Association between single nucleotide polymorphisms, TGF-ß1 promoter methylation, and polycystic ovary syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a common endocrine and metabolic disease in women. Hyperandrogenaemia (HA) and insulin resistance (IR) are the basic pathophysiological characteristics of PCOS. The aetiology of PCOS has not been fully identified and is generally believed to be related to the combined effects of genetic, metabolic, internal, and external factors. Current studies have not screened for PCOS susceptibility genes in a large population. Here, we aimed to study the effect of TGF-ß1 methylation on the clinical PCOS phenotype. METHODS: In this study, three generations of family members with PCOS with IR as the main characteristic were selected as research subjects. Through whole exome sequencing and bioinformatic analysis, TGF-ß1 was screened as the PCOS susceptibility gene in this family. The epigenetic DNA methylation level of TGF-ß1 in peripheral blood was detected by heavy sulfite sequencing in patients with PCOS clinically characterised by IR, and the correlation between the DNA methylation level of the TGF-ß1 gene and IR was analysed. We explored whether the degree of methylation of this gene affects IR and whether it participates in the occurrence and development of PCOS. RESULTS: The results of this study suggest that the hypomethylation of the CpG4 and CpG7 sites in the TGF-ß1 gene promoter may be involved in the pathogenesis of PCOS IR by affecting the expression of the TGF-ß1 gene. CONCLUSIONS: This study provides new insights into the aetiology and pathogenesis of PCOS.

MiR-221-5p regulates blood-brain barrier dysfunction through the angiopoietin-1/-2/Tie-2 signaling axis after subarachnoid hemorrhage.

AIM: To explore the potential role of microRNA miR-221-5p on the angiopoietin-1 (Ang-1)/Ang-2/Tie-2 signaling axis after subarachnoid hemorrhage (SAH) in a rat model. METHODS: Aspects of the rat's behavior were measured using the Kaoutzanis scoring system to test neurological responses. This included feeding behavior, body contraction, motor, and eye-opening responses. Brain sections were studied using transmission electron microscopy and Evans blue extravasation. Levels of Ang-1, Ang-2, and Tie-2 were determined by Western blot, while miR-221-5p was quantified using stem-loop real-time quantitative PCR (RT-qPCR). RESULTS: The SAH group responded worse to the neurological response test than the sham-operated group. The intercellular space was widened in the SAH group, but not in the sham-operated group. Evans blue dye leaked significantly more into brain tissue cells of the SAH group. Stem-loop qRT-PCR showed elevated miR-221-5p levels. Additionally, Ang-1 and Tie-2 were reduced but Ang-2 expression was increased after SAH. This led to a significant reduction of the Ang-1/Ang-2 ratio in the brain tissue, which was associated with the destruction of the blood-brain barrier. CONCLUSION: The data indicate that miR-221-5p might regulate blood-brain barrier dysfunction through the Ang-1/Ang-2/Tie-2 signaling axis, suggesting that it should be further investigated as a potential novel biomarker.

Identification of immune cell infiltration and effective biomarkers of polycystic ovary syndrome by bioinformatics analysis.

BACKGROUND: Patients with polycystic ovary syndrome (PCOS) exhibit a chronic inflammatory state, which is often accompanied by immune, endocrine, and metabolic disorders. Clarification of the pathogenesis of PCOS and exploration of specific biomarkers from the perspective of immunology by evaluating the local infiltration of immune cells in the follicular microenvironment may provide critical insights into disease pathogenesis. METHODS: In this study, we evaluated immune cell subsets and gene expression in patients with PCOS using data from the Gene Expression Omnibus database and single-sample gene set enrichment analysis. RESULTS: In total, 325 differentially expressed genes were identified, among which TMEM54 and PLCG2 (area under the curve = 0.922) were identified as PCOS biomarkers. Immune cell infiltration analysis showed that central memory CD4+ T cells, central memory CD8+ T cells, effector memory CD4+ T cells, γδ T cells, and type 17 T helper cells may affect the occurrence of PCOS. In addition, PLCG2 was highly correlated with γδ T cells and central memory CD4+ T cells. CONCLUSIONS: Overall, TMEM54 and PLCG2 were identified as potential PCOS biomarkers by bioinformatics analysis. These findings established a basis for further exploration of the immunological mechanisms of PCOS and the identification of therapeutic targets.

