CircMETTL15 induces TMTC3 production by absorbing miR-944 to promote hepatocellular carcinoma cell malignancy.

Previous data have suggested the involvement of circular RNA (circRNA) in hepatocellular carcinoma (HCC) progression. Up to now, the effect of circMETTL15 on HCC development remains unknown. This study aims to analyze the function of circMETTL15 in HCC development and the underlying mechanism. RNA expression of circMETTL15, miR-944, and transmembrane O-mannosyltransferase targeting cadherins 3 (TMTC3) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was evaluated by Western blot analysis assay or immunohistochemistry assay. Cell proliferation was investigated by cell counting kit-8 assay, 5-Ethynyl-29-deoxyuridine (EdU) assay, and cell colony formation assay. Cell migration and invasion were assessed by wound-healing assay and transwell assay, respectively. Angiogenic capacity was analyzed by tube formation assay. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to identify the interplay between miR-944 and circMETTL15 or TMTC3. Xenograft mouse model assay was conducted to reveal the effect of circMETTL15 on tumor formation in vivo. CircMETTL15 and TMTC3 expression were significantly upregulated, while miR-944 expression was downregulated in HCC tissues and cells. CircMETTL15 knockdown led to decreased cell proliferation, migration, invasion, and tube formation. Besides, the inhibitors of miR-944, a target miRNA of circMETTL15, partially restored circMETTL15 silencing-mediated effects on the proliferation, migration, invasion, and tube formation of HCC cells. MiR-944 overexpression also inhibited HCC cell malignancy by targeting TMTC3. Furthermore, circMETTL15 absence inhibited tumor formation by regulating miR-944 and TMTC3 in vivo. In conclusion, circMETTL15 induced HCC development through the miR-944/TMTC3 pathway, raising the potential of circMETTL15 as a target for HCC therapy.

Association of gene polymorphisms and the decreased expression of long non-coding RNA LOC553103 with rheumatoid arthritis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in many key bioprocesses, including the occurrence and development of rheumatoid arthritis (RA). We aimed to analyze the association of genetic variants of long non-coding RNA LOC553103 and its peripheral blood mononuclear cells (PBMC) expression with RA. METHODS: We enrolled 457 RA patients and 551 healthy controls and conducted a case-control study to analyze the relationship between LOC553103 gene rs272879 and the susceptibility of RA by TaqMan single nucleotide polymorphism genotyping. Among them, we sampled 92 cases and 92 controls, respectively, to detect the PBMC level of LOC553103 using quantitative real-time polymerase chain reaction technology. We explored the association between LOC553103 rs272879 and its PBMC expression levels in 71 RA patients. Mann-Whitney, Chi-square, and Spearman correlation analysis were used for statistical analysis and P-value <.05 was considered statistically significant. RESULTS: The genotype frequency of LOC553103 rs272879 CC was increased, and CG was decreased in RA patients compared to the control group (χ2 = 6.772, P = .034). The LOC553103 expression level in PBMC of RA patients was downregulated compared to healthy control (Z = -4.497, P < .001). Moreover, negative correlations were observed between the PBMC level of LOC553103 and erythrocyte sedimentation rate (rs = -0.262, P = .018), white blood cell count (rs = -0.382, P = .004), platelet (rs = -0.293, P = .030), and disease activity score in 28 joints (rs = -0.271, P = .016) in RA patients. CONCLUSIONS: This study provides the first evidence supporting an association between LOC553103 gene polymorphisms and susceptibility of RA and a relationship of PBMC level of LOC553103 with clinical manifestations and laboratory indicators of RA patients.

Clinical outcomes of laparoscopic-assisted natural orifice specimen extraction colectomy using a Cai tube for left-sided colon cancer: a prospective randomized trial.

