Effect of oral glucose tolerance test-based insulin resistance on embryo quality in women with/without polycystic ovary syndrome.

Objective: To explore the effects of insulin resistance (IR) on embryo quality and pregnancy outcomes in women with or without polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Methods: A retrospective cohort study concerning patients with/without PCOS who received gonadotropin-releasing hormone (GnRH)-antagonist protocol for IVF/ICSI from January 2019 to July 2022 was conducted. All the patients included underwent oral glucose tolerance test plus the assessment of insulin release within 6 months before the controlled ovarian stimulation. The Matsuda Index was calculated to diagnose IR. Two populations (PCOS and non-PCOS) were included and each was divided into IR and non-IR groups and analyzed respectively. The primary outcome was the high-quality day 3 embryo rate. Results: A total of 895 patients were included (751 with PCOS and 144 without PCOS). For patients with PCOS, the IR group had a lower high-quality day 3 embryo rate (36.8% vs. 39.7%, p=0.005) and available day 3 embryo rate (67.2% vs. 70.6%, p<0.001). For patients without PCOS, there was no significant difference between the IR and non-IR groups in high-quality day 3 embryo rate (p=0.414) and available day 3 embryo rate (p=0.560). There was no significant difference in blastocyst outcomes and pregnancy outcomes for both populations. Conclusion: Based on the diagnosis by the Matsuda Index, IR may adversely affect the day 3 embryo quality in patients with PCOS but not pregnancy outcomes. In women without PCOS, IR alone seems to have less significant adverse effects on embryo quality than in patients with PCOS. Better-designed studies are still needed to compare the differences statistically between PCOS and non-PCOS populations.

RNA editing landscape of adipose tissue in polycystic ovary syndrome provides insight into the obesity-related immune responses.

Background: Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder with wide-ranging metabolic implications, including obesity. RNA editing, a post-transcriptional modification, can fine-tune protein function and introduce heterogeneity. However, the role of RNA editing and its impact on adipose tissue function in PCOS remain poorly understood. Methods: This study aimed to comprehensively analyze RNA-editing events in abdominal and subcutaneous adipose tissue of PCOS patients and healthy controls using high-throughput whole-genome sequencing (WGS) and RNA sequencing. Results: Our results revealed that PCOS patients exhibited more RNA-editing sites, with adenosine-to-inosine (A-to-I) editing being prevalent. The expression of ADAR genes, responsible for A-to-I editing, was also higher in PCOS. Aberrant RNA-editing sites in PCOS adipose tissue was enriched in immune responses, and interleukin-12 biosynthetic process. Tumor necrosis factor (TNF) signaling, nuclear factor kappa B (NF-κB) signaling, Notch signaling, terminal uridylyl transferase 4 (TUT4), hook microtubule tethering protein 3 (HOOK3), and forkhead box O1 (FOXO1) were identified to be of significant differences. Differentially expressed genes (DEGs) in PCOS adipose tissue were enriched in immune responses compared with controls, and the DEGs between subcutaneous and abdominal adipose tissue were also enriched in immune responses suggesting the important role of subcutaneous adipose tissue. Furthermore, we identified the correlations between RNA editing levels and RNA expression levels of specific genes, such as ataxia-telangiectasia mutated (ATM) and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) in inflammation pathways and ATM, TUT4, and YTH N6-methyladenosine RNA-binding protein C2 (YTHDC2) in oocyte development pathway. Conclusions: These findings suggest that RNA-editing dysregulation in PCOS adipose tissue may contribute to inflammatory dysregulations. Understanding the interplay between RNA editing and adipose tissue function may unveil potential therapeutic targets for PCOS management. However, further research and validation are required to fully elucidate the molecular mechanisms underlying these associations.

Effects of different gonadotropin preparations in GnRH antagonist protocol for patients with polycystic ovary syndrome during IVF/ICSI: a retrospective cohort study.

