Cordyceps militaris Extract and Cordycepin Alleviate Oxidative Stress, Modulate Gut Microbiota and Ameliorate Intestinal Damage in LPS-Induced Piglets.

Cordycepin is considered a major bioactive component in Cordyceps militaris extract. This study was performed to evaluate the ameliorative effect of Cordyceps militaris extract (CME) and cordycepin (CPN) supplementation on intestinal damage in LPS-challenged piglets. The results showed that CPN or CME supplementation significantly increased the villus height (p < 0.01) and villus height/crypt depth ratio (p < 0.05) in the jejunum and ileum of piglets with LPS-induced intestinal inflammation. Meanwhile, CPN or CME supplementation alleviated oxidative stress and inflammatory responses by reducing the levels of MDA (p < 0.05) and pro-inflammatory cytokines in the serum. Additionally, supplementation with CPN or CME modulated the structure of the intestinal microbiota by enriching short-chain fatty acid-producing bacteria, and increased the level of butyrate (p < 0.05). The RNA-seq results demonstrated that CME or CPN altered the complement and coagulation-cascade-related genes (p < 0.05), including upregulating gene KLKB1 while downregulating the genes CFD, F2RL2, CFB, C4BPA, F7, C4BPB, CFH, C3 and PROS1, which regulate the complement activation involved in inflammatory and immune responses. Correlation analysis further demonstrated the potential relation between the gut microbiota and intestinal inflammation, oxidative stress, and butyrate in piglets. In conclusion, CPN or CME supplementation might inhibit LPS-induced inflammation and oxidative stress by modulating the intestinal microbiota and its metabolite butyrate in piglets.

Preimplantation genetic testing as a means of preventing hereditary congenital myasthenic syndrome caused by RAPSN.

BACKGROUND: Congenital myasthenic syndrome is a heterogeneous group of inherited neuromuscular transmission disorders. Variants in RAPSN are a common cause of CMS, accounting for approximately 14%-27% of all CMS cases. Whether preimplantation genetic testing for monogenic disease (PGT-M) could be used to prevent the potential birth of CMS-affected children is unclear. METHODS: Application of WES (whole-exome sequencing) for carrier testing and guidance for the PGT-M in the absence of a genetically characterized index patient as well as assisted reproductive technology were employed to prevent the occurrence of birth defects in subsequent pregnancy. The clinical phenotypes of stillborn fetuses were also assessed. RESULTS: The family carried two likely pathogenic variants in RAPSN(NM_005055.5): c.133G>A (p.V45M) and c.280G>A (p.E94K). And the potential birth of CMS-affected child was successfully prevented, allowing the family to have offspring devoid of disease-associated variants and exhibiting a normal phenotype. CONCLUSION: This report constitutes the first documented case of achieving a CMS-free offspring through PGT-M in a CMS-affected family. By broadening the known variant spectrum of RAPSN in the Chinese population, our findings underscore the feasibility and effectiveness of PGT-M for preventing CMS, offering valuable insights for similarly affected families.

Inhibition of ATM promotes PD-L1 expression by activating JNK/c-Jun/TNF-α signaling axis in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer. Anti-PD-1/PD-L1 treatment for advanced TNBC is still limited to PD-L1-positive patients. Ataxia telangiectasia mutated (ATM) is a switch molecule for homologous recombination and repair. In this study, we found a significant negative correlation between ATM and PD-L1 in 4 TNBC clinical specimens by single-cell RNA sequencing (scRNA-seq), which was confirmed by immunochemical staining in 86 TNBC specimens. We then established ATM knockdown TNBC stable cell lines to perform in vitro studies and animal experiments, proving the negative regulation of PD-L1 by ATM via suppression of tumor necrosis factor-alpha (TNF-α), which was confirmed by cytokine array analysis of TNBC cell line and analysis of clinical specimens. We further found that ATM inhibits TNF-α via inactivating JNK/c-Jun by scRNA-seq, Western blot and luciferase reporter assays. Finally, we identified a negative correlation between changes in phospho-ATMS1981 and PD-L1 levels in TNBC post- and pre-neoadjuvant therapy. This study reveals a novel mechanism by which ATM negatively regulates PD-L1 by downregulating JNK/c-Jun/TNF-α in TNBC, shedding light on the wide application of immune checkpoint blockade therapy for treating multi-line-resistant TNBC.