BACKGROUND: The role of laparoscopic-assisted natural orifice specimen extraction (LA-NOSE) colectomy in the treatment of left-sided colon cancer has not been well defined, and there remains confusion about how to conveniently exteriorize specimens through natural orifices. Therefore, we introduced a homemade invention, the Cai tube, to facilitate the extraction of specimens and compared the clinical outcomes of LA-NOSE with conventional laparoscopic (CL) colectomy for left-sided colon cancer. METHODS: From March 2015 to August 2017, patients with left-sided colon cancer were randomly divided into LA-NOSE and CL groups. Specimens were extracted through the anus with the help of a Cai tube (Patent Number: ZL201410168748.2) in the LA-NOSE group. The primary outcome measure was postoperative pain. Secondary outcomes were the duration of operation, postoperative recovery, surgical morbidity, pathological quality of the specimen, and long-term outcomes, including 3-year overall survival, disease-free survival, local recurrence, and overall recurrence. RESULTS: A total of 60 patients (30 per group) were recruited for this study. None of the patients required emergency conversion to conventional laparoscopic or open surgery during the operation. The postoperative maximum pain score was significantly lower in the LA-NOSE group (mean 2.5 vs. 5.1, P = 0.001), as was the additional analgesia requirement (mean 2/30 vs. 10/30, P = 0.021). Patients in the LA-NOSE group experienced a shorter first time to passage of flatus (mean 2.2 vs. 3.1 days, P = 0.026). All patients could control their defecation at 6 months after surgery. The comparison between the two groups showed no significant differences in the operative time, bleeding volume, postoperative hospital stay, surgical morbidity rates, number of lymph nodes harvested, or resection margin status. The mean follow-up was 48 months (range 7-59) and was similar in both groups. The results showed no differences in long-term outcomes between the two groups. CONCLUSION: In the treatment of left-sided colon cancer, compared with conventional laparoscopic colectomy, LA-NOSE colectomy using the Cai tube exhibited lower postoperative pain, shorter recovery of gastrointestinal function, and similar long-term outcomes. REGISTRATION NUMBER: ChiCTR-OOR-15007060 ( http://www.chictr.org.cn/ ).

The effects of music therapy on peripherally inserted central catheter in hospitalized children with leukemia.

To explore the effect of music therapy on children with leukemia who have peripherally inserted central catheters (PICC).In this study, we divided 107 patients undergoing PICC into music group (47 cases) and control group (60 cases). The music group received music therapy during PICC, while the control group was given no complementary treatment. The total length of catheterization, the use of sedatives and the changes of pain level and emotion level before and after PICC placement were compared between two groups.Compared with the control group, the total PICC placement time of the music group was significantly shorter (35(30-40) vs. 60(60-60); Z = -8.307; p < 0.001), and the use of sedative medications was also significantly reduced (4.35% (n = 2) vs. 91.84% (n = 45); p < 0.001). Moreover, the pain of catheterization was significantly alleviated. The median difference of pain scores of the music group was significantly less (2(1-3) vs. 5(5-5); p < 0.001). The mood of patients was also improved. The median difference of emotional scores of the music group was significantly more (5(4.75-6) vs. 3(3-3); p < 0.001) than the control group.Music therapy is effective to use in PICC. It can shorten the treatment time, reduce the use of sedative medications, and improve the children's emotion and pain response significantly, which is worth clinical application.

Laparoscopic-Assisted Natural Orifice Specimen Extraction Gastrectomy Using an Auxiliary Incision-Free Tube for Gastric Cancer.

BACKGROUND: Laparoscopic-assisted natural orifice specimen extraction (LA-NOSE) gastrectomy effectively avoids the need for an abdominal incision, unlike conventional laparoscopic gastrectomy. In this study, we documented our experience with LA-NOSE gastrectomy using an auxiliary incision-free tube (Cai tube, a homemade invention: ZL201410168748.2) in 9 gastric cancer patients and summarized the clinical results. METHODS: From July 2018 to June 2020, a total of 9 patients with gastric cancer were recruited for this study. LA-NOSE gastrectomy (subtotal or total) using the auxiliary incision-free tube and D2 lymph node dissection were performed. Specimens were extracted through the anterior wall of the upper rectum in 4 male patients and the posterior fornix of the vagina in 5 female patients using the auxiliary incision-free tube. RESULTS: All 9 patients underwent successful laparoscopic gastrectomy with NOSE using the auxiliary incision-free tube. No perioperative death, re-admission within 60 days post operation, natural orifice wound infection or tumor implantation was observed. The mean operating time was 365.3±41.7 min, and the mean estimated blood loss was 87.8±39.3 ml. The mean duration of hospital stay was 11.3±1.2 days, while the mean maximum pain score (visual analogue score, VAS) was 2.3±0.9 on postoperative day (POD) 1, and the mean time to ambulation was 1.3±0.5 days. The 60-day postoperative morbidity rate was 11.1% (1/9). After a mean follow-up of 14.7±9.6 months, there was no transrectal or transvaginal access-site recurrence, no anterior rectectomy or posterior fornix colpotomy-related complications, and no local recurrence or distant metastasis. CONCLUSIONS: Our preliminary experience indicates that this new technique, LA-NOSE gastrectomy using the auxiliary incision-free tube, is feasible for selected patients with gastric cancer.