Purpose: To compare the effects of recombinant FSH alfa (rFSH-alfa), rFSH-beta, highly purified human menopausal gonadotropin (HP-hMG) and urinary FSH (uFSH) in women with polycystic ovarian syndrome who have undertaken the GnRH antagonist protocol during IVF/ICSI treatment. Method: A single-center retrospective cohort study including women with PCOS who received the GnRH antagonist protocol from January 2019 to July 2022 was conducted. Patients were divided into rFSH-alfa group, HP-hMG group, uFSH group, and rFSH-beta group, and the number of oocytes retrieved, clinical pregnancy rate of the fresh cycle (primary outcomes), embryo quality, and severe OHSS rate (secondary outcomes) were compared. Results: No statistical differences were found among the four groups in fresh cycle clinical pregnancy rate (p=0.426), nor in the subgroup analyses. The HP-hMG group had a smaller number of oocytes retrieved and a higher high-quality D3 embryo rate than the three FSH groups (p<0.05). No statistical differences were found among the four groups in the severe OHSS rate (p=0.083). Conclusion: For women with PCOS undergoing the GnRH antagonist protocol, the clinical pregnancy rates of fresh IVF/ICSI-ET cycle are similar for all four types of Gn. With a lower risk of OHSS and a similar number of high-quality and available embryos, HP-hMG may have an advantage in the PCOS population.

Single-cell transcriptome analyses reveal disturbed decidual homoeostasis in obstetric antiphospholipid syndrome.

OBJECTIVES: Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies in circulation and pathological pregnancy. However, the pathogenesis of OAPS remains unknown. We aimed to reveal cellular compositions and molecular features of decidual cells involved in the development of OAPS using single-cell RNA sequencing (scRNA-seq). METHODS: We performed unbiased scRNA-seq analysis on the first-trimester decidua from five OAPS patients and five healthy controls (HCs), followed by validations with flow cytometry, immunohistochemical staining and immunofluorescence in a larger cohort. Serum chemokines and cytokines were measured by using ELISA. RESULTS: A higher ratio of macrophages but a lower ratio of decidual natural killer (dNK) cells was found in decidua from OAPS compared with HCs. Vascular endothelial cells shrinked in OAPS decidua while having upregulated chemokine expression and conspicuous responses to IFN-γ and TNF-α. Macrophages in OAPS had stronger phagocytosis function, complement activation signals and relied more on glycolysis. dNK cells were more activated in OAPS and had enhanced cytotoxicity and IFN-γ production. Downregulation of granules in OAPS dNK cells could be associated with suppressed glycolysis. Moreover, stromal cells had a prosenescent state with weakened immune surveillance for senescent cells in OAPS. In addition, the cellular interactions between decidual immune cells and those of immune cells with non-immune cells under disease state were altered, especially through chemokines, IFN-γ and TNF-α. CONCLUSION: This study provided a comprehensive decidual cell landscape and identified aberrant decidual microenvironment in OAPS, providing some potential therapeutic targets for this disease.

Rhizopus oryzae causes the leaf rot disease of Epimedium sagittatum in Guizhou, China.

Epimedium sagittatum is a collective term for herbaceous plants belonging to the family Berberidaceae. Their dried leaves and stems have significant therapeutic effects on tumor inhibition, hypertension control, and coronary heart disease (Ke et al. 2023; Zhao et al. 2019). In 2021 and 2022, plants with similar leaf rot symptoms ranging from 30% to 55% was observed on E. sagittatum in Congjiang County, Guizhou province. The initial symptoms of the disease manifest locally on the leaf, with yellowing on the surface edge of the affected tissue, browning in the middle part, and brown-white discoloration in the innermost part (Supplementary Figure S1B). As the disease progresses, the entire infected leaf gradually softens, while the veins remain intact (Supplementary Figure S1C). Ultimately, the leaf withers and dehisces. The nine samples with typical symptoms were collected from Congjiang County, Guizhou province (26.598°N, 106.707°E). Twenty-seven fungi were isolated, including ten isolates of Rhizopus and seventeen isolates of seven other genera. On isolate YYH-CJ-17 many sporangia were formed and turned to a brown-gray to black color on potato dextrose agar medium (PDA) after culturing 5 days under dark at 25 ℃ (Supplementary Figure S2A and S2B). The branches of mycelium were finger-shaped or root-shaped. The sporangium was spherical or nearly spherical, 60-250 µm in diameter, and sporangiospores were elliptical or spherical and 4-8 µm in diameter. The obtained 547 bp ITS fragment (accession OR225970) and 1231 bp EF-1α region (accession OR242258) from isolate YYH-CJ-17 were compared with NR database using the BLAST tool provided by NCBI, which revealed more than 99.5% identity (query cover more than 98%) with the sequences of ITS (accessions MF522822.1) and EF-1α (accession AB281541.1) of Rhizopus oryzae Went & H.C. Prinsen Geerlings (Gao et al. 2022; Zhang et al. 2022). The phylogenetic tree constructed with the ITS and EF-1α gene sequences demonstrates that strain YYH-CJ-17 clusters with R. oryzae in the same branch and the bootstrap value was greater than 99% (Supplementary Figure S3). Based on the morphological characteristics and ITS and EF-1a sequences, the isolate YYH-CJ-17 is identified as R. oryzae. Pathogenicity tests were performed on detached healthy leaves and living plants of E. sagittatum. Healthy leaves of E. sagittatum were subjected to inoculation with isolate YYH-CJ-17 with 5 × 105 CFU mL-1 concentration in sterile culture dishes. The progression of the disease was marked by the gradual softening of the infected leaves and the expansion of the lesions, which ultimately produced black-brown sporangium (Supplementary Figure S4A). Furthermore, the E. sagittatum living plants were sprayed with 5 × 105 CFU mL-1 conidial suspension of isolate YYH-CJ-17, with ddH2O as a negative control, and then were cultivated at 25℃ and 90% humidity for 21 days in the greenhouse. This assay found that the E. sagittatum leaves treated with isolate YYH-CJ-17 exhibited the same symptoms observed on plants in fields (Supplementary Figure S4B). The fungus re-isolated from the inoculated leaves were identified as R. oryzae by ITS sequencing and were blasted with NR database, which highest matched with the sequence of ITS (accessions MF522822.1) mentioned above, thus fulfilling Koch's postulates. R. oryzae has been identified as a causative agent of a diverse array of host diseases, including leaf mildew of tobacco, fruit rot of yellow oleander and pears, and soft rot of bananas (Farooq et al. 2017; Khokhar et al. 2019; Kwon et al. 2012; Pan et al. 2021). To the best of our knowledge, this is the first report of leaf rot on E. sagittatum caused by R. oryzae in China, which will provide clear prevention and management target for the leaf rot disease of E. sagittatum.