Novel IARS1 variants cause syndromic developmental disorder with epilepsy in a Chinese patient and the literature review.

BACKGROUND: Isoleucinyl-tRNA synthetase (IARS) is encoded by the IARS1 gene and catalyzes the binding of isoleucine to specific tRNA. OBJECTIVE: This study aims to investigate the pathogenicity of novel IARS1 variants and the genotype-phenotype association, in order to expand the spectrum of pathogenic variants and phenotypes of IARS1-related disease and provide new evidence for the phenotypic spectrum of IARS1 variants. METHODS: Clinical data of the proband were collected, and trio whole-exome sequencing (WES) was performed on the proband and the parents. Candidate variants were validated using Sanger sequencing. Bioinformatics software was utilized to analyze the functional consequences of identified variants and predict their potential deleteriousness. RESULTS: A 17-month-old female patient presented with microcephaly, left external ear malformation, decreased muscle strength and tone in all limbs, epileptic seizures, global developmental delay, and developmental regression. Trio WES identified compound heterozygous variants in the IARS1 gene, c.120-1G>A and c.2164C>A, which were novel pathogenic and likely pathogenic variants, respectively. The phenotype of developmental regression has not been reported before. Only one patient with IARS1 compound heterozygous variants has been reported in the world to have an epileptic phenotype, and this is the second patient with an epileptic phenotype. Bioinformatics analysis revealed that the splicing variant disrupted the canonical splice donor site, while the missense variant altered the local electrostatics of the IARS1 protein surface, potentially leading to functional abnormalities. CONCLUSION: This study identified novel IARS1 variants and the phenotype of developmental regression, expanding the spectrum of pathogenic variants and phenotypes of IARS1-related diseases and providing new evidence for the rare phenotype of epileptic seizures caused by IARS1 variants.

Atypical scanning strategies of emotional faces for individuals with high autistic traits.

Autism has become one of the primary diseases causing disability in children, and the incidence has risen rapidly in recent years. The preclinical study on individuals with high autistic traits is extremely important to reduce genetic risks of autism because high autistic traits is the susceptibility marker of autism. However, few studies explored the face scanning pattern of people with high autistic traits in typical developing populations. In this study, we designed a facial emotion recognition experiment including four emotions (happy, neutral, sad, angry) and three angles (0°, 45°, 90°) , and informed the participants to identify the facial emotion. Forty-two college students with typical development were recruited and divided into high autistic traits (HAT) group and low autistic traits (LAT) group by the Autism-Spectrum Quotient, and we collected the eye movement data using eye-tracking technology when they performed the task. The response time, recognition accuracy, AOI based proportional fixation time and pupil diameter were computed and analyzed for both groups. HATs showed significantly lower recognition accuracy and lower pupil diameter than LATs when recognizing negative emotions (P<0.05) , indicating HATs kept poor autonomic nervous arousal. What ' s more, the proportional fixation time of HATs were significantly more in mouth area but less in eye area than that of LAT group (P<0.05) , revealed HATs had an atypical emotional faces scanning strategies that paid less attention to eyes and more attention to mouth. Our research provides a feasible objective biomarker for screening high autistic traits population.

[Genetic analysis of a child with Complex cortical dysplasia with other brain malformations type 6 due to a p.M73V variant of TUBB gene].

