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.

Role of crustacean female sex hormone in regulating immune response in the mud crab, Scylla paramamosain.

Crustacean female sex hormone (CFSH) is responsible for sexual differentiation in crustaceans. The CFSH exhibited an interleukin-17 domain homologous to vertebrate IL-17, a family of inflammatory cytokines that play vital roles in immune defense. However, the immunoregulation of CFSH in crustaceans is a mystery. Therefore, this study aimed to investigate the immune regulatory roles of CFSH and CFSHR in the mud crab Scylla paramamosain. This study's immunofluorescence result revealed that Sp-CFSHR was highly expressed in granulocytes and semi-granulocytes but had moderate expression in hyalinocytes. The expression level of Sp-CFSH transcript in eyestalk ganglia and Sp-CFSHR in hemocytes were significantly up-regulated by the Poly (I:C) stimulation but significantly down-regulated in response to the lipopolysaccharide (LPS) stimulation. In our study, in vitro experiment exhibited that the nuclear transcription factors NF-κB signaling molecules (Sp-Dorsal and Sp-Relish), Sp-STAT, apoptosis-related gene Sp-IAP, and phagocytosis related gene (Sp-Rab5) expressions were significantly increased in hemocytes by recombinant CFSH (rCFSH) in vitro, but the pro-inflammatory cytokine gene (Sp-IL-16) expression was significantly suppressed. Finally, the rCFSH injection significantly up-regulated Sp-Dorsal, Sp-Relish, Sp-IAP, Sp-Caspase, Sp-ALF2, and C-type lectin (Sp-CTL-B) expressions in hemocytes as well as enhanced the bacterial clearance of the mud crab. In conclusion, our results suggested that CFSH may be a counterpart of vertebrate IL-17 in crustaceans that can enhance innate immunity to defense against Vibrionaceae infection via the NF-κB and/or JAK-STAT signaling pathways. This study provides the first evidence that CFSH is involved in the immunoregulation in crustaceans and enriches the insight of neuroendocrine-immune regulatory system, which providing new ideas for disease prevention in the mud crab industry.

A novel prognostic signature of chemokines for survival and immune infiltration in kidney renal clear cell carcinoma.

Objective: Studies have revealed the alteration of chemokines in the tumour microenvironment in renal clear cell carcinoma (KIRC), which is closely related with immune infiltration and the prognosis of patients with KIRC. This research aims to comprehensively clarify the signature of chemokines in KIRC and the correlation between chemokines and immune infiltration in the TME of KIRC. Methods: The chemokine expression in KIRC were investigated by using multiple multiomics and bioinformatics tools. Hub-chemokines that were significantly related with the cancer stage and survival were identified. The role of hub-chemokines in the tumor microenvironment of KIRC was further assessed by using enrichment analysis, cancer-related pathway and immune infiltration analysis. Results: A total of 20 chemokines were significantly elevated in KIRC. Based on the correlation with KIRC stages and survival, 13 hub-chemokines were identified. Among the hub-chemokines, the high expression of CXCL2, CXCL5 and CXCL13 were related with worse survival of KIRC patients. The hub-chemokines were associated with the activation of multiple cancer-related signaling pathways. The functions of hub-chemokines were mainly enriched in chemokine-mediated signaling pathway, immunocytes chemotaxis and chemokine activity. CCL4, CCL5, CXCL9, CXCL10 and CXCL11 were related with various types immune infiltration such as CD8+T cell, neutrophil, B cell and dendritic cell. Using the hub-chemokine CXCL10, multiple immune checkpoints including LAG3, CTLA-4 and PD-1 were identified. Conclusion: Our research sheds light on the chemokines and their important role in promoting the tumor microenvironment of KIRC. The findings could provide more data about the prognosis prediction and treatment targets for KIRC.

Family resilience is a protective buffer in the relationship between infertility-related stress and psychological distress among females preparing for their first in vitro fertilization-embryo transfer.

