting ROS and ERK1/2 may serve as a viable therapeutic strategy for thyroid cancer.

To identify coping difficulties after discharge and influencing factors of pregnant women with gestational diabetes mellitus.A cross-sectional descriptive survey was conducted with gestational diabetes mellitus women from four tertiary hospitals in the Shandong Peninsula in China.The study consists of 252 gestational diabetes mellitus women. Survey measures included demographic information, quality of discharge teaching scale, readiness for hospital discharge scale and postdischarge coping difficulty scale. Multiple linear regression analysis was used to explore the factors of coping difficulties after discharge.The situation of coping difficulties in pregnant women with gestational diabetes mellitus after discharge is not optimistic. Age, education level, type of birth, parity, quality of discharge teaching and discharge readiness are six factors that significantly influence postdischarge coping difficulties.

Aims The negative effect of the COVID-19 pandemic on sleep quality of clinically stable psychiatric patients is unknown. This study examined the prevalence of sleep disturbances and their association with quality of life (QOL) in clinically stable older psychiatric patients during the COVID-19 pandemic. Methods This multicenter, cross-sectional study involved older patients attending maintenance treatment at outpatient departments of four major psychiatric hospitals in China. Patients’ socio-demographic and clinical characteristics were collected. Sleep disturbances, depressive symptoms, and QOL were assessed with the Insomnia Severity Index, the 9-item Patient Health Questionnaire, and 2 items of the World Health Organization Quality of Life-Brief version, respectively. Binary logistic regression analysis was conducted to examine the independent associations of socio-demographic and clinical variables with sleep disturbances, while the association between sleep disturbances and QOL was explored with analysis of covariance. Results A total of 941 patients were recruited. The prevalence of sleep disturbances was 57.1% (95% CI: 53.9–60.2%). Analysis of covariance revealed that QOL was significantly lower in patients with sleep disturbances compared to those without. Multivariate logistic regression analysis showed that sleep disturbances were positively and independently associated with more severe depressive symptoms (OR = 1.32, 95% CI: 1.26–1.37). Compared to patients with major depressive disorder, those with other psychiatric diagnoses had a significantly higher prevalence of sleep disturbances (OR = 1.44, 95% CI: 1.00–2.08). Conclusion Sleep disturbances were common among clinically stable older psychiatric patients during the COVID-19 pandemic. Considering the negative association with QOL, this subpopulation needs regular assessment and timely treatment to reduce their sleep disturbances and improve their QOL.

Objectives The Coronavirus Disease 2019 (COVID-19) pandemic has profound negative effects on the mental health of clinically stable older patients with psychiatric disorders. This study examined the influential nodes of psychiatric problems and their associations in this population using network analysis. Methods Clinically stable older patients with psychiatric disorders were consecutively recruited from four major psychiatric hospitals in China from May 22 to July 15, 2020. Depressive and anxiety syndromes (depression and anxiety hereafter), insomnia, posttraumatic stress symptoms (PTSS), pain, and fatigue were measured using the Patient Health Questionnaire, General Anxiety Disorder, Insomnia Severity Index, Posttraumatic Stress Disorder Checklist - Civilian Version, and Numeric Rating Scales for pain and fatigue, respectively. Results A total of 1063 participants were included. The network analysis revealed that depression was the most influential node followed by anxiety as indicated by the centrality index of strength. In contrast, the edge connecting depression and anxiety was the strongest edge, followed by the edge connecting depression and insomnia, and the edge connecting depression and fatigue as indicated by edge-weights. The network structure was invariant by gender based on the network structure invariance test (M = .14, P = .20) and global strength invariance tests (S = .08, P = .30). Conclusions Attention should be paid to depression and its associations with anxiety, insomnia, and fatigue in the screening and treatment of mental health problems in clinically stable older psychiatric patients affected by the COVID-19 pandemic.

