Regulation of MicroRNAs After Spinal Cord Injury in Adult Zebrafish.

Spinal cord injury (SCI) is a central nerve injury that often leads to loss of motor and sensory functions at or below the level of the injury. Zebrafish have a strong ability to repair after SCI, but the role of microRNAs (miRNAs) after SCI remains unclear. Locomotor behavior analysis showed that adult zebrafish recovered about 30% of their motor ability at 2 weeks and 55% at 3 weeks after SCI, reflecting their strong ability to repair SCI. Through miRNA sequencing, mRNA sequencing, RT-qPCR experiment verification, and bioinformatics predictive analysis, the key miRNAs and related genes in the repair of SCI were screened. A total of 38 miRNAs were significantly different, the top ten miRNAs were verified by RT-qPCR. The prediction target genes were verified by the mRNAs sequencing results at the same time point. Finally, 182 target genes were identified as likely to be networked regulated by the 38 different miRNAs. GO and KEGG enrichment analysis found that miRNAs targeted gene regulation of many key pathways, such as membrane tissue transport, ribosome function, lipid binding, and peroxidase activity. The PPI network analysis showed that miRNAs were involved in SCI repair through complex network regulation, among which dre-miR-21 may enhance cell reversibility through nop56, and that dre-miR-125c regulates axon growth through kpnb1 to repair SCI.

A two-layer neural circuit controls fast forward locomotion in Drosophila.

Fast forward locomotion is critical for animal hunting and escaping behaviors. However, how the underlying neural circuit is wired at synaptic resolution to decide locomotion direction and speed remains poorly understood. Here, we identified in the ventral nerve cord (VNC) a set of ascending cholinergic neurons (AcNs) to be command neurons capable of initiating fast forward peristaltic locomotion in Drosophila larvae. Targeted manipulations revealed that AcNs are necessary and sufficient for fast forward locomotion. AcNs can activate their postsynaptic partners, A01j and A02j; both are interneurons with locomotory rhythmicity. Activated A01j neurons form a posterior-anteriorly descendent gradient in output activity along the VNC to launch forward locomotion from the tail. Activated A02j neurons exhibit quicker intersegmental transmission in activity that enables fast propagation of motor waves. Our work revealed a global neural mechanism that coordinately controls the launch direction and propagation speed of Drosophila locomotion, furthering the understanding of the strategy for locomotion control.

Analysis of job satisfaction among clinical research coordinators.

BACKGROUND: While CRCs play a crucial role in clinical trials, their job satisfaction has not received enough attention. OBJECTIVE: To assess the job satisfaction of CRCs and to explore the relevant factors. METHODS: The survey was programmed into an online questionnaire platform and distributed to CRCs in China for self-evaluation. The Minnesota Satisfaction Questionnaire (MSQ) was used to assess job satisfaction, and data on demographic characteristics, working situations, burnout and social support also were collected to identify factors associated with job satisfaction. Data analysis was performed using the R software program. Factors associated with job satisfaction were explored using ordinal logistic regression models. RESULTS: 2,840 participants were included in this survey, and the mean value of overall job satisfaction was characterized as "moderate to not fully satisfied". Additionally, both burnout and overall social support were reported at moderate levels. Ordinal logistic regression analysis revealed that age, monthly income, sleep duration per day, weekly working time, a fixed workplace, subjective support, utilization of support, emotional exhaustion, depersonalization and reduced personal accomplishment were significantly associated with all types of job satisfaction (p <  0.05). Among all the factors, a fixed workplace was more strongly associated with job satisfaction than the other factors (OR = 0.596, p <  0.001). CONCLUSIONS: Implementing the fixed-point CRC mode to promote the provision of a fixed workplace, improving the CRC career development path, increasing income, subjective support and utilization of support, reducing weekly working time, job burnout will help to predict job satisfaction in CRCs.

Hydrosilylation of Arynes with Silanes and Silicon-Based Polymer.

Benzyne derived from hexadehydrogenated Diels Alder (HDDA) reactions was found to be an efficient hydrosilylation acceptors. Various silanes can react smoothly with HDDA-derived benzyne to give the arylation products. Lewis acid such as boron trifluoride etherate can accelerate these hydrosilylation reactions. Polyhydromethylsiloxane (PHMS), a widely used organosilicon polymer, was also successfully modified using our method. About 5 % of Si-H bonds in the polymer were inserted by benzynes, giving a functional PHMS with much more solubility in methanol and with a blue-emitting fluorescence behavior. Mechanism research shows that the insertion of benzyne into the Si-H bond probably undergoes a synergistic pathway, which is quite different from the traditional radical-initiated hydrosilylation or transition-metal-catalyzed hydrosilylation.

