Deficiency of histone deacetylases 3 in macrophage alleviates monosodium urate crystals-induced gouty inflammation in mice.

BACKGROUND: Gout is caused by monosodium urate (MSU) crystals deposition to trigger immune response. A recent study suggested that inhibition of Class I Histone deacetylases (HDACs) can significantly reduce MSU crystals-induced inflammation. However, which one of HDACs members in response to MSU crystals was still unknown. Here, we investigated the roles of HDAC3 in MSU crystals-induced gouty inflammation. METHODS: Macrophage specific HDAC3 knockout (KO) mice were used to investigate inflammatory profiles of gout in mouse models in vivo, including ankle arthritis, foot pad arthritis and subcutaneous air pouch model. In the in vitro experiments, bone marrow-derived macrophages (BMDMs) from mice were treated with MSU crystals to assess cytokines, potential target gene and protein. RESULTS: Deficiency of HDAC3 in macrophage not only reduced MSU-induced foot pad and ankle joint swelling but also decreased neutrophils trafficking and IL-1ß release in air pouch models. In addition, the levels of inflammatory genes related to TLR2/4/NF-κB/IL-6/STAT3 signaling pathway were significantly decreased in BMDMs from HDAC3 KO mice after MSU treatment. Moreover, RGFP966, selective inhibitor of HDAC3, inhibited IL-6 and TNF-α production in BMDMs treated with MSU crystals. Besides, HDAC3 deficiency shifted gene expression from pro-inflammatory macrophage (M1) to anti-inflammatory macrophage (M2) in BMDMs after MSU challenge. CONCLUSIONS: Deficiency of HDAC3 in macrophage alleviates MSU crystals-induced gouty inflammation through inhibition of TLR2/4 driven IL-6/STAT3 signaling pathway, suggesting that HDAC3 could contribute to a potential therapeutic target of gout.

A giant left atrial myxoma transits across patent foramen ovale a PFO mimicking biatrial myxoma: a case report.

Background: Multiple myxomas are rare and often associated with Carney syndrome. We present a giant left atrial myxoma that passes through a patent foramen ovale (PFO), mimicking biatrial myxoma. Case summary: A 46-year-old female was admitted to the hospital with a cardiac neoplasm without symptoms. The physical examination did not reveal any abnormalities in the skin and endocrine system. Transthoracic echocardiography revealed a large, hypoechoic mass attached to the atrial septum, occupying both the left and right atria. This mass appeared as a bilateral atrial mass on echocardiography. Contrast-enhanced echocardiography revealed a slight enhancement in the mass. The patient was scheduled for surgery without any contraindications. During the operation, a large jelly-like mass originating from the left atrial side of the fossa ovale was found, extending to the right atrium through a PFO. The entire mass was successfully removed, and the atrial septum was repaired. Histopathology confirmed the diagnosis of cardiac myxoma. At the 3-month follow-up, no cardiac abnormalities were observed. Discussion: Multiple myxomas have been reported in certain cases of Carney syndrome. A single left atrial myxoma that passes through an atrial septal defect or a PFO can sometimes be misdiagnosed as a bilateral atrial myxoma. Echocardiography plays a crucial role in providing diagnostic information by accurately identifying the location of the myxoma pedicle.

Pressure and Flame Propagation Characteristics of Suspended Coal Dust Explosions Induced by Gas Explosions.

In order to explore the pressure and flame propagation characteristics of gas-coal dust composite explosions, a semiclosed pipeline explosion test platform was built. The shock wave overpressure and explosion flame propagation law of different concentrations of suspended coal dust participating in gas explosions were studied in depth through experiments, and the coal dust motion law was simulated and analyzed based on Fluent software. The experimental results show that the peak pressure of gas-coal dust composite explosion is significantly higher than that of single-phase gas explosion, and the pressure peak increase ratio at the pipeline outlet is the highest; as the suspended coal dust concentration increases, the pressure rise rate at point 3 gradually decreases. Under the condition of 600 g/m3 coal dust participating in the explosion, the explosion pressure increase speed reduction ratio is 25.65%, the pressure wave secondary peak decreases, and the fluctuation frequency increases. When the explosion flame front passes through the suspended coal dust area, the flame shape changes from 'v' shape to 'finger' shape and propagates forward. The gas-coal dust composite explosion flame propagation speed shows a secondary acceleration phenomenon, after the flame front passes through the coal dust suspension area. As the coal dust concentration increases, the explosion core area moves away from the flame front. The coal dust cloud moves to the right, showing a concave rectangle; the larger the coal dust concentration, the smaller the moving speed. The experimental results and analysis provide an experimental basis for further exploring the mechanism and dynamic mechanism of gas-coal dust coupling explosion.

