An unappreciated cell survival-independent role for BAFF initiating chronic lymphocytic leukemia.

Background: Chronic Lymphocytic Leukemia (CLL) is characterized by the expansion of CD19+ CD5+ B cells but its origin remains debated. Mutated CLL may originate from post-germinal center B cells and unmutated CLL from CD5+ mature B cell precursors. Irrespective of precursor types, events initiating CLL remain unknown. The cytokines BAFF and APRIL each play a significant role in CLL cell survival and accumulation, but their involvement in disease initiation remains unclear. Methods: We generated novel CLL models lacking BAFF or APRIL. In vivo experiments were conducted to explore the impact of BAFF or APRIL loss on leukemia initiation, progression, and dissemination. Additionally, RNA-seq and quantitative real-time PCR were performed to unveil the transcriptomic signature influenced by BAFF in CLL. The direct role of BAFF in controlling the expression of tumor-promoting genes was further assessed in patient-derived primary CLL cells ex-vivo. Results: Our findings demonstrate a crucial role for BAFF, but not APRIL, in the initiation and dissemination of CLL cells. In the absence of BAFF or its receptor BAFF-R, the TCL1 transgene only increases CLL cell numbers in the peritoneal cavity, without dissemination into the periphery. While BAFF binding to BAFF-R is dispensable for peritoneal CLL cell survival, it is necessary to activate a tumor-promoting gene program, potentially linked to CLL initiation and progression. This direct role of BAFF in controlling the expression of tumor-promoting genes was confirmed in patient-derived primary CLL cells ex-vivo. Conclusions: Our study, involving both mouse and human CLL cells, suggests that BAFF might initiate CLL through mechanisms independent of cell survival. Combining current CLL therapies with BAFF inhibition could offer a dual benefit by reducing peripheral tumor burden and suppressing transformed CLL cell output.

On-Off Ratiometric Fluorescence Europium(III) Metal-Organic Framework for Quantitative Detection of the Inflammatory Marker Neopterin.

Benefiting from the unique photoluminescence behavior of the lanthanide(III) ions and organic ligands, a lanthanide(III) metal-organic framework (Ln-MOF) material can simultaneously demonstrate photoluminescence of lanthanide(III) cations and organic molecules and endow its superior applications of fluorescence sensing behaviors. Herein, we present a europium(III) MOF material {[Eu2(BPTA)·(CH3COO)2·3DMA]·0.5DMA·3H2O}n (1) (where H4BPTA is 3,3',5,5'-biphenyltetracarboxylic acid) for photoluminescence performance of quantitatively sensing the inflammatory marker neopterin (Neo). The obtained 1 comprises Eu2(COO)4 paddlewheel secondary building units, which could be bridged by BPTA4- ligands to extend a 2D framework. The fluorescence titration indicates 1 can achieve simultaneous fluorescence behavior of Eu3+ ions and Neo via on-off ratiometric effects and thus could be exploited as the ratiometric fluorescence sensor matrix. Such a fluorescence phenomenon of 1 as a ratiometric sensor for quantitative detection of Neo via an on-off ratiometric effect is never observed in MOF chemistry. Moreover, naked-eye visible color variations of the fluorescence for 1 could be observed from red to blue with increasing concentrations of Neo, confirmed by fluorescent test strips as well as portable fluorescent hydrogels. And 1 also shows a low detection limit of 15.11 nM. A synergetic contribution of the competitive absorption, fluorescence resonance energy-transfer, and photoinduced electron-transfer mechanisms between Neo and the framework of 1 realizes the on-off ratiometric fluorescence behavior for Neo detection, supported by the UV-vis spectral overlap experiment and DFT calculations.

Evaluating the efficacy of MEANGS for mitochondrial genome assembly of cartilaginous and ray-finned fish species.

