Targeting PCSK9 to upregulate MHC-II on the surface of tumor cells in tumor immunotherapy.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), the last member of the proprotein convertase family, functions as a classic regulator of low-density lipoprotein (LDL) by interacting with low-density lipoprotein receptor (LDLR). Recent studies have shown that PCSK9 can affect the occurrence and development of tumors and can be used as a novel therapeutic target. However, a comprehensive pan-cancer analysis of PCSK9 has yet to be conducted. METHODS: The potential oncogenic effects of PCSK9 in 33 types of tumors were explored based on the datasets of The Cancer Genome Atlas (TCGA) dataset. In addition, the immune regulatory role of PCSK9 inhibition was evaluated via in vitro cell coculture and the tumor-bearing mouse model. Finally, the antitumor efficacy of targeted PCSK9 combined with OVA-II vaccines was verified. RESULTS: Our results indicated that PCSK9 was highly expressed in most tumor types and was significantly correlated with late disease stage and poor prognosis. Additionally, PCSK9 may regulate the tumor immune matrix score, immune cell infiltration, immune checkpoint expression, and major histocompatibility complex expression. Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Combining PCSK9 inhibitors could enhance the efficacies of OVA-II tumor vaccine monotherapy. CONCLUSIONS: Conclusively, our pan-cancer analysis provided a more comprehensive understanding of the oncogenic and immunoregulatory roles of PCSK9 and demonstrated that targeting PCSK9 could increase the efficacy of long peptide vaccines by upregulating DC infiltration and MHC-II expression on the surface of tumor cells. This study reveals the critical oncogenic and immunoregulatory roles of PCSK9 in various tumors and shows the promise of PCSK9 as a potent immunotherapy target.

CT radiomics based on the peritumoral adipose region of gastric adenocarcinoma for preoperative prediction of lymph node metastasis.

PURPOSE: To construct and validate CT radiomics model based on the peritumoral adipose region of gastric adenocarcinoma to preoperatively predict lymph node metastasis (LNM). METHODS AND METHODS: 293 consecutive gastric adenocarcinoma patients receiving radical gastrectomy with lymph node dissection in two medical institutions were stratified into a development set (from Institution A, n = 237), and an external validation set (from Institution B, n = 56). Volume of interest of peritumoral adipose region was segmented on preoperative portal-phase CT images. The least absolute shrinkage and selection operator method and stepwise logistic regression were used to select features and build radiomics models. Manual classification was performed according to routine CT characteristics. A classifier incorporating the radiomics score and CT characteristics was developed for predicting LNM. Area under the receiver operating characteristic curve (AUC) was used to show discrimination between tumors with and without LNM, and the calibration curves and Brier score were used to evaluate the predictive accuracy. Violin plots were used to show the distribution of radiomics score. RESULTS: AUC values of radiomics model to predict LNM were 0.938, 0.905, and 0.872 in the training, internal test, and external validation sets, respectively, higher than that of manual classification (0.674, all P values < 0.01). The radiomics score of the positive LNM group were higher than that of the negative group in all sets (both P-values < 0.001). The classifier showed no improved predictive power compared with the radiomics signature alone with AUC values of 0.916 and 0.872 in the development and external validation sets, respectively. Multivariate analysis showed that radiomics score was an independent predictor. CONCLUSIONS: Radiomics model based on peritumoral adipose region could be a useful approach for preoperative LNM prediction in gastric adenocarcinoma.

The rapidly evolving X-linked MIR-506 family fine-tunes spermatogenesis to enhance sperm competition.

Despite rapid evolution across eutherian mammals, the X-linked MIR-506 family miRNAs are located in a region flanked by two highly conserved protein-coding genes (SLITRK2 and FMR1) on the X chromosome. Intriguingly, these miRNAs are predominantly expressed in the testis, suggesting a potential role in spermatogenesis and male fertility. Here, we report that the X-linked MIR-506 family miRNAs were derived from the MER91C DNA transposons. Selective inactivation of individual miRNAs or clusters caused no discernible defects, but simultaneous ablation of five clusters containing 19 members of the MIR-506 family led to reduced male fertility in mice. Despite normal sperm counts, motility, and morphology, the KO sperm were less competitive than wild-type sperm when subjected to a polyandrous mating scheme. Transcriptomic and bioinformatic analyses revealed that these X-linked MIR-506 family miRNAs, in addition to targeting a set of conserved genes, have more targets that are critical for spermatogenesis and embryonic development during evolution. Our data suggest that the MIR-506 family miRNAs function to enhance sperm competitiveness and reproductive fitness of the male by finetuning gene expression during spermatogenesis.