Most available four-dimensional (4D)-magnetic resonance imaging (MRI) techniques are limited by insufficient image quality and long acquisition times or require specially designed sequences or hardware that are not available in the clinic. These limitations have greatly hindered the clinical implementation of 4D-MRI.This study aims to develop a fast ultra-quality (UQ) 4D-MRI reconstruction method using a commercially available 4D-MRI sequence and dual-supervised deformation estimation model (DDEM).Thirty-nine patients receiving radiotherapy for liver tumors were included. Each patient was scanned using a time-resolved imaging with interleaved stochastic trajectories (TWIST)-lumetric interpolated breath-hold examination (VIBE) MRI sequence to acquire 4D-magnetic resonance (MR) images. They also received 3D T1-/T2-weighted MRI scans as prior images, and UQ 4D-MRI at any instant was considered a deformation of them. A DDEM was developed to obtain a 4D deformable vector field (DVF) from 4D-MRI data, and the prior images were deformed using this 4D-DVF to generate UQ 4D-MR images. The registration accuracies of the DDEM, VoxelMorph (normalized cross-correlation [NCC] supervised), VoxelMorph (end-to-end point error [EPE] supervised), and the parametric total variation (pTV) algorithm were compared. Tumor motion on UQ 4D-MRI was evaluated quantitatively using region of interest (ROI) tracking errors, while image quality was evaluated using the contrast-to-noise ratio (CNR), lung-liver edge sharpness, and perceptual blur metric (PBM).The registration accuracy of the DDEM was significantly better than those of VoxelMorph (NCC supervised), VoxelMorph (EPE supervised), and the pTV algorithm (all, p 0.001), with an inference time of 69.3 ± 5.9 ms. UQ 4D-MRI yielded ROI tracking errors of 0.79 ± 0.65, 0.50 ± 0.55, and 0.51 ± 0.58 mm in the superior-inferior, anterior-posterior, and mid-lateral directions, respectively. From the original 4D-MRI to UQ 4D-MRI, the CNR increased from 7.25 ± 4.89 to 18.86 ± 15.81; the lung-liver edge full-width-at-half-maximum decreased from 8.22 ± 3.17 to 3.65 ± 1.66 mm in the in-plane direction and from 8.79 ± 2.78 to 5.04 ± 1.67 mm in the cross-plane direction, and the PBM decreased from 0.68 ± 0.07 to 0.38 ± 0.01.This novel DDEM method successfully generated UQ 4D-MR images based on a commercial 4D-MRI sequence. It shows great promise for improving liver tumor motion management during radiation therapy.

Nilotinib has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph

Current guidelines recommend oral anticoagulation (OAC) following transcatheter aortic valve replacement (TAVR) in patients with clinical indication, but the optimal antithrombotic regimen remains uncertain. We aimed to compare the efficacy and safety of non-vitamin K oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in patients undergoing TAVR with concomitant indication of OAC.Comparing with VKAs therapy, NOACs are similar in reducing the all-cause mortality and major bleeding in post-TAVR patients requiring OAC medication.We searched the databases of PubMed, Embase, and Cochrane library databases to identify studies that investigated NOACs versus VKAs after TAVR in patients with another indication of OAC, which were published before 28th September 28, 2021. The effectiveness of outcomes was all-cause mortality and stroke or systemic embolism, while the main safety outcome was major and/or life-threatening bleeding. The hazard ratio (HR) with 95% confidence interval (CI) was used as a measure of treatment effect.Our search identified eight studies. We included 4947 post-TAVR patients with another indication of OAC allocated to the NOAC (n = 2146) or VKA groups (n = 2801). There were no significant differences in the all-cause mortality (HR: 0.91, 95% CI: 0.77-1.08, p = .29, IAmong post-TAVR patients who required OAC therapy, NOACs therapy compared to VKAs is similar in reducing the all-cause mortality, stroke or systemic embolism, and major and/or life-threatening bleeding events.