Flexible all-solid-state supercapacitors based on PPy/rGO nanocomposite on cotton fabric.

Polypyrrole (PPy) has high electrochemical activity and low cost, so it has great application prospects in wearable supercapacitors. Herein, we have successfully prepared polypyrrole/reduced graphene oxide (PPy/rGO) nanocomposite cotton fabric (NCF) by chemical polymerization, which exhibits splendid electrochemical performance compared with the individual. The addition of rGO can block the deformation of PPy caused by the expansion and contraction. The as-prepared PPy-0.5/rGO NCF electrode exhibits the brilliant specific capacitance (9300 mF cm-2at 1 mA cm-2) and the capacitance retention with 94.47% after 10 000 cycles. At the same time, the superior capacitance stability under different bending conditions and reuse capability have been achieved. All-solid-state supercapacitor has high energy density of 167µWh cm-2with a power density of 1.20 mW cm-2. Therefore, the PPy-0.5/rGO NCF electrode has a broad application prospect in high-performance flexible supercapacitor fabric electrode.

Tree peony variegated flowers show a small insertion in the F3'H gene of the acyanic flower parts.

BACKGROUND: The tree peony (Paeonia suffruticosa Andr.) cultivar 'Er Qiao' is appreciated for its unstable variegated flower coloration, with cyanic and acyanic flowers appearing on different branches of the same plant and occasionally in a single flower or petal. However, the variegation mechanism is still unclear. RESULTS: In this study, we found significantly higher contents and more diverse sets of anthocyanins in the cyanic petals than in the acyanic petals. Comparative transcriptome analysis between the two flower types revealed 477 differentially expressed genes (DEGs). Quantitative real-time PCR results verified that the transcript levels of the flavonol synthase (FLS) gene were significantly increased in the acyanic petals. Furthermore, we found that a GCGGCG insertion at 246 bp in the flavonoid 3'-hydroxylase (F3'H) gene-coding region constitutes a duplication of the 241-245 bp section and was consistently found only in acyanic flowers. Sequence alignment of the F3'H gene from different plant species indicated that only the acyanic petals of 'Er Qiao' contained the GCGGCG insertion. The transformation of Arabidopsis tt7-1 lines demonstrated that the ectopic expression of F3'H-cyanic, but not F3'H-acyanic, could complement the colors in the hypocotyl and seed coat. CONCLUSION: In summary, we found that an indel in F3'H and the upregulation of FLS drastically reduced the anthocyanin content in acyanic petals. Our results provide molecular candidates for a better understanding of the variegation mechanisms in tree peony.

Discovery of new serum biomarker panels for systemic lupus erythematosus diagnosis.

OBJECTIVE: Clinical diagnosis of SLE is currently challenging due to its heterogeneity. Many autoantibodies are associated with SLE and are considered potential diagnostic markers, but systematic screening and validation of such autoantibodies is lacking. This study aimed to systematically discover new autoantibodies that may be good biomarkers for use in SLE diagnosis. METHODS: Sera from 15 SLE patients and 5 healthy volunteers were analysed using human proteome microarrays to identify candidate SLE-related autoantibodies. The results were validated by screening of sera from 107 SLE patients, 94 healthy volunteers and 60 disease controls using focussed arrays comprised of autoantigens corresponding to the identified candidate antibodies. Logistic regression was used to derive and validate autoantibody panels that can discriminate SLE disease. Extensive ELISA screening of sera from 294 SLE patients and 461 controls was performed to validate one of the newly discovered autoantibodies. RESULTS: A total of 31, 11 and 18 autoantibodies were identified to be expressed at significantly higher levels in the SLE group than in the healthy volunteers, disease controls and healthy volunteers plus disease control groups, respectively, with 25, 7 and 13 of these differentially expressed autoantibodies being previously unreported. Diagnostic panels comprising anti-RPLP2, anti-SNRPC and anti-PARP1, and anti-RPLP2, anti-PARP1, anti-MAK16 and anti- RPL7A were selected. Performance of the newly discovered anti-MAK16 autoantibody was confirmed by ELISA. Some associations were seen with clinical characteristics of SLE patients, such as disease activity with the level of anti-PARP1 and rash with the level of anti-RPLP2, anti-MAK16 and anti- RPL7A. CONCLUSION: The combined autoantibody panels identified here show promise for the diagnosis of SLE and for differential diagnosis of other major rheumatic immune diseases.