Predicting the risk of lung cancer using machine learning: A large study based on UK Biobank.

In response to the high incidence and poor prognosis of lung cancer, this study tends to develop a generalizable lung-cancer prediction model by using machine learning to define high-risk groups and realize the early identification and prevention of lung cancer. We included 467,888 participants from UK Biobank, using lung cancer incidence as an outcome variable, including 49 previously known high-risk factors and less studied or unstudied predictors. We developed multivariate prediction models using multiple machine learning models, namely logistic regression, naïve Bayes, random forest, and extreme gradient boosting models. The performance of the models was evaluated by calculating the areas under their receiver operating characteristic curves, Brier loss, log loss, precision, recall, and F1 scores. The Shapley additive explanations interpreter was used to visualize the models. Three were ultimately 4299 cases of lung cancer that were diagnosed in our sample. The model containing all the predictors had good predictive power, and the extreme gradient boosting model had the best performance with an area under curve of 0.998. New important predictive factors for lung cancer were also identified, namely hip circumference, waist circumference, number of cigarettes previously smoked daily, neuroticism score, age, and forced expiratory volume in 1 second. The predictive model established by incorporating novel predictive factors can be of value in the early identification of lung cancer. It may be helpful in stratifying individuals and selecting those at higher risk for inclusion in screening programs.

Free triiodothyronine to free thyroxine ratio as a marker of poor prognosis in euthyroid patients with acute coronary syndrome and diabetes after percutaneous coronary intervention.

Objectives: In recent years, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, a new comprehensive index for evaluating thyroid function, which could reflect thyroid function more stably and truly than serum thyroid hormone level, has been demonstrated to correlate with the risks of diabetes and cardiovascular disease in euthyroid adults. However, the correlation between thyroid hormone sensitivity and long-term prognosis in euthyroid patients with acute coronary syndrome (ACS) and diabetes after percutaneous coronary intervention (PCI) remains unclear. Methods: A total of 1,786 euthyroid patients with ACS who successfully underwent PCI at Beijing Anzhen Hospital from August 2021 to April 2022 were included in our study, which was divided into three groups according to tertiles of thyroid hormone sensitivity index. Cox regression, Kaplan-Meier, and receiver operating characteristic analyses were applied to analyze the associations between the FT3/FT4 ratio with ACS and diabetes after PCI. Results: Our analysis indicated that a lower level of FT3/FT4 ratio in euthyroid patients with acute coronary syndrome (ACS) and diabetes after PCI showed significantly higher incidences of major adverse cardiac and cerebrovascular events (MACCE) when compared with a higher level of FT3/FT4 ratio. After adjusting for other covariates, patients with a lower level of FT3/FT4 ratio were negatively associated with the risk of MACCE than those with a higher level of FT3/FT4 ratio (adjusted OR =1.61, 95% CI 1.05-2.47, P = 0.028). In subgroup analyses, individuals were stratified by age, sex, BMI, ACS type, hypertension, and dyslipidemia, showing that there were no significant interactions between the FT3/FT4 ratio and all subgroups for MACCE. In addition, the FT3/FT4 ratio performed better on ROC analyses for cardiac death prediction [area under the curve (AUC), 0.738]. Conclusion: A reduced level of FT3/FT4 ratio was a potential marker of poor prognosis in euthyroid patients with ACS and diabetes after PCI.

Endometrial microbiota alteration in female patients with endometrial polyps based on 16S rRNA gene sequencing analysis.

