Structural Basis of the Activation of Heterotrimeric Gs-Protein by Isoproterenol-Bound ß1-Adrenergic Receptor.

Cardiac disease remains the leading cause of morbidity and mortality worldwide. The ß1-adrenergic receptor (ß1-AR) is a major regulator of cardiac functions and is downregulated in the majority of heart failure cases. A key physiological process is the activation of heterotrimeric G-protein Gs by ß1-ARs, leading to increased heart rate and contractility. Here, we use cryo-electron microscopy and functional studies to investigate the molecular mechanism by which ß1-AR activates Gs. We find that the tilting of α5-helix breaks a hydrogen bond between the sidechain of His373 in the C-terminal α5-helix and the backbone carbonyl of Arg38 in the N-terminal αN-helix of Gαs. Together with the disruption of another interacting network involving Gln59 in the α1-helix, Ala352 in the ß6-α5 loop, and Thr355 in the α5-helix, these conformational changes might lead to the deformation of the GDP-binding pocket. Our data provide molecular insights into the activation of G-proteins by G-protein-coupled receptors.

Cholinergic macrophages promote the resolution of peritoneal inflammation.

The non-neural cholinergic system plays a critical role in regulating immune equilibrium and tissue homeostasis. While the expression of choline acetyltransferase (ChAT), the enzyme catalyzing acetylcholine biosynthesis, has been well documented in lymphocytes, its role in the myeloid compartment is less understood. Here, we identify a significant population of macrophages (Mϕs) expressing ChAT and synthesizing acetylcholine in the resolution phase of acute peritonitis. Using Chat-GFP reporter mice, we observed marked upregulation of ChAT in monocyte-derived small peritoneal Mϕs (SmPMs) in response to Toll-like receptor agonists and bacterial infections. These SmPMs, phenotypically and transcriptionally distinct from tissue-resident large peritoneal macrophages, up-regulated ChAT expression through a MyD88-dependent pathway involving MAPK signaling. Notably, this process was attenuated by the TRIF-dependent TLR signaling pathway, and our tests with a range of neurotransmitters and cytokines failed to induce a similar response. Functionally, Chat deficiency in Mϕs led to significantly decreased peritoneal acetylcholine levels, reduced efferocytosis of apoptotic neutrophils, and a delayed resolution of peritonitis, which were reversible with exogenous ACh supplementation. Intriguingly, despite B lymphocytes being a notable ChAT-expressing population within the peritoneal cavity, Chat deletion in B cells did not significantly alter the resolution process. Collectively, these findings underscore the crucial role of Mϕ-derived acetylcholine in the resolution of inflammation and highlight the importance of the non-neuronal cholinergic system in immune regulation.

Seeded growth of large single-crystal copper foils with high-index facets.

The production of large single-crystal metal foils with various facet indices has long been a pursuit in materials science owing to their potential applications in crystal epitaxy, catalysis, electronics and thermal engineering1-5. For a given metal, there are only three sets of low-index facets ({100}, {110} and {111}). In comparison, high-index facets are in principle infinite and could afford richer surface structures and properties. However, the controlled preparation of single-crystal foils with high-index facets is challenging, because they are neither thermodynamically6,7 nor kinetically3 favourable compared to low-index facets6-18. Here we report a seeded growth technique for building a library of single-crystal copper foils with sizes of about 30 × 20 square centimetres and more than 30 kinds of facet. A mild pre-oxidation of polycrystalline copper foils, followed by annealing in a reducing atmosphere, leads to the growth of high-index copper facets that cover almost the entire foil and have the potential of growing to lengths of several metres. The creation of oxide surface layers on our foils means that surface energy minimization is not a key determinant of facet selection for growth, as is usually the case. Instead, facet selection is dictated randomly by the facet of the largest grain (irrespective of its surface energy), which consumes smaller grains and eliminates grain boundaries. Our high-index foils can be used as seeds for the growth of other Cu foils along either the in-plane or the out-of-plane direction. We show that this technique is also applicable to the growth of high-index single-crystal nickel foils, and we explore the possibility of using our high-index copper foils as substrates for the epitaxial growth of two-dimensional materials. Other applications are expected in selective catalysis, low-impedance electrical conduction and heat dissipation.