Functional identification of PsMYB57 involved in anthocyanin regulation of tree peony.

BACKGROUND: R2R3 myeloblastosis (MYB) genes are widely distributed in plants and comprise one of the largest transcription factor gene families. They play important roles in the regulatory networks controlling development, metabolism, and stress responses. Researches on functional genes in tree peony are still in its infancy. To date, few MYB genes have thus far been reported. RESULTS: In this study, we constructed a comprehensive reference gene set by transcriptome sequencing to obtain R2R3 MYB genes. The transcriptomes of eight different tissues were sequenced, and 92,837 unigenes were obtained with an N50 of 1662 nt. A total of 48,435 unigenes (77.98%) were functionally annotated in public databases. Based on the assembly, we identified 57 R2R3 MYB genes containing full-length open reading frames, which clustered into 35 clades by phylogenetic analysis. PsMYB57 clustered with anthocyanin regulation genes in Arabidopsis and was mainly transcribed in the buds and young leaves. The overexpression of PsMYB57 induced anthocyanin accumulation in tobacco, and four detected anthocyanin structural genes, including NtCHS, NtF3'H, NtDFR, and NtANS, were upregulated. The two endogenous bHLH genes NtAn1a and NtAn1b were also upregulated and may work in combination with PsMYB57 in regulating anthocyanin structural genes. CONCLUSIONS: Our study offers a useful reference to the selection of candidate MYB genes for further functional studies in tree peony. Function analysis of PsMYB57 is helpful to understand the color accumulation in vegetative organs of tree peony. PsMYB57 is also a promising resource to improve plant color in molecular breeding.

Inhibition of SERPINA3N-dependent neuroinflammation is essential for melatonin to ameliorate trimethyltin chloride-induced neurotoxicity.

Trimethyltin chloride (TMT) is a potent neurotoxin that causes neuroinflammation and neuronal cell death. Melatonin is a well-known anti-inflammatory agent with significant neuroprotective activity. Male C57BL/6J mice were intraperitoneally injected with a single dose of melatonin (10 mg/kg) before exposure to TMT (2.8 mg/kg, ip). Thereafter, the mice received melatonin (10 mg/kg, ip) once a day for another three consecutive days. Melatonin dramatically alleviated TMT-induced neurotoxicity in mice by attenuating hippocampal neuron loss, inhibiting epilepsy-like seizures, and ameliorating memory deficits. Moreover, melatonin markedly suppressed TMT-induced neuroinflammatory responses and astrocyte activation, as shown by a decrease in inflammatory cytokine production as well as the downregulation of neurotoxic reactive astrocyte phenotype markers. Mechanistically, serine peptidase inhibitor clade A member 3N (SERPINA3N) was identified as playing a central role in the protective effects of melatonin based on quantitative proteome and bioinformatics analysis. Most importantly, melatonin significantly suppressed TMT-induced SERPINA3N upregulation at both the mRNA and protein levels. The overexpression of Serpina3n in the mouse hippocampus abolished the protective effects of melatonin on TMT-induced neuroinflammation and neurotoxicity. Melatonin protected cells against TMT-induced neurotoxicity by inhibiting SERPINA3N-mediated neuroinflammation. Melatonin may be a promising and practical agent for reducing TMT-induced neurotoxicity in clinical practice.

Circular RNA expression profile and potential function of hsa_circ_0045272 in systemic lupus erythematosus.

