Platycodon D protects human nasal epithelial cells from pyroptosis through the Nrf2/HO-1/ROS signaling cascade in chronic rhinosinusitis.

BACKGROUND: Pyroptosis has been demonstrated being closely associated with the inflammatory progression in chronic rhinosinusitis (CRS). However, platycodon D (PLD) has emerged as a key anti-inflammatory mediator in the inflammatory progression of various respiratory diseases. This study aims at investigating whether PLD could reduce inflammatory progression of CRS by inhibiting pyroptosis. METHODS: Nasal mucosal tissues from patients with CRS and the control group (simple nasal septal deviation) were analyzed for morphological difference using hematoxylin & eosin staining and for the expression of pyroptosis-related makers by immunofluorescence (IF). Human nasal epithelial cells (HNEpCs) were cultured and co-stimulated with lipopolysaccharide (LPS)/adenosine triphosphate (ATP) to construct an in vitro cellular model simulating CRS. After pretreatment with PLD, EthD-I staining, TUNEL staining, transmission electron microscopy (TEM), and GSDMD-NT detection were performed to evaluate pyroptosis markers. The NLRP3 inflammasome was detected by IF and western blotting (WB). Reactive oxygen species (ROS) were detected by H2DCFDA staining, and mitochondrial membrane potential was evaluated by JC-1 staining. Mitochondrial morphology and structure were observed using TEM. The Nrf2/HO-1 antioxidant signaling pathway was detected using WB. RESULTS: The nasal mucosa structure of patients with CRS exhibited significant damage, with a marked increase in the expression of pyroptosis-related proteins compared with the control group. LPS/ATP co-stimulation resulted in an increased expression of IL-18 and IL-1ß in HNEpCs, causing significant damage to nuclear and cell membranes, GSDMD-NT accumulation around the cell membrane, and intracellular NLRP3 inflammasome activation. Furthermore, it led to increased ROS expression, significantly decreased mitochondrial membrane potential, and damaged mitochondrial structure. However, pretreatment with PLD significantly reversed the aforementioned trends and activated the Nrf2/HO-1 antioxidant signaling pathway. CONCLUSIONS: The results of this study confirm that NLRP3-mediated pyroptosis plays a crucial role in the pathological process of nasal mucosal impairment in patients with CRS. PLD inhibits NLRP3-mediated pyroptosis, preventing inflammatory damage in HNEpCs of patients with CRS by activating the Nrf2/HO-1 antioxidant signaling pathway, which in turn reduces ROS production and ameliorates mitochondrial damage.

The effectiveness of hysteroscopy for the treatment of cesarean scar pregnancy: a retrospective cohort study.

BACKGROUND: Cesarean scar pregnancy (CSP) is a long-term complication of cesarean section characterized by the localization of a subsequent gestational sac within the scar area or niche developed as a result of a previous cesarean section. Its incidence has increased substantially because of the high global cesarean section rate in recent decades. Several surgical and drug treatments exist for this condition; however, there is currently no optimal treatment. This study compared the effectiveness of direct hysteroscopic removal of the gestational tissue and hysteroscopy combined with vacuum suction for the treatment of CSP. METHODS: From 2017 to 2023, 521 patients were diagnosed with CSP at our hospital. Of these patients, 45 underwent hysteroscopy. Among them, 28 underwent direct hysteroscopic removal (hysteroscopic removal group) and 17 underwent hysteroscopy combined with vacuum suction (hysteroscopic suction group). The clinical characteristics and outcomes of the hysteroscopic removal group and hysteroscopic suction group were analyzed. RESULTS: Among the 45 patients, the amount of bleeding and hospitalization cost were significantly higher in the hysteroscopic removal group than in the hysteroscopic suction group (33.8 mL vs. 9.9 mL, P < 0.001; and 8744.0 yuan vs. 5473.8 yuan, P < 0.001; respectively). The operation time and duration of hospitalization were significantly longer in the hysteroscopic removal group than in the hysteroscopic suction group (61.4 min vs. 28.2 min, P < 0.001; and 3.8 days vs. 2.4 days, P = 0.026; respectively). Three patients in the hysteroscopic removal group had uterine perforation and received laparoscopic repair during operation. No complications occurred in the hysteroscopic suction group. One patient in the hysteroscopic removal group received ultrasound-guided suction curettage due to postoperative moderate vaginal bleeding, and one patient in the hysteroscopic suction group received ultrasound-guided suction curettage due to postoperative gestational residue and elevated serum beta-human chorionic gonadotropin levels. Reproductive function was preserved in all patients. CONCLUSIONS: Hysteroscopy is an effective method for treating CSP. Compared with direct hysteroscopic removal, hysteroscopy combined with vacuum suction is more suitable for CSP. However, multicenter prospective studies with large sample sizes are required for verification of these findings.