Publisher Correction: Structural basis of ligand recognition at the human MT1 melatonin receptor.

Change history: In this Letter, the rotation signs around 90°, 135° and 15° were missing and in the HTML, Extended Data Tables 2 and 3 were the wrong tables; these errors have been corrected online.

XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity.

The human MT1 and MT2 melatonin receptors1,2 are G-protein-coupled receptors (GPCRs) that help to regulate circadian rhythm and sleep patterns3. Drug development efforts have targeted both receptors for the treatment of insomnia, circadian rhythm and mood disorders, and cancer3, and MT2 has also been implicated in type 2 diabetes4,5. Here we report X-ray free electron laser (XFEL) structures of the human MT2 receptor in complex with the agonists 2-phenylmelatonin (2-PMT) and ramelteon6 at resolutions of 2.8 Å and 3.3 Å, respectively, along with two structures of function-related mutants: H2085.46A (superscripts represent the Ballesteros-Weinstein residue numbering nomenclature7) and N862.50D, obtained in complex with 2-PMT. Comparison of the structures of MT2 with a published structure8 of MT1 reveals that, despite conservation of the orthosteric ligand-binding site residues, there are notable conformational variations as well as differences in [3H]melatonin dissociation kinetics that provide insights into the selectivity between melatonin receptor subtypes. A membrane-buried lateral ligand entry channel is observed in both MT1 and MT2, but in addition the MT2 structures reveal a narrow opening towards the solvent in the extracellular part of the receptor. We provide functional and kinetic data that support a prominent role for intramembrane ligand entry in both receptors, and suggest that there might also be an extracellular entry path in MT2. Our findings contribute to a molecular understanding of melatonin receptor subtype selectivity and ligand access modes, which are essential for the design of highly selective melatonin tool compounds and therapeutic agents.

Structural basis of ligand recognition at the human MT1 melatonin receptor.

Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone that maintains circadian rhythms1 by synchronization to environmental cues and is involved in diverse physiological processes2 such as the regulation of blood pressure and core body temperature, oncogenesis, and immune function3. Melatonin is formed in the pineal gland in a light-regulated manner4 by enzymatic conversion from 5-hydroxytryptamine (5-HT or serotonin), and modulates sleep and wakefulness5 by activating two high-affinity G-protein-coupled receptors, type 1A (MT1) and type 1B (MT2)3,6. Shift work, travel, and ubiquitous artificial lighting can disrupt natural circadian rhythms; as a result, sleep disorders affect a substantial population in modern society and pose a considerable economic burden7. Over-the-counter melatonin is widely used to alleviate jet lag and as a safer alternative to benzodiazepines and other sleeping aids8,9, and is one of the most popular supplements in the United States10. Here, we present high-resolution room-temperature X-ray free electron laser (XFEL) structures of MT1 in complex with four agonists: the insomnia drug ramelteon11, two melatonin analogues, and the mixed melatonin-serotonin antidepressant agomelatine12,13. The structure of MT2 is described in an accompanying paper14. Although the MT1 and 5-HT receptors have similar endogenous ligands, and agomelatine acts on both receptors, the receptors differ markedly in the structure and composition of their ligand pockets; in MT1, access to the ligand pocket is tightly sealed from solvent by extracellular loop 2, leaving only a narrow channel between transmembrane helices IV and V that connects it to the lipid bilayer. The binding site is extremely compact, and ligands interact with MT1 mainly by strong aromatic stacking with Phe179 and auxiliary hydrogen bonds with Asn162 and Gln181. Our structures provide an unexpected example of atypical ligand entry for a non-lipid receptor, lay the molecular foundation of ligand recognition by melatonin receptors, and will facilitate the design of future tool compounds and therapeutic agents, while their comparison to 5-HT receptors yields insights into the evolution and polypharmacology of G-protein-coupled receptors.