Cluster analysis reveals a homogeneous subgroup of PCOS women with metabolic disturbance associated with adverse reproductive outcomes.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a heterogeneous and complex reproductive endocrinological disease that could lead to infertility. There were many attempts to classify PCOS but it remains unclear whether there is a specific subgroup of PCOS that is associated with the best or worst reproductive outcomes of assisted reproductive techniques (ART). METHODS: Infertile PCOS patients who underwent their first cycle of in vitro fertilization (IVF) in West China Second University Hospital, Sichuan University from January 2019 to December 2021 were included. Basic clinical and laboratory information of each individual were extracted. Unsupervised cluster analysis was performed. Controlled ovarian stimulation parameters and reproductive outcomes were collected and compared between the different clusters of PCOS. RESULTS: Our analysis clustered women with PCOS into "reproductive", "metabolic", and "balanced" clusters based on nine traits. Reproductive group was characterized by high levels of testosterone (T), sex hormone-binding globulin (SHBG), follicular stimulation hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH). Metabolic group was characterized by high levels of body mass index (BMI), fasting insulin, and fasting glucose. Balanced group was characterized by low levels of the aforementioned reproductive and metabolic parameters, except for SHBG. Compared with PCOS patients in reproductive and balanced clusters, those in metabolic cluster had lower rates of good quality day 3 embryo and blastocyst formation. Moreover, PCOS patients in the reproductive cluster had greater fresh embryo transfer (ET) cancelation rate and clinical pregnancy rate after fresh ET than metabolic cluster (odds ratio [OR] = 3.37, 95% confidence interval [CI]: 1.77-6.44, and OR = 6.19, 95% CI: 1.58-24.24, respectively). And compared with PCOS of metabolic cluster, PCOS of balanced cluster also had higher chance for fresh ET cancelation (OR = 2.83, 95% CI: 1.26-6.35). CONCLUSION: Our study suggested that PCOS patients in metabolic cluster may be associated with adverse reproductive outcomes and might need individualized treatment and careful monitoring before and during ART.

Associations between vaginal microbiota and endometrial polypoid lesions in women of reproductive age: a cross-sectional study.