OBJECTIVE: To explore the genetic basis for a child with multiple malformations. METHODS: A child who had presented at Shanxi Provincial Children's Hospital in February 2021 was selected as the study subject. Clinical data of the patient was collected, and whole exome sequencing (WES) was carried out to screen pathogenic variants associated with the phenotype. Candidate variant was validated by Sanger sequencing of her family members. RESULTS: The child had normal skin, but right ear defect, hemivertebral deformity, ventricular septal defect, arterial duct and patent foramen ovale, and separation of collecting system of the left kidney. Cranial MRI showed irregular enlargement of bilateral ventricles and widening of the distance between the cerebral cortex and temporal meninges. Genetic testing revealed that she has harbored a heterozygous variant of NM_178014.4: c.217A>G (p.Met73Val) in the TUBB gene, which was unreported previously and predicted to be likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The child was diagnosed with Complex cortical dysplasia with other brain malformations 6 (CDCBM6). CONCLUSION: CDCBM is a rare and serious disease with great genetic heterogeneity, and CDCBM6 caused by mutations of the TUBB gene is even rarer. Above finding has enriched the variant and phenotypic spectrum of the TUBB gene, and provided important reference for summarizing the genotype-phenotype correlation of the CDCBM6.

Correlation of TGF-ß signaling pathway gene polymorphisms with unexplained recurrent spontaneous abortion.

BACKGROUND: The association of key genes in the transforming growth factor-ß (TGF-ß) signaling pathway and their gene polymorphisms with unexplained recurrent spontaneous abortion (URSA) is unclear. OBJECTIVE: To investigate the association of gene polymorphisms related to the TGF-ß signaling pathway in URSA women. METHODS: The study population consisted of 80 women with URSA and 90 normal control women, of which 10 women with URSA and 10 normal control women underwent high-throughput sequencing to select loci, and the remaining 70 women with URSA and 80 normal control women underwent flight mass spectrometry experiments to verify gene loci polymorphism. A total of 7 polymorphic loci in interleukin-6 (IL-6), TGF-ß1, TNF-α, SMAD1, and TNFRSF4 genes were screened by high-throughput sequencing combined with a review of databases. An SNP flight mass spectrometer (Mass ARRAY detection system) was applied to detect the polymorphisms and their frequencies in 70 women with URSA and 80 normal control women at the 7 gene loci. RESULTS: Among the 7 loci of IL-6, TGF-ß1, TNF-α, SMAD1, and TNFRSF4 genes, 2 loci were found to have significantly different allele and genotype frequency distributions between the 70 URSA and 80 normal controls, one was the IL-6 gene -174G/C locus (rs1800795), the risk of disease was 2.636 and 3.231 times higher in individuals carrying the C allele and CC genotype than in those carrying the G allele and GG genotype, respectively; the other was the TGF-ß1 gene -509T/C locus (rs1800469), and the risk of disease was 1.959 and 3.609 times higher in individuals carrying the T allele and TT genotype than in those carrying the C allele and CC genotype, respectively. The remaining 5 genetic loci have no statistically significant. CONCLUSION: IL-6 gene -174G/C locus (rs1800795) genotype CC and allele C may be the causative factor of URSA, TGF-ß1 gene -509T/C locus (rs1800469) genotype TT and allele T may be the causative factor of URSA, and polymorphisms of the 2 loci may be associated with URSA.

Prenatal diagnosis in a fetuses with a clenched hands, overlapping fingers, and clubfoot due to MED12 deficiency in three affected siblings: A case report.

A fetal clenched hand with overlapping fingers is more common in aneuploidy syndrome and was not well-documented in MED12 deficiency. This study reports the clinical and genetic findings of three affected siblings from a Chinese family. The chromosome karyotype analysis diagram shows that karyotypes of the three children were normal. Trio whole-exome sequencing and Sanger sequencing verification found that there was a MED12 R296Q variant in normal mothers and their two offspring. A pattern of clenched hand with overlapping fingers (clinodactyly) and clubfoot was found in all the three affected siblings by three-dimensional ultrasound. The discovery of this case shows that even if the chromosome karyotype is normal, comprehensive prenatal genetic diagnosis is required when the ultrasound results show a clenched hand with clinodactyly and clubfoot symptoms.

Effects of tumor-infiltrating lymphocytes on nonresponse rate of neoadjuvant chemotherapy in patients with invasive breast cancer.