How can I help?: Specific strategies used in interpersonal emotion regulation in a relationship context.

Most emotion regulation research investigates how individuals manage their own emotions but in everyday life, emotion regulation often takes place in an interpersonal context-that is, through the intervention of others, especially close relationship partners. In this manuscript, we describe a 2-week daily diary study of 197 couples, in which we examined the nature and effectiveness of partners' attempts at interpersonal emotion regulation. Organized around the extended process model of emotion regulation (Gross, 2015), we examined the frequency and perceived effectiveness of six strategies for regulating negative emotions and two strategies for regulating positive emotions, as well as the impact of emotional regulation effectiveness on relationship satisfaction. Results indicated that situation modification was the most common approach to regulating negative emotions, whereas savoring was most common for positive emotions. Most strategies were perceived to be effective by both regulators and their targets, with the exception of suppression for negative emotion, for which evidence was mixed, and dampening for positive emotion, which was not viewed as effective. The influence of emotion regulation on relationship satisfaction depended on one's perspective: Regulators felt that their effective efforts benefitted their relationships, but even when targets experienced emotion regulation as effective, they indicated no improvements in relationship satisfaction, perhaps because the emotion-eliciting events were still salient to them. Broadly speaking, this research highlights the value of examining emotion regulation in an interpersonal context, and in the context of partners' ordinary, everyday social interaction. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Xiaoqinglong decoction improves allergic rhinitis by inhibiting NLRP3-mediated pyroptosis in BALB/C mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoqinglong decoction (XQLD), first recorded in Shang Han Lun, is a traditional Chinese medicine prescribed for the treatment of allergic rhinitis (AR). XQLD alleviates the clinical symptoms of AR by inhibiting the occurrence of an inflammatory response, but the specific regulatory mechanism remains unclear. AIM OF THE STUDY: NLRP3-mediated pyroptosis is closely related to AR pathogenesis. Hence, this study aimed to explore the potential role of NLRP3-mediated pyroptosis pathway in the AR-associated pharmacological mechanism of XQLD. MATERIALS AND METHODS: BALB/C mice models of AR was established by using ovalbumin (OVA) and aluminum hydroxide sensitization. After intragastric administration of different dosages of XQLD, nasal allergic symptoms were observed. The expression of OVA-sIgE and Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum was detected by ELISA. The histopathological morphology and expression of inflammatory factors in nasal mucosa along with pyroptosis were investigated. Molecular docking was performed to analyze the binding of representative compounds of XQLD with NLRP3. Activation of the NLRP3 inflammasome was detected by immunofluorescence and western blotting. RESULTS: XQLD significantly improved the nasal allergic symptoms of mice, reduced the degree of goblet cell proliferation, mast cell infiltration, and collagen fiber hyperplasia in nasal mucosa. Meanwhile, it could downregulate the expression of Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum and nasal mucosa. XQLD significantly reduced the number of GSDMD and TUNEL double-positive cells and IL-1ß and IL-18 expression. Molecular docking confirmed that seven representative compounds of XQLD had good binding properties with NLRP3 and were able to inhibit the activation of the NLRP3 inflammasome. CONCLUSIONS: The representative compounds of XQLD might inhibit pyroptosis in nasal mucosa mediated by the NLRP3 inflammasome to helping the recovery of AR, which provides a new modern pharmacological proof for XQLD to treat AR.

[Metabolomics of nasal lavage fluid in patients with allergic rhinitis treated by Xiaoqinglong Decoction].