The assembly of complete and circularized mitochondrial genomes (mitogenomes) is essential for population genetics, phylogenetics and evolution studies. Recently, Song et al. developed a seed-free tool called MEANGS for de novo mitochondrial assembly from whole genome sequencing (WGS) data in animals, achieving highly accurate and intact assemblies. However, the suitability of this tool for marine fish remains unexplored. Additionally, we have concerns regarding the overlap sequences in their original results, which may impact downstream analyses. In this Letter to the Editor, the effectiveness of MEANGS in assembling mitogenomes of cartilaginous and ray-finned fish species was assessed. Moreover, we also discussed the appropriate utilization of MEANGS in mitogenome assembly, including the implementation of the data-cut function and circular detection module. Our observations indicated that with the utilization of these modules, MEANGS efficiently assembled complete and circularized mitogenomes, even when handling large WGS datasets. Therefore, we strongly recommend users employ the data-cut function and circular detection module when using MEANGS, as the former significantly reduces runtime and the latter aids in the removal of overlapped sequences for improved circularization. Furthermore, our findings suggested that approximately 2× coverage of clean WGS data was sufficient for MEANGS to assemble mitogenomes in marine fish species. Moreover, due to its seed-free nature, MEANGS can be deemed one of the most efficient software tools for assembling mitogenomes from animal WGS data, particularly in studies with limited species or genetic background information.

Streptomyces-based whole-cell biosensors for detecting diverse cell envelope-targeting antibiotics.

Cell envelope-targeting antibiotics are potent therapeutic agents against various bacterial infections. The emergence of multiple antibiotic-resistant strains underscores the significance of identifying potent antimicrobials specifically targeting the cell envelope. However, current drug screening approaches are tedious and lack sufficient specificity and sensitivity, warranting the development of more efficient methods. Genetic circuit-based whole-cell biosensors hold great promise for targeted drug discovery from natural products. Here, we performed comparative transcriptomic analysis of Streptomyces coelicolor M1146 exposed to diverse cell envelope-targeting antibiotics, aiming to identify regulatory elements involved in perceiving and responding to these compounds. Differential gene expression analysis revealed significant activation of VanS/R two-component system in response to the glycopeptide class of cell envelope-acting antibiotics. Therefore, we engineered a pair of VanS/R-based biosensors that exhibit functional complementarity and possess exceptional sensitivity and specificity for glycopeptides detection. Additionally, through promoter screening and characterization, we expanded the biosensor's detection range to include various cell envelope-acting antibiotics beyond glycopeptides. Our genetically engineered biosensor exhibits superior performance, including a dynamic range of up to 887-fold for detecting subtle antibiotic concentration changes in a rapid 2-h response time, enabling high-throughput screening of natural product libraries for antimicrobial agents targeting the bacterial cell envelope.

Construction of a nomogram for central lymph node metastasis in papillary thyroid cancer based on gender grouping.

BACKGROUND: The status of central lymph nodes is crucial for determining the surgical approach to papillary thyroid carcinoma (PTC). Because of the differences between genders in central lymph node metastasis (CLNM), we aimed to construct separate predictive models for CLNM according to gender. METHODS: In our study, a total of 1258 PTC patients who underwent thyroid cancer surgery from September 2021 to March 2023 were analyzed retrospectively. The data were analysed univariately and multivariately using SPSS software grouped according to gender and nomograms of CLNM were plotted using R software. The variables included in this study were sex, Age, body mass index, Diabetes, chronic lymphocytic thyroiditis (CLT), Suspicious central lymph node (SCLN), A/T, Margin, Microcalcification (MC), BRAF, Number, Location, CLNM. RESULTS: The preoperative nomogram in male patients included four clinical variables: CLT, Margin, Number, Size. The preoperative nomogram of female patients included six clinical variables: Age, SCLN, Margin, MC, Number, Size. The calibration curves showed great agreement in both the training group and the validation group. The decision curve analysis showed the feasibility of nomogram in predicting CLNM in both man and woman. CONCLUSION: Based on the successful establishment of nomogram, we can analyze the variability of CLNM between male and female, which may provide clinicians with personalized clinical schemes in the treatment of PTC.

Synthesis of Bis(silylene) Iron Chlorides and Their Catalytic Activity for Dinitrogen Silylation.