High level of tumor-infiltrating lymphocytes (TILs) can predict the rate of total pathological complete remission (tpCR) of breast cancer patients who receive neoadjuvant chemotherapy (NACT). This study focused on evaluating the data of patients whose primary tumor and/or lymph node metastasis show nonresponse (NR) to NACT, trying to provide a basis for the clinical decision which patients will develop NACT resistance. The study included breast cancers from 991 patients who received NACT. ROC curve analysis confirmed that TILs showed significant predictive value for NR of hormone receptor (HR)+HER2- and triple-negative breast cancer (TNBC). Among HR+HER2- breast cancer, TILs ≥ 10% was an independent predictor for low NR rate. Furthermore, positive correlation of TILs with Ki67 index and Miller-Payne grade, and negative correlation with ER and PR H-scores were only identified in this subgroup. In TNBC, TILs ≥ 17.5% was an independent predictor for low NR rate. The predictive value of low TILs on NR may facilitate to screen patients with HR+HER2- or TNBC who may not benefit from NACT. HR+HER2- breast cancer with low levels of TILs should be carefully treated with neoadjuvant chemotherapy, and other alternatives such as neoadjuvant endocrine therapy can be considered.

Mental health and academic achievement among Chinese adolescents during COVID-19 pandemic: The mediating role of self-regulation learning.

The changes that COVID-19 pandemic has brought upon the world are unprecedented. Its impact on students' learning is equally profound, making it critical to heed students' academic achievement effects that may derive from these alterations. Therefore, the present study explored an integrative model of mental health, self-regulated learning and academic achievement among adolescents during the pandemic. Participants were 1001 senior high school students (Mage = 17.00, SDage = 0.78, 48.7% female) from China. Results showed that the degree to which students were mentally healthy was not significantly related to academic achievement, whereas academic achievement and mental health were positively associated with self-regulated learning. Following structural equation modelling analysis, the effect of mental health on academic achievement was fully mediated by self-regulated learning. Taken together, the findings emphasised the necessity of developing self-regulated learning strategies during public health emergencies and have clinical and educational implications for planning psychological interventions in order to improve mental health and academic performance as well.

Dynamic eye avoidance patterns in the high autistic traits group: An eye-tracking study.

Introduction: Reduced fixation to the eye area is the main characteristic of social deficits associated with Autism Spectrum Disorder; a similar pattern may exist in individuals with high autistic traits. However, their scanning patterns to the eye area of emotional faces are still unclear on the time scale. Methods: In the present study, we recruited 46 participants and divided them into the high autistic traits (HAT) group (23 participants) and the low autistic traits (LAT) group (20 participants) based on their Autism Spectrum Quotient (AQ) scores. Moreover, we captured their eye movement patterns when observing different angular emotional faces. We extracted the proportional fixation time to the eye area under different time windows. Results: The results showed that the fixation time of the HAT group was always significantly smaller than that of the LAT group (p < 0.05), and the difference between the two groups increased in the middle and late stages of face presentation. The results of the linear regression analysis showed that the proportional fixation time was negatively correlated with AQ scores (p < 0.05), indicating that the proportional fixation time to the eye area could be a potential indicator to measure the level of autistic traits. We then calculated the latency to orient the eye area and the latency to disengage the eye area to explore the priority of observation of the eyes. The results showed that compared with the LAT group, the HAT group has a longer latency to orient the eye area (p < 0.05) and has longer latency to disengage the eye area (p < 0.05), illustrating that the HAT group saw the eyes more slowly and left them faster.

STAT3 and PD-L1 are negatively correlated with ATM and have impact on the prognosis of triple-negative breast cancer patients with low ATM expression.