Introduction: The potential role of the endometrial microbiota in the pathogenesis of endometrial polyps (EPs) warrants further investigation, given the current landscape of limited and inconclusive research findings. We aimed to explore the microecological characteristics of the uterine cavity in patients with EPs and investigate the potential of endometrial microbiota species as novel biomarkers for identifying EPs. Methods: Endometrial samples were collected from 225 patients who underwent hysteroscopies, of whom 167 had EPs, whereas 58 had non- hyperproliferative endometrium status. The endometrial microbiota was assessed using 16S rRNA gene sequencing. We characterized the endometrial microbiota and identified microbial biomarkers for predicting EPs. Results: The endometrial microbial diversity and composition were significantly different between the EP and control groups. Predictive functional analyses of the endometrial microbiota demonstrated significant alterations in pathways involved in sphingolipid metabolism, steroid hormone biosynthesis, and apoptosis between the two groups. Moreover, a classification model based on endometrial microbial ASV-based biomarkers along with the presence of abnormal uterine bleeding symptoms achieved powerful classification potential in identifying EPs in both the discovery and validation cohorts. Conclusion: Our study indicates a potential association between altered endometrial microbiota and EPs. Endometrial microbiota-based biomarkers may prove valuable for the diagnosis of EPs. Clinical trial registration: Chinese Clinical Trial Registry (ChiCTR2100052746).

Branched-chain amino acids and the risks of dementia, Alzheimer's disease, and Parkinson's disease.

Background: We aimed to examine the association between blood levels of Branched-chain amino acids (BCAAs) - specifically isoleucine, leucine, and valine - and the susceptibility to three neurodegenerative disorders: dementia, Alzheimer's disease (AD), and Parkinson's disease (PD). Methods: Based on data from the UK Biobank, a Cox proportional hazard regression model and a dose-response relationship were used to analyze the association between BCAAs and the risks of dementia, AD, and PD. We also generated a healthy lifestyle score and a polygenic risk score. Besides, we conducted a sensitivity analysis to ensure the robustness of our findings. Results: After adjusting for multiple covariates, blood concentrations of isoleucine, leucine, and valine were significantly associated with a reduced risk of dementia and AD. This association remained robust even in sensitivity analyses. Similarly, higher levels of isoleucine and leucine in the blood were found to be associated with an increased risk of PD, but this positive correlation could potentially be explained by the presence of covariates. Further analysis using a dose-response approach revealed that a blood leucine concentration of 2.14 mmol/L was associated with the lowest risk of dementia. Conclusion: BCAAs have the potential to serve as a biomarker for dementia and AD. However, the specific mechanism through which BCAAs are linked to the development of dementia, AD, and PD remains unclear and necessitates additional investigation.

A novel GSK3ß inhibitor 5n attenuates acute kidney injury.

Acute kidney injury (AKI) is a clinical syndrome with high morbidity and mortality caused by various factor. The specific strategies for AKI are still lacking. GSK3ß is widely expressed in the kidneys. In acute models of injury, GSK3ß promotes the systemic inflammatory response, increases the proinflammatory release of cytokines, induces apoptosis, and alters cell proliferation. We screened a series of 3-(4-pyridyl)-5-(4-sulfamido-phenyl)-1,2,4-oxadiazole derivatives which are recognized as new GSK3ß inhibitors, and found that 5n had the least toxicity and the best cell protection. We then tested the anti-inflammatory and reno-protective effect of 5n in cisplatin-treated tubular epithelial cells. 5n had anti-inflammation effect indicated by phosphor-NF-κB detection. Finally, we found that 5n ameliorated renal injury and inflammation in cisplatin-induced AKI mouse model. Silencing GSK3ß inhibited cell injury and inflammation induced by cisplatin. We found that GSK3ß interacted with PP2Ac to modulate the activity of NF-κB. In conclusion, 5n, the novel GSK3ß inhibitor, protects against AKI via PP2Ac-dependent mechanisms which may provide a potential strategy for the treatment of AKI in clinic.

Risk factors for anxiety and its impacts on acute exacerbation in older patients with chronic obstructive pulmonary disease.

