Data independent acquisition reveals in-depth serum proteome changes in uremic pruritus.

Introduction: Uremic pruritus (UP) is a prevalent symptom in patients suffering from uremia, yet its underlying etiology and mechanisms remain incompletely elucidated. Given the significant incidence of UP, identifying specific alterations in proteins present in the blood of UP patients could offer insights into the potential biological pathways associated with UP and facilitate the exploration of biomarkers. Methods: In this study, we employed LC-MS/MS-based data-independent acquisition (DIA) mode to analyze serum samples obtained from 54 UP patients categorized as DKD-UP, HN-UP, and GN-UP (n = 18 for each subgroup), along with 18 uremic patients without pruritus (Negative) and 18 CKD patients without pruritus (CKD). Through DIA mode analysis, a total of 7075 peptides and 959 proteins were quantified. Within these, we identified four upregulated and 13 downregulated Differentially Expressed Proteins (DEPs) in DKD-UP versus Negative, five upregulated and 22 downregulated DEPs in HN-UP versus Negative, and three upregulated and 23 downregulated DEPs in GN-UP versus Negative. Furthermore, we conducted an intersection analysis of the DEPs across these three comparison groups to derive a set of common DEPs (COMP). Subsequently, a total of 67 common DEPs were identified in the three UP groups when compared to the CKD group, with 40 DEPs showing upregulation and 27 DEPs displaying downregulation. Results: Following Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses, we observed that the DEPs distinguishing UP from CKD were primarily associated with mitochondrial function (MT-CYB, PRDX2, TOMM22), inflammation (CD59, CSF1), renal injury (WFDC2), and neural function (CAP1, VGF). Discussion: Our findings contribute to a potential molecular comprehension of UP pathogenesis, shedding light on the identification of these DEPs as plausible biomarkers for UP.

PTBP1 promotes the progression of hepatocellular carcinoma by enhancing the oncogenic splicing switch of FGFR2.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer accounting for 90% of cases. It is a highly invasive and deadly cancer with a gradual onset. Polypyrimidine tract-binding protein 1 (PTBP1) is an important RNA-binding protein involved in RNA metabolism and has been linked to oncogenic splicing events. While the oncogenic role of PTBP1 in HCC cells has been established, the exact mechanism of action remains unclear. This study aimed to investigate the functional connection between PTBP1 and dysregulated splicing events in HCC. Through immunoprecipitation-mass spectrometry analyses, we discovered that the proteins bound to PTBP1 were significantly enriched in the complex responsible for the alternative splicing of FGFR2 (fibroblast growth factor receptor 2). Further RNA immunoprecipitation and quantitative PCR assays confirmed that PTBP1 down-regulated the FGFR2-IIIb isoform levels and up-regulated the FGFR2-IIIc isoform levels in HCC cells, leading to a switch from FGFR2-IIIb to FGFR2-IIIc isoforms. Subsequent functional evaluations using CCK-8, transwell, and plate clone formation assays in HCC cell lines HepG2 and Huh7 demonstrated that FGFR2-IIIb exhibited tumor-suppressive effects, while FGFR2-IIIc displayed tumor-promoting effects. In conclusion, this study provides insights into the PTBP1-mediated alternative splicing mechanism in HCC progression, offering a new theoretical basis for the prevention and treatment of this malignancy. Mechanistically, the isoform switch from FGFR2-IIIb to FGFR2-IIIc promoted epithelial-mesenchymal transformation (EMT) of HCC cells and activated the FGFR cascades ERK and AKT pathways.

Omega-3 polyunsaturated fatty acids and its metabolite 12-HEPE rescue busulfan disrupted spermatogenesis via target to GPR120.