Discovery and Manipulation of van der Waals Polarons in Sb2O3 Ultrathin Molecular Crystal.

Manipulating single electrons at the atomic scale is vital for mastering complex surface processes governed by the transfer of individual electrons. Polarons, composed of electrons stabilized by electron-phonon coupling, offer a pivotal medium for such manipulation. Here, using scanning tunneling microscopy and spectroscopy (STM/STS) and density functional theory (DFT) calculations, we report the identification and manipulation of a new type of polaron, dubbed van der Waals (vdW) polaron, within mono- to trilayer ultrathin films composed of Sb2O3 molecules that are bonded via vdW attractions. The Sb2O3 films were grown on a graphene-covered SiC(0001) substrate via molecular beam epitaxy. Unlike prior molecular polarons, STM imaging observed polarons at the interstitial sites of the molecular film, presenting unique electronic states and localized band bending. DFT calculations revealed the lowest conduction band as an intermolecular bonding state, capable of ensnaring an extra electron through locally diminished intermolecular distances, thereby forming an intermolecular vdW polaron. We also demonstrated the ability to generate, move, and erase such vdW polarons using an STM tip. Our work uncovers a new type of polaron stabilized by coupling with intermolecular vibrations where vdW interactions dominate, paving the way for designing atomic-scale electron transfer processes and enabling precise tailoring of electron-related properties and functionalities.

Safety and efficacy of sirolimus in recurrent intravenous leiomyomatosis, pulmonary benign metastatic leiomyomatosis, and leiomyomatosis peritonealis disseminata: a pilot study.

BACKGROUND: Intravenous leiomyomatosis (IVL), pulmonary benign metastatic leiomyomatosis (PBML), and leiomyomatosis peritonealis disseminata (LPD) are leiomyomas with special growth patterns and high postoperative recurrence rates. We report the safety and efficacy of a pilot study of sirolimus in the treatment of recurrent IVL, PBML, and recurrent LPD. METHODS: This was a pilot study to evaluate the safety and efficacy of sirolimus in the treatment of leiomyomatosis (ClinicalTrials.gov identifier NCT03500367) conducted in China. Patients received oral sirolimus 2 mg once a day for a maximum of 60 months or until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. The primary end point of this study was the objective response rate. Secondary end points included safety and tolerability, disease control rate, and progression-free survival. RESULTS: A total of 15 patients with leiomyomatosis were included in the study, including five with recurrent IVL, eight with PBML and two with recurrent LPD. The median follow-up time was 15 months (range 6-54 months), nine patients (60%) had treatment-related adverse events (including all levels), and two patients had treatment-related grade 3 or 4 adverse events. The objective response rate was 20.0% (95% CI, 7.1-45.2%), and the disease control rate was 86.7% (95% CI, 62.1-96.3%). Partial response was achieved in three patients. The median response time in the three partial response patients was 33 months (range 29-36 months), and the sustained remission time of these three patients reached 0, 18, and 25 months, respectively. CONCLUSIONS: Sirolimus was safe and effective in the treatment of recurrent IVL, PBML, and recurrent LPD. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03500367. Registered on 18 April 2018.

Computed Diffusion-Weighted Images of Rectal Cancer: Image Quality, Restaging, and Treatment Response after Neoadjuvant Therapy.