In this study, three tetracoordinated bis(silylene) iron(II) chlorides, namely, [SiCHRSi]FeCl2 (1) (R = H), (2) (R = CH3), and (3) (R = Ph), were synthesized through the reactions of the three different bis(silylene) ligands [LSiCHRSiL] (L = PhC(NtBu)2, L1 (R = H), L2 (R = CH3), L3 (R = Ph)) with FeCl2·(THF)1.5 in THF. The bis(silylene) Fe complexes 1-3 could be used as effective catalysts for dinitrogen silylation, with complex 3 demonstrating the highest turnover number (TON) of 746 equiv among the three complexes. The catalytic mechanism was explored, revealing the involvement of the pentacoordinated bis(dinitrogen) iron(0) complexes [SiCHRSi]Fe(N2)2(THF), (4)-(6), as the active catalysts in the dinitrogen silylation reaction. Additionally, the cyclic silylene compound 10 was obtained from the reaction of L1 with KC8. Single-crystal X-ray diffraction analyses confirmed the molecular structures of complexes 1-3 and 10 in the solid state.

Research Trends of Acupuncture Therapy for Chronic Pain-Related Depression or Anxiety from 2003 to 2023: A Bibliometric Analysis.

Background: Chronic pain (CP) as a long-lasting stressor can often cause mood disorders, such as depression or anxiety. The comorbidity of CP and mood disorders poses challenges for treatment and increases healthcare costs. Acupuncture has emerged as a widely utilized approach to alleviate both CP and mood disorders. However, there is a lack of well-established bibliometric analyses in this area of research. Therefore, this study aimed to identify the current hotspots and research trends regarding the use of acupuncture for treating CP-related depression or anxiety. Methods: We searched the Web of Science Core Collection spanning from 2003 to 2023 to identify relevant literature about the use of acupuncture for treating CP-related depression or anxiety. Bibliometric and visualization analyses were performed using CiteSpace 5.7.R5 and Vosviewer 1.6.19 software. Results: A total of 254 articles published between 2003 and 2023 were included, revealing an upward trajectory with some fluctuations in publication numbers over the past two decades. China and the Beijing University of Chinese Medicine were the most productive country and institution in this field. Fang JQ and Vickers AJ ascended as the most prolific and influential authors, respectively. Trials was the journal with the highest number of publications, while Pain and BMJ-British Medical Journal exhibited the highest citation and centrality, respectively. "Acupuncture", "depression", and "chronic pain" were the top three keywords. The hotspots in this domain encompass types of chronic pain that predispose to negative mood, including fibromyalgia, irritable bowel syndrome (IBS), and neuropathic pain. Randomized controlled trials (RCTs), mechanisms, and evidence-based evaluations are the main research directions. Conclusion: This study uses bibliometric techniques to analyze the research hotspots and forefronts of acupuncture as a therapeutic approach for CP-related depression or anxiety. Our objective is to provide researchers with valuable references and identify research focal points for future investigations.

Optimal therapeutic strategies for pineal region lesions.

Background: The removal of pineal region lesions are challenging, and therapeutic strategies for their removal remain controversial. The current study was conducted to identify the characteristics and the optimal therapeutic strategies for pineal region lesions. Methods: This retrospective study reviewed the treatments of 101 patients with pineal region lesions, and different characteristics and therapeutic strategies were observed. Results: There were no statistical differences in the total resection ratio, complications, and prognosis outcomes between the hydrocephalus group and non-hydrocephalus group, except patients in the hydrocephalus group were younger and pediatric patients had an increased level of intracranial infections. Treatments of lesions and hydrocephalus secondary to pineal region lesions were two integral parts to therapeutic strategies. For the management of lesions, germinoma or non-germinoma were diagnosed preoperatively, and resection or diagnostic radiation were chosen to deal with pineal region lesions. Endoscopic-assisted surgery provided a higher total resection rate. For the management of hydrocephalus, endoscopic third ventriculostomy (ETV) had the better therapeutic effect. Additionally, cerebrospinal fluid (CSF) diversion before radiotherapy or resection did not improve prognosis outcome, but it was necessary for patients with severe hydrocephalus. Logistical regression analysis indicated that age, lesion size, reoperation ratio, and intracranial complications were predictors of prognosis outcome. Conclusion: More attention should be paid to intracranial infections in pediatric patients with hydrocephalus secondary to pineal region lesions, and CSF diversion before radiotherapy or resection did not promote prognosis outcome, but it was necessary for patients with severe hydrocephalus. Age, lesion size, reoperation ratio, and intracranial complications may be the predictors of prognosis outcome. Most importantly, the surgical algorithm for pineal region lesions which was based on preoperatively diagnosis (non-germinoma and germinoma) is useful, especially for developing countries.