Hyperactive lateral habenula mediates the comorbidity between rheumatoid arthritis and depression-like behaviors.

Rheumatoid arthritis (RA) patients have a high prevalence for depression. On the other hand, comorbid with depression is associated with worse prognosis for RA. However, little is known about the underlying mechanisms for the comorbidity between RA and depression. It remains to be elucidated which brain region is critically involved in the development of depression in RA, and whether alterations in the brain may affect pathological development of RA symptoms. Here, by combining clinical and animal model studies, we show that in RA patients, the level of depression is significantly correlated with the severity of RA disease activity and affects patients' quality of life. The collagen antibody-induced arthritis (CAIA) mouse model of RA also develops depression-like behaviors, accompanied by hyperactivity and alterations in gene expression reflecting cerebrovascular disruption in the lateral habenula (LHb), a brain region critical for processing negative valence. Importantly, inhibition of the LHb not only alleviates depression-like behaviors, but also results in rapid remission of RA symptoms and amelioration of RA-related pathological changes. Together, our study highlights a critical but previously overlooked contribution of hyperactive LHb to the comorbidity between RA and depression, suggesting that targeting LHb in conjunction with RA treatments may be a promising strategy for RA patients comorbid with depression.

Selection of endovascular treatment strategies and analysis of the efficacy of different locations and types of splenic artery aneurysms.

PURPOSE: To analyze the selection of endovascular treatment strategies and the efficacy of various locations and types of splenic artery aneurysms (SAAs). METHODS: Sixty-three cases of patients diagnosed with SAA from January 2016 to October 2021 were collected, and their clinical data and follow-up results were analyzed. RESULTS: Among the 63 patients, 55 had true SAAs, and 8 had false SAAs. The average diameter of the true SAAs was 2.0 ± 0.8 cm. There were 10 cases of intra-aneurysm embolization, 24 cases of intra-aneurysm and aneurysm-bearing artery embolization, 10 cases of bare stent-assisted coil embolization, and 11 cases of stent grafts. The false SAAs had an average diameter of 2.3 ± 1.1 cm. Aneurysm-bearing artery embolization was applied in 5 cases, and stent grafts were applied in 3 cases. The incidence of complications after embolization of the aneurysm-bearing artery was higher (P < 0.01). Postembolization syndrome occurred in 10 patients; 7 patients developed splenic infarction to varying degrees, 1 patient had mildly elevated blood amylase, and 1 patient developed splenic necrosis with abscess formation, all of which improved after active treatment. The average length of hospital stay was 5.5 ± 3.2 days. The average follow-up time was 17.2 ± 16.1 months, and the aneurysm cavity of all patients was completely thrombotic. CONCLUSION: Endovascular treatments of SAAs are safe and effective. For various locations and types of SAAs, adequate selection of treatment is necessary. Stent grafts are recommended for their safety, economy, practicality, and preservation of the physiological functions of the human body.

Identification and verification of a prognostic signature based on a miRNA-mRNA interaction pattern in colon adenocarcinoma.

The expression characteristics of non-coding RNA (ncRNA) in colon adenocarcinoma (COAD) are involved in regulating various biological processes. To achieve these functions, ncRNA and a member of the Argonaute protein family form an RNA-induced silencing complex (RISC). The RISC is directed by ncRNA, especially microRNA (miRNA), to bind the target complementary mRNAs and regulate their expression by interfering with mRNA cleavage, degradation, or translation. However, how to identify potential miRNA biomarkers and therapeutic targets remains unclear. Here, we performed differential gene screening based on The Cancer Genome Atlas dataset and annotated meaningful differential genes to enrich related biological processes and regulatory cancer pathways. According to the overlap between the screened differential mRNAs and differential miRNAs, a prognosis model based on a least absolute shrinkage and selection operator-based Cox proportional hazards regression analysis can be established to obtain better prognosis characteristics. To further explore the therapeutic potential of miRNA as a target of mRNA intervention, we conducted an immunohistochemical analysis and evaluated the expression level in the tissue microarray of 100 colorectal cancer patients. The results demonstrated that the expression level of POU4F1, DNASE1L2, and WDR72 in the signature was significantly upregulated in COAD and correlated with poor prognosis. Establishing a prognostic signature based on miRNA target genes will help elucidate the molecular pathogenesis of COAD and provide novel potential targets for RNA therapy.

