Role of non-coding RNAs and exosomal non-coding RNAs in vasculitis: A narrative review.

A category of very uncommon systemic inflammatory blood vessel illnesses known as vasculitides. The pathogenesis and etiology of vasculitis are still poorly known. Despite all of the progress made in understanding the genetics and causes behind vasculitis, there is still more to learn. Epigenetic dysregulation is a significant contributor to immune-mediated illnesses, and epigenetic aberrancies in vasculitis are becoming more widely acknowledged. Less than 2 % of the genome contains protein-encoding DNA. Studies have shown that a variety of RNAs originating from the non-coding genome exist. Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) have attracted the most attention in recent years as they are becoming more and more important regulators of different biological processes, such as diseases of the veins. Extracellular vehicles (EVs) such as exosomes, are membrane-bound vesicular structures that break free either during programmed cell death, such as apoptosis, pyroptosis, and necroptosis or during cell activation. Exosomes may be involved in harmful ways in inflammation, procoagulation, autoimmune reactions, endothelial dysfunction/damage, intimal hyperplasia and angiogenesis, all of which may be significant in vasculitis. Herein, we summarized various non-coding RNAs that are involved in vasculitides pathogenesis. Moreover, we highlighted the role of exosomes in vasculitides.

Simultaneous transfer of one good-quality and one poor-quality cleavage stage embryo does not improve pregnancy outcomes.

Embryo quality and quantity are key factors that determine the success of IVF-ET. Yet it is still unclear if, for those patients with only one good-quality embryo in an IVF cycle, the inclusion of a poor-quality embryo increases the procedure's success rate. This is a common question for both clinicians and patients in determining their course of treatment. The purpose of this work was to answer this intriguing question in the context of prognosis of patients undergoing fresh cycles with only one good-quality and more than one poor-quality cleavage-stage embryos. To control for confounding effects, we only included patients at similar age, body mass index (BMI), level of basal follicle stimulating hormone (FSH) and endometrial thickness from January 2015 to June 2021. A propensity score-matched analysis was performed to extract the matched pairs. Then we evaluated pregnancy outcome, including the rate of clinical pregnancy, live birth, embryo implantation, early miscarriage, and ectopic pregnancy. We found that the clinical pregnancy rate (34.8 vs. 38.0%, p = 0.553), live birth rate (27.1 vs. 29.9%, p = 0.598), early miscarriage rate (18.1 vs. 9.5%, p = 0.171) and ectopic pregnancy rate (1.3 vs. 1.2%, p = 1.000) did not significantly differ between those two groups, notwithstanding significant difference of the implantation rate (34.8 vs. 21.3%, p <0.001). Our work indicates that, for prognosis patients at approximately 34 years old with only one good-quality embryo, having additional poor-quality embryos does not seem to help to improve ART success rates per intended embryo transfer. In conclusion, we found that simultaneous transfer of one good-quality and one poor-quality cleavage stage embryo does not improve pregnancy outcomes.

Improvement of Qilin pills on male reproductive function in tripterygium glycoside-induced oligoasthenospermia in rats.

This study established an oligoasthenospermic rat model using tripterygium glycosides (TGs) and investigated the mechanism by which Qilin pills (QLPs) ameliorate reproductive hypofunction. Thirty-two male Sprague Dawley rats were allocated to four equal-sized groups: (1) the control group received continuous physiological levels of saline; (2) the oligoasthenospermia model group was induced with TGs by daily intragastric administration for 28 days; (3 and 4) oligoasthenospermic rats were treated intragastrically with low dose (1.62 g kg-1  d-1 ) and high dose (3.24 g kg-1  d-1 ) of QLPs once daily for 60 days. The QLP-treated rats showed a marked increase (p < .05) in testicular mass, testicular index and semen parameters compared with the untreated rats. Histopathologically, the QLP-treated groups exhibited restored seminiferous tubules in contrast to the model group. Reactive oxygen species and malondialdehyde levels were dramatically decreased (p < .05) in the testes of the QLP-treated rats. QLP treatment partly reverted (p < .05) the circulatory levels of reproductive hormones (FSH, LH, testosterone, prolactin and SHBG) and hepatic and renal function (AST, Cr and urea). Our results showed that oral QLP treatment had a curative effect on the testicular mass, sperm quality, testicular pathomorphology, antioxidants, plasmatic hormones, and liver and renal function of rats.