Sleep characteristics, including taking a nap and sleep apnea, have been proven to have effects on cognitive function, and apolipoprotein E polymorphism ε4 (APOEε4) has been confirmed to be a risk factor for mild cognitive impairment (MCI), but epidemiological studies linking sleep characteristics and APOEε4 are scarce. We aimed to explore the longitudinal association between sleep characteristics and MCI in an overall cohort, in APOEε4 carriers and in APOEε4 non-carriers.We included 3053 older adults from the Tianjin Elderly Nutrition and Cognition Cohort (TENCC) study, recruited from March 2018 to June 2019, and followed up from March 2021 to June 2021. All participants underwent detailed neuropsychological evaluation that allowed psychometric MCI classification. Information on self-reported sleep characteristics was gathered via face-to-face interviews. Crude and multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression models.In the multivariable-adjusted models, taking a nap at noon was associated with decreased risk of MCI in all participants (yes vs. no: HR 0.723, 95% CI 0.592, 0.883) and in APOEε4 non-carriers (yes vs. no: HR 0.719, 95% CI 0.576, 0.897). Sleep apnea was associated with increased risk of MCI in all participants (vs. good: HR 2.213, 95% CI 1.171, 4.180) and in APOEε4 non-carriers (vs. good: HR 2.217, 95% CI 1.085, 4.529).This study suggests that taking a nap at noon might be a potential protective factor against development of MCI in APOEε4 non-carriers, and sleep apnea might be associated with increased incidence of MCI in APOEε4 non-carriers.

The present study aimed to investigate the clinical efficacy of simultaneous management of condylar osteochondroma and its secondary dentofacial deformities using an intraoral surgical approach.Six patients with condylar osteochondroma were treated with intraoral vertical ramus osteotomies and condylar resection. The free rising branch was used for reconstructing the temporomandibular joint. The simultaneous orthognathic surgery and plastic surgery were performed sequentially to correct the secondary dentofacial deformities. The indexes of aesthetic symmetry, occlusion relationship, temporomandibular joint function, condylar height, and volume change were assessed in the subsequential follow up.The mean follow up period was 31 months. All patients had no tumor recurrence. The ipsilateral joint function, occlusal relationship, and facial symmetry were satisfied. The ipsilateral condylar reconstruction had no obvious bone resorption and the ramus height was maintained well. Postoperative assessment showed the preoperative design was accurately fulfilled.The simultaneous condylar osteochondroma resection and temporomandibular joint reconstruction using intraoral approach avoids extraoral scars and correct facial asymmetry without compromising the long-term joint function and occlusal relationship.

Anxiety disorders are debilitating psychiatric diseases that affect ∼16% of the world's population. Although it has been proposed that the central nucleus of the amygdala (CeA) plays a role in anxiety, the molecular and circuit mechanisms through which CeA neurons modulate anxiety-related behaviors are largely uncharacterized. Soluble epoxide hydrolase (sEH) is a key enzyme in the metabolism of polyunsaturated fatty acids (PUFAs), and has been shown to play a role in psychiatric disorders. Here, we reported that sEH was enriched in neurons in the CeA and regulated anxiety-related behaviors in adult male mice. Deletion of sEH in CeA neurons but not astrocytes induced anxiety-like behaviors. Mechanistic studies indicated that sEH was required for maintaining the the excitability of sEH positive neurons (sEHCeAneurons) in the CeA. Using chemogenetic manipulations, we found that sEHCeAneurons bidirectionally regulated anxiety-related behaviors. Notably, we identified that sEHCeAneurons directly projected to the bed nucleus of the stria terminalis (BNST; sEHCeA–BNST). Optogenetic activation and inhibition of the sEHCeA–BNSTpathway produced anxiolytic and anxiogenic effects, respectively. In summary, our studies reveal a set of molecular and circuit mechanisms of sEHCeAneurons underlying anxiety.SIGNIFICANCE STATEMENTSoluble epoxide hydrolase (sEH), a key enzyme that catalyzes the degradation of EETs, is shown to play a key role in mood disorders. It is well known that sEH is mostly localized in astrocytes in the prefrontal cortex and regulates depressive-like behaviors. Notably, sEH is also expressed in central nucleus of the amygdala (CeA) neurons. While the CeA has been studied for its role in the regulation of anxiety, the molecular and circuit mechanism is quite complex. In the present study, we explored a previously unknown cellular and circuitry mechanism that guides sEHCeAneurons response to anxiety. Our findings reveal a critical role of sEH in the CeA, sEHCeAneurons and CeA-bed nucleus of the stria terminalis (BNST) pathway in regulation of anxiety-related behaviors.