INTRODUCTION: Triple-negative breast cancer (TNBC) is known for its aggressive behaviors and lacking of effective treatment. Programmed cell death ligand-1 (PD-L1) inhibitor has just been approved for using in the management of advanced TNBC. To accurately screen TNBC sensitive to anti-PD-L1 treatment and to explore the feasibility of the ataxia-telangiectasia mutation protein (ATM) inhibitor combined with PD-L1 inhibitor, radiotherapy and chemotherapy, we focus on whether ATM participates in the regulation of PD-L1 and affects the prognosis of patients through c-Src, signal transducer and activator of transcription 1&3 (STAT1 and STAT3). MATERIALS AND METHODS: We used immunohistochemical staining to explore the relationship of ATM with c-Src, STAT1, STAT3, PD-1/PD-L1, Tumor-infiltrating lymphocytes (TILs), as well as other clinicopathologic features in 86 pathological stage III TNBCs. Their impact on prognosis was also explored. RESULTS: We found ATM expression was negatively correlated with STAT1, STAT3, PD-L1, TILs and CD8 + cells in TNBC. STAT1 positively correlated the expression of PD-L1. In TNBC with ATM low expression, STAT3 was an independent factor for improved prognosis, while PD-L1 was an independent negative prognostic factor. Furthermore, in low ATM group, the phosphorylation of tyrosine at position 419 of c-Src (p-c-src Y419) was correlated with the overexpression of STAT3. CONCLUSION: Locally advanced TNBC with low ATM expression may be more likely to benefit from anti-PD-L1 inhibitors. The feasibility of ATM functional inhibitor combined with immune checkpoint blockade therapies in the treatment of TNBC is also worthy of further exploration. Our study suggests that STAT3 has different impacts on tumor progression in different tumors.

miR-30 inhibits the progression of osteosarcoma by targeting MTA1.

OBJECTIVES: MicroRNAs (miRNAs) have been considered as a new class of novel diagnostic and predictive biomarker in many diseases. However, there are few studies on miRNA in osteosarcoma (OS). This study aimed to investigate the roles of miR-30 on OS occurrence and development. METHODS: PCR was used to detect mRNA levels of miR-30 and MTA1 in cancer tissues, adjacent non-cancerous tissues from OS patients. Western blot was used to detect MTA1 protein expression in all tissues and cell lines (hFOb1.19,Saos-2, MG63, and U2OS). The correlation between miR-30 and MTA1 was predicted through bioinformatics software, and identified by a luciferase reporting experiment. In vitro, functional test detected the specific effects of miR-30 and MTA1 on the development of OS. RESULTS: miR-30 expression was significantly reduced, while the expression of MTA1 was increased in OS tissues and cells. Luciferase reporting experiment showed that miR-30 sponged MTA1 which was negatively correlated with miR-30 expression. Furthermore, rescue tests revealed that MTA1 restrained the functions of miR-30 on cell proliferation and migration of OS. CONCLUSION: Our finding showed that miR-30 modulated the proliferation and migration by targeting MTA1 in OS.

Supplementation with Fermented Feedstuff Enhances Orexin Expression and Secretion Associated with Increased Feed Intake and Weight Gain in Weaned Pigs.

The health status of weaned pigs is crucial for their subsequent growth performance. Supplementation with fermented feedstuff is able to improve the feed intake and growth of weaned pigs; however, the exact mechanism behind this is not clear. Hence, in the present study a total of 320 Duroc × Landrace × Yorkshire weaned pigs were selected and allocated to the following two groups: unfermented diet group (UFD) and fermented diet group (FD). The experimental period lasted 21 days. At the end of the experiment, feces, blood, and gastrointestinal tissue samples (including the stomach, jejunum, and ileum) were collected and used for further analysis. The results of growth performance suggested that the FD group had significantly increased (p < 0.05) average daily feed intake (ADFI) and average daily gain (ADG) during the first week, during the last two weeks, and over the entire three-week period compared with the UFD group. The results of the apparent nutrient digestibility of pigs showed that, compared with the UFD group, the FD group showed increased phosphorus (p < 0.05) and CP (p < 0.1) digestibility. There were no significant differences in the serum biochemical parameters between the UFD and FD groups. Moreover, our results showed that the FD group showed significantly increased gene expression of SGLT1 and PepT1 in the jejunum (p < 0.05). Compared with the UFD group, the FD group showed an increased (p < 0.05) serum orexin level and prepro-orexin (PPOX) expression in the gastric fundus, jejunum, and ileum mucosa and increased IGF-1 and IGFR expression in the jejunum. Collectively, these results indicated that supplementation with fermented feedstuff in the diet effectively enhanced the feed intake and growth of weaned pigs and that this may have been caused by the increased orexin, IGF-1, and IGFR serum levels.

Carcinoma-associated fibroblasts promote the proliferation and metastasis of osteosarcoma by transferring exosomal LncRNA SNHG17.