The present study aimed to evaluate psychological distress and scrutinized whether family resilience plays a moderating role in the association between infertility-related stress and psychological distress among infertile females preparing for their first IVF-ET. A total of 492 infertile females completed self-reported measures including the Kessler 10 Psychological Distress Scale (K10), the fertility problem inventory (FPI), and the Family Resilience Assessment Scale (FRAS). The results showed 21 (65.2%) participants reported moderate or higher levels of psychological distress. While controlling for economic status, we found psychological distress to be positively linked to infertility-related stress (ß=0.483, P<0.001), and negatively related to family resilience (ß=-0.145, P=0.001). The simple slopes analysis showed that infertility-related stress had a weaker positive association with psychological distress for individuals at 1 SD (ß = 0.443, P < 0.001) above the mean on family resilience compared to those at 1 SD (ß = 0.537, P < 0.001) below the mean. Thus, it suggests that clinical practice should conduct family resilience-oriented interventions to facilitate family resilience among infertile females preparing for their first IVF-ET, with the goal to reduce psychological distress.

[Construction of Nursing Quality Index System in Assisted Reproduction Hospitals Based on the Model of "Three-Dimensional Quality Structure"].

Objective To construct a nursing quality index system for the assisted reproduction hospitals integrating outpatient department,wards,and operating rooms and provide a reference for the application of the system in the quality control of clinical reproductive care. Method On the basis of Donabedian's health care quality model of structure-process-outcome,we established a nursing quality index system for assisted reproduction hospitals via literature retrieval,semi-structured interviews,Delphi method,and analytic hierarchy process. Results The two rounds of expert's questionnaire survey demonstrated the response rates of 100% and 92%,the expert authority coefficients of 0.911 and 0.919,and the Kendall coefficients of concordance of 0.228 and 0.253,respectively (all P<0.001).The nursing quality index system for assisted reproduction hospitals was established,which consisted of 3 first-level indicators,13 second-level indicators,and 39 third-level indicators. Conclusion The nursing quality index system of assisted reproduction hospitals is comprehensive,systematic and reasonable,which can be used as quality management standard and provide a reference for clinical application.

Leptin protects brain from ischemia/reperfusion-induced infarction by stabilizing the blood-brain barrier to block brain infiltration by the blood-borne neutrophils.

The cellular and molecular mechanisms underlying leptin-mediated brain protection against cerebral ischemia were investigated at the blood-brain barrier (BBB) and neutrophil level. Through the ischemia/reperfusion (I/R) animal model, we found that leptin expression level was significantly decreased in ischemic hemisphere. Brain injection with leptin (15 µg/kg, intracisternally) could block the I/R-increased BBB permeability, activation of matrix metallopeptidase 9 (MMP-9) and brain infiltration of blood-borne neutrophils to reduce the infarct volume of ischemic brain. The brain expression level of tight junction protein ZO-1 as well as number and motility of neutrophils in blood was all increased by the same injection, indicating BBB stability (rather than reduction in neutrophils) played a major role in the leptin-inhibited brain infiltration of neutrophils. Leptin-mediated protection of BBB was further confirmed in vitro, through a BBB cellular model under the in vitro ischemic condition (G/R: glucose-oxygen-serum deprivation followed by GOS restoration). The results showed that leptin again could block the G/R-increased neutrophil adherence to EC layer as well as BBB permeability, likely by stimulating the endothelial expression of ZO-1 and VE-Cadherin. The study has demonstrated that leptin could protect ischemic brain via multiple ways (other than neuronal protection), by inhibiting the BBB permeability, brain infiltration of the blood-borne neutrophils and neutrophil adherence to vascular ECs. The role of leptin in vascular biology of stroke could further support its therapeutic potential in other neurodegenerative diseases, associated with BBB disorder.

The role of ferroptosis in chronic intermittent hypoxia-induced liver injury in rats.