Circular RNAs (circRNAs) represent a class of non-coding RNAs that form covalently closed RNA circles with extensive expression and conservation in mammals. Circular RNAs regulate gene expression through acting as competitive endogenous RNAs (ceRNAs) and modulating gene transcription. Accumulating evidence supports the implication of circRNAs in a variety of human diseases, but studies of circRNA role in systemic lupus erythematosus (SLE) are lacking. The present study measured the circRNA expression profiles in T cells from patients with SLE and healthy controls with human circRNA microarray and identified 127 differentially expressed circRNAs in SLE patients. Down-regulation of hsa_circ_0045272 in SLE T cells was verified with quantitative PCR. Jurkat cells with stable hsa_circ_0045272 knockdown were generated using specific lentiviral short hairpin RNA for functional studies. Flow cytometric analysis indicated that hsa_circ_0045272 knockdown significantly up-regulated the early apoptosis of Jurkat cells. Meanwhile, ELISA showed that hsa_circ_0045272 knockdown significantly enhanced interleukin-2 production of activated Jurkat cells. Then, ceRNAs were predicted for hsa_circ_0045272 and the significant down-regulation of two mRNAs predicted as ceRNAs, NM_003466 (PAX8) and NM_015177 (DTX4), but not their corresponding proteins, was validated. Furthermore, dual luciferase reporter assay indicated binding of hsa_circ_0045272 with hsa-miR-6127. Circular RNA-mRNA co-expression networks showed the correlation of circRNAs with mRNAs and provided additional clues to circRNA functions. Our study demonstrated dysregulated circRNAs in SLE and revealed the function of hsa_circ_0045272 in negatively regulating apoptosis and interleukin-2 secretion and its potential mechanism. The implication of hsa_circ_0045272 and other abnormal circRNAs in SLE merits further investigation.

Association of interleukin-10 gene single nucleotide polymorphisms with rheumatoid arthritis in a Chinese population.

PURPOSE OF THE STUDY: Increasing numbers of studies show that interleukin (IL)-10 plays a key role in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and acts as an immunomodulatory cytokine. The purpose of the present study was to analyse the relationship between gene single nucleotide polymorphisms (SNPs) in the IL-10 gene and RA susceptibility. STUDY DESIGN: We genotyped three SNPs (rs1800890, rs3024495, rs3024505) of the IL-10 gene in a Chinese population of 354 RA patients and 367 controls. Genotyping was conducted using TaqMan SNP genotyping assays. Plasma IL-10 levels were measured by ELISA. RESULTS: The A allele of the rs1800890 variant was significantly related to decreased risk for RA compared with the T allele (A vs T: OR 0.580, 95% CI 0.345 to 0.975, P=0.038). No significant association between the genotype distribution of these SNPs and RA susceptibility was detected. The genotype effect of the dominant model was also evaluated, but no statistical difference was found. Further analysis in RA patients demonstrated that none of these SNPs were associated with rheumatoid factor (RF) or anti-citrullinated protein antibody (anti-CCP). In addition, no significant differences in plasma IL-10 levels were observed among RA patients with different genotypes. CONCLUSIONS: The IL-10 rs1800890 variant might contribute to RA susceptibility in the Chinese population. Replication studies in different ethnic groups are required to further examine the critical role of IL-10 gene variation in the pathogenesis of RA.

Comprehensive long non-coding RNA expression profiling reveals their potential roles in systemic lupus erythematosus.

Long non-coding RNAs can regulate gene transcription, modulate protein function, and act as competing endogenous RNA. Yet, their roles in systemic lupus erythematosus remain to be elucidated. We determined the expression profiles of lncRNAs in T cells of SLE patients and healthy controls using microarrays. Up to 1935 lncRNAs and 1977 mRNAs were differentially expressed. QRT-PCR showed downregulated uc001ykl.1 and ENST00000448942 in SLE patients. Expression of uc001ykl.1 correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein, whereas ENST00000448942 level correlated with ESR and anti-Sm antibodies. Short time-series expression miner analysis revealed some lncRNAs whose expressions might correlate with disease activity of SLE patients. Coding-non-coding gene coexpression analyses showed differential lncRNAs might operate via modulating expressions of their correlated, relevant mRNAs in SLE. Differential lncRNAs might also function through their ceRNAs. Our study established that the aberrant expression profiles of lncRNAs may play a role in SLE and thus warrant further investigation.

