Metabolic landscape and pathogenic insights: a comprehensive analysis of high ovarian response in infertile women undergoing in vitro fertilization.

BACKGROUND: In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis. METHODS: We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL. RESULTS: The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR. CONCLUSION: Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.

Clinical features and 1-year outcomes of variable obstruction in participants with preserved spirometry: results from the ECOPD study in China.

BACKGROUND: There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes. METHODS: Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC <0.70) were compared with those without variable obstruction (prebronchodilator FEV1/FVC ≥0.70). We performed subgroup analyses in never smokers, former and current smokers, and different variable obstruction types (postbronchodilator FVC

P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. METHODS: The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. RESULTS: P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. CONCLUSION: P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.

Two new iridoid glycosides from the whole plant of Rehmania piasezkii.

Two new iridoid glycosides, piasezkiiosides A (1) and B (2), were isolated from aqueous extract of the whole plant of Rehmannia piasezkii. Their structures were established from the spectroscopic data, chemical transformation, and X-ray diffraction analysis. Compound 1 exhibited weak hepatoprotective activity against APAP-induced HepG2 cell damage.

Association between Body Mass Index and Medication-Overuse Headache among Individuals with Migraine: A Cross-Sectional Study.

INTRODUCTION: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. METHODS: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd Edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. RESULTS: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.11; p = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤23.9 kg/m2), those with Q4 (BMI ≥28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04-3.17; p = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03-1.24), less than high school (OR, 1.08; 95%, 1.01-1.15), without depression (OR, 1.06; 95%, 1.01-1.12), and without anxiety (OR, 1.06; 95%, 1.01-1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. CONCLUSION: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.

Massage ameliorates lumbar disc herniation-related radicular pain in rats by suppressing TLR4/NLRP3 inflammasome signaling transduction.

BACKGROUND: Lumbar disc herniation (LDH) is a common spinal disease that can cause severe radicular pain. Massage, also known as Tuina in Chinese, has been indicated to exert an analgesic effect in patients with LDH. Nonetheless, the mechanism underlying this effect of massage on LDH remains unclarified. METHODS: Forty Sprague-Dawley rats were randomly divided into four groups. A rat LDH model was established by autologous nucleus pulpous (NP) implantation, followed by treatment with or without massage. A toll-like receptor 4 (TLR4) antagonist TAK-242 was administrated to rats for blocking TLR4. Behavioral tests were conducted to examine rat mechanical and thermal sensitivities. Western blotting was employed for determining TLR4 and NLRP3 inflammasome-associated protein levels in the spinal dorsal horn (SDH). Immunofluorescence staining was implemented for estimating the microglial marker Iba-1 expression in rat SDH tissue. RESULTS: NP implantation induced mechanical allodynia and thermal hyperalgesia in rat ipsilateral hindpaws and activated TLR4/NLRP3 inflammasome signaling transduction in the ipsilateral SDH. Massage therapy or TAK-242 administration relieved NP implantation-triggered pain behaviors in rats. Massage or TAK-242 hindered microglia activation and blocked TLR4/NLRP3 inflammasome activation in ipsilateral SDH of LDH rats. CONCLUSION: Massage ameliorates LDH-related radicular pain in rats by suppressing microglia activation and TLR4/NLRP3 inflammasome signaling transduction.

Tumor-infiltrating macrophage associated lncRNA signature in cutaneous melanoma: implications for diagnosis, prognosis, and immunotherapy.

Along with the increasing knowledge of long noncoding RNA, the interaction between the long noncoding RNA (lncRNA) and tumor immune infiltration is increasingly valued. However, there is a lack of understanding of correlation between regulation of specific lncRNAs and tumor-infiltrating macrophages within melanoma. In this research, a macrophage associated lncRNA signature was identified by multiple machine learning algorithms and the robust and effectiveness of signature also validated in other independent datasets. The signature contained six specific lncRNAs (PART1, LINC00968, LINC00954, LINC00944, LINC00518 and C20orf197) was constructed, which could diagnose melanoma and predict the prognosis of patients. Moreover, our signature achieves higher accuracy than the previous well-established markers and regarded as an independent prognostic indicator. The pathway enrichment revealed that these lncRNAs were closely correlated with many immune processes. In addition, the signature was associated with different immune microenvironment and applied to predict response of immune checkpoint inhibitor therapy (low risk of patients well respond to anti-PD-1 therapy and high risk is insensitive to anti-CTLA-4 therapy). Therefore, our finding supplies a more accuracy and effective lncRNA signature for tumor-infiltrating macrophages targeting treatment approaches and affords a new clinical application for predicting the response of immunotherapies in melanomas.