Background: Anxiety is common in patients with chronic obstructive pulmonary disease (COPD), especially in older patients with the definition of age over 60 years old. Few studies have focused on anxiety in older COPD patients. This study aimed to analyze the risk factors of anxiety in older COPD patients and the impacts of anxiety on future acute exacerbation. Methods: The general information, questionnaire data, previous acute exacerbation and pulmonary function were collected. Hamilton Anxiety Rating Scale (HAMA) was used to evaluate the anxiety of older COPD patients. The patients were followed up for one year, the number and the degrees of acute exacerbations of COPD were recorded. Results: A total of 424 older COPD patients were included in the analysis. 19.81% (N = 84) had anxiety symptoms, and 80.19% (N = 340) had no anxiety symptoms. There were increased pack-years, more comorbidities, and more previous acute exacerbations in older COPD patients with anxiety compared to those without anxiety (P < 0.05). Meanwhile, a higher modified Medical Research Council (mMRC), a higher COPD assessment test (CAT) score and a shorter six-minute walking distance (6MWD) were found in older COPD patients with anxiety (P < 0.05). The BODE index, mMRC, CAT score, comorbidities and acute exacerbations were associated with anxiety. Eventually, anxiety will increase the risk of future acute exacerbation in older COPD patients (OR = 4.250, 95% CI: 2.369-7.626). Conclusion: Older COPD patients with anxiety had worsening symptoms, more comorbidities and frequent acute exacerbation. Meanwhile, anxiety may increase the risk of acute exacerbation in the future. Therefore, interventions should be provided to reduce the risk of anxiety in older COPD patients at an early stage.

Transcription factor CmHSFA4-CmMYBS3 complex enhances salt tolerance in chrysanthemum by repressing CmMYB121 expression.

Excessive soil salinity not only hampers plant growth and development but can also lead to plant death. Previously, we found that heat shock factor A4 (CmHSFA4) enhances the tolerance of chrysanthemum (Chrysanthemum morifolium) to salt. However, the underlying molecular mechanism remains unclear. In this study, we identified a candidate MYB transcription factor, CmMYB121, which responded to salt stress. We observed that the CmMYB121 transcription is suppressed by CmHSFA4. Moreover, overexpression of CmMYB121 exacerbated chrysanthemum sensitivity to salt stress. CmHSFA4 directly bound to the promoter of CmMYB121 at the heat shock element (HSE). Protein-protein interaction assays identified an interaction between CmHSFA4 and CmMYBS3, a transcriptional repressor, and recruited the corepressor TOPLESS (CmTPL) to inhibit CmMYB121 transcription by impairing the H3 and H4 histone acetylation levels of CmMYB121. Our study demonstrated that a CmHSFA4-CmMYBS3-CmTPL complex modulates CmMYB121 expression, consequently regulating the tolerance of chrysanthemum to salt. The findings shed light on the responses of plants to salt stress.

STING Agonist cGAMP Attenuates Sleep Deprivation-Induced Neuroinflammation and Cognitive Deficits via TREM2 Up-Regulation.

Sleep deprivation (SD) has been associated with several adverse effects, including cognitive deficit. Emerging evidence suggests microglia-associated neuroinflammation is a potential trigger of cognitive deficit after SD. Stimulator of interferon genes (STING) constitutes an important factor in host immune response to pathogenic organisms and is found in multiple cells, including microglia. STING is involved in neuroinflammation during neuronal degeneration, although how STING signaling affects SD-induced neuroinflammation remains unexplored. In the present study, the chronic sleep restriction (CSR) model was applied to examine the effects of STING signaling on cognition. The results revealed that cGAMP, a high-affinity and selective STING agonist, significantly improved cognitive deficit, alleviated neural injury, and relieved neuroinflammation in CSR mice by activating the STING-TBK1-IRF3 pathway. Moreover, triggering receptor expressed on myeloid cells 2 (TREM2) was upregulated in CSR mice treated with cGAMP, and this effect was abolished by STING knockout. TREM2 upregulation induced by cGAMP regulated the microglia from pro-inflammatory state to anti-inflammatory state, thereby relieving neuroinflammation in CSR mice. These findings indicate cGAMP-induced STING signaling activation alleviates SD-associated neuroinflammation and cognitive deficit by upregulating TREM2, providing a novel approach for the treatment of SD-related nerve injury.

6-O-angeloylplenolin inhibits osteoclastogenesis in vitro via suppressing c-Src/NF-κB/NFATc1 pathways and ameliorates bone resorption in collagen-induced arthritis mouse model.