PURPOSE: Obstructive sleep apnea (OSA) has been related to an increased risk of liver injury. Ferroptosis is a form of programmed cell death implicated in multiple physiological and pathological processes. This study aimed to explore the role of ferroptosis in chronic intermittent hypoxia (CIH)-induced liver injury as well as to uncover the underlying mechanisms using a CIH rat model. METHODS: Fourteen male Sprague-Dawley rats were randomly allocated to either the normal control (NC) (n = 7) or the CIH group (n = 7). Rats were exposed to intermittent hypoxia for 8 weeks in CIH group. Liver function, histological changes, and markers of oxidative stress were evaluated. The protein levels of hypoxia-inducible factor-1α, nuclear factor E2-related factor 2 (Nrf2), Acyl-CoA synthetase long-chain family member 4 (ACSL4), and glutathione peroxidase 4 (GPX4) in liver were examined by Western blot analysis. RESULTS: CIH treatment caused significant increase of serum alanine aminotransferase, aspartate aminotransferase, and malondialdehyde (MDA). Liver MDA was significantly higher in CIH group than that in NC group. Histology showed that CIH treatment induced discernible swelled, disordered hepatocytes, necrosis, and infiltrated inflammatory cells. CIH treatment significantly reduced the expression of GPX4, while markedly up-regulated expression of ACSL4, indicating elevation in hepatic ferroptosis. In addition, the protein expression of Nrf2 in CIH group was significantly lower than that in NC group. CONCLUSIONS: Ferroptosis played a crucial role in CIH-induced liver injury. The hepatic ferroptosis in CIH rat model might be mediated by the dysregulation of Nrf2. This highlights a potential therapeutic target for the treatment of OSA-related liver injury.

Effect of chronic intermittent hypoxia on gene expression profiles of rat liver: a better understanding of OSA-related liver disease.

PURPOSE: Obstructive sleep apnea (OSA) and OSA-associated chronic intermittent hypoxia (CIH) have been suggested to be associated with increased risk of liver disease. Little is known about the biological pathophysiology and underlying molecular mechanisms. Here we use whole-genome expression profiling to explore the transcriptomic changes induced by CIH in rat liver. METHODS: Rats (n = 3) were exposed to CIH for 8 weeks and were compared with rats exposed to normoxia (n = 3). Illumina HiSeq 4000 platform was used to examine differentially expressed genes (DEGs) in the liver between control group and CIH rat model. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate DEGs. Biological functions of DEGs were determined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. RESULTS: Compared with control group, 318 genes were identified to be dysregulated in the liver of CIH rat model, with 211genes upregulated and 107 genes downregulated. Bioinformatics analysis showed that these genes were extensively related to various physiologic processes such as hepatic metabolism, apoptotic process, and oxidative stress. 10 genes with 5 upregulated and 5 downregulated were selected and further verified by qRT-PCR. CONCLUSIONS: CIH resulted in altered gene expression patterns in the liver of rat. The DEGs were related to various physiological and pathological processes in CIH rat liver. These data provide a better understanding of the mechanisms and underlying molecular changes of OSA-related liver disease.

Paper-based electrochemiluminescence determination of streptavidin using reticular DNA-functionalized PtCu nanoframes and analyte-triggered DNA walker.

A paper-based electrochemiluminescence (ECL) biosensor characterized by the signal amplification of reticular DNA-functionalized PtCu nanoframes (DNA-PtCuTNFs) and analyte-triggered DNA walker was developed for sensitive streptavidin assay. Silver microflower functionalized paper-based sensing platform was prepared to fix the hairpin strand (S1). With addition of the streptavidin, plenty of DNA walkers consisting of the walking strands (S2) labeled with biotin and streptavidin were established, which protected S2 from digestion via the terminal protection mechanism. The sequential introduction of the DNA walker and capture probe initiated the hairpin structure opening of S1 and strand displacement reaction (SDR) happening, causing the S2 release. Subsequently, S1 hybridized with S3. The free S2 further hybridized with adjacent S1 to trigger the next cycle. After multiple cycles, the DNA-PtCuTNFs, the fire-new signal enhancer, with remarkable peroxidase activity, were successfully attached onto the paper electrode via metal-catalyst-free click chemistry. Based on the SDR of the DNA walker and the catalysis of DNA-PtCuTNFs, a significantly boosted ECL signal of luminol was obtained. Under the optimal conditions, the developed sensor for streptavidin assay exhibited a low detection limit of 33.4 fM with a linear range from 0.1 pM to 0.1 µM. Graphical abstract.

Addressable TiO2 Nanotubes Functionalized Paper-Based Cyto-Sensor with Photocontrollable Switch for Highly-Efficient Evaluating Surface Protein Expressions of Cancer Cells.