Long-term observation of V4c implantable collamer lenses implantation for moderate to extreme high myopia correction: five years follow-up.

BACKGROUND: This study aims to assess the long term effectiveness, safety, predictability and stability of V4c implantable collamer lenses (ICL) for correction of moderate to extreme high myopia. METHODS: We reviewed 125 eyes from 64 patients who implanted V4c ICL at the Refractive Surgery Center of West China Hospital in Chengdu, China, between May 2015 and January 2017. The median spherical equivalent was -11.50 D (interquartile range [IQR]: -13.00 to -9.00 D). We followed up with the patients over five years and evaluated several parameters, including uncorrected visual acuity (UDVA), corrected visual acuity (CDVA), axial length, refractive error, endothelial cell density (ECD), intraocular pressure (IOP), white-to-white distance (WTW), and vault. We performed a correlation analysis to explore the potential impacts on vault following implantation. RESULTS: The median safety index (postoperative CDVA/preoperative CDVA) during the last follow-up was 1.00 (interquartile range [IQR]: 1.00-1.20), and the efficacy indices (postoperative UDVA/preoperative CDVA) were 1.20 (IQR: 1.00-1.25), 1.20 (IQR: 1.00-1.33), and 0.8 (IQR: 0.65-1.00) at postoperative 1 week, 1 month, and 5 years, respectively. At the five-year mark, 16% of the eyes were within ±0.50 D of expected correction, and 73% were within ±2.00 D. No significant difference in ECD was observed between pre-operative and post-operative measurements. Compared to baseline, we observed a significant increase in IOP at the one-week follow-up, which decreased significantly at the one-month visit. Furthermore, we identified ICL size and spherical equivalent (SE) as independent variables in a multiple linear regression model that accurately predicted the five-year vault after surgery. CONCLUSION: In conclusion, V4c ICL implantation is an effective and safe treatment for moderate to extreme high myopia with good predictability and stability over the long-term.

MRI, clinical, and radiomic models for differentiation of uterine leiomyosarcoma and leiomyoma.

PURPOSE: To assess the predictive ability of conventional MRI features and MRI texture features in differentiating uterine leiomyoma (LM) from uterine leiomyosarcoma (LMS). METHODS: This single-center, IRB-approved, HIPAA-compliant retrospective study included 108 patients (69 LM, 39 LMS) who had pathology, preoperative MRI, and clinical data available at our tertiary academic institution. Two radiologists independently evaluated 14 features on preoperative MRI. Texture features based on 3D segmentation were extracted from T2W-weighted MRI (T2WI) using commercially available texture software (TexRAD™, Feedback Medical Ltd., Great Britain). MRI conventional features, and clinical and MRI texture features were compared between LM and LMS groups. Dataset was randomly divided into training (86 cases) and testing (22 cases) cohorts (8:2 ratio); training cohort was further subdivided into training and validation sets using ten-fold cross-validation. Optimal radiomics model was selected out of 90 different machine learning pipelines and five models containing different combinations of MRI, clinical, and radiomics variables. RESULTS: 12/14 MRI conventional features and 2/2 clinical features were significantly different between LM and LMS groups. MRI conventional features had moderate to excellent inter-reader agreement for all but two features. Models combining MRI conventional and clinical features (AUC 0.956) and MRI conventional, clinical, and radiomics features (AUC 0.989) had better performance compared to models containing MRI conventional features alone (AUC 0.846 and 0.890) or radiomics features alone (0.929). CONCLUSION: While multiple MRI and clinical features differed between LM and LMS groups, the model combining MRI, clinical, and radiomic features had the best predictive ability but was only marginally better than a model utilizing conventional MRI and clinical data alone.

Nomogram to predict gas-related complications during transoral endoscopic resection of upper gastrointestinal submucosal lesions: Clinical significance.

Transoral endoscopic resections in treating upper gastrointestinal submucosal lesions have the advantages of maintaining the integrity of the gastrointestinal lumen, avoiding perforation and reducing gastrointestinal fistulae. They are becoming more widely used in clinical practice, but, they may also present a variety of complications. Gas-related complications are one of the most common, which can be left untreated if the symptoms are mild, but in severe cases, they can lead to rapid changes in the respiratory and circulatory systems in a short period, which can be life-threatening. Therefore, it is important to predict the occurrence of gas-related complications early and take preventive measures actively. Based on the authors' results in the prepublication of the article "Nomogram to predict gas-related complications during transoral endoscopic resection of upper gastrointestinal submucosal lesions," and in conjunction with our evaluation and additions to the relevant content, radiographs may help screen patients at high risk for gas-related complications. Controlling blood glucose levels, shortening the duration of surgery, and choosing the most appropriate surgical resection may positively impact the prognosis of patients at high risk for gas-related complications during transoral endoscopic resection of upper gastrointestinal submucosal lesions.