BACKGROUND: Computed diffusion-weighted images (cDWI) of random b value could be derived from acquired DWI (aDWI) with at least two different b values. However, its comparison between aDWI and cDWI images in locally advanced rectal cancer (LARC) patients after neoadjuvant therapy (NT) is needed. PURPOSE: To compare the cDWI and aDWI in image quality, restaging, and treatment response of LARC after NT. STUDY TYPE: Retrospective. POPULATION: Eighty-seven consecutive patients. FIELD STRENGTH/SEQUENCE: 3.0 T/DWI. ASSESSMENT: All patients underwent two DWI sequences, including conventional acquisition with b = 0 and 1000 s/mm2 (aDWIb1000 ) and another with b = 0 and 700 s/mm2 on a 3.0-T MR scanner. The images of the latter were used to compute the diffusion images with b = 1000 s/mm2 (cDWIb1000 ). Four radiologists with 3, 4, 14, and 25 years of experience evaluated the images to compare the image quality, TN restaging performance, and treatment response between aDWIb1000 and cDWIb1000 . STATISTICAL TESTS: Interclass correlation coefficients, weighted κ coefficient, paired Wilcoxon, and McNemar or Fisher test were used. A significance level of 0.05 was used. RESULTS: The cDWIb1000 images were superior to the aDWIb1000 ones in both subjective and objective image quality. In T restaging, the overall diagnostic accuracy of cDWIb1000 images was higher than that of aDWIb1000 images (57.47% vs. 49.43%, P = 0.289 for the inexperienced radiologist; 77.01% vs. 63.22%, significant for the experienced radiologist), with better sensitivity in determining ypT0-Tis tumors. Additionally, it increased the sensitivity in detecting ypT2 tumors for the inexperienced radiologist and ypT3 tumors for the experienced radiologist. N restaging and treatment response were found to be similar between two sequences for both radiologists. DATA CONCLUSION: Compared to aDWIb1000 images, the computed ones might serve as a wise approach, providing comparable or better image quality, restaging performance, and treatment response assessment for LARC after NT. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Combinational delivery of TLR4 and TLR7/8 agonist enhanced the therapeutic efficacy of immune checkpoint inhibitors to colon tumor.

Immunotherapy is regarded as a potent cancer treatment, with DC vaccines playing a crucial role. Although clinical trials have demonstrated the safety and efficacy of DC vaccines, loading antigens in vitro is challenging, and their therapeutic effects remain unpredictable. Moreover, the diverse subtypes and maturity states of DCs in the body could induce both immune responses and immune tolerance, potentially affecting the vaccine's efficacy. Hence, the optimization of DC vaccines remains imperative. Our study discovered a new therapeutic strategy by using CT26 and MC38 mouse colon cancer models, as well as LLC mouse lung cancer models. The strategy involved the synergistic activation of DCs through intertumoral administration of TLR4 agonist high-mobility group nucleosome binding protein 1 (HMGN1) and TLR7/8 agonist (R848/resiquimod), combined with intraperitoneal administration of TNFR2 immunosuppressant antibody. The experimental results indicated that the combined use of HMGN1, R848, and α-TNFR2 had no effect on LLC cold tumors. However, it was effective in eradicating CT26 and MC38 colon cancer and inducing long-term immune memory. The combination of these three drugs altered the TME and promoted an increase in anti-tumor immune components. This may provide a promising new treatment strategy for colon cancer.

A study of knowledge and acceptance of kidney xenotransplantation among Chinese kidney transplant recipients and candidates.