This study used nasal lavage fluid for metabolomics to explore its feasibility, and applied it to the clinical metabolomics study of Xiaoqinglong Decoction in the treatment of allergic rhinitis(AR), aiming to investigate the molecular mechanism of Xiaoqing-long Decoction in the treatment of AR through differential changes in local nasal metabolism. AR patients were selected as the research subjects, and nasal lavage fluid was collected as the sample. Metabolomics analysis using liquid chromatography-mass spectrometry was performed on normal group, AR group, and Xiaoqinglong Decoction group. The differences in metabolic profiles among the groups were compared using principal component analysis and partial least squares discriminant analysis, and differential metabolites were identified and subjected to corresponding metabolic pathway analysis. The results showed that Xiaoqinglong Decoction significantly improved the symptoms of AR patients. The metabolomics analysis revealed 20 differential metabolites between AR group and Xiaoqinglong Decoction group. The core metabolite with a trending return in comparison to normal group was trimethyladipic acid. The metabolites were involved in multiple pathways, including ß-alanine metabolism, glutathione metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. The feasibility of applying nasal lavage fluid in nasal metabolomics was preliminarily demonstrated. Differential metabolites and enriched pathways in the treatment of AR patients with Xiaoqinglong Decoction were identified, indicating that it may improve rhinitis symptoms through the regulation of various metabolites, including antioxidant effects and correction of Th1/Th2 imbalance.

Interaction between ozone and paternal smoking on fetal congenital heart defects among pregnant women at high risk: a multicenter maternal-fetal medicine study.

BACKGROUND: Evidence remains limited on the association between maternal ozone (O3) exposure and congenital heart defects (CHDs) in offspring, and few studies have investigated the interaction and modification of paternal smoking on this association. METHODS: Using a sample including pregnant women at high risk of fetal CHD (with metabolic disease, first-trimester viral infection, family history of CHD, etc.) from a maternal-fetal medicine study covering 1313 referral hospitals in China during 2013-2021, we examined the associations between maternal O3 exposure during 3-8 weeks of gestational age and fetal CHD in offspring and investigated the interaction and modification of paternal smoking on this association. CHD was diagnosed by fetal echocardiograms, maximum daily 8-hour average O3 exposure data at a 10 km × 10 km spatial resolution came from the Tracking Air Pollution in China dataset, and paternal smoking was collected using questionnaires. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 27,834 pregnant women at high risk of fetal CHD, 17.4% of fetuses were diagnosed with CHD. Each 10 µg/m3 increase in maternal O3 exposure was associated with a 17% increased risk of CHD in offspring (OR = 1.17, 95% CI = 1.14-1.20). Compared with paternal nonsmoking and maternal low O3 exposure, the ORs (95% CI) of CHD for smoking and low O3 exposure, nonsmoking and high O3 exposure, and smoking and high O3 exposure were 1.25 (1.08-1.45), 1.81 (1.56-2.08), and 2.23 (1.84-2.71), respectively. Paternal smoking cessation seemingly mitigated the increased risk of CHD. CONCLUSIONS: Maternal O3 exposure and paternal smoking were interactively associated with an increased risk of fetal CHD in offspring, which calls for effective measures to decrease maternal exposure to O3 pollution and secondhand smoke for CHD prevention.

Xiao-qing-long-tang ameliorates OVA-induced allergic rhinitis by inhibiting ILC2s through the IL-33/ST2 and JAK/STAT pathways.

BACKGROUND: Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa that is mediated by immunoglobulin E (IgE). Xiao-qing-long-tang (XQLT) is a traditional Chinese medicine compound that is widely used to treat respiratory diseases such as AR. However, the underlying mechanism of the effect of XQLT on AR remains unclear. PURPOSE: To elucidate the effect of XQLT on ovalbumin (OVA)-induced AR and the mechanisms of action. METHODS: The therapeutic efficacy of XQLT was evaluated in a well-established OVA-induced AR mouse model. Nasal symptoms were analyzed, type 2 cytokines and OVA-sIgE levels were measured, nasal mucosa tissues were collected for histological analysis, and the changes of Group 2 innate lymphoid cells (ILC2s) and the IL-33/ST2 and JAK/STAT signaling pathways in the nasal mucosa were observed. RESULTS: XQLT significantly alleviated the nasal symptoms and histological damage to the nasal mucosa in AR mice, and reduced the levels of type 2 cytokines and OVA-sIgE. In addition, after XQLT treatment, the numbers of ILC2s in the nasal mucosa of AR mice were reduced, and the mRNA levels of the transcription factors GATA3 and ROR-α were decreased. Moreover, IL-33/ST2 signaling pathway was inhibited. The costimulatory cytokine associated JAK/STAT signaling pathway was also inhibited in ILC2s. CONCLUSION: Our study demonstrated that XQLT regulated ILC2s through the IL-33/ST2 and JAK/STAT pathways to ameliorate type 2 inflammation in OVA-induced AR. These findings suggest that XQLT might be used to treat AR.