Auto-segmentation of Adult-Type Diffuse Gliomas: Comparison of Transfer Learning-Based Convolutional Neural Network Model vs. Radiologists.

Segmentation of glioma is crucial for quantitative brain tumor assessment, to guide therapeutic research and clinical management, but very time-consuming. Fully automated tools for the segmentation of multi-sequence MRI are needed. We developed and pretrained a deep learning (DL) model using publicly available datasets A (n = 210) and B (n = 369) containing FLAIR, T2WI, and contrast-enhanced (CE)-T1WI. This was then fine-tuned with our institutional dataset (n = 197) containing ADC, T2WI, and CE-T1WI, manually annotated by radiologists, and split into training (n = 100) and testing (n = 97) sets. The Dice similarity coefficient (DSC) was used to compare model outputs and manual labels. A third independent radiologist assessed segmentation quality on a semi-quantitative 5-scale score. Differences in DSC between new and recurrent gliomas, and between uni or multifocal gliomas were analyzed using the Mann-Whitney test. Semi-quantitative analyses were compared using the chi-square test. We found that there was good agreement between segmentations from the fine-tuned DL model and ground truth manual segmentations (median DSC: 0.729, std-dev: 0.134). DSC was higher for newly diagnosed (0.807) than recurrent (0.698) (p < 0.001), and higher for unifocal (0.747) than multi-focal (0.613) cases (p = 0.001). Semi-quantitative scores of DL and manual segmentation were not significantly different (mean: 3.567 vs. 3.639; 93.8% vs. 97.9% scoring ≥ 3, p = 0.107). In conclusion, the proposed transfer learning DL performed similarly to human radiologists in glioma segmentation on both structural and ADC sequences. Further improvement in segmenting challenging postoperative and multifocal glioma cases is needed.

Hyperglycosylation of prosaposin in tumor dendritic cells drives immune escape.

Tumors develop strategies to evade immunity by suppressing antigen presentation. In this work, we show that prosaposin (pSAP) drives CD8 T cell-mediated tumor immunity and that its hyperglycosylation in tumor dendritic cells (DCs) leads to cancer immune escape. We found that lysosomal pSAP and its single-saposin cognates mediated disintegration of tumor cell-derived apoptotic bodies to facilitate presentation of membrane-associated antigen and T cell activation. In the tumor microenvironment, transforming growth factor-ß (TGF-ß) induced hyperglycosylation of pSAP and its subsequent secretion, which ultimately caused depletion of lysosomal saposins. pSAP hyperglycosylation was also observed in tumor-associated DCs from melanoma patients, and reconstitution with pSAP rescued activation of tumor-infiltrating T cells. Targeting DCs with recombinant pSAP triggered tumor protection and enhanced immune checkpoint therapy. Our studies demonstrate a critical function of pSAP in tumor immunity and may support its role in immunotherapy.

A new cytotoxic disaccharide glycoside from the tubers of Arisaema franchetianum.

A new disaccharide glycoside, franchoside A (1), and 17 known compounds were isolated from the tubers of Arisaema franchetianum Engler. The chemical structure of the previously undescribed compound 1 was elucidated on the basis of detailed spectroscopic analyses. Compounds 1, 2, 6, 10, 14 and 18 showed significant cytotoxic activities at varying IC50 values in the range of 4.0-10.6 µM against five cancer cell lines. Compounds 8, 10, 13 and 17 (10 µM) exhibited moderate anti-inflammatory activities by inhibiting the NF-κB signaling pathway and the release of NO from RAW264.7 macrophages induced by lipopolysaccharide (LPS), while compounds 1, 9, 14, 15 and 16 showed weak anti-inflammatory activities.

Radiomics signature based on robust features derived from diffusion data for differentiation between benign and malignant solitary pulmonary lesions.