Zebrafish live imaging: a strong weapon in anticancer drug discovery and development.

Developing anticancer drugs is a complex and time-consuming process. The inability of current laboratory models to reflect important aspects of the tumor in vivo limits anticancer medication research. Zebrafish is a rapid, semi-automated in vivo screening platform that enables the use of non-invasive imaging methods to monitor morphology, survival, developmental status, response to drugs, locomotion, or other behaviors. Zebrafish models are widely used in drug discovery and development for anticancer drugs, especially in conjunction with live imaging techniques. Herein, we concentrated on the use of zebrafish live imaging in anticancer therapeutic research, including drug screening, efficacy assessment, toxicity assessment, and mechanism studies. Zebrafish live imaging techniques have been used in numerous studies, but this is the first time that these techniques have been comprehensively summarized and compared side by side. Finally, we discuss the hypothesis of Zebrafish Composite Model, which may provide future directions for zebrafish imaging in the field of cancer research.

Using ultrasonic-assisted sodium bicarbonate treatment to improve the gel and rheological properties of reduced-salt pork myofibrillar protein.

To study the impact of ultrasonic duration (0, 30, and 60 min) and sodium bicarbonate concentration (0% and 0.2%) on the gel properties of reduced-salt pork myofibrillar protein, the changes in cooking yield, colour, water retention, texture properties, and dynamic rheology were investigated. The findings revealed that added sodium bicarbonate significantly increased (P < 0.05) cooking yield, hardness, springiness, and strength of myofibrillar protein while reducing centrifugal loss. Furthermore, the incorporation of sodium bicarbonate led to a significant decrease in L⁎, a⁎, b⁎, and white values of cooked myofibrillar protein; these effects were further amplified with increasing ultrasonic duration (P < 0.05). Additionally, storage modulus (G') significantly increased for myofibrillar protein treated with ultrasonic-assisted sodium bicarbonate treatment resulting in a more compact gel structure post-cooking. In summary, the results demonstrated that ultrasonic-assisted sodium bicarbonate treatment could enhance the tightness of reduced-salt myofibrillar protein gel structure while improving the water retention and texture properties.

Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine（Part 5）： Retrieval and Synthesis of Key Information on Rational Drug Use / 中医杂志

Recommendations for Chinese patent medicine （CPM） based on key information on rational drug use are one of the important conditions for enhancing guideline enforceability as well as facilitating guideline implementation. In this study， we discussed in detail of the key information on the rational use of CPM in five aspects， which are dosage， drug discontinuation， drug-drug and drug-food interactions， safety and economy. Following the process of multi-source search， synthesis and prioritization， it is suggested to collect key information on the rational use of CPM from a multi-source search of drug instructions， policy documents， literature， and clinical experts' experiences. Then the searched information should be summarized and prioritized with the principle that taking drug instructions as the basis and other-sources information for check and supplementation. Finally， methodological recommendations for the retrieval and synthesis of key information on rational drug use in guideline recommendations has been formed.

Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine： 2.Establishment of Guideline Working Group and Management of Conflict of Interests / 中医杂志

This paper summarized the key points and methods in terms of the establishment of the guideline working group and the management of conflict of interests， trying to provide reference for the development of clinical practice guidelines for Chinese patent medicine （CPM）. The establishment of the working group is the first important step for developing CPM guidelines. Considering the characteristics of the clinical practice guidelines for CPM， this study suggests that the three key elements of ‘multidisciplinarity’， ‘clinical relevance’ and ‘geographical representativeness’ should be put focus on when forming the working group. The guideline advisory committee， clinical expert group， evidence systematic evaluation group， secretary group and the external review group should be established. All group members should clarify the conflict of interest， and the process and management method of the conflict of interest should be clearly reported.