The Roles of Aerobic Exercise and Folate Supplementation in Hyperhomocysteinemia-Accelerated Atherosclerosis.

Background: Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Effective interventions to reduce HHcy-accelerated atherosclerosis are required. Objectives: This study aimed to investigate the effects of aerobic exercise (AE) and folate (FA) supplementation on plasma homocysteine (Hcy) level and atherosclerosis development in a mouse model. Methods: Six-week-old female apoE-/- mice were grouped into five groups (N = 6-8): HHcy (1.8 g/L DL-homocysteine (DL-Hcy) in drinking water), HHcy + AE (1.8 g/L DL-Hcy and aerobic exercise training on a treadmill), HHcy + FA (1.8 g/L DL-Hcy and 0.006% folate in diet), HHcy + AE + FA (1.8 g/L DL-Hcy, 0.006% folate, and aerobic exercise training on a treadmill), and a control group (regular water and diet). All treatment was sustained for 8 weeks. Triglyceride, cholesterol, lipoprotein, and Hcy levels were determined enzymatically. Plaque and monocyte chemoattractant protein-1 (MCP-1) expression levels in mouse aortic roots were evaluated by immunohistochemistry. Results: Compared to the HHcy group (18.88 ± 6.13 µmol/L), plasma Hcy concentration was significantly reduced in the HHcy + AE (14.79 ± 3.05 µmol/L, p = 0.04), HHcy + FA (9.4 ± 3.85 µmol/L, p < 0.001), and HHcy + AE + FA (9.33 ± 2.21 µmol/L, p < 0.001) groups. Significantly decreased aortic root plaque area and plaque burden were found in the HHcy + AE and HHcy + AE + FA groups compared to those in the HHcy group (both p < 0.05). Plasma MCP-1 level and MCP-1 expression in atherosclerotic lesions were significantly decreased in the HHcy + AE and HHcy + AE + FA groups compared to the HHcy group (all p < 0.05). Conclusions: AE reduced atherosclerosis development in HHcy apoE-/- mice independently of reducing Hcy levels. FA supplementation decreased plasma Hcy levels without attenuating HHcy-accelerated atherosclerosis. AE and FA supplementation have distinct mechanisms in benefiting atherosclerosis.

Molecular mechanisms involved in the IL-6-mediated upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) expression in the chorionic villi and decidua of women in early pregnancy.

BACKGROUND: IL-6 induces the upregulation of indoleamine 2,3-dioxygenase (IDO1) at the maternal-foetal interface, but the regulation mechanisms of IDO1 by IL-6 at this interface have not been fully understood. METHODS: Western blotting, qRT-PCR and/or immunohistochemistry were employed to measure the expression of IDO1, IL-6, SHP-1/2, SOCS3 and STAT3/p (STAT3 and pSTAT3) in tissues of chorionic villi and decidua (TCVD) in vivo and in cultured TCVD that were treated with IL-6 in the presence or absence of an IL-6 inhibitor. RESULTS: Mutually positive relationships among the protein levels of IL-6, IDO1, SHP-1/2 and STAT3/p was observed, and the expression of IDO1, SHP-1/2 and STAT3/p was increased in a dose-dependent manner in TCVD in vivo and in cultured TCVD treated with IL-6 at increasing concentrations (0-100 ng/ml). The level of IL-6 was negatively related to SOCS3 level in TCVD. The expression of SOCS3 was increased in a dose-dependent manner, and SOCS3 level was positively correlated with SHP-1, SHP-2 and STAT3/p level in cultured TCVD treated with 0-2 ng/ml IL-6; however, opposite results were observed after treatment with 2-100 ng/ml IL-6. The IL-6-induced upregulation of IDO1, SHP-1, SHP-2 and STAT3/p expression could be reversed, while the IL-6-induced upregulation of SOCS3 expression was exacerbated by Corylifol A. CONCLUSIONS: In normal pregnancy, IL-6 upregulates the expression of IDO1 by promoting SHP-1/2 expression via STAT3/p and simultaneously negatively regulates the expression of SOCS3. High expression of IL-6 causes the upregulation of IDO1 expression and the downregulation of SOCS-3 expression, which may be beneficial for maintaining immunological tolerance.