Parthenogenesis affects interspecific competition between Megalurothrips usitatus and Frankliniella intonsa (Thysanoptera: Thripidae) in changing environment: evidence from life table study.

The thrips Megalurothrips usitatus Bagnall and Frankliniella intonsa Trybom (Thysanoptera: Thripidae) are important pests in cowpea-growing areas of south China. Parthenogenesis is an important reproductive form of thysanopterans, and plays an important role in maintaining population growth. To understand the developmental and reproductive characteristics of these 2 thrips species during parthenogenesis, we compared the age-stage life tables of M. usitatus and F. intonsa on cowpea pods under natural regimes during the summer and winter. The results showed that the total preadult period and total preoviposition period of M. usitatus were significantly longer than those of F. intonsa in both seasons. Moreover, longevity of adult M. usitatus (29.53 days) was shorter compared with adult F. intonsa (34.00 days) in summer, whereas higher fecundity (220.8 eggs/female) and more oviposition days (37.83 days) were observed in M. usitatus compared with F. intonsa in winter (fecundity = 179.83 eggs/female, oviposition days = 33.03 days). The net and gross reproductive rates of M. usitatus were significantly greater than those of F. intonsa during winter. In addition, the intrinsic and finite rates of increase of M. usitatus were significantly lower than those of F. intonsa, and the mean generation time of M. usitatus was significantly longer than that of F. intonsa both in summer and winter. These results indicated that parthenogenesis has species specificity among thrips, which in turn affects population development, especially under changing environments.

Resveratrol drives ferroptosis of acute myeloid leukemia cells through Hsa-miR-335-5p/NFS1/ GPX4 pathway in a ROS-dependent manner.

To explore the potential target to induce ferroptosis for treating acute myeloid leukemia (AML) as well as its mechanism and latent drugs. Using the keyword "acute myelogenous leukemia", the related dataset in TCGA and GEO were used for searching differentially expressed genes. After the filtrate by ROC curve, AUC values, and survival analysis, RT-qPCR as well as Western-blot analysis were performed to verify the high expression level of NFS1 in AML-193 and OCI-AML-3 cells. After CCK-8 detection with and without various cell death inhibitors, ferroptosis were further detected by the expression level of GPX4. After taking the intersection in Starbase and TargetScan, the upstream regulatory miRNA of NFS1 was found. Then the relation of hsa-miR-335-5p, NFS1, as well as GPX4, was ascertained by knockdown and overexpression study in AML-193 and OCI-AML-3 cells. In addition, cellular ROS was detected by DCFH-DA. Finally, resveratrol was used to intensify ferroptosis of AML-193 and OCI-AML-3 cells. NFS1 was highly expressed in AML cells, positively associated with AML-related mortality, and can be used to diagnose AML. Knockout of NFS1 facilitated ROS accumulation and ferroptosis-associated labile iron pool increase. si-NFS1 can inhibit the expression level of GPX4, facilitate ROS accumulation and induce ferroptosis-associated labile iron pool increase. Besides, overexpressed GPX4 can lead to down-regulated cell death after si-NFS1 treatment. Hsa-miR-335-5p was found as the upstream regulator of NFS1. The expression of NFS1 can be up-regulated by sh-hsa-miR-335-5p transfection and can be inhibited by hsa-miR-335-5p transfection. Resveratrol was found can increase the expression level of hsa-miR-335-5p and decrease the expression of NFS1 and GPX4. Resveratrol can intensify ferroptosis of AML cells via Hsa-miR-335-5p/NFS1/ GPX4 pathway through a ROS-dependent manner.

MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier.