Comparing the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia in preterm infants / 中华儿科杂志

Objective: To compare the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia (BPD) in preterm infants with gestational age<32 weeks. Methods: The retrospective cohort study was conducted to collect the clinical data of 285 preterm infants with BPD admitted to the Department of Neonatology, Children's Hospital Affiliated to Zhengzhou University from January 2019 to September 2021, who were followed up regularly after discharge. The primary composite adverse outcome was defined as death or severe respiratory morbidity from 36 weeks of corrected gestational age to 18 months of corrected age, and the secondary composite adverse outcome was defined as death or neurodevelopmental impairment. According to the primary or secondary composite adverse outcomes, the preterm infants were divided into the adverse prognosis group and the non-adverse prognosis group. The 2001 National Institute of Child Health and Human Development (NICHD) criteria, 2018 NICHD criteria, and 2019 Neonatal Research Network (NRN) criteria were used to diagnose and grade BPD in preterm infants. Chi-square test, Logistic regression analysis, receiver operating characteristic (ROC) curve and Delong test were used to analyze the prognostic value of the 3 diagnostic criteria. Results: The 285 preterm infants had a gestational age of 29.4 (28.1, 30.6) weeks and birth weight of 1 230 (1 000, 1 465) g, including 167 males (58.6%). Among 285 premature infants who completed follow-up, the primary composite adverse outcome occurred in 124 preterm infants (43.5%), and the secondary composite adverse outcome occurred in 40 preterm infants (14.0%). Multivariate Logistic regression analysis showed that severe BPD according to the 2001 NICHD criteria, gradeⅡand Ⅲ BPD according to the 2018 NICHD criteria and grade 2 and 3 BPD according to the 2019 NRN criteria were all risk factors for primary composite adverse outcomes (all P<0.05). ROC curve showed that the area under the curve (AUC) of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.70 and 0.70 vs. 0.61, Z=4.49 and 3.35, both P<0.001), but there was no significant difference between the 2018 NICHD and 2019 NRN criteria (Z=0.38, P=0.702). Multivariate Logistic regression analysis showed that the secondary composite adverse outcomes were all associated with grade Ⅲ BPD according to the 2018 NICHD criteria and grade 3 BPD according to the 2019 NRN criteria (both P<0.05). ROC curve showed that the AUC of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.71 and 0.71 vs. 0.58, Z=2.93 and 3.67, both P<0.001), but there was no statistically significant difference between the 2018 NICHD and 2019 NRN criteria (Z=0.02, P=0.984). Conclusion: The 2018 NICHD and 2019 NRN criteria demonstrate good and comparable predictive value for the primary and secondary composite adverse outcomes in preterm infants with BPD, surpassing the predictive efficacy of the 2001 NICHD criteria.

Integrated 'omics analysis for the gut microbiota response to moxibustion in a rat model of chronic fatigue syndrome.

OBJECTIVE: To observe the efficacy of moxibustion in the treatment of chronic fatigue syndrome (CFS) and explore the effects on gut microbiota and metabolic profiles. METHODS: Forty-eight male Sprague-Dawley rats were randomly assigned to control group (Con), CFS model group (Mod, established by multiple chronic stress for 35 d), MoxA group (CFS model with moxibustion Shenque (CV8) and Guanyuan (CV4), 10 min/d, 28 d) and MoxB group (CFS model with moxibustion Zusanli (ST36), 10 min/d, 28 d). Open-field test (OFT) and Morris-water-maze test (MWMT) were determined for assessment the CFS model and the therapeutic effects of moxibustion.16S rRNA gene sequencing analysis based gut microbiota integrated untargeted liquid chromatograph-mass spectrometer (LC-MS) based fecal metabolomics were executed, as well as Spearman correlation analysis, was utilized to uncover the functional relevance between the potential metabolites and gut microbiota. RESULTS: The results of our behavioral tests showed that moxibustion improved the performance of CFS rats in the OFT and the MWMT. Microbiome profiling analysis revealed that the gut microbiomes of CFS rats were less diverse with altered composition, including increases in pro-inflammatory species (such as Proteobacteria) and decreases in anti-inflammatory species (such as Bacteroides, Lactobacillus, Ruminococcus, and Prevotella). Moxibustion partially normalized these changes in the gut microbiota. Furthermore, CFS was associated with metabolic disorders, which were effectively ameliorated by moxibustion. This was demonstrated by the normalization of 33 microbiota-related metabolites, including mannose (P = 0.001), aspartic acid (P = 0.009), alanine (P = 0.007), serine (P = 0.000), threonine (P = 0.027), methionine (P = 0.023), 5-hydroxytryptamine (P = 0.008), alpha-linolenic acid (P = 0.003), eicosapentaenoic acid (P = 0.006), hypoxanthine (P = 0.000), vitamin B6 (P = 0.000), cholic acid (P = 0.013), and taurocholate (P = 0.002). Correlation analysis showed a significant association between the perturbed fecal microbiota and metabolite levels, with a notable negative relationship between LCA and Bacteroides. CONCLUSIONS: In this study, we demonstrated that moxibustion has an antifatigue-like effect. The results from the 16S rRNA gene sequencing and metabolomics analysis suggest that the therapeutic effects of moxibustion on CFS are related to the regulation of gut microorganisms and their metabolites. The increase in Bacteroides and decrease in LCA may be key targets for the moxibustion treatment of CFS.