RESEARCH QUESTION: What are the different characteristics of vaginal microbial composition between patients with endometrial polypoid lesions and controls? DESIGN: This cohort study compared the pre-operative microbial compositions of vaginal samples in a cohort of 703 women with endometrial polypoid lesions [293 and 410 women diagnosed and not diagnosed with polyps pathologically (polyps group and not-polyps group, respectively] and 703 women in the control group. Bacterial abundance, diversity, differential taxa and microbial network structure were assessed using 16S rRNA gene sequencing. Predictive algorithms were used to determine the functional pathways of vaginal microbiota within the cohort. RESULTS: The control group exhibited higher relative abundance of Lactobacillus crispatus in comparison with the polypoid lesions group (P = 0.0427). Beta diversity of vaginal microbiota differed significantly between the groups (P < 0.05). Comparing the polyps group with the not-polyps group, Leptotrichia spp. and Cutibacterium spp. were more abundant in the polyps group, and Fannyhessea spp., Acinetobacter spp. and Achromobacter spp. were more abundant in the not-polyps group. The control group exhibited higher abundance of Bifidobacterium spp., Achromobacter spp. and Escherichia/Shigella spp. (false discovery rate < 0.05). Furthermore, the polyps group and not-polyps group displayed more complex co-occurrence networks compared with the control group. CONCLUSIONS: The results of this study provide compelling evidence supporting associations between vaginal microbiota and endometrial polypoid lesions, highlighting the potential relationship between a well-balanced vaginal microbial ecosystem and a healthy intrauterine environment.

Sugarcane streak mosaic virus P1 protein inhibits unfolded protein response through direct suppression of bZIP60U splicing.

The unfolded protein response (UPR) is a cell-designated strategy that maintains the balance of protein folding in the endoplasmic reticulum (ER). UPR features a network of signal transduction pathways that reprogram the transcription, mRNA translation, and protein post-translational modification to relieve the ER stresses from unfolded/misfolded proteins. Infection with plant viruses can induce the UPR, and activated UPR often promotes plant viral infections in turn. However, the mechanism used by plant viruses to balance UPR and achieve robust infection remain largely unknown. In this study, P1SCSMV was identified as a virus-encoded RNA silencing suppressor (VSR). Heterologous overexpression of P1SCSMV via potato virus X (PVX) was found lead to programmed cell death (PCD) in Nicotiana benthamiana. Furthermore, P1SCSMV was also found to inhibit the PVX infection-triggered UPR by downregulating UPR-related genes and directly induced the distortion and collapse of the ER polygonal meshes on PVX-P1SCSMV infected N. benthamiana. Moreover, self-interaction, VSR activity, UPR inhibition, and cell death phenotype of P1SCSMV were also found to be dependent on its bipartite nuclear localization signal (NLS) (251RKRKLFPRIPLK262). P1SCSMV was found to directly bind to the stem-loop region of NbbZIP60U via its NLS and inhibit the UPR pathways, ultimately resulting in a PCD phenotype in PVX-P1SCSMV infected N. benthamiana leaves. This study also revealed the balancing role of potyviruses encoded P1SCSMV in the UPR pathway to achieve robust viral infection. This may represent a novel virulence strategy for plant viruses.

A randomized clinical study on the efficacy of vonoprazan combined with amoxicillin duo regimen for the eradication of Helicobacter pylori.

BACKGROUND: Helicobacter pylori (H pylori) can cause gastritis, peptic ulcers, gastric cancer, and many other gastrointestinal diseases. The 14-day neo-dual therapy for H pylori is considered by most countries to have good eradication rates, while the 7- and 10-day studies have been more widely explored, however, we find that their results are different. The applicability of the shorter and less expensive 10-day neo-dual therapy to our country has not yet been confirmed. METHODS: The patients were divided into 3 groups of 200 each by randomization method. Group A: patients received vonoprazan 20 mg, bid + amoxicillin(1 g), tid, for 14 days. Group B: vonoprazan (20 mg) bid + amoxicillin (1 g) tid, duration of treatment is 10 days, group C: rabeprazole (20 mg) bid + bismuth potassium citrate tablets/tinidazole tablets/clarithromycin tablets, combined package (4.2 g), bid, duration of treatment 14 days. The main comparisons were H pylori eradication rate, adverse drug reaction profile and cost-effect ratio in each group. RESULTS: The eradication rates of groups A, B, and C were 92.5%, 91.6%, and 80.1%, respectively. There was no significant difference in the eradication rates of groups A and B (P > .05), groups A and B had statistically significantly better eradication rates than group C (P < .05). The incidence of adverse reactions in groups A, B, and C was 9.5%, 8.5%, and 17.0%, respectively. There was no difference in the incidence of adverse reactions between A and B: (P > .05), The incidence of adverse reactions was statistically significantly lower in groups A and B than in group C (P < .05). Logistic regression analysis showed nonsmokers had a higher eradication rate (OR 2.587, 95% CI: 1.377-4.859, P = .003), and taller patients were more likely to have successful eradication (OR 1.052, 95% CI: 1.008-1.097, P = .020). Group B had the lowest cost-benefit analysis results. CONCLUSION: Group B had an acceptable eradication rate, the lowest incidence of adverse effects, and the lowest cost analysis. Eradication is more likely to be successful in patients who do not smoke and in those who are taller.