Refractory and progressively worsening nasal obstruction: case report of nasal osteoblastoma and literature review.

Nasal osteoblastoma (OB) is a rare and locally aggressive osteogenic tumor that has rarely been reported, and there is a lack of effective evidence data for its diagnosis and treatment. In this study, we report a 31-year-old female patient who presented with nasal congestion and associated progressive painless swelling of the left maxillofacial region. A preoperative computed tomography (CT) examination of the paranasal sinuses was performed, and based on the imaging presentation, the surgeon was unable to differentiate between OB, osteoid osteoma (OO), fibrous dysplasia of bone (FDB) and osteoblastic fibroma (OF). After excluding contraindications to surgery, the patient underwent nasal endoscopic excision of the left nasal mass, which was found to be gravel-like and difficult to remove cleanly during the operation. The mass was brittle and bled easily, resulting in inadequate exposure of the operative field, prolonged operation time, and substantial intraoperative blood loss. This indicates that definite preoperative diagnosis (biopsy of deeper parts of the mass is recommended) and appropriate preoperative preparations (e.g., preoperative angiography and embolization, adequate blood preparation) are very important. The intraoperative frozen and postoperative pathological results clearly identified the tumor as OB. No local recurrence of the tumor was observed at the 11-month postoperative follow-up.

Alveolar ridge preservation in sockets with severe periodontal destruction using autogenous partially demineralized dentin matrix: A randomized controlled clinical trial.

BACKGROUND: The preservation and reconstruction of alveolar ridge volume in extraction sockets of molars affected by severe periodontitis is a critical challenge that requires clinical attention. PURPOSE: This randomized controlled clinical trial was designed to evaluate the efficiency of autogenous partially demineralized dentin matrix (APDDM) for alveolar ridge preservation (ARP) in severely periodontally compromised sockets compared to spontaneous healing (SH) on radiographic and histomorphometric outcomes. MATERIALS AND METHODS: Thirty-two patients with 32 periodontally compromised molars were randomized into either the test group, which received ARP using APDDM covered with a collagen sponge, or the control group, which underwent SH. Linear and volumetric changes were assessed using superimposed cone-beam computed tomography (CBCT) acquired pre-extraction and after a 4-month healing time. Histomorphometric evaluation was performed on trephine cores harvested during implant placement. RESULTS: All sites healed uneventfully. The ridge width at 1 mm apical to the bone crest increased by 5.03, 4.50, and 5.20 mm in the mesial, middle, distal area in the APDDM group, while decreasing by -1.98, -2.19, and -1.98 mm in the SH group, respectively (p < 0.05). The height increase of the central bone was significantly higher in the APDDM group than in the SH group (p < 0.05). The height decrease of the buccal (mesial, middle, distal) bone plate was lower in the APDDM group than in the SH group (p < 0.05). After a 4-month healing time, bone volume increased by 37.07% in the APDDM group and by only 2.33% in the SH group (p < 0.05). Histomorphometric analysis revealed that APDDM particles were surrounded by newly formed bone, with partially absorbed residual APDDM materials observed. New bone, APDDM remnants, and connective tissue occupied 39.67 ± 8.28%, 23.66 ± 9.22%, and 36.67 ± 17.05% of the areas in the APDDM group, respectively. CONCLUSIONS: ARP using APDDM was effective, resulting in a significant increase in both linear and volumetric changes in severely periodontally compromised extraction sockets compared to SH. These findings suggest that APDDM may serve as a promising new clinical option for the reconstruction of alveolar ridge dimensions.

Identification and Functional Evaluation of Alternative Splice Variants of Dax1 in Mouse Embryonic Stem Cells.

Dax1 (Nr0b1; Dosage-sensitive sex reversal-adrenal hypoplasia congenital on the X-chromosome gene-1) is an important component of the transcription factor network that governs pluripotency in mouse embryonic stem cells (ESCs). Functional evaluation of alternative splice variants of pluripotent transcription factors has shed additional insight on the maintenance of ESC pluripotency and self-renewal. Dax1 splice variants have not been identified and characterized in mouse ESCs. We identified 18 new transcripts of Dax1 with putative protein-coding properties and compared their protein structures with known Dax1 protein (Dax1-472). The expression pattern analysis showed that the novel isoforms were cotranscribed with Dax1-472 in mouse ESCs, but they had transcriptional heterogeneity among single cells and the subcellular localization of the encoded proteins differed. Cell function experiments indicated that Dax1-404 repressed Gata6 transcription and functionally replaced Dax1-472, while Dax1-38 and Dax1-225 partially antagonized Dax1-472 transcriptional repression. This study provided a comprehensive characterization of the Dax1 splice variants in mouse ESCs and suggested complex effects of Dax1 variants in a self-renewal regulatory network.