Effectiveness and safety of Pingxiao capsule as adjuvant therapy in treatment of breast cancer: a systematic review and Meta-analysis.

OBJECTIVE: To systematically review the effectiveness and safety of Pingxiao capsule adjuvant chemotherapy in the treatment of breast cancer. METHODS: A total of 8 databases including the Cochrane Library, PubMed, EMBASE, Engineering Index, Chinese Biomedical Literature Database, Wanfang database, China National Knowledge Infrastructure Database, and China Science and Technology Journal Database were searched for the Randomized Controlled Trials (RCTs) of Pingxiao capsule combined with chemotherapy in the treatment of breast cancer published before June 2022. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias. R language was used for estimating risks of bias of included studies, data analysis, and plotting. RESULTS: A total of 15 RCTs involving 1272 patients were included in this study. Meta-analysis results indicated that compared with chemotherapy alone, Pingxiao capsule combined with chemotherapy could significantly improve breast cancer patients' objective response rate of breast cancer patients [rate ratio () = 1.35, 95% confidence interval () (1.12, 1.63), = 0.0017], the disease control rate [=1.16, 95% (1.08, 1.25), < 0.0001], the quality of life [ =1.42, 95% (1.16, 1.74), = 0.007], and the level of the immune cells [CD3+: standardized mean difference () =1.42, 95% (0.76, 2.09), < 0.001; CD4+: =1.18, 95% (0.70, 1.66), < 0.001]. In addition, Pingxiao capsule combined with chemotherapy can also significantly reduce CD8+ level ( < 0.0001) and reduce the symptoms of decreased white blood cell count [ = 0.62, 95% (0.39, 0.85), < 0.0001], and the occurrence of adverse reactions such as gastrointestinal adverse reactions and limb pain ( < 0.05). CONCLUSIONS: Pingxiao capsule can significantly improve the efficacy of chemotherapy, the quality of life and immune function of patients, and reduce the clinical side effects caused by chemotherapy. However, high-quality randomized clinical trials with large samples are required for further verification of these results.

Lipid levels in the Jiarong Tibetan's diet at high altitudes: a cross-sectional survey.

Despite the ongoing debate on the inconsistent and controversial effects of Tibetan diet on blood lipid levels at high altitude, this cross-sectional study was conducted to analyze the relationship between dietary practices and blood lipid levels among Jiarong Tibetan population. A total of 476 Jiarong Tibetan residents were included, in which basic demographic data, physical activity records, simplified food frequency questionnaire, and biochemical data were collected. Using multivariate logistic regression analysis, the potential associations between the variables were examined, and it was found that fat energy supply ratio increased with the elevation of altitude, while the lipid level showed an inverted U-shaped variation. However, the findings suggested that a diet rich in unsaturated fatty acids might balance the effects of the Tibetan diet on the risk of lipid metabolism disorders. Therefore, it is crucial to concentrate on the fat composition rather than the amount of fat E% intake on the plateau. The results highlighted the importance of investigating the interaction between environment and genes in lipid levels among plateau Tibetan population. However, further large-scale prospective studies are required for better understanding of the complexities involved in dietary practices and their influences on blood lipid levels.

Electroacupuncture alleviates water avoidance stress-induced irritable bowel syndrome in mice by improving intestinal barrier functions and suppressing the expression of inflammatory cytokines.