One of the effective therapeutic strategies to treat rheumatoid arthritis (RA)-related bone resorption is to target excessive activation of osteoclasts. We discovered that 6-O-angeloylplenolin (6-OAP), a pseudoguaianolide from Euphorbia thymifolia Linn widely used for the treatment of RA in traditional Chinese medicine, could inhibit RANKL-induced osteoclastogenesis and bone resorption in both RAW264.7 cells and BMMs from 1 µM and protect a collagen-induced arthritis (CIA) mouse model from bone destruction in vivo. The severity of arthritis and bone erosion observed in paw joints and the femurs of the CIA model were attenuated by 6-OAP administered at both dosages (1 or 5 mg/kg, i.g.). BMD, Tb.N and BV/TV were also improved by 6-OAP treatment. Histological analysis and TRAP staining of femurs further confirmed the protective effects of 6-OAP on bone erosion, which is mainly due to reduced osteoclasts. Molecular docking indicated that c-Src might be a target of 6-OAP and that phosphorylation of c-Src was suppressed by 6-OAP treatment. CETSA and SPR assay further confirmed the potential interaction between 6-OAP and c-Src. Three signaling molecules downstream of c-Src that are vital to the differentiation and function of osteoclasts, NF-κB, c-Fos and NFATc1, were also suppressed by 6-OAP in vitro. In summary, the results demonstrated that the function of c-Src was disrupted by 6-OAP, which led to the suppression of downstream signaling vital to osteoclast differentiation and function. In conclusion, 6-OAP has the potential to be further developed for the treatment of RA-related bone erosion.

Identification of a Novel Mitochondrial tRNA Mutation in Chinese Family with Type 2 Diabetes Mellitus.

Background: Mutations in mitochondrial tRNA (mt-tRNA) could be the origin of some type 2 diabetes mellitus (T2DM) cases, but the mechanism remained largely unknown. Aim: The aim of this study was to assess the impact of a novel mitochondrial tRNACys/tRNATyr A5826G mutation on the development and progression of T2DM. Methods: A four-generation Han Chinese family with maternally inherited diabetes underwent clinical, genetic and biochemical analyses. The mitochondrial DNA (mtDNA) mutations of three matrilineal relatives were screened by PCR-Sanger sequencing. Furthermore, to see whether m.A5826G mutations affected mitochondrial functions, the cybrid cell lines were derived from three subjects with m.A5826G mutation and three controls without this mutation. ATP was evaluated by luminescent cell viability assay, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were determined by flow cytometry. The student's two-tailed, unpaired t-test was used to assess the statistical significance between the control and mutant results. Results: The age at onset of diabetes in this pedigree varied from 40 to 63 years, with an average of 54 years. Mutational analysis of mitochondrial genomes revealed the presence of a novel m.A5826G mutation. Interestingly, the m.A5826G mutation occurred at the conjunction between tRNACys and tRNATyr, a very conserved position that was critical for tRNAs processing and functions. Using trans-mitochondrial cybrid cells, we found that mutant cells carrying the m.A5826G showed approximately 36.5% and 22.4% reductions in ATP and MMP, respectively. By contrast, mitochondrial ROS levels increased approximately 33.3%, as compared with the wild type cells. Conclusion: A novel m.A5826G mutation was identified in a pedigree with T2DM, and this mutation would lead to mitochondrial dysfunction. Thus, the genetic spectrum of mitochondrial diabetes was expanded by including m.A5826G mutation in tRNACys/tRNATyr, our study provided novel insight into the molecular pathogenesis, early diagnosis, prevention and clinical treatment for mitochondrial diabetes.

Peripheral Control of the Assembly and Chirality of Anion-Based Octanuclear Cubes by Cation-π Networks.