Inspired by the well-known "Wheel of Fortune", a rotatable paper-photocontrollable switch (RPPS) was designed to form an addressable paper-based photoelectrochemical (PEC) cyto-sensor for ultrasensitive detection of a cell-surface protein. By simply rotating the RPPS, a light source can selectively activate the desired working zones of the cyto-sensor. To realize the high-performance paper-based PEC cyto-sensor, a cascaded photoactive interface consisting of neat TiO2 nanotubes arrays, Pt nanoparticles (NPs), and nitrogen-carbon dots was introduced into paper fibers, gaining signal-on PEC state (NTPP for short). Then the NTPP fixed with a hairpin probe H1 allowed the hybridization chain reaction (HCR) to happen with CuS NPs-labeled hairpin probe H2 by the free primer strand (PS) triggering; hence, the CuS NPs as the emulative sensitizers were introduced onto the NTPP with the photocurrent intensity decrement for signal-off PEC state. During this process, the PS carefully designed with specific sequences can recognize the target strand (TS) of MCF-7 cells and stimulate HCR by its trigger zone. The presence of MCF-7 cells destroyed the interaction between PS and ZnFe2O4 functionalized TS, causing the PS release from the mixture of PS and TS under the help of a magnet. Then, the released PS, acting as a primer probe, realized ultrasensitive detection of a cell-surface protein. On the basis of this novel protocol, multiple-signal amplification was skillfully imported into the addressable paper PEC chip, resulting in ultrasensitive quantification of carcinoembryonic antigen in the surface of MCF-7 cells. Given the fascinating analytical performances of the developed cyto-sensor, ultralow expression of antigens for MCF-7, A549, and PC 3 cells was discriminated effectively.

On the Performance of Cognitive Satellite-Terrestrial Relay Networks with Channel Estimation Error and Hardware Impairments.

This paper investigates the joint impact of channel estimation errors (CEEs) and hardware impairments (HIs) on the performance of a cognitive satellite-terrestrial relay network (CSTRN), where the terrestrial and satellite links are considered following Rayleigh fading and shadowed Rician (SR) fading distributions, respectively. Besides, the terrestrial relay is working in half-duplex decode-and-forward (DF) mode. By employing a general and practical model to account for both the CEEs and HIs at each link, the end-to-end signal-to-noise-plus-distortion-and-error ratio (SNDER) is first obtained for the CSTRN. Then, closed-form expressions for the outage probability (OP) and throughput of the CSTRN are obtained, which allows us to demonstrate the aggregate impact of CEEs and HIs. In order to gain insightful findings, we further elaborate on the asymptotic OP and throughput at the high signal-to-noise-ratio (SNR) condition and quantitatively determine the fundamental performance ceiling. Finally, Monte Carlo (MC) computer simulations are provided to verify the correctness of the analytical results. Besides, with representative numerical analysis's help, interesting findings are presented.

Secure Multiuser Communications in Wireless Sensor Networks with TAS and Cooperative Jamming.

In this paper, we investigate the secure transmission in wireless sensor networks (WSNs) consisting of one multiple-antenna base station (BS), multiple single-antenna legitimate users, one single-antenna eavesdropper and one multiple-antenna cooperative jammer. In an effort to reduce the scheduling complexity and extend the battery lifetime of the sensor nodes, the switch-and-stay combining (SSC) scheduling scheme is exploited over the sensor nodes. Meanwhile, transmit antenna selection (TAS) is employed at the BS and cooperative jamming (CJ) is adopted at the jammer node, aiming at achieving a satisfactory secrecy performance. Moreover, depending on whether the jammer node has the global channel state information (CSI) of both the legitimate channel and the eavesdropper's channel, it explores a zero-forcing beamforming (ZFB) scheme or a null-space artificial noise (NAN) scheme to confound the eavesdropper while avoiding the interference to the legitimate user. Building on this, we propose two novel hybrid secure transmission schemes, termed TAS-SSC-ZFB and TAS-SSC-NAN, for WSNs. We then derive the exact closed-form expressions for the secrecy outage probability and the effective secrecy throughput of both schemes to characterize the secrecy performance. Using these closed-form expressions, we further determine the optimal switching threshold and obtain the optimal power allocation factor between the BS and jammer node for both schemes to minimize the secrecy outage probability, while the optimal secrecy rate is decided to maximize the effective secrecy throughput for both schemes. Numerical results are provided to verify the theoretical analysis and illustrate the impact of key system parameters on the secrecy performance.