BACKGROUND & AIMS: MUC13 cell surface mucin is highly expressed on the mucosal surface throughout the intestine, yet its role against bacterial infection is unknown. We investigated how MUC13 impacts Salmonella typhimurium (S Tm) infection and elucidated its mechanisms of action. METHODS: Muc13-/- and wild-type littermate mice were gavaged with 2 isogenic strains of S Tm after pre-conditioning with streptomycin. We assessed clinical parameters, cecal histology, local and systemic bacterial load, and proinflammatory cytokines after infection. Cecal enteroids and epithelial cell lines were used to evaluate the mechanism of MUC13 activity after infection. The interaction between bacterial SiiE and MUC13 was assessed by using siiE-deficient Salmonella. RESULTS: S Tm-infected Muc13-/- mice had increased disease activity, histologic damage, and higher local and systemic bacterial loads. Mechanistically, we found that S Tm binds to MUC13 through its giant SiiE adhesin and that MUC13 acts as a pathogen-binding decoy shed from the epithelial cell surface after pathogen engagement, limiting bacterial invasion. In addition, MUC13 reduces epithelial cell death and intestinal barrier breakdown by enhancing nuclear factor kappa B signaling during infection, independent of its decoy function. CONCLUSIONS: We show for the first time that MUC13 plays a critical role in antimicrobial defense against pathogenic S Tm at the intestinal mucosal surface by both acting as a releasable decoy limiting bacterial invasion and reducing pathogen-induced cell death. This further implicates the cell surface mucin family in mucosal defense from bacterial infection.

Ratiometric Fluorescence Thermometry, Quantitative Gossypol Detection, and CO2 Chemical Fixation by a Multipurpose Europium (III) Metal-Organic Framework.

A lanthanide-based molecular crystalline material endows metal-organic frameworks (MOFs) with many fascinating applications such as fluorescence detection and CO2 chemical fixation. Herein, we describe and study a multipurpose europium(III) MOF with the formula of {[Eu2(TATAB)2]·2.5H2O·2DMF}n (Eu-MOF) (where H3TATAB is 4,4',4″-((1,3,5-triazine-2,4,6-triyl)tris(azanediyl))tribenzoic acid ligand) for photoluminescence sensor matrix and CO2 chemical fixation. This Eu-MOF features 1D square channels along the c direction with a pore size of ca.14.07 Å × 14.07 Å, occupied by lattice water and DMF molecules. The obtained Eu-MOF can achieve simultaneous luminescence of the H3TATAB ligand and Eu3+ ions, which can be developed as the sensor matrix for ratiometric fluorescence thermometry. The luminescence of the Eu-MOF demonstrates an obvious color change from red to yellow as temperature rises from 303 to 373 K and the Eu-MOF has a satisfying relative sensitivity of 3.21% K-1 and a small temperature uncertainty of 0.0093 K at 333 K. Moreover, sensitive detection of gossypol was achieved with a quenching constant Ksv of 1.18 × 105 M-1 and a detection limit of 4.61 µM. A combination of the competitive absorption and photoinduced electron transfer caused by host-guest interactions and strengthened π-π packing effect synergistically between gossypol molecules and the Eu-MOF skeleton realizes the "turn-off" sensing of gossypol. Importantly, the nature of the Eu-MOF allows showing CO2 chemical fixation under mild conditions. Thus, the Eu-MOF can be utilized as a multipurpose material for ratiometric fluorescence thermometry, quantitative gossypol detection, and CO2 chemical fixation.

Assessing the effectiveness of imidacloprid and thiamethoxam via root irrigation against Megalurothrips usitatus (Thysanoptera: Thripidae) and its residual effects on cowpea.