Decreased flow-mediated dilatation in patients with rheumatoid arthritis: a meta-analysis.

OBJECTIVES: To derive a more precise comparison of flow-mediated dilatation (FMD%) of the brachial artery between patients with rheumatoid arthritis (RA) and normal controls by performing a meta-analysis of appropriate studies. METHODS: PubMed and EMBASE databases were searched for all relevant articles. STATA (V.12.0) software was used to perform the meta-analysis. Quality estimation of all appropriate studies was evaluated according to the Newcastle-Ottawa Scale (NOS). Standardised mean difference (SMD) with 95% CIs were calculated with a random-effects model. The Cochrane Q test and I2 statistic were used to evaluate the heterogeneity. Funnel plot and Egger's test were conducted to assess the publication bias. RESULTS: In total, 464 articles were obtained after searching the two databases. Ten studies were included in the meta-analysis on the basis of the inclusion and exclusion criteria. Significant heterogeneity was observed among these 10 studies (Q=102.89, p<0.001, I2=91.3%) with random-effects modelling. The results showed that the RA group had significantly lower FMD% (SMD: -1.405; 95% CI -1.992 to -0.817; p<0.001) than the control group. Egger's test (p=0.004) indicated that the funnel plot showed a skewed or asymmetrical shape and publication bias existed. Sensitivity analyses suggested the robustness and credibility of our results. CONCLUSIONS: FMD% in patients with RA is significantly decreased compared with healthy controls. FMD% is an important early marker of atherosclerosis. It may be used as a parameter to forecast cardiovascular disease in patients with RA.

Genetic Links Between Metabolic Syndrome and Osteoarthritis: Insights from Cross-Trait Analysis.

BACKGROUND: Previous observational studies have indicated a bidirectional association between metabolic syndrome (MetS) and osteoarthritis (OA). However, it remains unclear whether these bidirectional associations reflect causal relationships or shared genetic factors, and the underlying biological mechanisms of this association are not fully understood. METHODS: Leveraging summary statistics from genome-wide association studies (GWASs) conducted by the UK Biobank and the Glucose and Insulin-related Traits Consortium (MAGIC), we performed global genetic correlation analyses, genome-wide cross-trait meta-analyses, and a bidirectional two-sample Mendelian randomization analyses using summary statistics from GWASs to comprehensively assess the relationship of MetS and OA. RESULTS: We first detected an extensive genetic correlation between MetS and OA (rg=0.393, P=1.52×10-18), which was consistent in four MetS components, including waist circumference, triglycerides, hypertension and high-density lipoprotein cholesterol and OA with rg ranging from -0.229 to 0.490. We then discovered 32 variants jointly associated with MetS and OA through multi-trait Analysis of GWAS. Co-localization analysis founded 12 genes shared between MetS and OA, with functional implications in several biological pathways. Finally, MR analysis suggested genetic liability to MetS significantly increased the risk of OA, but no reverse causality was found. CONCLUSION: Our results illustrate a common genetic architecture, pleiotropic loci, as well as causality between MetS and OA, potentially enhancing our knowledge of high comorbidity and genetic processes that overlap between the two disorders.

Comparative long-term outcomes of natural orifice specimen extraction surgery and conventional laparoscopic colectomy for left-sided colorectal cancer: a propensity score-matched analysis.