Development and validation of a prognostic nomogram for predicting cancer-specific survival in lymph node-negative elderly esophageal cancer patients: A SEER-based study.

In this study, we explored the prognostic risk factors of elderly patients (≥65 years old) with lymph node-negative esophageal cancer (EC) and established a nomogram to evaluate the cancer-specific survival of patients. The surveillance, epidemiology, and end results database was used to collect data on patients diagnosed with EC. Univariate and multivariate Cox analyses were used to determine independent prognostic factors, and the nomogram for predicting cancer-specific survival of EC patients was constructed based on the independent prognostic factors obtained from the multivariate Cox analysis. To evaluate the predictive ability of the nomogram, calibration curves, concordance index (C-index), receiver operating characteristic curves, and decision curve analysis were conducted. Kaplan-Meier method was used to analyze the long-term outcomes of EC patients with different risk stratifications. A total of 3050 cases with lymph node-negative EC were randomized into the training cohort (1525) and the validation cohort (1525). Cancer-specific mortality at 1, 3, and 5 years in the entire cohort was 30.7%, 41.8%, and 59.2%, respectively. In multivariate Cox analysis, age (P < .001), marital status (P < .001), tumor size (P < .001), Tumor-node-metastasis stage (P < .001), chemotherapy (P = .011), radiotherapy (P < .001), and surgery (P < .001) were independent prognostic factors. The C-index for the training cohort was 0.740 (95% confidence interval [CI]: 0.722-0.758), and the C-index for the validation cohort was 0.738 (95% CI: 0.722-0.754). The calibration curve demonstrated the great calibration ability of the nomogram. Based on the area under the receiver operating characteristic curve, the nomogram demonstrated a higher sensitivity than the tumor-node-metastasis stage. Decision curve analysis showed the good clinical utility of the nomogram. The risk stratification system was established using the Kaplan-Meier curve and verified by the log-rank test (P < .001). The nomogram and risk stratification system can improve the accuracy of prediction to help clinicians identify high-risk patients and make treatment decisions.

Prognostic impact of metastatic patterns and treatment modalities on overall survival in lung squamous cell carcinoma: A population-based study.

This study aimed to investigate the impact of distinct metastasis patterns on the overall survival (OS) of individuals diagnosed with organ metastatic lung squamous cell carcinoma (LUSC). OS was calculated using the Kaplan-Meier method, and univariate and multivariate Cox regression analyses were conducted to further assess prognostic factors. A total of 36,025 cases meeting the specified criteria were extracted from the Surveillance, Epidemiology, and End Results database. Among these patients, 30.60% (11,023/36,025) were initially diagnosed at stage IV, and 22.03% (7936/36,025) of these individuals exhibited metastasis in at least 1 organ, including the liver, bone, lung, and brain. Among the 4 types of single metastasis, patients with bone metastasis had the lowest mean OS, at 9.438 months (95% CI: 8.684-10.192). Furthermore, among patients with dual-organ metastases, those with both brain and liver metastases had the shortest mean OS, at 5.523 months (95% CI: 3.762-7.285). Multivariate Cox regression analysis revealed that metastatic site is an independent prognostic factor for OS in patients with single and dual-organ metastases. Chemotherapy was beneficial for patients with single and multiple-organ metastases; although surgery was advantageous for those with single and dual-organ metastases, it did not affect the long-term prognosis of patients with triple organ metastases. Radiotherapy only conferred benefits to patients with single-organ metastasis. LUSC patients exhibit a high incidence of metastasis at the time of initial diagnosis, with significant differences in long-term survival among patients with different patterns of metastasis. Among single-organ metastasis cases, lung metastasis is the most frequent and is associated with the longest mean OS. Regarding treatment options, patients with single-organ metastasis can benefit from chemotherapy, surgery, and radiotherapy, and those with metastasis in 2 organs can benefit from chemotherapy and surgery. Patients with metastasis in more than 2 organs, however, can only benefit from chemotherapy. Understanding the variations in metastasis patterns assists in guiding pretreatment assessments and in determining appropriate therapeutic interventions for LUSC.