Mendelian randomization to evaluate the causal relationship between liver enzymes and the risk of six specific bone and joint-related diseases.

Background: Studies of liver dysfunction in relation to bone and joint-related diseases are scarce, and its causality remains unclear. Our objective was to investigate whether serum liver enzymes are causally associated with bone and joint-related diseases using Mendelian randomization (MR) designs. Methods: Genetic data on serum liver enzymes (alkaline phosphatase (ALP); alanine transaminase (ALT); gamma-glutamyl transferase (GGT)) and six common bone and joint-related diseases (rheumatoid arthritis (RA), osteoporosis, osteoarthritis (OA), ankylosing spondylitis, psoriatic arthritis, and gout) were derived from independent genome-wide association studies of European ancestry. The inverse variance-weighted (IVW) method was applied for the main causal estimate. Complementary sensitivity analyses and reverse causal analyses were utilized to confirm the robustness of the results. Results: Using the IVW method, the positive causality between ALP and the risk of osteoporosis diagnosed by bone mineral density (BMD) at different sites was indicated (femoral neck, lumbar spine, and total body BMD, odds ratio (OR) [95% CI], 0.40 [0.23-0.69], 0.35 [0.19-0.67], and 0.33 [0.22-0.51], respectively). ALP was also linked to a higher risk of RA (OR [95% CI], 6.26 [1.69-23.51]). Evidence of potential harmful effects of higher levels of ALT on the risk of hip and knee OA was acquired (OR [95% CI], 2.48 [1.39-4.41] and 3.07 [1.49-6.30], respectively). No causal relationship was observed between GGT and these bone and joint-related diseases. The study also found that BMD were all negatively linked to ALP levels (OR [95% CI] for TBMD, FN-BMD, and LS-BMD: 0.993 [0.991-0.995], 0.993 [0.988-0.998], and 0.993 [0.989, 0.998], respectively) in the reverse causal analysis. The results were replicated via sensitivity analysis in the validation process. Conclusions: Our study revealed a significant association between liver function and bone and joint-related diseases.

High ligation versus low ligation of the inferior mesenteric artery in laparoscopic rectal cancer surgery: a retrospective study on surgical and long-term outcome.

BACKGROUND: In laparoscopic low anterior resection for rectal cancer surgery, there has been controversy to whether the inferior mesenteric artery (IMA) should be ligated at the origin of its aorta (high ligation (HL)) or below the branches of the left colonic artery (LCA) (low ligation (LL)). This study was intended to clarify oncological outcome and long-term prognosis of retrospective analysis. METHODS: Analyzed the cases who underwent laparoscopic low anterior resection (LAR) in Shanghai Ruijin Hospital from January 2015 to December 2016, 357patients scheduled into 2 groups according to the level of IMA ligation: HL (n = 247) versus LL (n = 110). RESULTS: The primary endpoint is long-term outcomes, and the secondary endpoint is the incidence rate of major postoperative complications. There were no significant differences in 5-year overall survival (P = 0.92) and 5-year disease-free survival (P = 0.41). There were no differences between the clinical baseline levels in each group. The incidence of low anterior resection syndrome (LARS) in the two groups was statistically significant (P = 0.037). No significant differences were observed in operative time (P = 0.092) and intraoperative blood loss (P = 0.118). In the HL group, 6 cases (2.4%) had additional colonic excision due to poor anastomotic blood supply; none of the colonic anastomosis in the low ligation group had ischemic manifestations, and length from the proximal margin (P = 0.076), length from the distal margin (P = 0.184), the total number of lymph nodes excised (P = 0.065), and anastomotic leakage incidence (P = 0.33). CONCLUSION: Low ligation of the IMA which reserved LCA with vascular root lymph node dissection in laparoscopic low anterior resection for rectal cancer surgery may help protect the blood supply of the anastomosis, and will not increase postoperative complications while enhance recovery, without compromising radical excision and long-term prognosis.

Monitoring weed mechanical and chemical damage stress based on chlorophyll fluorescence imaging.