BACKGROUND: Classifying and characterizing pulmonary lesions are critical for clinical decision-making process to identify optimal therapeutic strategies. The purpose of this study was to develop and validate a radiomics nomogram for distinguishing between benign and malignant pulmonary lesions based on robust features derived from diffusion images. MATERIAL AND METHODS: The study was conducted in two phases. In the first phase, we prospectively collected 30 patients with pulmonary nodule/mass who underwent twice EPI-DWI scans. The robustness of features between the two scans was evaluated using the concordance correlation coefficient (CCC) and dynamic range (DR). In the second phase, 139 patients who underwent pulmonary DWI were randomly divided into training and test sets in a 7:3 ratio. Maximum relevance minimum redundancy, least absolute shrinkage and selection operator, and logistic regression were used for feature selection and construction of radiomics signatures. Nomograms were established incorporating clinical features, radiomics signatures, and ADC(0, 800). The diagnostic efficiency of different models was evaluated using the area under the curve (AUC) and decision curve analysis. RESULTS: Among the features extracted from DWI and ADC images, 42.7% and 37.4% were stable (both CCC and DR ≥ 0.85). The AUCs for distinguishing pulmonary lesions in the test set for clinical model, ADC, ADC radiomics signatures, and DWI radiomics signatures were 0.694, 0.802, 0.885, and 0.767, respectively. The nomogram exhibited the best differentiation performance (AUC = 0.923). The decision curve showed that the nomogram consistently outperformed ADC value and clinical model in lesion differentiation. CONCLUSION: Our study demonstrates the robustness of radiomics features derived from lung DWI. The ADC radiomics nomogram shows superior clinical net benefits compared to conventional clinical models or ADC values alone in distinguishing solitary pulmonary lesions, offering a promising tool for noninvasive, precision diagnosis in lung cancer.

Seven new pentasaccharides from the roots of Rehmannia glutinosa.

Seven new pentasaccharides (1-7), rehmaglupentasaccharides A-G, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known verbascose (8) and stachyose (9) were also obtained in the current investigation, and the structure of stachyose was unequivocally defined using X-ray diffraction data. Compounds 1-9 were tested for their cytotoxicity against five human tumor cell lines, influence on dopamine receptor activation, and proliferation effects against Lactobacillus reuteri.

Comprehensive Analysis of TICRR in Hepatocellular Carcinoma Based on Bioinformatics Analysis.

Hepatocellular carcinoma (HCC) is one of the leading cause of cancer-associated death in the world. However, due to the complexity of HCC, it is urgent for us to find a reliable and accurate biomarker for HCC gene therapy.TopBP1-interacting checkpoint and replication regulator (TICRR), known as Treslin in vertebrate and sld3 in yeast, is involved in the tumorigenesis, progression, matastasis, diagnosis, and predicting prognosis of HCC. Disappointingly, the mechanism of TICRR expression in HCC is still not described in detail and requires further analysis. In this study, TCGA ( www.tcga-data.nci.nih.gov/tcga/ ) datasets and GEO ( www.ncbi.nlm.nih.gov/geo ) datasets were used to analyze the expression of TICRR in HCC, the relevance of TICRR mRNA expression and clinicopathological characteristics in patients with HCC, and the relationship between TICRR expression and immune infiltration level in Patients with HCC. Based on MethSurv database, the impact of TICRR in patients with HCC was investigated. In addition, GO/KEGG enrichment analysis of TICRR co-expression was performed using the R package. TICRR was found drastically highly expressed in a variety of cancer types including HCC.ROC curve analysis showed that TICRR had higher accuracy in predicting HCC compared with AFP. The expression level of TICRR was marked positively correlated with tumor stage and prognosis in Patients with HCC.GO/KEGG enrichment analysis showed that TICRR was associated with cell division and cell cycle as well as p53 signaling pathway. In addition, patients with high TICRR methylation of cg05841809, cg09403165, and cg03312532 CpG sites were significantly correlated with poor prognosis of HCC. This study demonstrated that increased TICRR expression in HCC might play an important role in the tumorigenesis, progression, diagnosis, and predicting prognosis of HCC. Therefore, TICRR might be used as a promising diagnostic and prognostic biomarker for HCC gene therapy.

Effect of GnRH agonist trigger with or without low-dose hCG on reproductive outcomes for PCOS women with freeze-all strategy: a propensity score matching study.