Sex Hormones Predict the Incidence of Erectile Dysfunction: From a Population-Based Prospective Cohort Study (FAMHES).

INTRODUCTION: The decline of testosterone has been known to be associated with the prevalence of erectile dysfunction (ED), but the causal relationship between sex hormones and ED is still uncertain. AIM: To prove the association between sex hormones and ED, we carried out a prospective cohort study based on our previous cross-sectional study. METHODS: We performed a prospective cohort study of 733 Chinese men who participated in Fangchenggang Area Males Health and Examination Survey from September 2009 to December 2009 and were followed for 4 years. Erectile function was estimated by scores of the five-item International Index of Erectile Dysfunction (IIEF-5) and relative ratios (RRs) were estimated using the Cox proportional hazards regression model. MAIN OUTCOME MEASURES: Data were collected at follow-up visit and included sex hormone measurements, IIEF-5 scores, physical examination, and health questionnaires. RESULTS: Men with the highest tertile of free testosterone (FT) (RR = 0.21, 95% confidence interval [CI]: 0.09-0.46) and the lowest tertile of sex hormone-binding globulin (SHBG) (RR = 0.38, 95% CI: 0.19-0.73) had decreased risk of ED. In young men (aged 21-40), a decreased risk was observed with the increase of FT and bioavailable testosterone (BT) (adjusted RR and 95% CI: 0.78 [0.67-0.92] and 0.75 [0.62-0.95], respectively). Total testosterone (TT) (RR = 0.89, 95% CI: 0.81-0.98) was inversely associated with ED after adjusting for SHBG, while SHBG (RR = 1.04, 95% CI: 1.02-1.06) remained positively associated with ED after further adjusting for TT. Men with both low FT and high SHBG had highest ED risk (adjusted RR = 4.61, 95% CI: 1.33-16.0). CONCLUSIONS: High FT and BT levels independently predicted a decreased risk of ED in young men. Further studies are urgently needed to clarify the molecular mechanisms of testosterone acting on ED.

Incidence, risk factors, and a prognostic nomogram for distant metastasis in endometrial cancer: A SEER-based study.

OBJECTIVE: To evaluate the metastatic pattern, identify the risk factors, and establish a nomogram for predicting prognosis of endometrial cancer (EC) with distant metastasis. METHODS: A retrospective cohort study of women diagnosed with EC was conducted according to the Surveillance, Epidemiology, and End Results (SEER) database during 2010-2017. Multivariate logistic analysis and Cox analysis were performed to identify the risk factors in promoting distant metastasis and predictors associated with overall survival (OS) in this particular subpopulation. A nomogram was then constructed and validated by the concordance index (C-index), the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis. RESULTS: A total of 2799 cases of distant metastasis in EC patients were identified, with an overall incidence rate of 3.74% from 2010 to 2017. Black race, unmarried status, non-endometrioid histologic types, and grade IV were significant risk factors for distant metastasis in EC patients. Meanwhile, race, histology, grade, metastasis status, surgery, lymphadenectomy, and chemotherapy were identified as independent prognostic factors for OS. A nomogram to predict 1-, 3-, and 5-year OS was established, and presented favorable accuracy and clinical applicability. Patients were further divided into high- and low-risk groups according to the model. CONCLUSION: The nomogram was developed as a highly accurate, individualized tool to better predict the prognosis of EC patients with distant metastasis, which would help clinicians to identify high-risk patients, and adjust and tailor their treatment strategies.

Metabolic clues to aging: exploring the role of circulating metabolites in frailty, sarcopenia and vascular aging related traits and diseases.