Brainstem auditory evoked potential combined with high resolution cranial base CT can optimize the diagnosis of auditory nerve injury.

PURPOSE: Auditory nerve injury is one of the most common nerve injury complications of skull base fractures. However, there is currently a lack of auxiliary examination methods for its direct diagnosis. The purpose of this study was to find a more efficient and accurate means of diagnosis for auditory nerve injury. METHODS: Through retrospectively analyzing the results of brainstem auditory evoked potential (BAEP) and high-resolution CT (HRCT) in 37 patients with hearing impairment following trauma from January 1, 2018 to July 31, 2020, the role of the two inspection methods in the diagnosis of auditory nerve injury was studied. Inclusion criteria were patient had a clear history of trauma and unilateral hearing impairment after trauma; while exclusion criteria were: (1) severe patient with a Glasgow coma scale score ≤5 because these patients were classified as severe head injury and admitted to the intensive care unit, (2) patient in the subacute stage admitted 72 h after trauma, and (3) patient with prior hearing impairment before trauma. According to Goodman's classification of hearing impairment, the patients were divided into low/medium/severe injury groups. In addition, patients were divided into HRCT-positive and negative groups for further investigation with their BAEP results. The positive rates of BEAP for each group were observed, and the results were analyzed by Chi-square test (p < 0.05, regarded as statistical difference). RESULTS: A total of 37 patients were included, including 21 males and 16 females. All of them were hospitalized patients with GCS score of 6-15 at the time of admission. The BAEP positive rate in the medium and severe injury group was 100%, which was significantly higher than that in the low injury group (27.27%) (p < 0.01). The rate of BEAP positivity was significantly higher in the HRCT-positive group (20/30, 66.7%) than in the HRCT-negative group (1/7, 14.3%) (p < 0.05). Twenty patients (54.05%) were both positive for BEAP and HRCT test, and considered to have auditory nerve damage. Six patients (16.22%) were both negative for BEAP and HRCT test, and 10 patients (27.03%) were BAEP-negative but HRCT-positive: all the 16 patients were considered as non-neurological injury. The rest 1 case (2.70%) was BAEP-positive but HRCT-negative, which we speculate may have auditory nerve concussion. CONCLUSION: By way of BAEP combining with skull base HRCT, we may improve the accuracy of the diagnosis of auditory nerve injury. Such a diagnostic strategy may be beneficial to guiding treatment plans and evaluating prognosis.

A cross-sectional study of blood selenium concentration and cognitive function in elderly Americans: National Health and Nutrition Examination Survey 2011-2014.

BACKGROUND: Cognitive decline can develop into mild cognitive impairment, a high-risk factor in the progression of Alzheimer's disease. The antioxidant micronutrient selenium may have some effect on preventing cognitive decline, but the association between whole blood selenium concentration and cognitive function remains controversial. AIM: To investigate the association between whole blood selenium concentration and cognitive function score in elderly Americans. SUBJECTS AND METHODS: Data was obtained from the national health and nutrition survey between 2011 and 2014. A general linear model was used to adjust for possible risk factors to analyse the association between blood selenium concentration and cognitive function. RESULTS: 2068 participants were included in our study, and the average blood selenium concentration was high at 195.08 µg/L. The risk of lower cognitive scores was higher in people with lower blood selenium concentration (p < 0.05). The lower cognition may also be associated with one or more of the following characteristics: older, male, had a low poverty-income ratio, low education level, and consumed less alcohol. Related conditions such as stroke, diabetes and high blood pressure may also affect cognitive scores. CONCLUSIONS: Higher blood selenium is associated with higher cognitive scores in elderly Americans.

A temporary-sustainable team: A new multidisciplinary team model for severe trauma.

The treatment of severe trauma, especially multiple injuries, requires multidisciplinary collaboration. The current study aims to highlight the challenges of consultation mode for severe trauma in general hospitals and emphasizes the need to create a new temporary-sustainable team. It suggests developing an information consultation mode and enforcing the fine management to improve the quality and safety of the medical treatment. The management mode of a temporary-sustainable team will reduce the cost and improve the treatment efficiency. Overall, a temporary-sustainable team has significant advantages over a traditional multidisciplinary team for severe trauma treatment.