MiR-93 Inhibits Trophoblast Cell Proliferation and Promotes Cell Apoptosis by Targeting BCL2L2 in Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion (RSA) is a common health problem that affects 1-5% of women in reproductive age. Plenty of studies have indicated that microRNAs (miRNAs) are involved in the occurrence of miscarriage. MiR-93 has a wide range of functions in mammalian tissues and plays an important role in many diseases especially for cancers. However, it remains unknown whether miR-93 is associated with human RSA. In this report, clinical samples revealed that miR-93 expression was significantly elevated in the villi tissues of RSA patients. Upregulation of miR-93 inhibited human trophoblast cells HTR-8/SVneo cell proliferation, migration, and invasiveness, but promoted cell apoptosis in vitro. Conversely, the downregulation of miR-93 reversed these effects. Bcl-2 like protein 2 (BCL2L2), a potential target gene of miR-93, was inversely correlated with miR-93 expression in the villi of clinical samples. Furthermore, the luciferase reporter system demonstrated that miR-93 directly downregulated the expression of BCL2L2 by binding a specific sequence of its 3'-untranslated region (3'UTR). Collectively, these data strongly suggest that miR-93 regulates trophoblast cell proliferation, migration, invasive, and apoptosis by targeting BCL2L2 expression and is involved in the pathogenesis of RSA.

Effects of Qilin pills on spermatogenesis, reproductive hormones, oxidative stress, and the TSSK2 gene in a rat model of oligoasthenospermia.

BACKGROUND: Qilin pills (QLPs), a classic Traditional Chinese Medicine (TCM) formula for treating male infertility, effectively improve semen quality in clinical trials. This study was designed to evaluate the effects of QLPs on spermatogenesis, reproductive hormones, oxidative stress, and the testis-specific serinekinase-2 (TSSK2) gene in a rat model of oligoasthenospermia. METHODS: Forty adult male Sprague-Dawley (SD) rats were randomly divided into four groups. The rat model with oligoasthenospermia was generated by intragastric administration of tripterygium glycosides (TGs) once daily for 4 weeks. Then, two treatment groups were given different doses (1.62 g/kg and 3.24 g/kg) of QLPs once daily for 60 days. Sperm parameters, testicular histology and reproductive hormone measurements, oxidative stress tests, and TSSK2 expression tests were carried out. RESULTS: QLPs effectively improved semen parameters and testicular histology; restored the levels of FSH, LH, PRL, fT, and SHBG; reduced the levels of oxidative stress products (ROS and MDA); increased testicular SOD activity; and restored the expression of spermatogenesis-related gene TSSK2. CONCLUSION: QLPs have a therapeutic effect on a rat model of oligoasthenospermia, and this effect is manifested as improvement of semen quality and testis histology, gonadal axis stability, decreased oxidative stress, and the regulation of testis-specific spermatogenesis-related gene TSSK2.

Analysis of interleukin-17 and interleukin-18 levels in animal models of atherosclerosis.

This study investigated the correlation between the levels of interleukin (IL)-17 and IL-18 and atherosclerotic plaques. A total of 60 Apo E gene (Apo E-/-) mice were fed with high-fat diet in the model group and 20 wild male C57BL/6 mice were fed with the basic diet in the control group. The serum levels of IL-17 and IL-18 were determined by enzyme-linked immunosorbent assay. Carotid artery ultrasonography was performed and divided into stable plaque, unstable plaque and non-plaque groups. The severity of plaque was estimated by semi-quantitative method and divided into grades I, II and III. The expression levels of low-density lipoprotein cholesterol, plasma total cholesterol and blood glucose level in the model group induced by high-fat diet were significantly higher than those in the control group (P<0.05). The level in the model group was significantly higher than in the control group at the 16th week (P<0.05). The expression of IL-17 and IL-18 in the model group was significantly higher than that in the control group (t=6.903, 11.02, P<0.05). The concentration of IL-17 and IL-18 in the non-plaque group was significantly lower than that in the stable plaque and unstable plaque groups (P<0.05). The concentration of IL-17 and IL-18 in the stable plaque group was significantly lower than that in the unstable plaque group (P<0.05). Based on the correlation of IL-17 and IL-18 expressions in the model group, the expression of IL-18 increased with the expression of IL-17, indicating that the expression of IL-17 was positively correlated with that of IL-18 (r=0.7195, P<0.001). In conclusion, serum IL-17 and IL-18 played an important role in the formation and development of atherosclerotic plaque, and were related to the stability and severity of plaque. The expression of IL-17 and IL-18 was positively correlated.