Parallel Genome-Wide CRISPR Screens to Identify State-Dependent Self-Renewal Regulators of Mouse Embryonic Stem Cells.

The pluripotency of embryonic stem cells (ESCs) is more accurately viewed as a continuous developmental process rather than a fixed state. However, the factors that play general or state-specific roles in regulating self-renewal in different pluripotency states remain poorly defined. In this study, parallel genome-wide CRISPR/Cas9 knockout (KO) screens were applied in ESCs cultured in the serum plus LIF (SL) and in the 2i plus LIF (2iL) conditions. The candidate genes were classified into seven groups based on their positive or negative effects on self-renewal, and whether this effect was general or state-specific for ESCs under SL and 2iL culture conditions. We characterized the expression and function of genes in these seven groups. The loss of function of novel pluripotent candidate genes Usp28, Zfp598, and Zfp296 was further evaluated in mouse ESCs. Consistent with our screen, the knockout of Usp28 promotes the proliferation of SL-ESCs and 2iL-ESCs, whereas Zfp598 is indispensable for the self-renewal of ESCs under both culture conditions. The cell phenotypes of Zfp296 KO ESCs under SL and 2iL culture conditions were different. Our work provided a valuable resource for dissecting the molecular regulation of ESC self-renewal in different pluripotency states.

Diagnosis and Treatment Strategy of Nasogenic Olfactory Dysfunction.

Since the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a symptom of the onset of SARS-CoV-2, olfactory dysfunction (OD), has attracted tremendous attention. OD is not only a negative factor for quality of life but also an independent hazard and early biomarker for various diseases, such as Parkinson's and Huntington's diseases. Therefore, early identification and treatment of OD in patients are critical. Many etiological factors are responsible for OD based on current opinions. Sniffin'Sticks are recommended to identify the initial position (central or peripheral) for OD when treating patients clinically. It is worth emphasizing that the olfactory region in nasal cavity is recognized as the primary and critical olfactory receptor. Many nasal diseases, such as those with traumatic, obstructive and inflammatory causes, can lead to OD. The key question is no refined diagnosis or treatment strategy for nasogenic OD currently. This study summarizes the differences in medical history, symptoms, auxiliary examination, treatment and prognosis of different types of nasogenic OD by analyzing the current studies. We propose using olfactory training after 4-6 weeks of initial treatment for nasogenic OD patients with no significant improvement in olfaction. We hope that our research can provide valuable clinical guidance by systematically summarizing the clinical characteristics of nasogenic OD.

A multi-omics integrative analysis based on CRISPR screens re-defines the pluripotency regulatory network in ESCs.

A comprehensive and precise definition of the pluripotency gene regulatory network (PGRN) is crucial for clarifying the regulatory mechanisms in embryonic stem cells (ESCs). Here, after a CRISPR/Cas9-based functional genomics screen and integrative analysis with other functional genomes, transcriptomes, proteomes and epigenome data, an expanded pluripotency-associated gene set is obtained, and a new PGRN with nine sub-classes is constructed. By integrating the DNA binding, epigenetic modification, chromatin conformation, and RNA expression profiles, the PGRN is resolved to six functionally independent transcriptional modules (CORE, MYC, PAF, PRC, PCGF and TBX). Spatiotemporal transcriptomics reveal activated CORE/MYC/PAF module activity and repressed PRC/PCGF/TBX module activity in both mouse ESCs (mESCs) and pluripotent cells of early embryos. Moreover, this module activity pattern is found to be shared by human ESCs (hESCs) and cancers. Thus, our results provide novel insights into elucidating the molecular basis of ESC pluripotency.

Identification and functional comparison of novel alternatively spliced isoforms of human YAP.