BACKGROUND: Natural orifice specimen extraction surgery (NOSES) is currently widely used in left-sided colorectal cancer. Some clinical comparative studies have been conducted, providing evidence of its safety and oncological benefits. However, these studies are typically characterized by small sample sizes and short postoperative follow-up periods. Consequently, in this research, the authors adopt the propensity score matching method to undertake a large-scale retrospective comparative study on NOSES colectomy for left-sided colorectal cancer, with the goal of further augmenting the body of evidence-based medical support for NOSES. METHODS: This retrospective study involved patients who underwent NOSES colectomy and conventional laparoscopic (CL) colectomy for left-sided colorectal cancer between January 2014 and April 2021. In the NOSES group, specimens were extracted through the anus with the help of a Cai tube (homemade invention: ZL201410168748.2). The patients were matched at a ratio of 1:1 according to age, sex, BMI, tumor diameter, tumor location (descending and splenic flexure colon/ sigmoid colon/ middle and upper rectum), tumor height from anal verge, ASA grade, previous abdominal surgery, clinical pathologic stage, preoperative CEA. After matching, 132 patients in the NOSES group and 132 patients in the CL group were eligible for analysis. RESULTS: Compared with CL group, NOSES group was associated with decreased postoperative maximum pain score (2.6±0.7 vs. 4.7±1.7, P=0.000), less additional analgesia required (6.8 vs. 34.8%, P=0.000), faster time to passage of flatus (2.3±0.6 days vs. 3.3±0.7 days, P=0.000), less wound infection (0.0 vs. 6.1%, P=0.007), and longer operative time (212.5±45.8 min vs. 178.0±43.4 min, P=0.000). No significant differences were observed in estimated blood loss, time to resume regular diet, postoperative hospital stay, conversion to open surgery or conventional minilaparotomy, total morbidity, readmission, mortality, pathologic outcomes, and Wexner incontinence score between groups. After a median follow-up of 63.0 months, the 5-year overall survival rates were 88.3 versus 85.0% (P=0.487), disease-free survival rates were 82.9 versus 83.6% (P=0.824), and the local recurrence rates were 4.4 versus 4.0% (P=0.667) in the NOSES and CL groups, respectively. CONCLUSIONS: This study suggests that NOSES colectomy using a Cai tube for left-sided colorectal cancer is a safe and feasible option with better cosmetic results, less pain, faster recovery of gastrointestinal function, and comparable long-term clinical and oncologic outcomes to CL colectomy.

Mendelian Randomization Analysis of Circulating Cytokines and Risk of Autoimmune Neuroinflammatory Diseases.

Background: Cytokines act a vital role in autoimmune neuroinflammatory diseases (ANDs) with undetermined causal relationships. Mendelian randomization (MR) analysis was performed to estimate the causal effects of circulating levels of cytokines on the risk of ANDs. Methods: The causal relationship between 34 circulating cytokines and 4 kinds of ANDs, including multiple sclerosis (MS), neuromyelitis optica (NOM), chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) were explored using four methods of MR analysis. MR-PRESSO, MR-Egger regression methods and Cochran's Q statistic were utilized to identify the instrumental variables (IVs) with potential pleiotropy and heterogeneity. The Bonferroni correction was used for multiple group comparisons. P-value less than 3.68E-04 (0.05/ (34*4)) was considered statistically significant. Results: Negative causal effects of circulating levels of interleukin (IL)-8 (OR = 0.648, 95% CI: 0.494-0.851, P = 0.002) on risk of MS, chemokine (C-C Motif) ligand (CCL)-5 (OR = 0.295, 95% CI: 0.103-0.841, P = 0.022) and stem cell growth factor-beta (SCGF-ß) (OR = 0.745, 95% CI: 0.565-0.984, P = 0.038) on risk of CIDP, as well as positive causal effects of circulating levels of IL-2 receptor α (IL-2Rα) (OR = 1.216, 95% CI: 1.120-1.320, P = 3.20E-06) and chemokine C-X-C motif ligand (CXCL)-10 (OR = 1.404, 95% CI: 1.094-1.803, P = 0.008) on MS were observed. Nevertheless, only IL-2Rα still had a causal effect on MS after Bonferroni correction. Conclusion: The results identify a genetically predicted causal effect of IL-2Rα, IL-8 and CXCL-10 on MS, CCL-5 and SCGF-ß on CIDP.

Genetic causality between modifiable risk factors and the risk of rheumatoid arthritis: Evidence from Mendelian randomization.