Busulfan is an antineoplastic, which is always accompanied with the abnormal of spermatogonia self-renewal and differentiation. It has been demonstrated that the omega-3 polyunsaturated fatty acids (PUFAs) benefits mature spermatozoa. However, whether omega-3 can protect endogenous spermatogonia and the detailed mechanisms are still unclear. Evaluate of spermatogenesis function (in vivo) were examined by histopathological analysis, immunofluorescence staining, and western blotting. The levels of lipid metabolites in testicular tissue were determined via liquid chromatography. We investigated the effect of lipid metabolites on Sertoli cells provided paracrine factors to regulate spermatogonia proliferation and differentiation using co-culture system. In our study, we showed that omega-3 PUFAs significantly improved the process of sperm production and elevated the quantity of both undifferentiated Lin28+ spermatogonia and differentiated c-kit+ spermatogonia in a mouse model where spermatogenic function was disrupted by busulfan. Mass spectrometry revealed an increase in the levels of several omega-3 metabolites in the testes of mice fed with omega-3 PUFAs. The eicosapentaenoic acid metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) up-regulated bone morphogenic protein 4 (BMP4) expression through GPR120-ERK1/2 pathway activation in Sertoli cells and restored spermatogonia proliferation and differentiation. Our study provides evidence that omega-3 PUFAs metabolite 12-HEPE effectively protects spermatogonia and reveals that GPR120 might be a tractable pharmacological target for fertility in men received chemotherapy or severe spermatogenesis dysfunction.

IL-33 Suppresses the Progression of Atherosclerosis via the ERK1/2-IRF1-VCAM-1 Pathway.

PURPOSE: This study was designed to explore the effects of interleukin 33 (IL-33) on the progression of atherosclerosis and the possible mechanism. METHODS: The adhesion assay was performed on isolated peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC). The expression of proteins and messenger RNA (mRNA) were detected by western blot and quantitative real-time polymerase chain reaction (PCR), including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin. The effect of IL-33 on the interaction of growth stimulation expressed gene 2 (ST2) with myeloid differentiation factor 88 (MyD88) and interleukin-1 receptor-associated kinase (IRAK) 1/4 were investigated using co-immunoprecipitation assay. An apolipoprotein (Apo) E-/- mice model was used to confirm the effect of IL-33 on atherosclerosis progression. Area of plaques was recorded by hematoxylin-eosin (H&E) staining. The severity of atherosclerosis plaque was evaluated using immunohistochemistry assay, and lipid accumulation was measured by an oil red O staining. In contrast, western blot was performed to detect the expression levels of VCAM-1, extracellular signal-regulated kinase (ERK) 1/2, and interferon regulatory factor 1 (IRF1). RESULTS: Our study observed that IL-33 suppressed cell adhesion and the expression of VCAM-1 in tumor necrosis factor-α (TNF-α) exposed HUVEC. Moreover, the addition of IL-33 significantly inhibited the expression of IRF1 and the binding level of IRF1 to VCAM-1 and also promoted the phosphorylation level of IRAK1/4 and ERK1/2 compared to TNF-α-stimulated HUVEC. The ST2 neutralizing antibody or ERK pathway inhibitor SCH772984 reversed the regulatory effects of IL-33 on HUVEC, suggesting that IL-33 suppressed IRF1 and VCAM-1 dependent on binding to ST2 and activating the ERK1/2 signaling pathway. Further investigation in vivo confirmed that IL-33 decreased the expressions of IRF1 and VCAM-1 by activating the phosphorylation of ERK1/2 in the thoracic aorta of Apo E-/- mice. CONCLUSION: In conclusion, our results demonstrated that IL-33 plays a protective role in the progression of atherosclerosis by inhibiting cell adhesion via the ERK1/2-IRF1-VCAM-1 pathway. This study may provide a potential therapeutic way to prevent the development of atherosclerosis.

Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota. METHODS: We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated. RESULTS: We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1ß, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues. CONCLUSION: These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance.