DNA hypermethylation and X chromosome inactivation are major determinants of phenotypic variation in women heterozygous for G6PD mutations.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked incompletely dominant enzyme deficiency that results from G6PD gene mutations. Women heterozygous for G6PD mutations exhibit variation in the loss of enzyme activity but the cause of this phenotypic variation is unclear. We determined DNA methylation and X-inactivation patterns in 71 G6PD-deficient female heterozygotes and 68 G6PD non-deficient controls with the same missense mutations (G6PD Canton c.1376G>T or Kaiping c.1388G>A) to correlate determinants with variable phenotypes. Specific CpG methylations within the G6PD promoter were significantly higher in G6PD-deficient heterozygotes than in controls. Preferential X-inactivation of the G6PD wild-type allele was determined in heterozygotes. The incidence of preferential X-inactivation was 86.2% in the deficient heterozygote group and 31.7% in the non-deficient heterozygote group. A significant negative correlation was observed between X-inactivation ratios of the wild-type allele and G6PD/6-phosphogluconate dehydrogenase (6PGD) ratios in heterozygous G6PD Canton (r=-0.657, p<0.001) or Kaiping (r=-0.668, p<0.001). Multivariate logistic regression indicated that heterozygotes with hypermethylation of specific CpG sites in the G6PD promoter and preferential X-inactivation of the wild-type allele were at risk of enzyme deficiency.

Prevalence of human papillomavirus infection in Guangdong Province, China: a population-based survey of 78,355 women.

BACKGROUND: The prevalence of human papillomavirus (HPV) infection and the distribution of different HPV genotypes vary greatly within different geographical and ethnic populations, especially in Asia. The HPV infection data based on regional population are extremely important for researchers to develop new efficient HPV screening assays and estimate the effect of vaccines on preventing from cervical cancer. METHODS: A total of 78,355 women from Guangdong Province, China, whose ages were from 18 to 75 years were enrolled in this study. All epidemiological data were obtained by face-to-face interview. Cervical exfoliated cells were collected, and HPV-DNA test was conducted with the matrix-assisted laser desorption/ionization time-of flight mass spectrometry. RESULTS: The overall HPV infection prevalence in the study population was 7.3%. The top 6 HPV genotypes were HPV16 (1.5%), HPV52 (1.2%), HPV58 (1.0%), HPV18 (0.7%), HPV45 (0.5%), and HPV6 (0.5%), accounting for 69.7% of all detected HPV infection types. Two peaks of HPV infection were detected in the population of old age group (>50; 9.6%) and young group (<25; 8.2%). Infection with single genotype HPV (6.2% in all; 85.7% in HPV-positive women) was more frequent than infection with multiple HPV (1.0% and 14.3% respectively). Results of multivariate logistic regression revealed that sexual active years, numbers of sexual partner, and numbers of pregnancy were risk factors of HPV infection. CONCLUSIONS: This study provides useful epidemiological information on cervical HPV infection prevalence in general female population from Guangdong Province, China. In this population, HPV infection prevalence was 7.3%, and genotypes HPV16, HPV52, and HPV58 showed a relatively high prevalence.

HPV genotypes and associated cervical cytological abnormalities in women from the Pearl River Delta region of Guangdong province, China: a cross-sectional study.

BACKGROUND: It is important to understand the specific HPV genotype distribution in screen-detected lesions. HPV Genotype is helpful for separating HPV-positive women at greater risk of cancer from those who can regress spontaneously and for preventing cervical cancer at early stage. The aim of this study was to investigate the high-risk HPV genotype distribution among cervical cytology abnormality in Pearl River Delta Region, Southern China METHODS: 5585 HPV-infected women were screened from 77069 women in Pearl River Delta Region. Information was obtained from 3226 screened subjects through questionnaires and personal interviews. Exfoliated cervical cells were collected by doctors for HPV test with MassARRAY (Sequenom, Sandiego, CA) technique based on the matrix-assisted laser desorption/ionization time-of flight (MALDI-TOF) mass spectrometry (MS). The ThinPrep cytology test was performed to screen for cervical cancer. Unconditional logistic was used to determine the most common HPV carcinogenic types. RESULTS: Of the 3226 HPV-positive samples tested, 1744 (54.1%) with normal cervical cytology, 1482 (45.9%) with abnormal cytology. The five most common HPV types in this study were HPV16 (20.2%), HPV52 (17.1%), HPV58 (13.2%), HPV18 (9.5%), HPV6 (7.6%). Overall, HPV16 (OR = 10.5, 95% CI: 3.7 ~ 29.6), HPV33 (OR = 9.1, 95% CI: 2.8 ~ 29.2), HPV58 (OR = 6.3, 95% CI: 2.1 ~ 18.6), HPV31 (OR = 4.5, 95% CI: 1.3 ~ 15.5), multiple genotype infection (OR = 3.0, 95% CI: 1.7 ~ 14.7), especially HPV16 and HPV33, increased the risk of cytology abnormalities. CONCLUSIONS: HPV16, HPV31, HPV33, HPV58, and multiple HPV genotype infection increased the risk of cytology abnormalities in Pearl River Delta Region and might be useful for the screening, preventing, treating, and monitoring of pre-cancer lesions in southern China.