As a key effector of the Hippo pathway, yes-associated protein (YAP) is a major regulator of cell proliferation and apoptosis. In this study, 23 hYAP isoforms were identified in HEK293 cells, with 14 isoforms being reported for the first time. These isoforms were classified into hYAP-a and hYAP-b isoforms based on the variation in exon 1. The two groups of isoforms showed distinctly different subcellular localizations. hYAP-a isoforms could activate TEAD- or P73-mediated transcription, affect the proliferation rate, and enhance the cellular chemosensitivity of HEK293 cells. Moreover, different activation abilities and pro-cytotoxic effects were observed among hYAP-a isoforms. However, hYAP-b isoforms were not found to exert any significant biological effects. Our findings add to the knowledge of YAP gene structure and protein-coding capacity and will help in the elucidation of the function and related molecular mechanisms of the Hippo-YAP signaling pathway.

HDAC Downregulation of Xiaoqinglong Decoction in the Treatment of Allergic Rhinitis.

INTRODUCTION: As one of the most common allergic diseases, allergic rhinitis (AR) has attracted wide attention all over the world. More appropriate treatment of AR should be explored thoroughly. In recent years, traditional Chinese medicine has attracted more attention in AR treatment. As a classical Chinese medicine prescription, Xiaoqinglong decoction (XQLD) has been commonly used in treating AR. Even though its therapeutic effect on AR has been clinically confirmed, more molecular mechanism remains to be further investigated. Our research aimed to investigate the therapeutic mechanism of XQLD for AR management. METHODS: The study was evaluated in an ovalbumin sensitized mouse model and liquid chromatography-mass spectrometry was adopted to test the stability of XQLD's effective components. RESULTS: The results confirmed the stability and safety of the effective components of XQLD. XQLD significantly downregulated the expression of HDACs (HDAC1, HDAC3, and HDAC4) and Th2 inflammatory factors (IL4, IL5, and IL13) in AR mice. XQLD and the HDAC inhibitor JNJ-26481585 promoted the expression of epithelial tight junction proteins (claudin-1 and ZO-1) and decreased the expression of mucins (Muc5ac and Muc5b) in the nasal mucosa of AR mice. CONCLUSIONS: In conclusion, our findings present the beneficial effects of XQLD on AR and recovery of the nasal epithelium. We also identify the decreased HDAC as a potential target of XQLD for AR treatment. This study provides an important experimental proof for elucidating the therapeutic mechanism of XQLD.

Comparative expression analysis of TEADs and their splice variants in mouse embryonic stem cells.

Transcriptional enhanced associate domain (TEAD) transcription factors play important roles in embryonic stem cell (ESC) renewal and differentiation. Four TEAD transcription factors (Tead1, Tead2, Tead3 and Tead4) and their various splice variants have been discovered in mice, but the expression pattern of them during pluripotency state transition is unclear. Here, we investigated the expression of TEADs and their splice variants in mouse ESCs at different pluripotent/differentiating states and adult mouse tissues. Our results preliminarily revealed the diversity and heterogeneity of TEAD family, which is helpful for understanding their overlapping and distinctive functions. Furthermore, a novel splice variant of Tead1 was identified and named Tead1 isoform 4.

Risk Factors for Left Ventricular Thrombus Formation in Patients with Dilated Cardiomyopathy.

BACKGROUND: Left ventricular thrombus (LVT) is a common complication of dilated cardiomyopathy (DCM), causing morbidity and mortality. METHODS: This study retrospectively analyzed patients with DCM from January 2002 to August 2020 in Beijing Anzhen Hospital. Clinical characteristics were compared between the LVT group and the age and sex 1:4 matched with the LVT absent group. The receiver operator characteristic (ROC) curve was plotted to evaluate the diagnostic value of D-dimer predicting LVT occurrence in DCM. RESULTS: A total of 3,134 patients were screened, and LVT was detected in 72 (2.3%) patients on echocardiography. The patients with LVT had higher D-dimer, fibrinogen, and lower systolic blood pressure than those without LVT. The ejection fraction (EF) was lower and left ventricular end-systolic diameter was larger in the LVT group. Severe mitral regurgitation (MR) was more common in the LVT absent groups. The prevalence of atrial fibrillation was lower in the LVT group. The ROC curve analysis yielded an optimal cut-off value of 444 ng/mL DDU (D-dimer units) for D-dimer to predict the presence of LVT. Multivariable binary logistic regression analysis revealed that EF (OR = 0.90, 95% CI = 0.86-0.95), severe MR (OR = 0.19, 95% CI = 0.08-0.48), and D-dimer level (OR = 15.4, 95% CI = 7.58-31.4) were independently associated with LVT formation. CONCLUSION: This study suggested that elevated D-dimer levels (>444 ng/mL DDU) and reduced EF were independently associated with increased risk of LVT formation. Severe MR could decrease the incidence of LVT.