BACKGROUND: In recent years, the implementation of the first case of pig-to-human heart xenotransplantation and the report of three cases of pig-to-brain-dead human recipient kidney transplantation indicate that xenotransplantation is getting closer to clinical application. In the near future, China may also launch clinical trials of kidney xenotransplantation. Therefore, it is necessary to investigate the level of knowledge and acceptance of xenotransplantation among kidney transplant recipients and candidates in China. This study aims to investigate the level of comprehension and acceptance of kidney xenotransplantation in kidney transplant recipients and explore related factors, providing a reference for promoting the application and clinical trials of xenotransplantation in the near future. METHODS: A questionnaire was completed by 211 kidney transplant recipients and 21 candidates. Answers to the questionnaires were self-administered by the respondents. Scores were compared using nonparametric tests, as well as using Chi-square test or Fisher's exact test to compare differences in answers. RESULTS: Respondents demonstrated a high score of 75 (out of 100) on knowledge and acceptance of kidney xenotransplantation. The sector "Knowledge and Attitude" received the overall highest score from respondents (85.0 out of 100), while "Risks and Concerns" received the lowest score (50 out of 100). Interestingly, respondents paid more attention to infection risks but showed less concern about rejection or unknown risks. Furthermore, 191 respondents (82.3%) expected that pig kidney xenografts could function for at least 5 years or more. The scores were statistically significant in terms of age, gender, level of education, level of knowledge on the case of xenotransplantation clinical trial, and willingness to donate organs. cognition CONCLUSIONS: The awareness rates of xenotransplantation are high among kidney transplant recipients and candidates, for which the majority showed a generally favorable attitude towards this procedure. Respondents did not have a comprehensive understanding of the specific knowledge of xenotransplantation and expressed more concern about the risk of infection compared to the risk of rejection and other unknown risks, while also expecting long-term survival similar to allograft transplantation for pig kidney xenografts.

Pelvic floor muscle strength and influencing factors based on vaginal manometry among healthy women at different life stages: A multicentre cross-sectional study.

OBJECTIVE: To assess pelvic floor muscle (PFM) strength and influencing factors among healthy women at different life stages. DESIGN: Multicentre cross-sectional study. SETTING: Fourteen hospitals in China. POPULATION: A total of 5040 healthy women allocated to the following groups (with 1680 women per group): premenopausal nulliparous, premenopausal parous and postmenopausal. METHODS: The PFM strength was evaluated by vaginal manometry. Multivariate logistic regression was used to determine the influencing factors for low PFM strength. MAIN OUTCOME MEASURES: Maximum voluntary contraction pressure (MVCP). RESULTS: The median MVCP values were 36, 35 and 35 cmH2O in premenopausal nulliparous (aged 19-51 years), premenopausal parous (aged 22-61 years), and postmenopausal (aged 40-86 years) women, respectively. In the premenopausal nulliparous group, physical work (odds ratio, OR 2.05) was the risk factor for low PFM strength, which may be related to the chronic increased abdominal pressure caused by physical work. In the premenopausal parous group, the number of vaginal deliveries (OR 1.28) and diabetes (OR 2.70) were risk factors for low PFM strength, whereas sexual intercourse (<2 times per week vs. none, OR 0.55; ≥2 times per week vs. none, OR 0.56) and PFM exercise (OR 0.50) may have protective effects. In the postmenopausal group, the number of vaginal deliveries (OR 1.32) and family history of pelvic organ prolapse (POP) (OR 1.83) were risk factors for low PFM strength. CONCLUSIONS: Physical work, vaginal delivery, diabetes and a family history of POP are all risk factors for low PFM strength, whereas PFM exercises and sexual life can have a protective effect. The importance of these factors varies at different stages of a woman's life.

Outcomes of pessary fitting trials for patients with stage IV pelvic organ prolapse: a prospective study.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the efficacy of pessaries in the treatment of stage IV pelvic organ prolapse (POP) and identify the influencing factors. METHODS: One hundred and fifty-seven patients with stage IV symptomatic POP were admitted to the hospital for pessary fitting. A successful pessary fitting was defined as a patient fitted with a pessary at the initial fitting in whom use continued 2 weeks later. The rates of successful pessary fitting, patient satisfaction, remission of prolapse and urinary symptoms, and the occurrence of factors associated with successful pessary fitting were calculated and predictors of appropriate pessary type selection were analyzed. RESULTS: A total of 130 patients with stage IV POP had a successful pessary fitting (82.8%). The satisfaction rate associated with the two types of pessaries was more than 90%. The success rate among patients undergoing a ring pessary fitting trial was 44.6%, and 84.3% of the patients were self-managed. Prolapse symptoms significantly improved in 90% of cases, and urinary symptoms improved in 58-93% of cases from baseline. The number of vaginal deliveries, history of hysterectomy and vaginal introitus/total vaginal length (TVL) ratio were independent risk factors associated with unsuccessful pessary fitting. CONCLUSION: For patients with stage IV POP, the successful fitting rate is as high as 80% or more. More vaginal deliveries, a history of hysterectomy, and a larger vaginal introitus/TVL ratio (ratio >0.6) were predictors of unsuccessful pessary fitting.