TRIM40 ameliorates diabetic retinopathy through suppressing inflammation via Reelin/DAB1 signaling disruption: A mechanism by proteasomal degradation of DAB1.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Reelin, an extracellular matrix protein, and its effector protein Disabled1 (DAB1) have been linked to cellular events and retinal development. However, whether and how Reelin/DAB1 signaling causes DR remains to be investigated. In our study, significantly increased expression of Reelin, very low density lipoprotein receptor (VLDLR), ApoE receptor 2 (ApoER2) and phosphorylated DAB1 in retinas of streptozotocin (STZ)-induced DR mouse model was observed, along with enhanced expression of proinflammatory factors. Similar results are confirmed in high glucose (HG)-treated human retinal pigment epithelium cell line ARPE-19. Surprisingly, dysregulated tripartite motif-containing 40 (TRIM40), an E3 ubiquitin ligase, is found to be involved in DR progression by bioinformatic analysis. We observe a negative correlation between TRIM40 and p-DAB1 protein expression levels under HG conditions. Importantly, we find that TRIM40 over-expression markedly ameliorates HG-induced p-DAB1, PI3K, p-protein B kinase (AKT) and inflammatory response in HG-treated cells, but dose not affect Reelin expression. Of note, Co-IP and double immunofluorescence identify an interaction between TRIM40 and DAB1. Furthermore, we show that TRIM40 enhances K48-linked polyubiquitination of DAB1, thereby promoting DAB1 degradation. Finally, promoting TRIM40 expression by intravenous injection of the constructed adeno-associated virus (AAV-TRIM40) markedly ameliorates DR phenotypes in STZ-treated mice, as indicated by the decreased blood glucose and glycosylated hemoglobin (HbAlc) levels, and increased hemoglobin contents. Additionally, diabetes-related elevation of acellular capillaries was also meliorated in mice over-expressing TRIM40. The electroretinogram (ERG) deficits were strongly rescued in mice receiving AAV-TRIM40 injection. Moreover, AAV-TRIM40 attenuates the inflammation and p-DAB1 expression in retinal tissues of STZ-treated mice. Collectively, our findings disclose a mechanism through which TRIM40 limits DAB1 stability under physiological conditions and reveals TRIM40 as a potential therapeutic target for the intervention of Reelin/DAB1 signaling, contributing to DR treatment.

Age-related elevation of O-GlcNAc causes meiotic arrest in male mice.

In recent years, the postponement of childbearing has become a critical social issue. Male fertility is negatively associated with age because of testis aging. Spermatogenesis is impaired with age, but the molecular mechanism remains unknown. The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging.

Chronic oral exposure to short chain chlorinated paraffins induced testicular toxicity by promoting NRF2-mediated oxidative stress.

As a widespread environmental contaminant, short chain chlorinated paraffins (SCCPs) has attracted great attention. However, the toxicity of SCCPs on male reproductive system remains ambiguous. In this study, we treated mice with SCCPs by gavage and investigated the toxic effects of SCCPs on testis. According to the results, the sperm parameters of mice were significantly reduced after exposure to 1, 10, 100 mg/kg body mass per day SCCPs for 35 days. SCCPs resulted in disorderly arranged seminiferous epithelium and increased apoptotic cells in testes. Both in vivo and in vitro experiments indicated that the oxidative stress was induced after SCCPs exposure, and dysfunction of nuclear factor erythroid-related factor (NRF2) signaling pathway played a role in this process. Moreover, resveratrol, an NRF2 activator, could alleviate the damage of SCCPs onmale reproductive system. Our study indicated that oxidative stress is the key point for explaining the testicular toxicity caused by SCCPs, and NRF2 could be used as a potential target for clinical treatment to alleviate the reproductive toxicity induced by SCCPs.

Genetic Analysis of a Case of Sotos Syndrome with Suspected Germinal Mosaicism in Mother.

This study is to identify the pathogenic mutation of a child with Sots syndrome and provide prenatal diagnosis for his pregnant mother. Chromosome microarray technology was used to detect whether there were minor deletions/duplication in patients' chromosomes. The gene mutation of patients was screened by next-generation sequencing technology, and it was verified by Sanger sequencing. Prenatal diagnosis of the fetus was conducted according to the selected pathogenic sites, and genetic counseling was conducted for her parents. Chromosome microarray results showed that there was no minor deletion in a chromosome 5q35 region, and the second-generation sequencing results showed that there was a c.4138delG heterozygous mutation in the patient's NSD1 gene, and the pathogenic of this mutation was not reported in related databases. Sanger sequencing found that there was a c.4138delG heterozygous mutation in the NSD1 gene of the patient and her parents' genotype at this locus was wild type. The prenatal gene test results indicated that there was heterozygous mutation of NSD1 gene c.4138delG in the fetus, so it was suggested to terminate the pregnancy. Gentling results indicated that the fetus and the patient inherited the same maternal chromosome 5. The heterozygous mutation of NSD1 gene c.4138delG is the pathogenic mutation of this Sots syndrome patient, and the mother may be germinal mosaicism.

The mediating role of professional commitment between the clinical learning environment and learning engagement of nursing students in clinical practice: A cross-sectional study.