[Observation on effect of five evolutive phases and six climatic factors on pregnancy and sterility].

Objective： To verify statements about the effect of five evolutive phases and six climatic factors in 《huang di nei jing》 on pregnancy and sterility. Methods： Data of missed abortion from Nanjing Maternity and Child Health Care Hospital between 2006-2020 and Yangzhou Maternity and Child Health Care Hospital between 2012-2020 were collected. According to Chinese sexagenary cycle heavenly stems and earthly branches of each year between 2006-2020 was determined. And then based on the heavenly stems and earthly branches, evolutive phases and six climatic factors of each year were established. After that data of missed abortion in each year was compared. According to relative statements in 《huang di nei jing》 , it was observed whether the number of missed abortion cases in someone year increased significantly. Results: Totally there were 28059 cases of missed abortion from the two hospital were collected between 2006-2020 and 2012-2020 respectively. It was found that in the year of Shaoyang phase fire sitian and Jueyin wind wood in the spring (that is the year of 2010 and 2016) the number of missed abortion cases was higher obviously than the other year. When the year of Taiyang cold water in the spring (that is the year of 2009 and 2015), there was a relatively increased number of missed abortion cases. Conclusions: Five evolutive phases and six climatic factors have impacts on human pregnancy and sterility. It was an adverse condition for human reproduction in the year of Shaoyang phase fire sitian and Jueyin wind wood in the spring as well as Taiyang cold water in the spring. Until to now we can still verify statements about the effect of five evolutive phases and six climatic factors on pregnancy and sterility in 《huang di nei jing》.

[Clinical comprehensive evaluation of Jinsang Sanjie Pills/Capsules in treatment of vocal nodule/polyp of vocal cord].

This study used health technology assessment methods and multi-criteria decision analysis(MCDA) model, according to the guideline for clinical comprehensive evaluation of Chinese patent medicine, we developed this assessment tool. The comprehensive evaluation score of Jinsang Sanjie Pills/Capsules is calculated based on the additive model. This score is calculated by "quantitative evaluation software v1.0 for clinical comprehensive evaluation of Chinese patent medicines" which developed by the project team. The evaluation yielded the following results.(1)Effectiveness: compared with the control group, Jinsang Sanjie Pills/Capsules can improve the total effectiveness rate of vocal nodule/polyp of vocal cord, and improve the symptoms and signs.(2)Safety: Jinsang Sanjie Pills/Capsules did not show acute toxicity and long-term toxicity. The most common adverse reaction was gastrointestinal system damage, all of the adverse reactions were either improved or cured.(3)Economy: from the perspective of the health system, evaluating the single use or combination of Jinsang Sanjie Pills/Capsules with conventional medication in the treatment of vocal nodule/polyp of vocal cord is relatively effective and cost-effective compared to conventional medication, with a stable cost-effectiveness advantage.(4) Innovation: Jinsang Sanjie Pills/Capsules are used for the treatment of slow throat paralysis(vocal nodules, polyp of vocal cord, thickening of vocal mucosa) caused by heat toxin accumulation, Qi stagnation and blood stasis, and the resulting hoarseness. Jinsang Sanjie Pills/Capsules have good innovation and targeted indications.(5) Suitability: the investigated doctors, pharmacists and patients all believed that Jinsang Sanjie Pills/Capsules have good suitability.(6)Accessibility: Jinsang Sanjie Pills/Capsules are included in the category B of the National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance Drug Catalogue(2021 edition), which have good cost-effectiveness and affordability for medical insurance and self-paid patients. Jinsang Sanjie Pills/Capsules do not contain endangered animals and plants. The supply of raw materials can meet the demand of production at present. The comprehensive evaluation score is 76.06 points. Based on all dimensions of evidence, 71.4% experts consensus on Jinsang Sanjie Pills/Capsules is class A, which can be directly converted into decision making. This study comprehensively evaluated the clinical application value of Jinsang Sanjie Pills/Capsules in the treatment of vocal nodule/polyp of vocal cord, so as to provide evidence for their rational clinical use and regulatory decision-making.