Currently, mechanical and chemical damage is the main way to carry out weed control. The use of chlorophyll fluorescence (CF) technology to nondestructively monitor the stress physiological state of weeds is significant to reveal the damage mechanism of mechanical and chemical stresses as well as complex stresses. Under simulated real field environmental conditions, different species and leaf age weeds (Digitaria sanguinalis 2-5 leaf age, and Erigeron canadensis 5-10 leaf age) were subjected to experimental treatments for 1-7 days, and fluorescence parameters were measured every 24 h using a chlorophyll fluorometer. The aim of this study was to investigate the changes in CF parameters of different species of weeds (Digitaria sanguinalis, Erigeron canadensis) at their different stress sites under chemical, mechanical and their combined stresses. The results showed that when weeds (Digitaria sanguinalis and Erigeron canadensis) were chemically stressed in different parts, their leaf back parts were the most severely stressed after 7 days, with photosynthetic inhibition reaching R=75%. In contrast, mechanical stress differs from its changes, and after a period of its stress, each parameter recovers somewhat after 1 to 2 days of stress, with heavy mechanical stress R=11%. Complex stress had the most significant effect on CF parameters, mainly in the timing and efficiency of changes in Fv/Fm, Fq'/Fm', ETR, Rfd, NPQ and Y(NO), with R reaching 71%-73% after only 3-4 days of complex stress, and its changes in complex stress were basically consistent with the pattern of changes in its chemical stress. The results of the study will help to understand the effects of mechanical and chemical stresses and combined stresses on CF parameters of weeds and serve as a guide for efficient weed control operations and conducting weed control in the future.

Xiao Chai Hu Tang alleviates the pancreatic tumorigenesis via improving the mtDNA N6-Methyladenine modification mediated mitochondrial dysfunction in Syrian hamster model.

BACKGROUND: Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion of pancreatic ductal adenocarcinoma (PDAC), which is a highly malignant tumor and lack of effective treatment. Although Xiao Chai Hu Tang (XCHT) has a good therapeutic effect on pancreatic cancer patients with advanced stage, the effect and mechanism of XCHT remains unclear in pancreatic tumorigenesis. PURPOSE: To assess the therapeutic effects of XCHT on the malignant transformation from PanIN to PDAC and to reveal its mechanisms of pancreatic tumorigenesis. METHODS: Syrian golden hamster were induced by N-Nitrosobis (2-oxopropyl) amine (BOP) to establish the pancreatic tumorigenesis model. The morphological changes of pancreatic tissue were observed by H&E and Masson staining; the Gene ontology (GO) analysis the transcriptional profiling changes; the mitochondrial ATP generation, mitochondrial redox status, mitochondrial DNA (mtDNA) N6-methyladenine (6mA) level and relative mtDNA genes expressions were examined. In addition, immunofluorescence detect the cell localization of 6mA in human pancreatic cancer PANC1 cell. Using the TCGA database, the prognostic effect of mtDNA 6mA demethylation ALKBH1 expression on pancreatic cancer patients was analyzed. RESULTS: We confirmed the mtDNA 6mA levels were gradually increased with the mitochondrial dysfunction in PanINs progression. XCHT showed the effect to inhibit the occurrence and development of pancreatic cancer in Syrian hamster pancreatic tumorigenesis model. In addition, the lack of ALKBH1 mediated mtDNA 6mA increase, mtDNA coded genes down-expression and abnormal redox status were rescued by XCHT. CONCLUSIONS: ALKBH1/mtDNA 6mA mediated mitochondrial dysfunction to induce the occurrence and progression of pancreatic cancer. XCHT can improve ALKBH1 expression and mtDNA 6mA level, regulate the oxidative stress and expression of mtDNA coded genes. This study investigated a new molecular mechanism of pancreatic tumorigenesis, and revealed the therapeutic efficacy of XCHT in pancreatic tumorigenesis for the first time.

FOXD1 promotes chemotherapy resistance by enhancing cell stemness in colorectal cancer through ß­catenin nuclear localization.