Systemic neonicotinoid insecticides (NEOs) applied by seed-treatment or root application have emerged as a prevalent strategy for early-season insect pest management. This research investigated the effectiveness of imidacloprid and thiamethoxam, administered through root irrigation, in managing thrips in cowpea [Vigna unguiculata (Linn.) Walp.], and the residual properties of both insecticides in cowpea and soil. The results show that thrips density depends on the application rate of insecticides. At the maximum application rate (1,500 µg/ml, active ingredient), imidacloprid and thiamethoxam controlled thrips densities below the economic injury level (EIL, the EIL of thrips on cowpea was 7/flower) for 20 days and 25 days with the density of 6.90 and 6.93/flower at the end of the periods, respectively. Imidacloprid and thiamethoxam residues decreased gradually over time and decreased sharply after 15 days after treatment (DAT), the 2 insecticides were not detected (<0.001 mg/kg) at 45 DAT. According to our findings, the application of imidacloprid and thiamethoxam via root irrigation proved residual control lasting up to 20-25 days for controlling thrips damage at experimental rates, with a strong association to their residual presence in cowpea (0.6223 < R2 < 0.9545). Considering the persistence of the imidacloprid and thiamethoxam, the maximum tested application rate (1,500 µg/ml) was recommended. As the residues of imidacloprid and thiamethoxam were undetectable in cowpea pods at all tested rates, it may be suggested that the use of each insecticide is safe for consumers and effective against thrips, and could be considered for integrated thrips management in the cowpea ecosystem.

Electroacupuncture Attenuates Neuropathic Pain in a Rat Model of Cervical Spondylotic Radiculopathy: Involvement of Spinal Cord Synaptic Plasticity.

Purpose: Cervical spondylotic radiculopathy (CSR) is a common neurologic condition that causes chronic neck pain and motor functions, with neuropathic pain (NP) being the primary symptom. Although it has been established that electroacupuncture (EA) can yield an analgesic effect in clinics and synaptic plasticity plays a critical role in the development and maintenance of NP, the underlying mechanisms have not been fully elucidated. In this study, we explored the potential mechanisms underlying EA's effect on synaptic plasticity in CSR rat models. Materials and Methods: The CSR rat model was established by spinal cord compression (SCC). Electroacupuncture stimulation was applied to LI4 (Hegu) and LR3 (Taichong) acupoints for 20 min once a day for 7 days. Pressure pain threshold (PPT) and mechanical pain threshold (MPT) were utilized to detect the pain response of rats. A gait score was used to evaluate the motor function of rats. Enzyme-linked immunosorbent assay (ELISA), Western blot (WB), immunohistochemistry (IHC), immunofluorescence (IF), and transmission electron microscopy (TEM) were performed to investigate the effects of EA. Results: Our results showed that EA alleviated SCC-induced spontaneous pain and gait disturbance. ELISA showed that EA could decrease the concentration of pain mediators in the cervical nerve root. WB, IHC, and IF results showed that EA could downregulate the expression of synaptic proteins in spinal cord tissues and promote synaptic plasticity. TEM revealed that the EA could reverse the synaptic ultrastructural changes induced by CSR. Conclusion: Our findings reveal that EA can inhibit SCC-induced NP by modulating the synaptic plasticity in the spinal cord and provide the foothold for the clinical treatment of CSR with EA.

Insertion sequence transposition inactivates CRISPR-Cas immunity.

CRISPR-Cas immunity systems safeguard prokaryotic genomes by inhibiting the invasion of mobile genetic elements. Here, we screened prokaryotic genomic sequences and identified multiple natural transpositions of insertion sequences (ISs) into cas genes, thus inactivating CRISPR-Cas defenses. We then generated an IS-trapping system, using Escherichia coli strains with various ISs and an inducible cas nuclease, to monitor IS insertions into cas genes following the induction of double-strand DNA breakage as a physiological host stress. We identified multiple events mediated by different ISs, especially IS1 and IS10, displaying substantial relaxed target specificity. IS transposition into cas was maintained in the presence of DNA repair machinery, and transposition into other host defense systems was also detected. Our findings highlight the potential of ISs to counter CRISPR activity, thus increasing bacterial susceptibility to foreign DNA invasion.

A systematic review and meta-analysis of cohort studies on the potential association between NAFLD/MAFLD and risk of incident atrial fibrillation.