Self-assembly of sophisticated polyhedral cages has drawn much attention because of their elaborate structures and potential applications. Herein, we report the anion-coordination-driven assembly of the first A8L12 (A = anion, L = ligand) octanuclear cubic structures from phosphate anion and p-xylylene-spaced bis-bis(urea) ligands via peripheral templating of countercations (TEA+ or TPA+). By attaching terminal aryl rings (phenyl or naphthyl) to the ligand through a flexible (methylene) linker, these aryls actively participate in the formation of plenty of "aromatic pockets" for guest cation binding. As a result, multiple peripheral guests (up to 22) of suitable size are bound on the faces and vertices of the cube, forming a network of cation-π interactions to stabilize the cube structure. More interestingly, when chiral ligands were used, either diastereomers of mixed Λ- and Δ-configurations (with TEA+ countercation) for the phosphate coordination centers or enantiopure cubes (with TPA+) were formed. Thus, the assembly and chirality of the cube can be modulated by remote terminal groups and peripheral templating tetraalkylammonium cations.

Hyperthermia and cisplatin combination therapy promotes caspase-8 accumulation and activation to enhance apoptosis and pyroptosis in cancer cells.

BACKGROUND: Hyperthermia can play a synergistic role with chemotherapy in combination therapy. Although the association between caspase activation, apoptosis, and pyroptosis have been published for both cisplatin (CDDP) and hyperthermia therapies independently, the interactions between these molecular pathways in combination therapy are unknown. The present study aimed to investigate the possible interactions between caspase 8 activation, apoptosis, and pyroptosis in combination therapy. METHODS: Cells were treated with CDDP (15 µg/ml), followed by hyperthermia at optimized temperature (42.5 °C) in water-bath. After combination therapy, cell viability was analyzed by CCK-8, and cell death was analyzed by Annexin-V-FITC/PI and caspases activation. Immuno-staining and co-immuno-precipitation were used to examine the interaction between p62 and caspase-8. Pyroptosis was investigated by western blotting and transmission electron microscopy. E3 ligase Cullin 3 was knockdown by siRNA. In addition, caspase-8 activation was modulated by CRISPR-Cas9 gene-editing or pharmacological inhibition. RESULTS: Combination therapy promoted K63-linked polyubiquitination of caspase-8 and cellular accumulation of caspase-8. In turn, polyubiquitinated caspase-8 interacted with p62 and led to the activation of caspase-3. Knockdown of the E3 ligase Cullin 3 by siRNA reduced caspase-8 polyubiquitination and activation. In addition, combination therapy induced release of the pore-forming N-terminus from gasdermins and promoted pyroptosis along with caspase-8 accumulation and activation. Knockdown of caspase-8 by CRISPR/Cas9 based gene editing reduced the sensitivity of tumor cells to apoptosis and pyroptosis. CONCLUSIONS: Our study presented a novel mechanism in which hyperthermia synergized with chemotherapy in promoting apoptosis and pyroptosis in a caspase-8 dependent manner.

Associations between genomic aberrations, increased nuchal translucency, and pregnancy outcomes: a comprehensive analysis of 2,272 singleton pregnancies in women under 35.

Objectives: Regarding increased nuchal translucency (NT), the cutoff values used are heterogeneous in clinical practice, this study aims to assess the efficacy of prenatal detection for chromosomal abnormalities and pregnancy outcomes in fetuses with varying NT thicknesses, in order to provide data that supports informed prenatal diagnosis and genetic counseling for such cases. Methods: We included 2,272 pregnant women under 35 with singleton pregnancies who underwent invasive prenatal diagnosis between 2014 and 2022. The cohort comprised 2,010 fetuses with increased NT (≥2.5 mm) and 262 fetuses with normal NT but exhibiting a single soft marker. Prenatal diagnoses were supported by chromosomal microarray (CMA) and copy number variation sequencing (CNV-seq) analyses. Results: The detection rates of numerical chromosomal abnormalities were 15.4% (309/2,010) and 17.3% (297/1,717) in the NT ≥2.5 and ≥ 3.0 groups, respectively. Pathogenic/likely pathogenic CNV incidence increased with NT thickness (χ2 = 8.60, p < 0.05), peaking at 8.7% (22/254) in the NT 4.5-5.4 mm group. Structural defects were found in 18.4% of fetuses with NT values between 2.5 mm and 2.9 mm. Chromosomal abnormality rates in the isolated increased NT groups of 2.5-2.9 mm and 3.0-3.4 mm were 6.7% (16/239) and 10.0% (47/470), respectively, with no statistical significance (χ2 = 2.14, p > 0.05). Fetuses with NT thickness between 2.5 and 2.9 mm combined with the presence of soft markers or non-lethal structural abnormalities exhibited a significantly higher chromosomal abnormality risk (19.0%) compared to fetuses with isolated increased NT ranging from 3.5 to 4.4 mm (13.0%). Pregnancy termination rates increased with NT thickness (χ2 = 435.18, p < 0.0001), ranging from 12.0% (30/249) in the NT 2.5-2.9 mm group to 87.0% (141/162) in the NT ≥ 6.5 mm group. Conclusion: CMA or CNV-seq exhibited good performance in identifying genomic aberrations in pregnancies with increased NT thickness. NT ranging from 2.5 mm to 2.9 mm elevated the risk of fetal chromosomal abnormalities, particularly when combined with other soft markers.