Cancer-associated fibroblasts (CAFs) serve as a predominant regulator in the tumor microenvironment. However, the crosstalk between CAFs and OS cells remains mostly unclear. Recent studies explored that long non-coding RNA (LncRNAs) involved in regulating osteosarcoma (OS) formation and development, but their functions in CAFs are unknown. Here, we first investigated the SNHG17 was upregulated in OS tissues and correlated with the poor prognosis through the integrating clinical data. We then evaluated the function of SNHG17 in vitro using the stable SNHG17-depleted OS cells. HOS cells with SNHG17 knocked down were performed to generate the OS xenograft model. Through immunohistochemistry assay and TUNEL apoptosis assay, the role of SNHG17 on OS development was assessed in vivo. We then examined the SNHG17 expression in exosomes derived from CAFs, normal fibroblasts (NFs), and tumor tissues from the OS clinical samples. The interaction among SNHG17, miR-2861, and MMP2 was predicted by bioinformatics analysis and identified by RIP and luciferase assays. The cell proliferation, migration, and apoptosis of SJSA-1 and HOS cells co-cultured with CAFs-derived exosomes were assessed by CCK-8 and colony formation assays. We found that SNHG17 was upregulated in the tumor tissues and presented a pro-tumorigenic effect on OS both in vitro and in vivo. It also was an essential exosomal cargo of CAFs and could affect OS cell proliferation and migration in vitro. CAFs-released exosomal SNHG17 acted as an essential molecular sponge for miR-2861 in OS cells. Moreover, MMP2 was a direct target of miR-2861 and was regulated by SNHG17. Overall, our findings identified that SNHG17 was an essential exosomal cargo of OS-related CAFs that contributes to proliferation and metastasis of OS, supporting the therapeutic potency of targeting the crosstalk between cancer cells and CAFs.

Novel compound heterozygous missense mutations in GDAP1 cause Charcot-Marie-Tooth type 4A.

Homozygous or compound heterozygous mutations in the GDAP1 gene cause Charcot-Marie-Tooth (CMT4A) that are consistent with an autosomal recessive mode of inheritance. The case reported in this study is clinically and genetically diagnosed with recessive CMT4A that is caused by a compound novel heterozygous GDAP1 mutation. The genomic DNA of the proband with the clinical diagnosis of CMT was screened for GDAP1 mutations using a targeted next-generation sequencing (NGS) gene-panel that comprised of 27 CMT genes. Two novel compound heterozygous amino acid changing variants were identified in the GDAP1 gene, c.246C>G p.His82Gln in exon 2 and c.614T>G p.Leu205Trp in exon 5. The two amino acid changing variants were not previously reported in the 1000 Genome, Mutation Taster and gnomAD. Our findings expand the phenotypic characterization of the two novel heterozygous mutations associated with CMT4A (AR-CMT1A) and add to the repertoire of GDAP1 mutations related to autosomal recessive CMT in Chinese populations.

[Wiedemann-Steiner syndrome due to novel nonsense variant of KMT2A gene in a case].

OBJECTIVE: To explore the genetic basis for a child with unexplained global developmental delay (GDD), seizure, and facial deformity. METHODS: Whole exome sequencing (WES) was carried out for the patient. Candidate variants were verified by Sanger sequencing of the patient and his parents. RESULTS: WES revealed that the patient has carried a previously unreported de novo heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene, Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.4906C>T variant of KMT2A gene was predicted to be pathogenic (PVS1+ PS2+ PM2+PP3). CONCLUSION: The heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene probably underlay the disease in the child. Above finding has enriched the spectrum of pathogenic variants of the KMT2A gene.

lncRNA TUSC7 inhibits osteosarcoma progression through the miR­181a/RASSF6 axis.