OBJECTIVE: To evaluate the effects and related mechanisms of electroacupuncture (EA) on irritable bowel syndrome (IBS). METHODS: Male C57BL/6 mice were randomly allocated into normal, model, and EA groups. Experimental IBS mice models were established by exposure to water avoidance stress (WAS). Mice in the EA group were treated with EA at bilateral Tianshu (ST 25) and Zusanli (ST 36) for 7 consecutive days, 15 min each day. Abdominal withdrawal reflex (AWR) tests and intestinal motility tests were performed to evaluate visceral sensitivity and intestinal motility of mice. Expression levels of tight junction proteins (TJPs) and inflammatory cytokines in colon tissues were determined through immunofluorescence, real-time polymerase chain reactions (PCR) and Western blot assays. RESULTS: EA alleviated visceral hypersensitivity and intestinal hypermotility in WAS-induced IBS mice. Moreover, EA promoted the expression of zonula occludens (ZO)-1, claudin-1, and occludin while suppressing the expression of interleukin (IL)-8, interferon (IFN)-γ, and tumor necrosis factor (TNF)-αin water avoidance stress (WAS)-induced irritable bowel syndrome (IBS) mice. CONCLUSION: EA alleviated WAS-induced IBS in mice by promoting intestinal barrier functions and suppressing the expression of inflammatory cytokines.

Enhancing Enzyme Activity and Thermostability of Bacillus amyloliquefaciens Chitosanase BaCsn46A Through Saturation Mutagenesis at Ser196.

Chitosanase plays an important role in chitooligosaccharides (COS) production. We found that the chitosanase (BaCsn46A) of Bacillus amyloliquefacien was a good candidate for chitosan hydrolysis of COS. In order to further improve the enzyme properties of BaCsn46A, the S196 located near the active center was found to be a critical site impacts on enzyme properties by sequence alignment analysis. Herein, saturation mutation was carried out to study role of 196 site on BaCsn46A catalytic function. Compared with WT, the specific enzyme activity of S196A increased by 118.79%, and the thermostability of S196A was much higher than WT. In addition, we found that the enzyme activity of S196P was 2.41% of that of WT, indicating that the type of amino acid in 196 site could significant affect the catalytic activity and thermostability of BaCsn46A. After molecular docking analysis we found that the increase in hydrogen bonds and decrease in unfavorable bonds interacting with the substrate were the main reason for the change of enzyme properties which is valuable for future studies on Bacillus species chitosanase.

PsA inhibits the development of bovine embryos through epigenetic and oxidative stress.

OBJECTIVE: Histone deacetylases (HDACs) are the key regulators involved in the process of embryo development and tumor progression and are often dysregulated in numerous disordered cells, including tumor cells and somatic cell nuclear transfer (SCNT) embryos. Psammaplin A (PsA), a natural small-molecular therapeutic agent, is a potent histone deacetylase inhibitor (HDACi) that alters the regulation of histone. SAMPLES: Approximately 2,400 bovine parthenogenetic (PA) embryos. PROCEDURES: To investigate the effect of PsA on bovine preimplanted embryos, we analyzed the preimplantation development of PA embryos treated with PsA in this study. RESULTS: The blastocyst formation rate of bovine PA embryos decreased sharply with an increase in concentration and duration. Furthermore, the expression of the pluripotency-related gene Nanog was decreased, and the inhibitory effects on histone deacetylases 1 (HDAC1) and DNA methylation transferase 1 (DNMT1) were observed in bovine PA embryos. The acetylation level of histone H3 lysine 9 (H3K9) was enhanced by a PsA treatment of 10 µM for 6 h, while the DNA methylation appeared unchanged. Interestingly, we also found that PsA treatment enhanced the intracellular reactive oxygen species (ROS) generation and decreased the intracellular mitochondrial membrane potential (MMP)- and superoxide dismutase 1 (SOD1)-induced oxidative stress. Our findings improve the understanding of HDAC in embryo development and provide a theoretical basis and reproduction toxicity evaluation for the application of PsA. CLINICAL RELEVANCE: These results indicate that PsA inhibits the development of bovine preimplantation PA embryos, supplying data for the PsA clinical application concentration to avoid reproductive toxicity. In addition, the reproduction toxic effect of PsA may be modulated through increased oxidative stress on the bovine PA embryo, suggesting that PsA in combination with antioxidants, for example, melatonin, might be an effective clinical application strategy.

Comparison of high-flow nasal cannula and conventional oxygen therapy for high-risk patients during bronchoscopy examination: protocol for a randomized controlled trial.