Background and objective: The association between atrial fibrillation (AF) and non-alcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease (MAFLD) has been explored in recent cohort studies, however, the results have been controversial and inconclusive. This meta-analysis aimed to explore this potential association. Methods: We systematically searched PubMed, Embase, and Web of Science databases to identify all relevant cohort studies investigating the association between NAFLD/MAFLD and AF published from database inception to October 30, 2022. Random-effects models were utilized to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for summary purposes. Additionally, subgroup and sensitivity analyses were performed. Results: A total of 13 cohort studies with 14 272 735 participants were included. Among these, 12 cohort studies with 14 213 289 participants (median follow-up of 7.8 years) showed a significant association between NAFLD and an increased risk of incident AF (HR = 1.18, 95% CI: 1.12-1.23, P < 0.00001). Our subgroup analyses mostly yielded similar results, and the results of sensitivity analyses remained unchanged. However, meta-analysis of data from 2 cohort studies with 59 896 participants (median follow-up of 2.15 years) showed that MAFLD was not linked to incident AF (HR = 1.36, 95% CI: 0.63-2.92, P = 0.44). Conclusion: Current evidence shows that NAFLD may be linked to a slightly higher risk of developing AF, particularly among Asian populations and those diagnosed with NAFLD using FLI criteria. Nevertheless, there is not enough evidence to support the proposed association between MAFLD and an increased risk of AF. To better understand this relationship, future studies should consider factors such as specific population, the severity of NAFLD/MAFLD, diagnostic methods of NAFLD and AF, and cardiometabolic risk factors. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022371503.

Management of regional citrate anticoagulation for continuous renal replacement therapy: guideline recommendations from Chinese emergency medical doctor consensus.

Continuous renal replacement therapy (CRRT) is widely used for treating critically-ill patients in the emergency department in China. Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT. Regional citrate anticoagulation (RCA) has been shown to potentially be safer and more effective and is now recommended as the preferred anticoagulant method for CRRT. However, there is still a lack of unified standards for RCA management in the world, and there are many problems in using this method in clinical practice. The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association (CMDA) organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues, including the advantages and disadvantages of RCA in CRRT anticoagulation, the principle of RCA, parameter settings for RCA, monitoring of RCA (mainly metabolic acid-base disorders), and special issues during RCA. Based on the latest available research evidence as well as the paneled experts' clinical experience, considering the generalizability, suitability, and potential resource utilization, while also balancing clinical advantages and disadvantages, a total of 16 guideline recommendations were formed from the experts' consensus.

Downregulation of Nogo-B ameliorates cerebral ischemia/reperfusion injury in mice through regulating microglia polarization via TLR4/NF-kappaB pathway.

Many studies have shown a close association between Nogo-B and inflammation-related diseases. However, uncertainty does exist, regarding Nogo-B function in the pathological progression of cerebral ischemia/reperfusion (I/R) injury. Middle cerebral artery occlusion/reperfusion (MCAO/R) model was utilized in C57BL/6L mice to mimic ischemic stroke in vivo. Using oxygen-glucose deprivation and reoxygenation (ODG/R) model in microglia cells (BV-2) to establish cerebral I/R injury in vitro. Various methods, including Nogo-B siRNA transfection, mNSS and the rotarod test, TTC, HE and Nissl staining, immunofluorescence staining, immunohistochemistry, Western blot, ELISA, TUNEL and qRT-PCR were employed to probe into the effect of Nogo-B downregulation on cerebral I/R injury and the potential mechanisms. A small amount of Nogo-B expression (protein and mRNA) was observed in cortex and hippocampus before ischemia, then Nogo-B expression increased significantly on day 1, reaching the maximum on day 3, remaining stable on day 14 after I/R, and decreasing gradually after 21 days, but it still rose significantly compared with that observed preischemia. Nogo-B down-regulation could markedly reduce the neurological score and infarct volume, improve the histopathological changes and neuronal apoptosis, lower the number of CD86+/Iba1+ cells and the levels of IL-1ß, IL-6, and TNF-α, and raise the density of NeuN fluorescence, the number of CD206+/Iba1+ cells, and the level of IL-4, IL-10 and TGF-ß in brain of MCAO/R mice. Treatment with Nogo-B siRNA or TAK-242 in BV-2 cells could obviously decrease the CD86 fluorescence density and the mRNA expression of IL-1ß, IL-6 and TNF-α, increase CD206 fluorescence density and the mRNA expression of IL-10 after OGD/R injury. In addition, the expression of TLR4, p-IκBα and p-p65 proteins significantly increased in the brain after MCAO/R and BV-2 cells exposed to OGD/R. Treatment with Nogo-B siRNA or TAK-242 prominently reduced the expression of TLR4, p-IκBα and p-p65. Our findings suggest that the down-regulation of Nogo-B exerts protective effect on cerebral I/R injury by modulating the microglia polarization through inhibiting TLR4/NF-κB signaling pathway. Nogo-B may be a potential therapeutic target for ischemic stroke.