Comparative analysis of the vaginal microbiome of healthy and polycystic ovary syndrome women: a large cross-sectional study.

RESEARCH QUESTION: What are the different features of the vaginal microbiome (VMB) between patients with polycystic ovary syndrome (PCOS) and healthy women? DESIGN: A cross-sectional study was conducted at a single academic university-affiliated centre. A total of 1446 participants were recruited (PCOS group, n =713, control group, n = 733). Vaginal swabs were analysed using 16S rRNA gene sequencing. The diversity and composition of the microbiome were compared between the PCOS group and the control group. Microbial interaction networks and functional prediction were investigated. RESULTS: The PCOS group had a higher alpha diversity than the control group (Shannon P = 0.03, Simpson P = 0.02), and higher intra-group variability was observed in PCOS group (P < 2.2E-16). At the genus level, the proportion of Lactobacillus decreased (85.1% versus 89.3%, false discovery rate [FDR] = 0.02), whereas the proportion of Gardnerella vaginalis and Ureaplasma increased in the PCOS group (5.1% versus 3.3%, FDR = 0.006; 1.2% versus 0.6%, FDR = 0.002, respectively). Lactobacillus acidophilus, Prevotella buccalis and G. vaginalis were identified as the main differential species. L. acidophilus was positively correlated with serum levels of anti-Müllerian hormone (AMH), and triglyceride (P = 2.01E-05, P = 0.004, respectively). P. buccalis was negatively correlated with serum levels of AMH and testosterone (P = 0.002, P = 0.003, respectively). G. vaginalis was positively correlated with serum levels of AMH, oestradiol and progesterone (P = 0.004, P = 0.005, P = 0.03, respectively). The VMB interaction network indicated that Lactobacillus crispus, Prevotella timonensis, and P. buccalis could be key drivers in the PCOS group. Overall, 55 predicted genes were found to be differentially abundant between PCOS and the control (FDRs < 0.25). CONCLUSIONS: The PCOS group had a higher diversity of vaginal microbiome and showed an enhanced level of heterogeneity. The proportion of Lactobacillus in the PCOS group decreased, whereas the proportions of Gardnerella and Ureaplasma increased. These results warrant further research that can validate the correlation between PCOS and VMB.

Primary Skull Base Chordomas: A Clinicopathological Analysis of 94 Patients.

OBJECTIVE: To investigate prognostic factors in patients with primary skull base chordoma (PSBC) to guide future therapeutic advances. METHODS: This retrospective cohort study of 94 PSBC patients was conducted in 2 institutions from January 2006 to December 2013. Independent predictors for progression-free survival (PFS) and overall survival were established with multivariate Cox regression analysis. RESULTS: Age (P = 0.006), extent of resection (P = 0.037), and radiotherapy (RT) (P = 0.027) were established as independent predictors for PFS in PSBC patients. Similarly, age (P = 0.002), extent of resection (P = 0.048), and RT (P = 0.015) were established as independent predictors for overall survival. Meta-analysis manifested that lower MIB-1 correlated with longer PFS in skull base chordoma patients (P < 0.001). RT doubled the 5-year PFS rate from 28.6 ± 12.1% to 61.6 ± 10.7% (P = 0.031) and increased the 5-year overall survival rate from 54.5 ± 13.8% to 84.2 ± 8.4% (P = 0.020) in the subtotal resection/partial resection and MIB-1 labeling index (STR/PR+MIB-1 LI) <2% subgroup. In contrast, in the STR/PR+MIB-1 LI ≥2% subgroup, the survival benefit of RT remained uncertain. Further analysis revealed no survival difference between different RT modalities in STR/PR PSBC patients. CONCLUSIONS: In PSBC patients, age, extent of resection, and adjuvant RT all are independent predictors for PFS. Lower MIB-1 LI is associated with longer PFS in PSBC patients. Adjuvant RT is necessary for PSBC patients who undergo STR/PR with MIB-1 LI <2%. Patients who undergo GTR or STR/PR with MIB-1 LI ≥2% seem nonresponsive to RT.

The homeostasis model assessment of insulin resistance is a judgment criterion for metformin pre-treatment before IVF/ICSI and embryo transfer cycles in patients with polycystic ovarian syndrome.