[Application and Development of Rehabilitation System of Intelligent Lower Limb Rehabilitation Based on Intelligent Medical Treatment].

To develop an intelligent lower limb rehabilitation instrument which could realize the quantification and visualization of lower limbs' raising angle and frequency, using the smart client to realize the remote control, autonomous data acquisition and the establishment of database. Doctors had the access to the database in order to adjust the rehabilitation program in time to meet the individual requirement. We realized the design of intelligent lower limb instrument based on the Andriod smartphone, which is suitable for clinical and family use.

A Case-Control Study Indicates that no Association Exists Between Polymorphisms of IL-33 and IL-1RL1 and Preeclampsia.

BACKGROUND/AIMS: Preeclampsia (PE) is a systemic inflammatory response syndrome involving varieties of cytokines, and previous studies have shown that IL-33 and its receptor IL-1RL1 play pivotal roles in the development of it. As a polygenetic hereditary disease, it is necessary to study the gene analysis for PE. Therefore, the present study was to determine whether IL-33 rs3939286 and IL-1RL1 rs13015714 associated with susceptibility to PE in Chinese Han women. METHODS: 1,031 PE patients and 1,298 controls were enrolled and the genotyping for rs3939286 in IL-33 and rs13015714 in IL-1RL1 was performed by TaqMan allelic discrimination real-time PCR. Hardy-Weinberg equilibrium (HWE) was examined to ensure the group representativeness and Pearson's chi-square test was used to compare the differences in genetic distributions between the two groups. RESULTS: No significant differences in genotypic and allelic frequencies of the two polymorphisms loci were observed between cases and controls. There were also no significant differences in genetic distributions between mild/severe and early/late-onset PE and control groups. CONCLUSION: Although our data suggested that the polymorphisms of IL-33 rs3939286 and IL-1RL1 rs13015714 might not be critical risk factors for PE in Chinese Han women, the results need to be validated in different nations.

Association study of dopamine transporter gene (DAT1) variable tandem repeat sequence (VNTR) with obsessive-compulsive disorder in Chinese Han Population.

OBJECTIVE: Multiple evidence suggests an involvement of the dopamine neurotransmitter system in Obsessive-compulsive disorder (OCD). Therefore, we explore the association of 3'UTR region of 40 bp variable tandem repeat (VNTR) polymorphism in Dopamine Transporter Gene (DAT1) in Chinese Han population. METHODS: A total of 305 OCD patients and 435 healthy individuals were recruited for the study. OCD was diagnosed with the Forth Edition (DSM-IV) diagnostic criteria. After polymerase chain reaction of VNTR was used to evaluate the 40 bp VNTR polymorphism in DAT1, a case-control association analysis was performed by the χ(2) test. RESULTS: The results showed that no association was found between OCD patients and controls for the genotype distribution (X(2) =0.743, P=0.690, df=2) as well as allelic (X(2)=0.172, P=0.678, OR=0.928, 95% Cl=0.885-1.224) distribution. CONCLUSIONS: Our data suggest that the 40 bp VNTR polymorphism in DAT1 may not be associated with susceptibility to OCD in the Chinese Han population studied. However, this result needed to be replicated from different populations.

Methylation and Expression of Retinoblastoma and Transforming Growth Factor-ß1 Genes in Epstein-Barr Virus-Associated and -Negative Gastric Carcinomas.