Forkhead box D1 (FOXD1) serves a critical role in colorectal cancer (CRC). FOXD1 expression is an independent prognostic factor in patients with CRC; however, the molecular mechanism and signaling pathway of FOXD1 that regulates cell stemness and chemoresistance has not been fully characterized. The aim of the present study was to further validate the effect of FOXD1 on the proliferation and migration of CRC cells, and to delve into the possible potential of FOXD1 in the clinical treatment of CRC. The effect of FOXD1 on cell proliferation was assessed using Cell Counting Kit 8 (CCK­8) and colony formation assays. The effect of FOXD1 on cell migration was assessed by wound­healing and Transwell assays. The effect of FOXD1 on cell stemness was assessed by spheroid formation in vitro and limiting dilution assays in vivo. The expression of stemness associated proteins, leucine rich repeat containing G protein­coupled receptor 5 (LGR5), OCT4, Sox2 and Nanog, and epithelial­mesenchymal transition associated proteins, E­cadherin, N­cadherin and vimentin, were detected by western blotting. Proteins interrelationships were assessed by a co­immunoprecipitation assay. Oxaliplatin resistance was assessed using CCK­8 and apoptosis assays in vitro, and using a tumor xenograft model in vivo. By constructing FOXD1 overexpression and knockdown stably transfected strains of colon cancer cells, it was revealed that the overexpression of FOXD1 increased CRC cell stemness and chemoresistance. By contrast, knockdown of FOXD1 produced the opposite effects. These phenomena were caused by the direct interaction between FOXD1 and ß­catenin, thus promoting its nuclear translocation and the activation of downstream target genes, such as LGR5 and Sox2. Notably, inhibition of this pathway with a specific ß­catenin inhibitor (XAV­939) could impair the effects induced by the overexpression of FOXD1. In summary, these results indicated that FOXD1 may promote cell stemness and the chemoresistance of CRC by binding directly to ß­catenin and enhancing ß­catenin nuclear localization; therefore, it may be considered a potential clinical target.

Carbene-catalyzed [3 + 2 + 1] annulation via C-N radical coupling of iminyl radicals and ketyl radicals.

An N-heterocyclic carbene-catalyzed cascade [3 + 2 + 1] annulation to assemble vinyl azides, aldehydes, and trihalomethyl reagents (Togni's reagent or CCl4) towards 1,3-oxazin-6-ones was reported. The cascade was triggered by an NHC-catalyzed single electron transfer (SET) between aldehydes and trihalomethyl reagents, followed by the addition of trihalomethyl radicals to vinyl azides, a denitrogenated transformation into iminyl radicals, a C-N radical coupling of iminyl radicals and ketyl radicals, and a base-controlled dehalogenative cyclization.

Cytokine concentration in peripheral blood of patients with colorectal cancer.

Introduction: The role of tumour secretory cytokines and peripheral circulatory cytokines in tumour progression has received increasing attention; however, the role of tumour-related inflammatory cytokines in colorectal cancer (CRC) remains unclear. In this study, the concentrations of various cytokines in the peripheral blood of healthy controls and patients with CRC at different stages were compared. Methods: Peripheral blood samples from 4 healthy participants and 22 colorectal cancer patients were examined. Luminex beads were used to evaluate concentration levels of 40 inflammatory cytokines in peripheral blood samples. Results: In peripheral blood, compared with healthy controls and early stage (I + II) CRC patients, advanced CRC (III + IV) patients had increased concentrations of mononuclear/macrophage chemotactic-related proteins (CCL7, CCL8, CCL15, CCL2, and MIF), M2 polarization-related factors (IL-1ß, IL-4), neutrophil chemotactic and N2 polarization-related cytokines (CXCL2, CXCL5, CXCL6, IL-8), dendritic cells (DCs) chemotactic-related proteins (CCL19, CCL20, and CCL21), Natural killer (NK) cell related cytokines (CXCL9, CXCL10), Th2 cell-related cytokines (CCL1, CCL11, CCL26), CXCL12, IL-2, CCL25, and CCL27, and decreased IFN-γ and CX3CL1 concentrations. The differential upregulation of cytokines in peripheral blood was mainly concentrated in CRC patients with distant metastasis and was related to the size of the primary tumour; however, there was no significant correlation between cytokine levels in peripheral blood and the propensity and mechanism of lymph node metastasis. Discussion: Different types of immune cells may share the same chemokine receptors and can co-localise in response to the same chemokines and exert synergistic pro-tumour or anti-tumour functions in the tumour microenvironment. Chemokines and cytokines affect tumour metastasis and prognosis and may be potential targets for treatment.

Mechanisms Underlying the Recruitment of Inhibitory Interneurons in Fictive Swimming in Developing Xenopus laevis Tadpoles.