Air embolism caused by peripheral superficial vein catheterization: A case report.

BACKGROUND: Air embolization is usually an iatrogenic complication that can occur in both veins and arteries. Intravenous air embolization is mainly associated with large central vein catheters and mechanical ventilation. A 59-year-old woman was sent to our hospital with spontaneous cerebral hemorrhage and treated conservatively with a left forearm peripheral venous catheter infusion drug. After 48 hours, the patient's oxygen saturation decreased to 92 % with snoring breathing. Computer tomography of the head and chest revealed scattered gas in the right subclavian, the right edge of the sternum, the superior vena cava, and the leading edge of the heart shadow. METHODS: She was sent to the intensive care unit for high-flow oxygen inhalation and left-side reclining instantly. As the patient was at an acute stage of cerebral hemorrhage and did not take the Trendelenburg position. RESULTS: The computed tomography (CT) scan after 24 hours shows that the air embolism subsides. CONCLUSION SUBSECTIONS: Air embolism can occur in any clinical scenario, suggesting that medical staff should enhance the ability to identify and deal with air embolism. For similar cases in clinical practice, air embolism can be considered.

A real-world disproportionality analysis of cyclosporine from the FDA Adverse Event Reporting System (FAERS) database.

Cyclosporine is an immunosuppressant used to prevent organ rejection in kidney, liver, and heart allogeneic transplants. This study aimed to assess the safety of cyclosporine through the analysis of adverse events (AEs) related to cyclosporine in the US Food and Drug Administration Adverse Event Reporting System (FAERS). To detect AEs associated with cyclosporine, a pharmacovigilance analysis was conducted using four algorithms on the FAERS database: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM). A statistical analysis was performed on data extracted from the FAERS database, covering 19,582 case reports spanning from 2013 to 2022. Among these cases, 3,911 AEs were identified, with 476 linked to cyclosporine as the primary suspected drug. Cyclosporin-induced AEs targeted 27 System Organ Classes (SOCs). Notably, the highest case at the SOC level included eye disorders, injury, poisoning, and procedural complications, as well as immune system disorders, all of which are listed on the cyclosporine label. Furthermore, we discovered novel potential AEs associated with hepatobiliary disorders, among others. Moreover, unexpected adverse drug reactions (ADRs), such as biliary anastomosis complication and spermatozoa progressive motility decrease, were identified. Importantly, these newly identified ADRs were not mentioned on the cyclosporine label, which were involved in injury, poisoning, and procedural complications, and investigations at the SOC level. The study used pharmacovigilance analysis of FAERS database to identify new and unexpected potential ADRs relating to cyclosporine, which can provide safety tips for the safe use of cyclosporine.

Association between polycyclic aromatic hydrocarbons and infertility in U.S. women: National Health and Nutrition Examination Survey 2013-2016.