[Progress of research on mechanisms of acupuncture and moxibustion in the treatment of rheumatoid arthritis].

In the present paper, we summarize the literature about mechanisms of acupuncture and moxibustion ï¼»including ordinary acupuncture, electroacupuncture, fire needling, warm acupuncture (acupuncture with the needle warmed by burning moxa), cheek acupuncture, wheat-sized moxibustion, suspension moxibustion, etc.ï¼½ treatments of rheumatoid arthritis (RA) both domestically and abroad in recent years. Results indicate that the role of acupuncture and moxibustion therapies in improving RA involves multi-targets and multi-levels. These targets and levels include 1) improving joint and synovial inflammatory response by regulating inflammatory cytokines, inhibiting cell adhesion factor and interferon expression, 2) directly or indirectly regulating immune cell balance, 3) regulating peripheral and central neurotransmitters (plasma CCK-8 and ß-endorphin, hypothalamic prodynorphin, etc.), 4) regulating related signaling pathways (suppressing nuclear factor-kB/vascular endothelial growth factor, Janus tyrosine kinase-signal transducer and activator of transcription, transient receptor potential vanilloid and canonical Wnt/ß-catenin pathways), and activating cholinergic anti-inflammatory pathway, 5) regulating histocyte energy metabolism (improving amino acid supply and reducing negative nitrogen balance to improve immune regulation function), 6) maintaining the balance of bone cells and articular cartilage (by regulating the balance between synthesis and degradation of articular cartilage matrix, and the balance of bone cells and osteoclasts), 7) up-regulating energy metabolism gene (Atp50, Atp6V1B2) expression and regulating biological rhythm gene (clock, Per2, Rev-erb) expression, 8) regulating miRNAs-mediated chondrocyte apoptosis. All these provide experimental basis for acupuncture and moxibustion treatments of RA.

Prediction model of lymph node metastasis posterior to the right recurrent laryngeal nerve.

BACKGROUND: At present, it is still controversial whether lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) in papillary thyroid carcinoma (PTC) patients should be dissected. Failure to dissect metastatic lymph nodes results in continued metastasis from the positive lymph nodes to other regions. Our study aimed to establish a predictive model and predict the probability of metastasis of the lymph nodes posterior to the right recurrent laryngeal nerve (LNM-prRLN) in patients. METHODS: A total of 309 patients underwent surgery for thyroid cancer between May 2019 and September 2022. The risk factors were identified by univariate and multivariate analyses, and statistically significant risk factors identified in the multivariate analysis were included in the nomogram. We used the calibration curve and the receiver operating characteristic (ROC) curve to verify the accuracy of the prediction model. RESULTS: Multivariate analysis showed that irregular tumor margins (OR: 3.549, 95% CI 1.294-9.733, P = 0.014), extrathyroidal extension (OR: 4.507, 95% CI 1.694-11.993, P = 0.003), maximum tumor diameter > 1 cm (OR: 5.729, 95% CI 2.617-12.542, P < 0.001), overweight status (OR: 2.296, 95% CI 1.057-4.987, P = 0.036), high total cholesterol level (OR: 5.238, 95% CI 2.304-11.909, P < 0.001), and multifocality (OR: 11.954, 95% CI 5.233-27.305, P < 0.001) were independent risk factors for LNM-prRLN. The area under the ROC curve was 0.927. The calibration curve showed good agreement between the predicted and observed rates of LNM-prRLN. CONCLUSION: The probability of LNM-prRLN could be predicted by a nomogram based on the statistically significant risk factors identified in the multivariate analysis. This nomogram can guide clinicians when preoperatively evaluating the status of the LN-prRLN with regard to LNM-prRLN in PTC patients. For patients at high risk for LNM-prRLN, the preventive dissection of LN-prRLNs can be considered.