BACKGROUND: Previous studies have shown that learning engagement can significantly predict nursing students' academic achievement. Nursing educators put considerable effort into assessing and promoting students' engagement in school. However, nursing students' learning engagement in clinical practice has seldom been explored. OBJECTIVES: To investigate nursing students' learning engagement and influencing factors in clinical practice and examine the effects of the clinical learning environment and professional commitment on learning engagement, specifically to verify the mediation effect of professional commitment. DESIGN: A cross-sectional study. SETTINGS: The participants were from five hospitals in Jining, Shandong, China. PARTICIPANTS: A total of 318 nursing students who were at the end of clinical practice training (>8 months) were included in this study. METHODS: The Utrecht Work Engagement Scale for Students, the Clinical Learning Environment for Nursing Scale, and the Professional Commitment Scale were used for data collection. Regression and mediating analyses were used to explore the influencing factors of clinical learning engagement and the potential mediating role of professional commitment. RESULTS: The participants experienced moderate levels of engagement in clinical learning. The clinical learning environment indirectly affected nursing students' learning engagement in clinical practice through professional commitment. Night shifts and educational background also contributed to learning engagement. CONCLUSIONS: The findings provide new perspectives on promoting nursing students' clinical learning engagement. Professional commitment might be an important mediating variable in nursing education. There is a need to take steps to improve professional commitment of nursing students.

Effects of Satir model group intervention on coping style, self-consistency and congruence and subjective well-being among re-employment nurses / 中国实用护理杂志

Objective:To investigate the effects of Satir model group intervention on stress coping style, self-consistency and congruence and subjective well-being of re-employment nurses, in order to provide evidence for nursing managers to take targeted intervention measures.Methods:This was a quasi-experimental study. Convenience sampling was used to select 63 re-employment nurses from Shandong Provincial Third Hospital in 2021 as the research objects. The re-employment nurses were divided into control group (32 cases) and observation group (31 cases) by random number table method. The control group received humanistic care including heart-to-heart talk, group discussion and psychological lecture, and the observation group received Satir model group intervention for 6 weeks. Simplified Coping Style Questionnaire, Self Consistency and Congruence Scale and General Well-Being Scale were used to evaluate the intervention effect before intervention, immediately after intervention, 3 months after intervention, and 6 months after intervention.Results:There was no significant difference in coping style, self-consistency and congruence and subjective well-being between the two groups before intervention ( P>0.05). The positive coping scores of the observation group immediately after intervention, 3 months after intervention and 6 months after intervention were (28.94 ± 2.99), (28.71 ± 4.70) and (29.16 ± 3.23) points, significantly higher than the control group (23.38 ± 5.50), (24.72 ± 5.91), (24.65 ± 5.65) points, the differences were statistically significant ( t=4.96, 2.96, 3.87, all P<0.01); the total self-consistency and congruence scores were (94.52 ± 14.00), (99.87 ± 16.82), (91.84 ± 10.36) points, significantly lower than the control group (105.72 ± 10.75), (114.23 ± 20.10), (107.41 ± 13.39) points, the differences were statistically significant ( t=-3.57, -3.07, -5.15, all P<0.01); the total subjective well-being scores were (84.97 ± 7.37), (84.58 ± 10.33), (91.84 ± 7.01) points, which were higher than the control group (75.69 ± 7.94), (77.28 ± 8.27), (77.00 ± 8.48) points, and the differences were statistically significant ( t=4.80, 3.69, 7.56, all P<0.01). Conclusions:Satir model group intervention can improve the coping style, enhance the level of self-consistency and congruence and subjective well-being among re-employment nurses.

Based on Delphi method improved early graded rehabilitation nursing model for postoperative children with congenital heart disease / 中国实用护理杂志

Objective:To improve the early graded rehabilitation nursing model suitable for postoperative children with congenital heart disease, providing reference for related research and clinical practice.Methods:Searched databases like JBI, PubMed, Medline, CINAHL, CNKI, Wanfang Data and related websites for information on postoperative rehabilitation of children with congenital heart disease. We improved the first draft model with qualitative interview results and used Delphi method to conduct two rounds of consultation for 16 experts from 6 provinces and cities to further test the scientific and feasibility of the model.Results:The early graded rehabilitation nursing model for postoperative children with congenital heart disease includes 4 first-level items, 15 second-level items and 48 third-level items. The 4 first-level items are the evaluation of the early graded rehabilitation nursing model, the grading standard of the early graded rehabilitation nursing model, the implementation of the early graded rehabilitation nursing model, the effect evaluation and health education. Experts′ response rates were 100% in the 2 rounds, experts′ authority coefficient were 0.82 and 0.84 respectively, and the Kendall′ s W rank-order correlation coefficients of all levels of indicators were 0.188-0.246, 0.223-0.287 (all P<0.01). Conclusions:The improved early graded rehabilitation nursing model for postoperative children with congenital heart disease is scientific, pertinence and safe, which can provide guidance for clinical rehabilitation nursing practice.