Although there is a body of research indicating the potential impact of polycyclic aromatic hydrocarbons (PAHs) exposure on male infertility, the understanding of how PAH might affect female infertility is still limited. This study aimed to evaluate associations of PAHs, both individually and as a mixture, with female infertility using multiple logistic regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (QGC) models based on data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016. The study included 729 female participants. Multiple logistic regression results indicated that there was a significant association between the third tertile of 2-hydroxy fluorene (2-OHFLU) and female infertility, and the OR was 2.84 (95% CI: 1.24-6.53, P value = 0.015) compared with the first tertile after adjusting for the potential covariates. The BKMR model revealed a positive overall trend between mixed PAH exposure and female infertility, particularly when the mixture was at or above the 55th percentile, where 2-hydroxynaphthalene (2-OHNAP) and 1-hydroxypyrene (1-OHPYR) were the primary influences of the mixture. The univariate exposure-response function indicated positive associations between individual PAH exposure, specifically 2-OHNAP, 2-OHFLU, and 1-OHPYR, and female infertility. The QGC model also indicated a positive trend between exposure to a mixture of PAHs and female infertility, although it did not reach statistical significance (OR = 1.33, 95%CI: 0.86-2.07), with 1-OHPYR having the greatest positive effect on the outcome. This study suggested that exposure to PAHs may be associated with female infertility and further research is needed to consolidate and confirm these findings.

Vitamin D supplementation in the treatment of polycystic ovary syndrome: A meta-analysis of randomized controlled trials.

Background: Vitamin D level is closely associated with the development of polycystic ovary syndrome (PCOS). We aimed to systematically evaluate the effects of vitamin D supplementation on patients with PCOS, to provide reliable evidence to the clinical treatment of PCOS. Methods: We searched PubMed, Medline, EMbase, Cochrane Library, Web of Science, WanFang, China national knowledge infrastructure(CNKI) and Weipu databases for randomized controlled trials (RCTs) on vitamin D supplementation for the treatment of PCOS. Two reviewers independently screened literature, extracted data and evaluated the risk of bias of included RCTs. RevMan 5.3 software was used for meta-analysis. Results: 13 RCTs with 840 PCOS patients were included finally. Meta-analyses indicated that vitamin D supplementation increase the serum vitamin D level[mean difference(MD) = 17.81, 95% confidence interval(CI) (10.65, 24.97)] and endometrial thickness [MD = 1.78, 95%CI (0.49, 3.06), P = 0.007], reduce the serum hs-CRP [MD = -0.54, 95%CI (-1.00, -0.08)], parathyroid hormone[MD = -14.76, 95%CI (-28.32, -1.19)], total cholesterol[MD = -12.00, 95%CI (-18.36, -5.56)] and total testosterone level [MD = -0.17, 95%CI (-0.29, -0.05)] (all p < 0.05). No significant differences in the SHBG level [MD = 1.33, 95%CI (-2.70, 5.36)] and mF-G score [MD = 0.04, 95%CI (-0.79, 0.86)] between vitamin D and control group were found (all p > 0.05). Egger's tests showed that there were no publication biases in every synthesized result (all P > 0.05). Conclusion: Vitamin D may be helpful to improve the endocrine and metabolism-related indexes in patients with PCOS. More high-quality studies with larger sample size are warranted to further evaluate the role of vitamin D supplementation in patients with PCOS.

Assessment of the risk of unexplained recurrent spontaneous abortion based on the proportion and correlation of NK cells and T cells in peripheral blood.

BACKGROUND: Unexplained recurrent spontaneous abortion (URSA) is difficult to diagnose and treat clinically due to its unknown causeOBJECTIVE: Changes in natural killer (NK) cells, T lymphocytes, and Th1(IFNγ)/Th2(IL-4) cytokines were investigated in the peripheral blood of patients with URSA to examine the pathogenesis, clinical diagnosis, and inform potential treatment strategies for this condition. METHODS: For this study, we selected patients with URSA as the case group and included normal women in the control group. Flow cytometry was performed to detect lymphocytes and cytokines in the peripheral blood of all subjects. RESULTS: The proportion of NK cells, Th1 cells, and the Th1/Th2 ratio were significantly higher in the URSA group compared to the control group; whereas the proportion of CD3+T cells was lower. Pairwise correlation analysis revealed a positive correlation between the percentage of NK cells and CD3+T cells, as well as CD3+CD4+T cells. Canonical correlation analysis indicated a significant correlation between NK cells and T cells, including their subgroups. CONCLUSION: Patients with URSA have immune balance disorders, characterised by an increased proportion of peripheral blood NK cells, Th1, and Th1/Th2 ratio along with a decreased proportion of CD3+T cells. The proportion of NK cells and CD3+T may serve as predictive factors for URSA, while NK cells are closely related to the regulation of CD3+T cells and their subsets. By regulating the level of IFN-γ, NK cells can influence the proportion of CD3+T cells and induce a Th1 (IFNγ)/Th2 (IL-4) imbalance.