Osteosarcoma (OS) is one of the most aggressive malignancies, accompanied by an elevated incidence and a decreased rate of healing. Recently, several long non­coding RNAs (lncRNAs) have been reported to be involved in OS progression. Although tumor suppressor candidate 7 (TUSC7) was reported as a novel lncRNA, little is known about its biological functions in OS. The present study was designed to explore whether TUSC7 was involved in the pathological development of OS using various methods, including hematoxylin and eosin staining, Cell Counting Kit­8 assay, colony formation assay and Transwell assay. The present study revealed that TUSC7 expression was downregulated in OS tissues and cell lines compared with in normal tissues and cell lines. Functionally, the current results revealed that overexpression of TUSC7 inhibited OS cell proliferation, migration and invasion, while promoting apoptosis in vitro and in vivo. Next, the subcellular distribution of TUSC7 was examined by nuclear/cytoplasmic RNA fractionation and reverse transcription­quantitative PCR. Mechanistic studies revealed that TUSC7 exerted its role by sponging microRNA (miR)­181a in OS cell lines. Ras association domain family member 6 (RASSF6) was confirmed as a target gene of miR­181a, and the expression levels of RASSF6 were negatively regulated by miR­181a. Additionally, the results of rescue experiments suggested that overexpression of miR­181a neutralized the inhibitory effects of TUSC7 overexpression on OS cells. Overall, the present study demonstrated that the tumor suppressor role of TUSC7 in OS progression was mediated through the miR­181a/RASSF6 axis, which may represent a new therapeutic target for OS.

The Comparison of Intrathecal Ropivacaine with Bupivacaine for Knee Arthroscopy: A Meta-analysis of Randomized Controlled Trials.

The comparison of intrathecal ropivacaine with bupivacaine for knee arthroscopy remains controversial. We conduct a systematic review and meta-analysis to explore the efficacy of intrathecal ropivacaine versus bupivacaine for knee arthroscopy. We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through August 2019 for randomized controlled trials (RCTs) assessing the effect of intrathecal ropivacaine versus bupivacaine for knee arthroscopy. This meta-analysis is performed using the random effects model. Five RCTs are included in the meta-analysis. Overall, compared with intrathecal bupivacaine for knee arthroscopy, intrathecal ropivacaine is associated with increased onset time of motor block (mean difference [MD] = 2.05, 95% CI: 1.43-2.67, p < 0.00001) and decreased duration of sensory block (MD = -26.82, 95% CI: -31.96 to -21.67, p < 0.00001) but shows no remarkable influence on onset time of sensory block (MD = -0.09; 95% CI: -1.89 to 1.70, p = 0.92), duration of motor block (MD = -59.76; 95% CI: -124.44 to 4.91, p = 0.07), time to maximum block (MD = 2.35; 95% CI: -0.16 to 4.86, p = 0.07), first urination time (MD = -26.42, 95% CI: -57.34 to 4.51, p = 0.09), or first ambulation time (MD = 3.63, 95% CI: -25.20 to 32.47, p = 0.80).Intrathecal ropivacaine can substantially increase onset time of motor block and decrease the duration of sensory block than intrathecal bupivacaine for knee arthroscopy.

Mutation analysis of TCOF1 gene in Chinese Treacher Collins syndrome patients.

BACKGROUND: Treacher Collins syndrome (TCS) is a rare autosomal dominant or recessive disorder, that involves unique bilateral craniofacial malformations. The phenotypes of TCS are extremely diverse. Interventional surgery can improve hearing loss and facial deformity in TCS patients. METHOD: We recruited seven TCS families. Variant screening in probands was performed by targeted next-generation sequencing (NGS). The variants identified were confirmed by Sanger sequencing. The pathogenicity of all the mutations was evaluated using the guidelines of the American College of Medical Genetics and Genomics (ACMG) and InterVar software. RESULTS: Three frameshift variants, two nonsense variants, one missense variant, and one splicing variant of TCOF1 were identified in the seven TCS probands. Five variants including c.1393C > T, c.4111 + 5G>C, c.1142delC, c.2285_2286delCT, and c.1719delG had not been previously reported. Furthermore, we report the c.149A > G variant for the first time in a Chinese TCS patient. We provided prenatal diagnosis for family 4. Proband 7 chose interventional surgery. CONCLUSION: We identified five novel variants in TCOF1 in Chinese patients with TCS, which expands the mutation spectrum of TCOF1 in TCS. Bone conduction hearing rehabilitation can improve hearing for TCS patients and prenatal diagnosis can provide fertility guidance for TCS families.