INTRODUCTION: High-flow nasal cannula (HFNC) has been proven to improve oxygenation and avoid intubation in hypoxemic patients. It has also been utilized during endoscopy examination to reduce the incidence of hypoxia. However, little is known about the effects of HFNC versus conventional oxygen therapy (COT) on oxygenation during bronchoscopy examination via nasal route; particularly, no study has compared the use of HFNC with that of COT at similar FIO2 for patients who have high-risk factors of desaturation during bronchoscopy examination. METHODS AND ANALYSIS: This randomized controlled trial will be implemented in four academic centers in China. Patients who have high-risk factors including hypoxemia, hypercapnia, morbid obesity, and narrow airway will be enrolled to use HFNC or COT during bronchoscopy examination. In the HFNC group, the initial gas flow will be set at 50 L/min with a fraction of inspired oxygen (FIO2) at 0.45, if the patient tolerates, the flow can be increased to 60L/min at most, while in the COT group, oxygen flow will be set at 6 L/min via a conventional nasal cannula. After 5 min pre-oxygenation, the bronchoscope will be inserted via the nasal route. Vital signs, oxygenation (SpO2), and transcutaneous CO2 (PtCO2) will be continuously monitored. The primary outcome is the incidence of hypoxemia, defined as SpO2 < 90% for 10 s during bronchoscopy examination, and secondary outcomes include the need for treatment escalation and adverse events. DISCUSSION: Hypoxia is a common complication of bronchoscopy, our study attempted to demonstrate that HFNC may reduce the probability of hypoxia during bronchoscopy in high-risk patients. The results will be disseminated through peer-reviewed journals and national and international conferences. TRIAL REGISTRATION: http://www.chictr.org.cn/ : ChiCTR2100055038. Registered on 31 December 2021.

Effect of Berberine on Activation of TLR4-NFκB Signaling Pathway and NLRP3 Inflammasome in Patients with Gout.

OBJECTIVE: To determine the effects of berberine (BBR) on the activation of toll-like receptor 4 (TLR4), nuclear factor (NF)κB (NF-κB) signaling and NLRP3 inflammasome in patients with gout. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from 24 acute (AP) and 41 non-acute (NAP) phases of primary gout patients, respectively, as well as 30 healthy controls (HC). TLR4, NF-κB (p65), NLRP3, apoptosis-associated specklike protein containing a CARD (PYCARD), cysteinyl aspartate specific proteinase-1 (CASP1), and interleukin-1ß (IL-1ß) mRNA expression levels in PBMCs were measured by quantitative reverse transcriptase polymerase chain reaction. The protein levels of TLR4, myeloid differentiation factor 88 (MyD88), NF-κB (p50/65), inhibitor of kappa B kinase α/ß (IKKα/ß), NF-κB inhibitor α (IKBα), phospho-IKKα/ß (p-IKKα/ß), NLRP3, PYCARD, and CASP1 were monitored by Western blotting. Serum IL-1ß protein level was measured using enzyme-linked immunosorbent assay (ELISA). In addition, PBMCs from HC and macrophages derived from a spontaneously immortalized monocyte-like cell line (THP-1) were stimulated using monosodium urate (MSU, 100 µg/mL), 0.1% dimethyl sulfoxide, 25 µmol/L BBR, and 10, 25, and 50 µmol/L BBR+100 µg/mL MSU for different time periods. The protein levels of IL-1ß and IL-18 in cell culture supernatants was measured by ELISA, and the protein expressions of TLR4, MyD88, NF-κB (p50/p65), IKKα/ß, I κBß, p-IKKα/ß, NLRP3, PYCARD, and CASP1 in macrophages were analyzed by Western blotting. RESULTS: (1) TLR4, NF-κB (p65), PYCARD, CASP1, and IL-1ß mRNA levels in PBMCs were significantly higher in the AP group than in the HC group (P<0.05). The NLRP3 mRNA expression levels in PBMCs were found to be significantly lower in the AP and NAP groups than in the HC group (P<0.05, P<0.01). (2) The protein levels of TLR4, IKKß, MyD88, NF-κB, p-IKKα/ß, PYCARD, and CASP1 in PBMCs were significantly higher, and those of IκBα, IKKα, and NLRP3 were found to be significantly lower in the AP group than in the HC group (P<0.05 or P<0.01). (3) The serum IL-1ß protein levels were significantly higher in the AP and NAP groups than in the HC group (P<0.01). (4) The IL-1ß protein level was significantly lower in the culture supernatants of the PBMCs stimulated with MSU for 3 and 6 h in the 25 and 50 µmoL/L BBR groups compared with that in the MSU group (P<0.01). (5) The protein levels of IL-1ß and IL-18 were also significantly lower in the culture supernatants of macrophages stimulated with MSU for 3 and 6 h in BBR groups compared with those in the MSU group (P<0.01). (6) The protein levels of TLR4, MyD88, NF-κB (p50, p65, p105), IKKα/ß, p-IκBα, p-IKKα/ß, PYCARD, and CASP1 were significantly differed between the macrophages stimulated with MSU for 0.5 and 6 h in BBR groups compared with those in the MSU group (P<0.05 or P<0.01). CONCLUSIONS: Activation of TLR4-NFκB signaling and NLRP3 inflammasome by MSU crystals drives the progression of gout inflammation. BBR ameliorates gouty inflammation, which is mechanistically associated with its regulation of TLR4-NF-κB signaling and NLRP3 inflammasome expression.