Integrated analysis of lncRNA and mRNA expression profiles in patients with unexplained recurrent spontaneous abortion.

PROBLEM: Unexplained recurrent spontaneous abortion (URSA) is one of the most frustrating and confounding conditions in reproductive medicine, and its exact pathogenesis has not been clearly established. METHOD OF STUDY: In this study, we used RNA sequencing to characterize the mRNA and lncRNA expression profiles in peripheral blood. Thereafter, enrichment analysis was performed to determine the functions of the differentially expressed genes, and Cytoscape was used to construct lncRNA-mRNA interaction networks. RESULTS: Our results showed that the peripheral blood of patients with URSA has distinct mRNA and lncRNA expression profiles, with a total of 359 mRNAs and 683 lncRNAs being differentially expressed. Moreover, the top hub genes, including IGF1, PPARG, CCL3, RETN, SERPINE1, HESX1, and PRL, were identified and further validated using real-time quantitative PCR. Furthermore, we demonstrated a lncRNA-mRNA interaction network that achieved 12 key lncRNAs and their targeted mRNAs are involved in systemic lupus erythematosus, allograft rejection, and complement and coagulation cascades. Finally, the correlation between immune cell subtypes and IGF1 expression was evaluated; a negative correlation was observed with the proportion of natural killer cells, which increased significantly in URSA. CONCLUSION: We identified seven top hub genes, constructed a lncRNA-related network and suggested that IGF1 plays a key role in regulating maternal immune response by affecting NK and T cells' function, which helps to identify the pathogenesis of URSA.

[Application of analgesia and sedation under BIS monitoring combined with hydraulic coupling intracranial pressure monitoring in severe craniocerebral injury].

OBJECTIVE: To investigate the clinical value of analgesia and sedation under bispectral index (BIS) monitoring combined with hydraulic coupled intracranial pressure (ICP) monitoring in severe craniocerebral injury (sTBI). METHODS: (1) A prospective self-controlled parallel control study was conducted. A total of 32 patients with sTBI after craniotomy admitted to the intensive care unit (ICU) of the First People's Hospital of Huzhou from December 2020 to July 2021 were selected as the research objects. ICP was monitored by Codman monitoring system and hydraulically coupled monitoring system, and the difference and correlation between them were compared. (2) A prospective randomized controlled study was conducted. A total of 108 sTBI patients admitted to the ICU of the First People's Hospital of Huzhou from August 2021 to August 2022 were selected patients were divided into 3 groups according to the random number table method. All patients were given routine treatment after brain surgery. On this basis, the ICP values of the patients in group A (35 cases) were monitored by Codman monitoring system, the ICP values of the patients in group B (40 cases) were monitored by hydraulic coupling monitoring system, and the ICP values of the patients in group C (33 cases) were monitored combined with hydraulic coupling monitoring system, and the analgesia and sedation were guided by BIS. The ICP after treatment, cerebrospinal fluid drainage time, ICP monitoring time, ICU stay time, complications and Glasgow outcome score (GOS) at 6 months after surgery were compared among the 3 groups. In addition, patients in group B and group C were further grouped according to the waveforms. If P1 = P2 wave or P2 and P3 wave were low, they were classified as compensatory group. If the round wave or P2 > P1 wave was defined as decompensated group, the GOS scores of the two groups at 6 months after operation were compared. RESULTS: (1) There was no significant difference in ICP values measured by Codman monitoring system and hydraulic coupling monitoring system in the same patient (mmHg: 11.94±1.76 vs. 11.88±1.90, t = 0.150, P = 0.882; 1 mmHg≈0.133 kPa). Blan-altman analysis showed that the 95% consistency limit (95%LoA) of ICP values measured by the two methods was -4.55 to 4.68 mmHg, and all points fell within 95%LoA, indicating that the two methods had a good correlation. (2) There were no significant differences in cerebrospinal fluid drainage time, ICP monitoring time, ICU stay time, and incidence of complications such as intracranial infection, intracranial rebleeding, traumatic hydrocephalus, cerebrospinal fluid leakage, and accidental extubation among the 3 groups of sTBI patients (P > 0.05 or P > 0.017). The ICP value of group C after treatment was significantly lower than that of group A and group B (mmHg: 20.94±2.37 vs. 25.86±3.15, 26.40±3.09, all P < 0.05), the incidence of pulmonary infection (9.1% vs. 45.7%, 42.5%), seizure (3.0% vs. 31.4%, 30.0%), reoperation (3.0% vs. 31.4%, 40.0%), and poor prognosis 6 months after operation (33.3% vs. 65.7%, 65.0%) were significantly lower than those in group A and group B (all P < 0.017). According to the hydraulic coupling waveform, GOS scores of 35 patients in the compensated group were significantly higher than those of 38 patients in the decompensated group 6 months after operation (4.03±1.18 vs. 2.39±1.50, t = 5.153, P < 0.001). CONCLUSIONS: The hydraulic coupled intracranial pressure monitoring system has good accuracy and consistency in measuring ICP value, and it can better display ICP waveform changes than the traditional ICP monitoring method, and has better prediction value for prognosis evaluation, which can replace Codman monitoring to accurately guide clinical work. In addition, analgesia and sedation under BIS monitoring combined with hydraulic coupled ICP monitoring can effectively reduce ICP, reduce the incidence of complications, and improve the prognosis, which has high clinical application value.