Background: Physical weakness and cardiovascular risk increase significantly with age, but the underlying biological mechanisms remain largely unknown. This study aims to reveal the causal effect of circulating metabolites on frailty, sarcopenia and vascular aging related traits and diseases through a two-sample Mendelian Randomization (MR) analysis. Methods: Exposures were 486 metabolites analyzed in a genome-wide association study (GWAS), while outcomes included frailty, sarcopenia, arterial stiffness, atherosclerosis, peripheral vascular disease (PAD) and aortic aneurysm. Primary causal estimates were calculated using the inverse-variance weighted (IVW) method. Methods including MR Egger, weighted median, Q-test, and leave-one-out analysis were used for the sensitive analysis. Results: A total of 125 suggestive causative associations between metabolites and outcomes were identified. Seven strong causal links were ultimately identified between six metabolites (kynurenine, pentadecanoate (15:0), 1-arachidonoylglycerophosphocholine, androsterone sulfate, glycine and mannose) and three diseases (sarcopenia, PAD and atherosclerosis). Besides, metabolic pathway analysis identified 13 significant metabolic pathways in 6 age-related diseases. Furthermore, the metabolite-gene interaction networks were constructed. Conclusion: Our research suggested new evidence of the relationship between identified metabolites and 6 age-related diseases, which may hold promise as valuable biomarkers.

Systemic analysis of the expression and prognostic significance of USP31 in endometrial cancer.

Increasing evidence indicates that multiple mechanisms are involved in the metastasis and postoperative recurrence in patients with endometrial cancer (EC). Ubiquitin-specific protease 31 (USP31) has been studied in some human tumors, but its function remains unclear in EC. In this study, we tried to investigate the expression of USP31 in EC and its possible involvement in biological signaling pathways and define its predictive value for the prognosis. Data from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases confirmed the difference in USP31 expression between EC and normal endometrium. Specimens and clinical data of 259 patients with EC who underwent primary surgery at the First Affiliated Hospital of Chongqing Medical University were collected. The independent predictive value of USP31 for the prognosis of EC patients was determined by univariate and multivariate analyses. Kaplan-Meier analysis and receiver operating characteristic curves were used for confirming the ability of USP31 to predict the prognosis. Functional enrichment analyses were used for finding the hub genes associated with USP31 and to predict the biological signaling pathways that might be involved. Our study confirms that EC patients with low expression of USP31 may have a worse prognosis. Functional annotations suggest that USP31 may participate in the mitogen-activated protein kinase signaling pathway, nuclear factor κB pathway, early 2 factor targets, and inflammatory response. USP31 may act as a promising biomarker for research in EC.

Tongue coating microbiome composition reflects disease severity in patients with COVID-19 in Nanjing, China.

Our purpose is to investigate the relationship between the microbiota of patients' tongue coating microbiota and the severity of COVID-19, and to identify the severity of COVID-19 patients' condition as early as possible. The participants were categorized into three groups: healthy controls (Con group) consisting of 37 individuals, patients with mild to moderate symptoms (M group) comprising 49 individuals, and patients with severe and critical symptoms (S-C group) consisting of 44 individuals. We collected oral swabs from all participants and performed 16S rRNA gene sequencing to analyze the microbiome. The α and ß diversity differences were assessed respectively. Additionally, we employed the Linear Discriminant Analysis Effect Size (LEfSe) analysis to evaluate taxonomic differences among the three groups. Our findings revealed a significantly higher richness of tongue coating microbiota in both the S-C group and M group compared to the Con group. When compared with Con group, decreased Prevotella, Neisseria, Fusobacterium and Alloprevotella, and over-expressed Streptococcus and Rothia in M and S-C group were identified. LEfSe analysis indicated a greater abundance of Pseudomonas, Acinetbacter, Lactobacillus, Corynebacterium, Rothia in S-C group. Our study suggests a potential association between tongue coating microbiome and the severity of COVID-19 patients.

Berberine attenuates depression-like behavior by modulating the hippocampal NLRP3 ubiquitination signaling pathway through Trim65.