The effect of coronary stent policies on the risk of percutaneous coronary intervention among acute coronary syndrome patients in Shanghai: Real-world evidence.

OBJECTIVE: This study aimed to analyze the effect of coronary stent policies implemented in Shanghai on the risk of percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) inpatients based on real-world data. METHODS: Two retrospective cohorts of inpatients with a first diagnosis of ACS who had undergone PCI for the first time in the previous year in Shanghai hospitals were examined (one for the postpolicy period and the other for the prepolicy period). χ2 tests were used to compare categorical variables between the two cohorts. Single- and multivariate Cox proportional hazards models were used to compare the risk of major adverse cardiovascular events (MACEs) between the two cohorts. RESULTS: A total of 31,760 ACS patients were included in this study. The proportion of ACS inpatients who had at least one bid-winning stent and 3 or more coronary stents implanted for first-time PCI in the postpolicy cohort was higher than that in the prepolicy cohort (86.52% vs. 55.67% and 6.27% vs. 4.39%, respectively; all p values < 0.0001). The single- and multivariate Cox proportional hazards models revealed that the unadjusted and adjusted hazard ratios for MACEs at 1 year after PCI for the postpolicy cohort relative to the prepolicy cohort were 0.869 (P<0.0001) and 0.814 (P = 0.0007), respectively. CONCLUSIONS: The implementation of coronary stent policies changed coronary stent utilization but had no significant adverse effects on the risk of PCI among ACS patients in Shanghai in the short term. However, the reasons for changes in the number of coronary stents implanted should be analyzed and addressed in the future.

Effect of Consultation Number on the Assessment and Treatment of Polycystic Ovary Syndrome.

Background: The basic medical education stage is not enough to support physicians to fully diagnose and evaluate polycystic ovary syndrome (PCOS). The study aims to discover the difference in treatment choice between participants with different annual consultation number of PCOS, to promote lifelong learning, and drive balanced development within healthcare. Methods: This is a multicenter cross-sectional survey. Participants' basic information, knowledge of PCOS and treatment options were collected online. According to the annual consultation number of patients with PCOS, physicians were divided into three groups: 0-50 people/yr, 50-200 people/yr, and >200 people/yr, and the results were derived from χ2 test, Fisher exact test, and multivariate logistic regression analysis. Results: The study analyzed 1689 questionnaires, and 1206 physicians (71.4%) received less than 50 women per year, 388 physicians (30.0%) with an annual number of 50-200 women, and 95 physicians (5.6%) with patient turnover for more than 200 people. Reproductive endocrinologists generally have higher access to the clinic. As the number of visits increases, more and more physicians would perceive patients as more likely to have abnormal blood glucose and heavy weight. Physicians with large numbers of consultations are more likely to use Asian or Chinese standards to assess obesity. The multivariate analysis involved variables such as age, hospital level, specialty, and patient turnover annually, and more young doctors actively assessed lipid profile (odds ratio (OR) 1.56, 95% confidence interval (CI) (1.16, 2.16)), and primary hospitals (OR 0.65 CI (0.44, 0.89)) chose OGTT for blood glucose assessment less than tertiary hospitals. Physicians in secondary hospitals are more aggressive in evaluating androgens. Conclusion: Our survey found differences in endocrine assessment, metabolic screening, and treatment in PCOS women in terms of the number of obstetrician-gynecologists who received different patient consultation numbers. The importance of continuing education for physicians is emphasized, to promote lifelong learning.