A missense variant in NCF1 is associated with susceptibility to unexplained recurrent spontaneous abortion.

Unexplained recurrent spontaneous abortion (URSA) is a major concern in reproductive medicine. Neutrophil cytosolic factor 1 (NCF1) polymorphisms leading to low production of reactive oxygen species (ROS) are strongly associated with autoimmune diseases. We investigated the association of the missense single nucleotide polymorphism (SNP) rs201802880 (NCF1-339) in NCF1 with URSA and explored its function. We performed NCF1-339 SNP genotyping of samples from 152 Chinese patients with URSA and 72 healthy controls using nested PCR and TaqMan assays. ROS production and RELA (NF-κB subunit) expression in the blood of participants with different NCF1-339 genotypes were determined. The frequencies of the wild-type (GG) and mutant (GA) genotypes remarkably differed between the URSA and control groups. The mutant genotype was associated with an increased risk of recurrent abortion. Furthermore, ROS levels in the URSA group with the GG genotype were significantly higher than those in the group with the GA genotype (p < 0.05). RELA expression in URSA patients with the GA genotype was considerably higher than that in control individuals with the GG genotype. These findings indicate that mutations in NCF1 may increase the risk of URSA via the NADP/ROS/NF-κB signaling pathway, which has implications for the diagnosis and treatment of URSA.

Long non-coding RNA (lncRNA) HOXD-AS2 promotes glioblastoma cell proliferation, migration and invasion by regulating the miR-3681-5p/MALT1 signaling pathway.

Glioblastoma (GBM) is the most lethal type of brain cancer. An increasing number of studies suggest that long non-coding RNAs (lncRNAs) are implicated in tumor progression. LncRNA HOXD-AS2 was reported to be highly expressed in glioma and associated with glioma grade and poor prognosis. However, the molecular mechanism remains to be elucidated. In this study, we first analyzed differentially expressed lncRNAs in glioblastoma using RNA-seq dataset (156 GBM samples and 5 adjacent normal samples in TCGA (Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) database). HOXD-AS2 was found to be significantly up-regulated in GBM tissues, which was further confirmed in GBM patient tumor samples and GBM cell lines. Silencing HOXD-AS2 inhibited cell proliferation, migration and invasion, and promoted cell apoptosis. We further identified and validated miR-3681-5p as a target of HOXD-AS2, and miR-3681-5p was negatively regulated by HOXD-AS2. By negatively affecting miR-3681-5p, HOXD-AS2 could promote the expression of MALT1 to augment the aggressiveness of GBM cells. miR-3681-5p overexpression or MALT1 knockdown attenuated aggressiveness of GBM cells. Importantly, silencing HOXD-AS2 suppressed tumorigenesis of GBM cells in the xenograft mouse model. Collectively, our study clarified the role of miR-3681-5p/MALT1 axis underlying the oncogenic function of lncRNA HOXD-AS2 in GBM. Future work is required to study the mechanism by which HOXD-AS2 is upregulated in GBM cells, which can provide novel insights into therapeutic intervention for GBM treatment.