Analysis of clinical characteristics and risk factors of sarcopenia in elderly patients with chronic kidney disease stage 3-4 / 中华肾脏病杂志

Objective:To explore the clinical characteristics and risk factors of sarcopenia in elderly patients with chronic kidney disease (CKD) stage 3-4.Methods:It was a single-center, retrospective observational study. CKD stage 3-4 patients aged ≥60 years old from March 2019 to March 2022 in the Geriatrics Department of the First Affiliated Hospital of Zhengzhou University were enrolled in the study. General data of the patients were collected, and laboratory indicators, muscle strength, physical function and appendicular muscle mass index (ASMI) were measured. According to the diagnostic criteria of sarcopenia, the patients were divided into no sarcopenia CKD group and sarcopenia CKD group. Baseline data between these two groups were compared. Logistic regression analysis was used to analyze the related factors of sarcopenia in elderly CKD stage 3-4 patients.Results:A total of 162 CKD stage 3-4 patients were enrolled in this study, with 89 males (54.9%) and a median age of 75 (69, 82) years. Sarcopenia was diagnosed in 40 cases, and the prevalence was 24.7% (95% CI 18.1%-31.3%). Compared with no sarcopenia CKD group, age, proportion of dementia, cystatin C, urea nitrogen, C-reactive protein (CRP) and ratio of urine protein to creatinine were higher (all P<0.05), while body mass index (BMI), hemoglobin, carbon dioxide combining power, estimated glomerular filtration rate (eGFR), serum albumin and the proportion of regular exercise and using α-ketones were lower in sarcopenia CKD group (all P<0.05). Meanwhile, grip strength, walking speed, short physical performance battery score and ASMI were lower in sarcopenia CKD group (all P<0.05). Multivariable logistic regression analysis results showed that low eGFR ( OR=0.824, 95% CI 0.687-0.987, P=0.036), low BMI ( OR=0.463, 95% CI 0.304-0.704, P<0.001), low serum albumin ( OR=0.459, 95% CI 0.263-0.802, P=0.006) and high CRP ( OR=2.754, 95% CI 1.708-4.439, P<0.001) were the independent related factors of sarcopenia in elderly CKD patients. Conclusions:The prevalence of sarcopenia in elderly CKD stage 3-4 patients is high. Low eGFR, low BMI, low serum albumin and high CRP are the independent risk factors for sarcopenia in elderly CKD stage 3-4 patients.

Etiology and prognostic factors of necrotizing enterocolitis in infants after neonatal period with hematochezia / 中国小儿急救医学