Effects of family support system on the self-management behaviour of patients with T2DM: a multi-centre cross-sectional study in community settings.

BACKGROUND: The burden of type 2 diabetes mellitus (T2DM) in China continues to escalate. OBJECTIVE: To investigate the impact of family support system on the self-management behaviour of patients with T2DM. METHODS: In this cross-sectional study, 1,042 participants were sampled using a multistage stratified probability-proportionate-to-size method. On-site interviews were conducted using a structured questionnaire administered by 122 family doctors from 13 community health service centres in 8 administrative districts. A structural equation model was established to investigate the impact of individual factors and family support system on the self-management behaviour of T2DM patients. Statistical analysis was performed using the SPSS 25.0 software. RESULTS: The self-management behaviour pass rate among individuals with T2DM was 40.9%. In terms of individual factors, those with a high school education level or above demonstrated higher self-management behaviour scores than those with a junior high school education level or lower. The structural equation model revealed a path of interactions among individual factors, family support system-related factors, and the self-management behaviour of patients with T2DM: Family function → Family support → Patients' self-management behaviour → Quality of life. The coefficient of the direct path from family function to family support was 0.74 (P < 0.001), while the coefficient of the direct path from family support to self-management behaviour was 0.68 (P = 0.001). CONCLUSION: There is significant room for improvement in the self-management behaviour of T2DM patients in China. Family function can enhance the self-management behaviour of T2DM patients by promoting family support.

The neural oscillations in delta- and theta-bands contribute to divided attention in audiovisual integration.

One of key mechanisms implicated in multisensory processing is neural oscillations in distinct frequency band. Many studies explored the modulation of attention by recording the electroencephalography signals when subjects attended one modality, and ignored the other modality input. However, when attention is directed toward one modality, it may be not always possible to shut out completely inputs from a different modality. Since many situations require division of attention between audition and vision, it is imperative to investigate the neural mechanisms underlying processing of concurrent auditory and visual sensory streams. In the present study, we designed a task of audiovisual semantic discrimination, in which the subjects were asked to share attention to both auditory and visual stimuli. We explored the contribution of neural oscillations in lower-frequency to the modulation of divided attention on audiovisual integration. Our results implied that theta-band activity contributes to the early modulation of divided attention, and delta-band activity contributes to the late modulation of divided attention to audiovisual integration. Moreover, the fronto-central delta- and theta-bands activity is likely a marker of divided attention in audiovisual integration, and the neural oscillation on delta- and theta-bands is conducive to allocating attention resources to dual-tasking involving task-coordinating abilities.

Anti-TNFR2 enhanced the antitumor activity of a new HMGN1/3M-052 stimulated dendritic cell vaccine in a mouse model of colon cancer.

Immunotherapy is the new approach for cancer treatment that can be achieved through several strategies, one of which is dendritic cells (DCs) vaccine therapy. However, traditional DC vaccination lacks accurate targeting, so DC vaccine preparation needs to be optimized. Immunosuppressive CD4+Foxp3+ regulatory T cells (Tregs) in the tumor microenvironment can promote tumor immune escape. Therefore, targeting Tregs has become a strategy for tumor immunotherapy. In this study, we found that HMGN1 (N1, a dendritic cell-activating TLR4 agonist) and 3M-052 (a newly synthesized TLR7/8 agonist) synergistically stimulate DCs maturation and increase the production of proinflammatory cytokines TNFα and IL-12. In a colon cancer mice model, vaccination with N1 and 3M-052 stimulated and tumor antigen-loaded DCs combined with anti-TNFR2 inhibited tumor growth in mice, and the antitumor effect was mainly achieved through stimulation of cytotoxic CD8 T cell activation and depletion of Tregs. Overall, the combinating of DC activation by N1 and 3M-052 with inhibition of Tregs by antagonizing TNFR2 as a therapeutic strategy may represent a more effective strategy for cancer treatment.