Developing spinal circuits generate patterned motor outputs while many neurons with high membrane resistances are still maturing. In the spinal cord of hatchling frog tadpoles of unknown sex, we found that the firing reliability in swimming of inhibitory interneurons with commissural and ipsilateral ascending axons was negatively correlated with their cellular membrane resistance. Further analyses showed that neurons with higher resistances had outward rectifying properties, low firing thresholds, and little delay in firing evoked by current injections. Input synaptic currents these neurons received during swimming, either compound, unitary current amplitudes, or unitary synaptic current numbers, were scaled with their membrane resistances, but their own synaptic outputs were correlated with membrane resistances of their postsynaptic partners. Analyses of neuronal dendritic and axonal lengths and their activities in swimming and cellular input resistances did not reveal a clear correlation pattern. Incorporating these electrical and synaptic properties into a computer swimming model produced robust swimming rhythms, whereas randomizing input synaptic strengths led to the breakdown of swimming rhythms, coupled with less synchronized spiking in the inhibitory interneurons. We conclude that the recruitment of these developing interneurons in swimming can be predicted by cellular input resistances, but the order is opposite to the motor-strength-based recruitment scheme depicted by Henneman's size principle. This form of recruitment/integration order in development before the emergence of refined motor control is progressive potentially with neuronal acquisition of mature electrical and synaptic properties, among which the scaling of input synaptic strengths with cellular input resistance plays a critical role.SIGNIFICANCE STATEMENT The mechanisms on how interneurons are recruited to participate in circuit function in developing neuronal systems are rarely investigated. In 2-d-old frog tadpole spinal cord, we found the recruitment of inhibitory interneurons in swimming is inversely correlated with cellular input resistances, opposite to the motor-strength-based recruitment order depicted by Henneman's size principle. Further analyses showed the amplitude of synaptic inputs that neurons received during swimming was inversely correlated with cellular input resistances. Randomizing/reversing the relation between input synaptic strengths and membrane resistances in modeling broke down swimming rhythms. Therefore, the recruitment or integration of these interneurons is conditional on the acquisition of several electrical and synaptic properties including the scaling of input synaptic strengths with cellular input resistances.

XCHT alleviates the pancreatic fibrosis via VDR/NLRP3 signaling pathway in a mouse model of CP.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiao Chai Hu Tang (XCHT) derived from the classic medical book Shang Han Lun (Treatise on Febrile Diseases) in the Eastern Han Dynasty, which has been widely used in China and other Asian countries for the treatment of inflammation and fibrosis of chronic pancreatitis (CP), but the therapeutic mechanism of XCHT in pancreatic fibrosis remains unclear. AIM OF THE STUDY: This study aimed to evaluate the intervention effects and explore pharmacological mechanism of XCHT on inflammation and fibrosis in cerulein-induced CP model. MATERIALS AND METHODS: Fifty male C57BL/6 mice were randomly divided into five main groups, 10 animals in each: Control, CP model (50 µg/kg cerulein), high dose XCHT-treated CP group (60 g/kg XCHT), medium dose XCHT-treated CP group (30 g/kg XCHT) and low dose XCHT-treated CP group (15 g/kg XCHT). Different doses of XCHT were given to mice by gavage twice a day for 2 weeks after the CP model induction. Pancreatic tissues were harvested and the pancreatic inflammation and fibrosis were evaluated by histological score, Sirius red staining, and alpha-smooth muscle actin (α-SMA) immunohistochemical staining. ELISA, IHC and RT-qPCR were performed to detect the expression of Vitamin D3 (VD3) and Vitamin D receptor (VDR) in serum and pancreatic tissues, respectively. The expressions of NLRP3 inflammasome related genes and molecules were assayed by WB, IHC and RT-qPCR. RESULTS: The pathohistological results demonstrated that XCHT markedly inhibited the fibrosis and chronic inflammation of cerulein-induced CP, indicated by reduction of collagen I, collagen III, α-SMA, and NLRP3 expressions. XCHT significantly increased VD3 and VDR expression while reduced the pancreatic NLRP3 expression. Correspondingly, XCHT decreased the levels of NLRP3 downstream targets IL-1ß, TNF-α and IL-6. CONCLUSIONS: These results revealed that XCHT suppressed the pancreatic fibrosis and chronic inflammation in cerulein-induced CP model by enhancing the VD3/VDR expression and inhibiting the secretion of NLRP3-assoicated inflammatory factors.