Progestin resistance is a critical factor that prevents patients with endometrial cancer (EC) from receiving conservative therapy. However, the etiology remains elusive. Cancer stem cells (CSCs) may be a contributing factor to progestin resistance in EC. These cells share similar stemness properties with embryonic stem cells that have a multipotent but differential naïve phenotype. Embryonic stem cells are programed to self-renew, to differentiate and to show plasticity toward a normal cellular phenotype in their defined microenvironment. However, whether this microenvironment may promote CSC differentiation toward a better responsive phenotype and reverse progestin resistance has not yet been clarified. In the current study, we found that progestin resistance of endometrial CSCs can be improved or reversed by using in vitro fertilization (IVF)-generated embryonic sac-derived fluid containing the embryonic microenvironment. Furthermore, suppression or reversal of progestin resistance was mediated by placental alkaline phosphatase (ALPP), a factor secreted into the embryonic microenvironment by IVF-generated blastocysts. ALPP significantly reversed progestin resistance by facilitating endometrial CSC differentiation through downregulating the stemness genes NANOG, OCT4 and SOX2. We further showed that the downregulation of NANOG, OCT4 and SOX2 by ALPP was carried out by TET1/2-mediated epigenetic modulation of the promoter regions of these genes. Such changes at the molecular level initiated endometrial CSC differentiation and promoted a better responsive endometrial cancer phenotype. In fact, their response to progestin treatment was similar to that of well-differentiated endometrioid carcinoma cells without CSCs. ALPP could be a novel target in the process to overcome progestin resistance, and such findings may provide a new approach for the conservative treatment of endometrial cancer.

Invasion and metastasis of breast cancer cells is an important cause of death in breast cancer patients. In the tumor microenvironment, M2 polarization of macrophages can promote the invasion and metastasis of tumor cells. OVOL2 is an evolutionarily conserved transcription regulator, but its effect in macrophages has not been described previously. The aim of this study was to investigate the effects of OVOL2 on macrophage polarity and the role of these effects in the tumor metastasis. We found that overexpression of OVOL2 in macrophages significantly inhibited M2 polarization and thus inhibits breast cancer metastasis. We propose a novel mechanism in which OVOL2 inhibits M2 polarization of macrophages and thus reduces their ability to induce invasion and metastasis of breast cancer. By shedding new light on the regulation of metastasis in cancers, our study provides a new strategy for the targeted therapy of cancer.

Background: The efficacy of highly active antiretroviral therapy (HAART) therapy can be estimated by immunological response and the incidence of opportunistic infections. Objective: To evaluate the effectiveness of different durations of HAART in terms of immunological response markers (CD4 count and CD4/CD8 ratio) along with disease progression markers (incidence of oral lesions) in Chinese patients with HIV. Methods: This single-center, retrospective, real-world study included patients with HIV, grouped into treatment group and treatment-naïve group of which the former was further divided into (6, 12, and 18 months) based on the treatment duration. The CD4 and CD8 cell counts were analyzed by the FACSCalibur flow cytometry. Kruskal-Wallis test was applied to determine the outcome of different duration of HAART. Oral examination was carried out according to the WHO type IV examination Results: In 246 patients with HIV, CD4 counts increased significantly post-HAART compared with pre-HAART in all three treatment groups (P Conclusion: We observed a better response of HAART regimen with 18 months of duration than 12-months and 6-months therapies and reduction in oral lesions.