Background. Retinoblastoma (RB) and transforming growth factor-ß1 (TGF-ß1) are important tumor-related factors. Methods. A series of 30 EBV-associated gastric carcinoma (EBVaGC) and 38 matched EBV-negative gastric carcinoma (EBVnGC) tissues were examined for the promoter methylation of RB by methylation-specific PCR (MSP) method. The expression of RB and TGF-ß1 in gastric carcinoma tissues was detected by immunohistochemistry. Results. The methylation rate of RB gene in EBVaGC and EBVnGC was 80.0% (24/30) and 50.0% (19/38), respectively. The difference of RB methylation rate between EBVaGC and EBVnGC was significant (χ(2) = 6.490, P = 0.011). There was no significant difference for RB expression between EBVaGC (43.3%, 13/30) and EBVnGC (63.2%, 24/38), and also for TGF-ß1 between EBVaGC (56.7%, 17/30) and EBVnGC (63.2%, 24/38). RB methylation was not reversely correlated with RB expression in gastric carcinoma tissues (χ(2) = 2.943, P = 0.086, r = 0.208). RB methylation, loss expression of RB, and TGF-ß1 expression were significantly associated with tumor invasion and lymph node metastasis (P < 0.05), but was not associated with sex, age, histological subtype (differentiation status) and tumor location. Conclusions. Methylation of RB is a common event in gastric carcinomas and EBV induces methylation of RB in EBVaGC, which may contribute to the development of gastric carcinomas. EBV has no significant effect on induction of TGF-ß1 expression. Detection of RB methylation, RB expression, and TGF-ß1 expression may be helpful to judge the status of tumor invasion and lymph node metastasis in gastric carcinomas.

Sequence variation of Epstein-Barr virus (EBV) BZLF1 gene in EBV-associated gastric carcinomas and nasopharyngeal carcinomas in Northern China.

Epstein-Barr virus (EBV) BZLF1 gene can trigger EBV from latent infection to lytic replicative phase. The functions of BZLF1 are well known, while little is known about its gene polymorphism. In order to elucidate the sequence variations of BZLF1 and its association with malignancies, we analyzed BZLF1 gene in 24 EBV-associated gastric carcinomas, 41 nasopharyngeal carcinomas and 24 throat washing samples from healthy donors in Northern China using PCR-direct sequencing method. Three types and 8 subtypes of BZLF1 were identified. A dominant type BZLF1-A was found in 67 of 89 (75.3%) isolates. Type BZLF1-B was characterized by a common Ala deletion at residue 127, which was detected in 21 of 89 isolates (23.6%). Type BZLF1-C contained only one isolate (GC103), which had the same sequence with the prototype B95-8. Among 3 functional domains of BZLF1 protein, the transactivation domain had most mutations, followed by the bZIP domains (the DNA binding domain and dimerization domain). No prevalence of any subtypes or mutations in the functional domains among three specimen groups was found (P > 0.05). Our study indicates that BZLF1 subtypes and amino acid changes in functional domains are not preferentially associated with EBV-associated gastric carcinomas or nasopharyngeal carcinomas in Northern China. BZLF1 gene variations are geographically restricted rather than tumor-specific polymorphisms.

[Association study between a polymorphism of aldosterone synthetase gene and the pathogenesis of polycystic ovary syndrome].

OBJECTIVE: To investigate the relationship between -344T polymorphism in aldosterone synthetase (CYP11B2) gene promoter region and the pathogenesis of polycystic ovary syndrome (PCOS). METHODS: Ninety two patients with PCOS and controls were genotyped according to the fragment length (273 bp and or 202 bp) of CYP11B2 gene promoter by the technique of polymerase chain reaction-restriction fragment length polymorphism. The levels of luteinizing hormone, follicular stimulating hormone, estrodiol, progesterone, prolactin, testosterone, plasma renin activity (PRA), plasma angiotensin II (PANG II) and aldosterone in the basal state were also determined. Different genotypes between PCOS were compared about their levels of PRA, PANG II, aldosterone and testosterone. RESULTS: (1) The C allele frequencies of CYP11B2 gene in control and PCOS was 22% and 36%, respectively. (2) The frequency of variants (TC, CC) of CYP11B2 gene -344T polymorphism site in PCOS (57%) was significantly higher than that of control subjects (37%). (3) The level of PRA, PANG II, aldosterone, testosterone were all significantly higher in the genotype of -344CC than in that of -344TT in PCOS and normal women (P < 0.01). CONCLUSIONS: (1) The variants (T-->C) of -344T polymorphism site of CYP11B2 gene predisposes increased risk of PCOS. (2) The genotype of -344CC, -344TC may be susceptible genotype of PCOS and has related to the enhanced functional activity of ovarian renin angiotensin system in PCOS.