PURPOSE: This study aimed to compare the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone versus dual trigger comprising GnRHa and low-dose human chorionic gonadotropin (hCG) on reproductive outcomes in patients with polycystic ovary syndrome (PCOS) who received the freeze-all strategy. METHODS: A total of 615 cycles were included in this retrospective cohort study. Propensity score matching (PSM) was performed to control potential confounding factors between GnRHa-trigger group (0.2 mg GnRHa) and dual-trigger group (0.2 mg GnRHa plus 1000/2000 IU hCG) in a 1:1 ratio. Multivariate logistic regression was applied to estimate the association between trigger methods and reproductive outcomes. RESULTS: After PSM, patients with dual trigger (n = 176) had more oocytes retrieved, mature oocytes, and 2PN embryos compared to that with GnRHa trigger alone. However, the oocytes maturation rate, normal fertilization rate, and frozen embryos between the two groups were not statistically different. The incidence of ovarian hyperstimulation syndrome (OHSS) (14.8% vs. 2.8%, P < 0.001) and moderate/severe OHSS (11.4% vs. 1.7%, P < 0.001) were significantly higher in dual-trigger group than in GnRHa-alone group. Logistic regression analysis showed the adjusted odds ratio of dual trigger was 5.971 (95% confidence interval 2.201-16.198, P < 0.001) for OHSS. The pregnancy and single neonatal outcomes were comparable between the two groups (P > 0.05). CONCLUSION: For PCOS women with freeze-all strategy, GnRHa trigger alone decreased the risk of OHSS without damaging oocyte maturation and achieved satisfactory pregnancy outcomes.

Four new iridoid glycosides from the roots of Rehmannia glutinosa.

Four new iridoid glycosides (1-4), rehmaglutosides L-O, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known mellittoside (5) and ajugol (6) were also obtained in the current investigation, and the structure of mellittoside was unequivocally defined using X-ray diffraction data. Compounds 1-6 were tested for their cytotoxicity against five human tumor cell lines and proliferation effects on Lactobacillus Reuteri.

Retinitis pigmentosa with or without skeletal abnormalities due to homozygous mutations in the CWC27 gene: A case report.

RATIONALE: Retinitis pigmentosa with or without skeletal abnormalities (RPSKA) is an autosomal recessive disorder caused by mutations in the CWC27 gene. Skeletal dysplasia and non-syndromic retinitis pigmentosa are typical manifestations, and most patients present with retinopathy such as retinitis pigmentosa and limited visual field. Its clinical manifestations are complex and diverse, often involving multiple systems. Examples include short finger deformities, peculiar facial features, short stature, and neurodevelopmental abnormalities, and it is easy to misdiagnose clinically, and early diagnosis is crucial for prognosis. PATIENT CONCERNS: A 2-year and 2-month-old female child was admitted to the hospital due to "unsteady walking alone and slow reaction for more than half a year." After admission, the child was found to have delayed motor development, accompanied by special face, abnormal physical examination of the nervous system, cranial MRI Dandy-Walker malformation, considering developmental delay. DIAGNOSES: Whole exome sequencing of the family line revealed the presence of a c.617(exon7)C>A pure mutation in the CWC27 gene in the affected child (this locus has been reported in the clinical literature); the final diagnosis is RPSKA. INTERVENTIONS: Unfortunately, there is no specific drug for the disease; we give children rehabilitation training treatment. OUTCOMES: During follow-up process we found that children's condition is better than before. LESSONS SUBSECTIONS AS PER STYLE: We reported a case of RPSKA caused by mutations in the CWC27 gene. This study adds to our understanding of the clinical phenotype of TBL1XR1 mutations and provides a realistic and reliable basis for clinicians.

Insulin reverses impaired alveolar fluid clearance in ARDS by inhibiting LPS-induced autophagy and inflammatory.

Until now, acute respiratory distress syndrome (ARDS) has been a difficult clinical condition with a high mortality and morbidity rate, and is characterized by a build-up of alveolar fluid and impaired clearance. The underlying mechanism is not yet fully understood and no effective medications available. Autophagy activation is associated with ARDS caused by different pathogenic factors. It represents a new direction of prevention and treatment of ARDS to restrain autophagy to a reasonable level through pharmacological and molecular genetic methods. Na, K-ATPase is the main gradient driver of pulmonary water clearance in ARDS and could be degraded by the autophagy-lysosome pathway to affect its abundance and enzyme activity. As a normal growth hormone in human body, insulin has been widely used in clinical for a long time. To investigate the association of insulin with Na, K-ATPase, autophagy and inflammatory markers in LPS-treated C57BL/6 mice by survival assessment, proteomic analysis, histologic examination, inflammatory cell counting, myeloperoxidase, TNF-α and IL-1ß activity analysis etc. This was also verified on mouse alveolar epithelial type II (AT II) and A549 cells by transmission electron microscopy. We found that insulin restored the expression of Na, K-ATPase, inhibited the activation of autophagy and reduced the release of inflammatory factors caused by alveolar epithelial damage. The regulation mechanism of insulin on Na, K-ATPase by inhibiting autophagy function may provide new drug targets for the treatment of ARDS.