Weighted kernels improve multi-environment genomic prediction.

Crucial to variety improvement programs is the reliable and accurate prediction of genotype's performance across environments. However, due to the impactful presence of genotype by environment (G×E) interaction that dictates how changes in expression and function of genes influence target traits in different environments, prediction performance of genomic selection (GS) using single-environment models often falls short. Furthermore, despite the successes of genome-wide association studies (GWAS), the genetic insights derived from genome-to-phenome mapping have not yet been incorporated in predictive analytics, making GS models that use Gaussian kernel primarily an estimator of genomic similarity, instead of the underlying genetics characteristics of the populations. Here, we developed a GS framework that, in addition to capturing the overall genomic relationship, can capitalize on the signal of genetic associations of the phenotypic variation as well as the genetic characteristics of the populations. The capacity of predicting the performance of populations across environments was demonstrated by an overall gain in predictability up to 31% for the winter wheat DH population. Compared to Gaussian kernels, we showed that our multi-environment weighted kernels could better leverage the significance of genetic associations and yielded a marked improvement of 4-33% in prediction accuracy for half-sib families. Furthermore, the flexibility incorporated in our Bayesian implementation provides the generalizable capacity required for predicting multiple highly genetic heterogeneous populations across environments, allowing reliable GS for genetic improvement programs that have no access to genetically uniform material.

Pulmonary benign metastasizing leiomyoma in patients aged 45 years and younger: clinical features and novelty in treatment.

BACKGROUND: Pulmonary benign metastasizing leiomyoma (PBML) is the most common extrauterine spread of uterine leiomyoma, and its biological behavior is traditionally thought to be hormone dependent. Studies on older PBML patients have been previously reported, but limited literature has been published regarding the clinical features and treatment of PBML in young women. METHODS: A total of 65 cases of PBML in women aged 45 years and younger were reviewed, including 56 cases selected from PubMed and 9 cases from our hospital. The clinical characteristics and management of these patients were analyzed. RESULTS: The median age of all the patients at diagnosis was 39.0 years. PBML most commonly presented as bilateral solid lesions (60.9%), with other rare imaging manifestations. The median interval time from a pertinent gynecologic procedure to diagnosis was 6.0 years. A total of 16.7% of patients received careful observation, and all achieved stable status in a median follow-up time of 18.0 months. A total of 71.4% of patients were administered anti-estrogen therapies, including surgical castration (33.3%), gonadotropin-releasing hormone analog (23.8%) and anti-estrogen drugs (14.3%). Eight of 42 patients underwent surgical resection of metastatic lesions. Patients who underwent curative surgery for the removal of pulmonary lesions combined with adjuvant anti-estrogen therapies had favorable outcomes compared with those who only underwent surgical resection. The disease control rates of surgical castration, gonadotropin-releasing hormone analog, and anti-estrogen drugs were 85.7%, 90.0%, and 50.0%, respectively. For two patients, sirolimus (rapamycin) achieved successful relief of symptoms and control of pulmonary lesions without lowering hormone levels and causing estrogen deficiency symptoms. CONCLUSIONS: In the absence of standard treatment guidelines for PBML, maintaining a low-estrogen environment using different kinds of antiestrogen therapies has been the mainstream strategy and has satisfying curative effects. A wait-and-see strategy might be an option, but therapeutic approaches must be contemplated when complications or symptoms progress. For PBML in young women, the negative effect on ovarian function of anti-estrogen treatment, especially surgical castration, should be considered. Sirolimus might be a new treatment option for young PBML patients, especially for those who want to preserve ovarian function.