Purpose: The aim of this study was to explore the value of the homeostasis model assessment of IR (HOMA-IR) as a judgment criterion for metformin pre-treatment before in vitro fertilization/intracellular sperm injection (IVF/ICSI) and embryo transfer (ET) for polycystic ovarian syndrome (PCOS) patients. Materials and methods: The clinical and laboratory information of PCOS patients who received IVF/ICSI-ET from January 2017 to September 2021 was retrospectively analyzed. We compared the clinical pregnancy rate (primary outcome) and controlled ovarian stimulation (COS)-related parameters (secondary outcomes) between patients with and without metformin pre-treatment for all PCOS patients not grouped by HOMA-IR, PCOS patients with HOMA-IR < 2.71, and PCOS patients with HOMA-IR ≥ 2.71. Results: A total of 969 PCOS patients who received the GnRH-antagonist protocol were included in this study. For all PCOS patients, the metformin group showed comparable clinical pregnancy rates in fresh ET cycles and frozen ET cycles compared with the control group (55.9% vs. 57.1%, p = 0.821 and 63.8% vs. 60.9%, p = 0.497). For PCOS patients with HOMA-IR < 2.71, the clinical pregnancy rates in both fresh ET cycles and frozen ET cycles were statistically similar between the two groups (61.5% vs. 57.6%, p = 0.658 and 70.6% vs. 66.7%, p = 0.535). For PCOS patients with HOMA-IR ≥ 2.71, the clinical pregnancy rate in fresh ET cycles was comparable between the two groups (51.5% vs. 56.3, p = 0.590), but it was statistically higher in the metformin group than in the control group in frozen ET cycles (57.1% vs. 40.0%, p = 0.023). The metformin group had less oocytes retrieved, a lower cleaved oocyte rate, a lower available D3 embryo rate, a lower blastocyst formation rate, and a lower available blastocyst rate than the control group. Conclusion: HOMA-IR is a judgment criterion for metformin pre-treatment before IVF/ICSI-ET in patients with PCOS. Metformin pre-treatment could be added for PCOS patients with HOMA-IR ≥ 2.71 during frozen IVF/ICSI-ET cycles to improve the clinical pregnancy rate.

High-throughput precision MRI assessment with integrated stack-ensemble deep learning can enhance the preoperative prediction of prostate cancer Gleason grade.

BACKGROUND: To develop and test a Prostate Imaging Stratification Risk (PRISK) tool for precisely assessing the International Society of Urological Pathology Gleason grade (ISUP-GG) of prostate cancer (PCa). METHODS: This study included 1442 patients with prostate biopsy from two centres (training, n = 672; internal test, n = 231 and external test, n = 539). PRISK is designed to classify ISUP-GG 0 (benign), ISUP-GG 1, ISUP-GG 2, ISUP-GG 3 and ISUP GG 4/5. Clinical indicators and high-throughput MRI features of PCa were integrated and modelled with hybrid stacked-ensemble learning algorithms. RESULTS: PRISK achieved a macro area-under-curve of 0.783, 0.798 and 0.762 for the classification of ISUP-GGs in training, internal and external test data. Permitting error ±1 in grading ISUP-GGs, the overall accuracy of PRISK is nearly comparable to invasive biopsy (train: 85.1% vs 88.7%; internal test: 85.1% vs 90.4%; external test: 90.4% vs 94.2%). PSA ≥ 20 ng/ml (odds ratio [OR], 1.58; p = 0.001) and PRISK ≥ GG 3 (OR, 1.45; p = 0.005) were two independent predictors of biochemical recurrence (BCR)-free survival, with a C-index of 0.76 (95% CI, 0.73-0.79) for BCR-free survival prediction. CONCLUSIONS: PRISK might offer a potential alternative to non-invasively assess ISUP-GG of PCa.

Risk factors for the development of lung cancer among never smokers: A systematic review.