Objective:To analyze the etiology and prognostic factors of necrotizing enterocolitis(NEC) in infants after neonatal period with hematochezia.Methods:The clinical data of 62 infants older than 28 days with NEC and hematochezia diagnosed at Beijing Children′s Hospital, Capital Medical University from January 2016 to December 2021 were retrospectively analyzed, summarizing the etiology of NEC in this age group and analyze the factors affecting the prognosis of NEC.According to IgE detection results of food allergens, the infants were divided into milk protein positive group and milk protein negative group.According to the absolute value level of peripheral blood eosinophils, they were divided into increased eosinophils group(≥0.5×10 9/L) and normal eosinophils group(<0.5×10 9/L). They were divided into three groups according to co-infection: NEC group(no co-infection), NEC+ clostridium difficile associated diarrhea(CDAD) group, and NEC+ other infection group(salmonella infection or sepsis). According to different feeding methods, they were divided into normal amino acid group(osmotic pressure 310 mOsm/L), diluted amino acid group(osmotic pressure 233 mOsm/L), and deep hydrolysis group(osmotic pressure 185 mOsm/L). The relief time of clinical symptoms, the recovery time of intestinal gas accumulation, feeding time to achieve physiological requirements, and the length of hospital stay in each group were compared. Results:Among 62 cases, there were 27 males and 35 females.The median age of onset was 1.4(1.2, 2.3) months.The median birth weight was 3.2(2.9, 3.4)kg.Full-term infants accounted for 87.1%.Cesarean accounted for 62.9%.Fifty-three patients(85.5%)had allergic symptoms.Thirteen patients(21.0%)had family history of allergy.Cow milk protein allergy was diagnosed in 29 cases.Thirty-two cases(51.6%) had elevated peripheral blood eosinophils.The hospitalization time of milk protein positive group was longer than that of negative group( P=0.047). The clinical remission rate after hypoallergenic formula feeding for 1 day of increased eosinophils group was higher than that of normal eosinophil group(100.0% vs.65.0%, P=0.002). Ten patients(16.1%)were complicated with clostridium difficile infection, two patients(3.2%) with salmonella enteritis, and four patients(6.5%) with sepsis.Both the hospital stay and feeding time to achieve physiological requirements of NEC+ other infection group were longer than the other two groups( P<0.05). NEC+ CDAD group had a higher rate of repeated hospitalizations(40.0%, P=0.004). The mean recovery time of intestinal gas accumulation was(4.5±2.9)days.After(3.9±3.0)days, hypoallergenic formula feeding started.After one day of feeding, the clinical remission rate was 79.0%.The average time to achieve physiological requirements was(5.8±3.2)days.The clinical symptom relief time of diluted amino acid group was shorter( P=0.006), but there was no statistical difference in feeding time to achieve physiological requirements and hospitalization time between each group( P>0.05). Conclusion:Cow′s milk protein allergy and infection(especially CDAD)are closely related to the occurrence and development of NEC after neonatal period with hematochezia.The administration of diluted amino acid-based formulae close to the osmotic pressure of breast milk and targeted anti-infective therapy could shorten the clinical remission time of NEC and reduce the risk of repeated hospitalization.

Analysis of influencing factors of delayed nausea and vomiting in patients with primary liver cancer after transarterial chemoembolization based on two models / 中国实用护理杂志

Objective:To analyze the influencing factors of delayed nausea and vomiting in patients with primary liver cancer after transarterial chemoembolization based on Logistic regression model and decision tree model.Methods:This was a cross-sectional study. A total of 236 patients with primary liver cancer after transarterial chemoembolization in The Second Affiliated Hospital of Air Force Military Medical University from March 2021 to June 2022 were conveniently selected as the research subjects. The factors related to delayed nausea and vomiting were collected, and Logistic regression and decision tree models were established, respectively, and the differences between the two models were compared.Results:The incidence of delayed nausea and vomiting of patients with primary liver cancer after transarterial chemoembolization was 45.34% (107/236). Logistic regression model showed that age, anxiety, sleep disorder, emetic risk level of chemotherapeutic drugs, embolic agent type, and pain 24 hours after surgery were the influencing factors of delayed nausea and vomiting in patients with primary liver cancer after transarterial chemoembolization(all P<0.05). Decision tree model showed that age, sleep disorder, emetic risk level of chemotherapeutic drugs, embolic agent type, and pain 24 hours after surgery were the influencing factors of delayed nausea and vomiting in patients with primary liver cancer after transarterial chemoembolization (all P<0.05). The classification accuracy rates of Logistic regression, decision tree model and combined diagnosis of two models were 72.9%, 71.2% and 72.0% respectively; the areas under the ROC curve were 0.778, 0.781 and 0.806 respectively, with no significant difference (all P>0.05). Conclusions:The analysis results of Logistic regression and decision tree model on the influencing factors of delayed nausea and vomiting in patients with primary liver cancer after transarterial chemoembolization are highly consistent, which can be combined to provide a more comprehensive reference for the evaluation and intervention of medical staff.