OBJECTIVE: Increasing evidence suggests that inflammation appears to play a role in the genesis of depression. Berberine has potent anti-inflammatory effects and potential antidepressant activity, although the mechanism by which it works is yet unclear. Our study aimed to investigate the molecular mechanisms through which berberine treats depression and reduces inflammation. METHODS: The CUMS model and behavioral evaluation were utilized in this study to evaluate the efficacy of berberine in the treatment of depression. Berberine's effect on the inflammatory response in CUMS mice was evaluated via ELISA assays and western blotting. Nissl staining was used to observe hippocampal neuronal functional damage. Western blotting, ELISA, ubiquitination tests, and immunoprecipitation were utilized in conjunction with in vitro experiments to study the involvement of Trim65 in the antidepressant effects of berberine. RESULTS: The results suggest that berberine effectively alleviates depressive symptoms, suppresses the expression of genes associated with the NLRP3 inflammasome (NLRP3, cleaved caspase-1, ASC, GSDMD-N, Pro-IL-1ß, IL-1ß, Pro-IL-18, and IL-18), and reduces hippocampal neuronal functional damage in CUMS mice. Further studies showed that knockdown of Trim65 reversed the effects of berberine and increased NLRP3 inflammasome activity. Finally, K285, an important site for Trim65 binding to NLRP3, was identified. CONCLUSION: Our study describes the mechanism of berberine limiting NLRP3 inflammasome activity by promoting the conjugation of Trim65 to NLRP3 and NLRP3 ubiquitination, and suggests NLRP3 inflammasome activation as a prospective target for treating inflammation-associated disorders such as depression.

Comprehensive Assessment of ERα, PR, Ki67, P53 to Predict the Risk of Lymph Node Metastasis in Low-Risk Endometrial Cancer.

PURPOSE: According to international guidelines, selective lymph node dissection can be performed on patients with early-stage endometrial cancer. However, some patients at early stage have already occurred lymph node metastasis at the time of diagnosis. This study was aimed to find a method to predict the risk of lymph node metastasis in this part of patient. METHODS: We collected data from 571 patients as training cohort and 351 patients as validation cohort for this study. Then we performed univariate and multivariate analyses to confirm the correlation of frequently used factors and lymph node metastasis. Combined analysis of four commonly indicators (ERα, PR, P53 and Ki67) from pathological parameter sources was mainly carried out, and the combined ratio is defined as (ERα + PR)/(Ki67 + P53). Then the accuracy of the combined ratio and other factors in prediction were compared by AUC value. Also, the optimal truncation value was searched. Finally, patients followed up for more than two years were divided into groups by the threshold value, and their difference in survival was explored. RESULTS: This study showed that CA125, grade, LVSI, ERα, PR, P53, Ki67 have statistical significance (P-value <0.05). The AUC value of combined ratio is 0.876, which is the best. The best cutoff value of combined ratio is 1.38. CONCLUSION: The combined ratio cutoff value of 1.38 in this study can be used for prediction of risk of lymph node metastasis in early-stage endometrial cancer patients and provide a reference for therapeutic planning.

Prognostic Value of the Cutoffs for HALP in Endometrial Cancer.

OBJECTIVES: Using preoperative hemoglobin, albumin, lymphocyte, and platelet (HALP) scores, a cutoff value of HALP in endometrial cancer was identified, and the significance of HALP value in endometrial cancer prognosis was evaluated to guide the management of patients. MATERIALS AND METHODS: This study included 626 patients with endometrial cancer who underwent surgery at the First Affiliated Hospital of Chongqing Medical University between June 2015 and June 2020. A Cox regression model was used to analyze the correlation between HALP endometrial cancer recurrence and death, and the receiver operating characteristic curve was used to determine the optimal cutoff value of HALP for predicting the lymph node metastasis (LNM), recurrence, and death of endometrial cancer. Survival analysis was performed using the Kaplan-Meier method and log-rank test. RESULTS: Univariate analysis revealed that HALP was associated with a lower risk of recurrence and death of endometrial cancer. Multivariate analysis indicated that HALP was an independent protective factor for predicting recurrence and death in endometrial cancer. The thresholds of HALP for predicting LNM, recurrence, and death in endometrial cancer patients are around 33.8. Kaplan-Meier survival curves showed that the recurrence-free and the overall survival rates were significantly lower in the low-HALP group than that in the high-HALP group ( P <0.001). CONCLUSIONS: Preoperative HALP values in patients with endometrial cancer are important in predicting LNM, recurrence, and death of patients. HALP scores combined with traditional pathologic factors can better guide the prognostic management of patients.