Using a Clinical Decision Support System to Improve Anticoagulation in Patients with Nonvalve Atrial Fibrillation in China's Primary Care Settings: A Feasibility Study.

Background: To primarily investigate the effect of using a clinical decision support system (CDSS) in community health centers in Shanghai, China, on the proportion of patients prescribed guideline-directed antithrombotic therapy. This study also gauged the general practitioner (GP)'s acceptance of the CDSS who worked in the atrial fibrillation (AF) special consulting room of the CDSS group. Methods: This was a prospective cohort study that included a semistructured interview and a feasibility study for a cluster-randomized controlled trial. Eligible patients who sought medical care in the AF special consulting rooms in two community health centers in Shanghai, China, between April 1, 2020, and October 1, 2020, were enrolled, and their medical records from the enrollment date, up to October 1, 2021, were extracted. Based on whether the GPs in the AF special consulting rooms of the two sites used the CDSS or not, we classified the two sites as a software group and a control group. The CDSS could automatically assess the risks of stroke and bleeding and provide suggestions on treatment, follow-up, adjustment of anticoagulants or dosage, and other items. The primary outcome was the proportion of patients prescribed guideline-directed antithrombotic therapy. We also conducted a semistructured interview with the GP in the AF special consulting rooms of the software group regarding the acceptance of the CDSS and suggestions on the optimization of the CDSS and the study protocol of the cluster-randomized controlled trial in the future. Results: Eighty-four patients completed the follow-up. The mean age of these subjects was 75.71 years, the median time of clinical visits was six times per person, and the follow-up duration was 15 months. The basic demographics were similar between the two groups, except for age (t = 2.109, p = 0.038) and the HAS-BLED score (χ 2 = 4.363, p = 0.037). The primary outcome in the software group was 8.071 times higher than that in the control group (adjusted odds ratio (OR) = 8.071, 95% confidence interval (2.570-25.344), p < 0.001). The frequency of consultation between groups was not significantly different (p = 0.981). It seemed that the incidence of adverse clinical events in the software group was lower than that in the control group. The main reason for dropouts in both groups was "following up in other hospitals." The GP in the AF special consulting rooms of the software group accepted the CDSS well. Conclusions: The findings indicated that it was feasible to further promote the CDSS in the study among community health centers in China. The use of the CDSS might improve the proportion of patients prescribed guideline-directed antithrombotic therapy. The GP in the AF special consulting room of the software group showed a positive attitude toward the CDSS.

Abdominal pregnancy: a case report and review of 17 cases.

PURPOSE: To analyze the clinical characteristics of abdominal pregnancy, and to explore the diagnosis and prognosis of different treatment methods. METHODS: The cases of patients with abdominal pregnancy admitted to Peking Union Medical College Hospital between January 1, 1989 and January 1, 2021, were analyzed retrospectively. RESULTS: The median age of 17 patients was 34 years (22-42 years); the median gestational duration was 57 days (from 41 days to 32 weeks). Among all 17 patients, 15 (88.24%) presented with abdominal pain. The implantation sites of the gestational sac included the bladder peritoneal reflection, anterior wall of the rectum, omentum, serous membrane of the uterus, and inside or on the surface of uterosacral ligament. In all, only 29.41% cases (5/17) were diagnosed before surgery. All 17 patients were treated via surgery. Further, 58.82% (10/17) patients recovered without complications, 29.41% (5/17) developed fever, 5.88% (1/17) underwent reoperation because of intra-abdominal bleeding, and 5.88% (1/17) developed double lower limb venous thrombosis. All 17 patients survived. CONCLUSION: The preoperative diagnosis rate of abdominal pregnancy is low. Planting sites in the pelvic peritoneum and pelvic organs are more common than the others. Laparoscopic surgery in the first trimester of pregnancy can achieve better therapeutic effects. However, the blood supply of the placenta should be fully evaluated before surgery. When it is expected that attempts to remove the placenta will cause fatal bleeding, the placenta can be left in place, but long-term close follow-up should be paid attention to.