A Mendelian randomization study on causal effects of leisure sedentary behaviour on the risk of rheumatoid arthritis.

BACKGROUND: The causal inference between leisure sedentary behaviour (LSB) and rheumatoid arthritis (RA) is still controversial because of potential residual confounding and reverse causality. METHODS: The present study used publicly available large-scale genome-wide association studies (GWAS) of LSB (television watching, computer use, and driving) and RA to perform a two-sample Mendelian randomization (MR) study to evaluate the causal effect of LSB on the risk of RA. We detected significant causal associations using the multiplicative random effects-inverse variance weighted (MRE-IVW) method, the maximum likelihood, robust adjusted profile scores, the weighted median, MR-Egger regression, and several complementary sensitivity analyses. Risk factor analysis was also conducted to further investigate potential mediators linking causal inference. RESULTS: Increased genetic liability to leisure television watching was significantly associated with a higher risk of RA (MRE-IVW method; OR = 2.46, 95% CI 1.77-3.41; p = 8.35 × 10-8 ). MR estimates indicated that prolonged leisure computer use was causally associated with a lower risk of RA (MRE-IVW method; OR = 0.23, 95% CI 0.12-0.46; p = 2.19 × 10-5 ). However, we found no evidence for a causal effect of leisure driving on the risk of RA (MRE-IVW method; OR = 0.59, 95% CI 0.10-3.41; p = 0.557). No pleiotropy was detected by the sensitivity analysis. CONCLUSIONS: This study supports a causal association between prolonged leisure television watching and an increased risk of RA. Additionally, prolonged computer use might be a protective factor for RA.

Mendelian randomization study on the causal effects of systemic lupus erythematosus on major depressive disorder.

The vast majority of epidemiological studies suggested a link between systemic lupus erythematosus (SLE) and major depressive disorder (MDD). However, the causality for SLE on the risk of MDD remained unknown due to confounding factors or reverse causality. Herein, we investigated the causality between SLE and MDD in those of European ancestry by a Mendelian randomization (MR) approach. Summary genetic data of cases with SLE/MDD were derived from independent largest public genome-wide association study. Forty-six single nucleotide polymorphisms associated with SLE were used as instrumental variables. The main causal inference was carried out using the MRE-IVW method. Additional, reverse-direction MR and multivariable MR analyses were further performed. Result indicated that SLE was causally associated with a lower risk of MDD (using the MRE-IVW method, odds ratio [OR] = 0.983, 95% confidence interval [CI] = 0.974-0.991, p = 1.18 × 10-4). Complementary analysis found no heterogeneity or horizontal pleiotropy. Multivariate MR analysis yielded consistent results (OR = 0.981; 95% CI = 0.969-0.993; p = 2.75 × 10-3). Reverse-direction MR analysis suggested non-causal relationship of MDD on the risk of SLE (using the IVW method, OR = 0.846, 95% CI = 0.345-2.072; p = 0.714). Thus, this is the first study providing evidence of potential causal links between SLE and MDD and further related research is needed.

Balloon-occluded retrograde transvenous obliteration with lauromacrogol sclerosant foam for gastric varices.

Objectives: To evaluate the safety and efficacy of balloon-occluded retrograde transvenous obliteration (BRTO) using lauromacrogol sclerosant foam for gastric varices (GVs) with gastrorenal venous shunts. Methods: Data of GV patients treated with BRTO using lauromacrogol sclerosant foam in 2016-2020 were retrospectively analyzed along with procedural success rate, complications, and follow-up efficacy. Results: A total of 31 patients were treated with BRTO. The sclerosant foam was prepared by mixing iodinated oil, lauromacrogol, and air at a 1:2:3 ratio. The BRTO procedure was successfully completed in 93.5% of patients. One patient was allergic to the lauromacrogol injection. A mild postoperative fever occurred in three patients. One patient experienced grand mal seizures after the procedure. There was no significant difference in the median Child-Turcotte-Pugh scores before versus after BRTO. Complete GV resolution was observed in 93.1% of patients. One patient underwent endoscopic treatment for the development of high-risk esophageal varices. Another patient underwent transjugular intrahepatic portosystemic shunt placement for the aggravation of ascites. Conclusions: Lauromacrogol sclerosant foam is safe and effective in patients undergoing BRTO for GV.