This review aimed to summarize the up-to-date evidence on non-genetic factors for the development of never smoking lung cancer (NSLC) and to explore reasons behind the conflicting results. Relevant literature was searched in three electronic databases (PubMed, Embase and Web of Science) from 1 January 2000-31 July 2022. Cohort studies that investigated non-genetic risk factors for primary lung cancer in never smokers were included. The effect of non-genetic factors about NSLC were summarized with pooled relative risk (RR) and 95 % confidence intervals (CIs) through meta-analysis or narrative description when unexplained statistical heterogeneity was observed. The Newcastle-Ottawa Scale was used to appraise the methodological quality of included studies. Sixty cohort studies were included, covering population from Asia, Europe and America. Most included studies (42, 70.0 %) were of high methodological quality. Over 50 years old (RR = 5.26), environmental tobacco smoke (Pooled RR = 1.30), Chronic obstructive pulmonary disease (COPD) (RR = 2.67), family history of lung cancer (Pooled RR = 1.83) and higher level of neutrophil-lymphocyte ratio (RR = 1.73) increased the risk of NSLC. Dairy foods consumption (RR = 0.79), isoflavone intake (Pooled RR = 0.65), and riboflavin intake (RR = 0.62) decreased the risk among female population. Inconsistency or unclear definition for never smokers and risk factors could be observed in included studies. Most life behavior factors associated with NSLC can be modified through lifestyle changes. Future cohort studies are suggested to adopt a clearer definition on never smokers and exposure, conducting subgroup analysis when evidence indicating there is heterogeneity between genders, and explore dose-response relationship between the identified factors and NSLC.

Sugarcane Streak Mosaic Virus P1 Attenuates Plant Antiviral Immunity and Enhances Potato Virus X Infection in Nicotiana benthamiana.

The sugarcane streak mosaic virus (SCSMV) is the most important disease in sugarcane produced in southern China. The SCSMV encoded protein 1 (P1SCSMV) is important in disease development, but little is known about its detailed functions in plant-virus interactions. Here, the differential accumulated proteins (DAPs) were identified in the heterologous expression of P1SCSMV via a potato virus X (PVX)-based expression system, using a newly developed four-dimensional proteomics approach. The data were evaluated for credibility and reliability using qRT-RCR and Western blot analyses. The physiological response caused by host factors that directly interacted with the PVX-encoded proteins was more pronounced for enhancing the PVX accumulation and pathogenesis in Nicotiana benthamiana. P1SCSMV reduced photosynthesis by damaging the photosystem II (PSII). Overall, P1SCSMV promotes changes in the physiological status of its host by up- or downregulating the expression of host factors that directly interact with the viral proteins. This creates optimal conditions for PVX replication and movement, thereby enhancing its accumulation levels and pathogenesis. Our investigation is the first to supply detailed evidence of the pathogenesis-enhancing role of P1SCSMV, which provides a deeper understanding of the mechanisms behind virus-host interactions.

The Essential Role of Body Weight in Adjusting Gn Dosage to Prevent High Ovarian Response for Women With PCOS During IVF: A Retrospective Study.

Polycystic ovarian syndrome (PCOS) is the major cause of anovulatory infertility. Since women with PCOS are often accompanied by increased body weight and hyper response to controlled ovarian stimulation, individualized gonadotropin (Gn) dose is required to achieve a therapeutic effect while minimizing the risk of ovarian hyperstimulation simultaneously. We aimed to investigate the essential role of body weight in optimizing initial Gn dosage for PCOS patients during in vitro fertilization (IVF). We retrospectively included 409 infertile PCOS patients who used gonadotropin-releasing hormone (GnRH)-antagonist fixed protocol and underwent their first cycle of IVF in West China Second University Hospital from January 2019 to June 2021. Baseline characteristics controlled ovarian stimulation parameters, and reproductive outcomes were compared between patients with different body weights and different ovarian responses. Multivariable linear regression analyses were adopted to investigate the relationship between body weight and initial Gn dosage. Receiver operating characteristic (ROC) curves were drawn to find the optimal cut-off value of body weight in predicting the starting Gn dosage so as to prevent high ovarian response (HOR). We found that luteinizing hormone (LH) level and Anti-Mullerian hormone (AMH) level were lowest in the group with body weight over 70 kg and was highest in the group with body weight less than 50 kg. Increased body weight was significantly correlated to the rise of initial Gn dosage (Beta = 0.399, t = 8.921, p < 0.001). Normal ovarian response (NOR) patients had significantly less fresh cycle cancel rate and ovarian hyperstimulation syndrome (OHSS) rate which outweighed the fewer embryos compared with HOR patients. Using ROC curves, 53.25 kg (sensitivity, 84.2%; specificity, 53.8%) and 70.5 kg (sensitivity, 58.8%; specificity, 93.0%) were identified as the optimal cut-off values to predict the initial Gn dosage of no more than 150 IU and 225 IU, respectively. In conclusion, adjusting the initial Gn dosage based on body weight is crucial to preventing ovarian hyperstimulation while not influencing reproductive outcomes for PCOS patients during IVF.