OBJECTIVES: Emerging research has investigated the potential impact of several modifiable risk factors on the risks of rheumatoid arthritis (RA), but the findings did not yield consistent results. This study aimed to comprehensively explore the genetic causality between modifiable risk factors and the susceptibility of RA risk using the Mendelian randomization (MR) approach. METHODS: Genetic instruments for modifiable risk factors were selected from several genome-wide association studies at the genome-wide significance level (p < 5 × 10-8), respectively. Summary-level data for RA were sourced from a comprehensive meta-analysis. The causal estimates linking modifiable risk factors to RA risk were assessed using MR analysis with inverse variance weighting (IVW), MR-Egger, weighted, and weighted median methods. RESULTS: After Bonferroni correction for multiple tests, we found the presence of causality between educational attainment and RA, where there were protective effects of educational attainment (college completion) (odds ratio [OR] = 0.50, 95% CI = 0.36, 0.69, p = 2.87E-05) and educational attainment (years of education) (OR = 0.93, 95% CI = 0.90, 0.96, p = 4.18E-06) on the lower RA risks. Nevertheless, smoking initiation was observed to be associated with increased RA risks (OR = 1.27, 95% CI = 1.09, 1.47, p = .002). Moreover, there was no indication of horizontal pleiotropy of genetic variants during causal inference between modifiable risk factors and RA. CONCLUSIONS: Our study reveals the genetic causal impacts of educational attainment and smoking on RA risks, suggesting that the early monitoring and recognition of modifiable risk factors would be beneficial for the preventive counseling/treatment strategies for RA.

No genetic causal association between systemic lupus erythematosus and COVID-19.

Objective: Emerging evidence suggests an increased prevalence of coronavirus disease 2019 (COVID-19) in patients with systemic lupus erythematosus (SLE), the prototype of autoimmune disease, compared to the general population. However, the conclusions were inconsistent, and the causal relationship between COVID-19 and SLE remains unknown. Methods: In this study, we aimed to evaluate the bidirectional causal relationship between COVID-19 and SLE using bidirectional Mendelian randomization (MR) analysis, including MR-Egger, weighted median, weighted mode, and the inverse variance weighting (IVW) method. Results: The results of IVW showed a negative effect of SLE on severe COVID-19 (OR = 0.962, p = 0.040) and COVID-19 infection (OR = 0.988, p = 0.025), which disappeared after Bonferroni correction. No causal effect of SLE on hospitalized COVID-19 was observed (OR = 0.983, p = 0.148). In the reverse analysis, no causal effects of severe COVID-19 infection (OR = 1.045, p = 0.664), hospitalized COVID-19 (OR = 0.872, p = 0.109), and COVID-19 infection (OR = 0.943, p = 0.811) on SLE were found. Conclusion: The findings of our bidirectional causal inference analysis did not support a genetically predicted causal relationship between SLE and COVID-19; thus, their association observed in previous observational studies may have been caused by confounding factors.

The R2R3-MYB gene PsMYB58 positively regulates anthocyanin biosynthesis in tree peony flowers.

Tree peony (Paeonia suffruticosa Andr.) is a well-known ornamental flower in China with diverse colors. Flower color is one of the most important economic characteristics of tree peony and is mainly determined by anthocyanins. In this study, we cloned a PsMYB58 gene, which contained a 654 bp open reading frame (ORF), encoding a polypeptide of 218 amino acids. Sequence and phylogenetic analysis indicated that PsMYB58 is an anthocyanin regulatory R2R3-MYB gene. The transcription levels of PsMYB58 in different developmental stages of tree peony flowers were similar to those of the anthocyanin biosynthetic genes PsCHS, PsCHI, PsDFR, and PsANS. A bimolecular fluorescence complementation assay showed that PsMYB58 interacted with PsbHLH1 and PsbHLH3 in vivo. The overexpression of PsMYB58 in tobacco enhanced anthocyanin accumulation in various organs. Comparative transcriptome analysis showed that 943 genes were upregulated and 1203 downregulated in PsMYB58 transgenic tobacco, among which genes involved in the anthocyanin pathway were positively activated. Real-time quantitative PCR analysis verified that anthocyanin biosynthetic genes, including NtCHS, NtCHI, NtF3H, NtF3'H, NtDFR, and NtANS, and an anthocyanin regulatory bHLH gene, NtAN1b, were significantly upregulated in PsMYB58 transgenic tobacco. Our results indicated that PsMYB58 is a positive anthocyanin regulator in tree peony flowers. In summary, the functional identification of PsMYB58 furthers our understanding of the mechanism of peony flower color formation, thus providing a foundation for flower color improvement and molecular breeding.