Comprehensive Evaluation of Health Status of Traditional Chinese Medicine Constitution based on Improved Radar Chart / 中医杂志

ObjectiveTo present the health status of traditional Chinese medicine （TCM） constitutions more intuitively and comprehensively based on improved radar chart. MethodsParticipants who completed a 26-week comprehensive intervention based on TCM constitution from February 2013 to January 2014 in Zhuhai branch of Guangdong Provincial Hospital of Chinese Medicine were included in the study. They were divided into groups according to gender and age， i.e. young， middle-aged， and elderly male and female groups. TCM constitution scale and health survey short form （SF-36） were used to evaluate the 9 basic TCM constitution types and quality of life at three time points， including pre-intervention （T1）， at 13-week intervention （T2）， and at 26-week intervention （T3）. The improved radar charts were drawn to visually present the comprehensive evaluation results on the health status of 9 TCM constitutions， and graphic features （area S value， perimeter L value） were extracted to construct a comprehensive health index for TCM constitutions （H value）. Spearman correlation analysis was used to analyze the correlation between H value and SF-36 total score. ResultsAmong the included 509 participants， there were 45 elderly male， 76 elderly female， 60 middle-aged male， 140 middle-aged female， 53 young male and 135 young female. The radar charts for comprehensive evaluation of TCM constitution health status showed that the total areas for all groups increased at T3 compared to T1， with the most significant increase in the young population. In the middle-aged population， the fan-shaped areas of certain constitutions decreased at T2 than T1. At T3， the radar chart shapes for females were more balanced than males in the same age group. By calculating the features of function graphs， it was found that the S， L， and H values for the elderly population were relatively higher than those for the middle-aged and young population with the same gender， and the young population increased by highest ratio. The values measured at T3 compared to T1 showed average increase of 26% for S value （11% for the middle-aged and 14% for the elderly）， 22% for L value （10% for the middle-aged and the elderly each）， and 22% for H value （10% for the middle-aged and 9% for the elderly）. The female had lower S and L values， as well as higher H value than the male of the same age group measured at T3. The correlation coefficient between the H value of all participants and the total SF-36 score was 0.662 （P＜0.01）. ConclusionThe comprehensive evaluation model for the health status of TCM constitution based on the improved radar chart constructed in this study can present the health status of TCM constitutions and intervention effectiveness more comprehensively and intuitively. It is suggested to regulate the constitution in pursuit of the dynamic balance of the constitution health status， as well as consider the parts from the whole， and put focus on the balance of nine TCM constitutions.

Ultrasound-guided anhydrous ethanol and microwave ablation for functional parathyroid cyst: a case report / 南方医科大学学报

We report a case of functional parathyroid cyst treated by ultrasound-guided anhydrous ethanol sclerotherapy and microwave ablation. The 63-year-old female patient was diagnosed to have functional parathyroid cyst with hypercalcemia, high PTH and cystic space-occupying lesions in the neck by ultrasound, radionuclide scanning and PTH measurement of the cystic fluid. The patient refused to receive cyst resection, and anhydrous ethanol sclerotherapy with microwave ablation was performed under ultrasound guidance. The procedure was completed smoothly without any complications either during or after the operation. Follow-up examination of the patient at 18 months after the operation showed a significant reduction of the mass and normal blood calcium and iPTH levels, demonstrating a clinical cure of the patient. Ablative treatment of functional parathyroid cyst has not been documented so far. This approach provides a minimally invasive treatment modality for such cases where surgical resection is not an option, but its efficacy and safety need to be evaluated in more cases with longer follow-up time.

Association between vitamin D level and blood eosinophil count in healthy population and patients with chronic obstructive pulmonary disease / 南方医科大学学报

OBJECTIVE@#To investigate the prevalence of vitamin D deficiency and its association with blood eosinophil count in healthy population and patients with chronic obstructive pulmonary disease (COPD).@*METHODS@#We analyzed the data of a total 6163 healthy individuals undergoing routine physical examination in our hospital between October, 2017 and December, 2021, who were divided according to their serum 25(OH)D level into severe vitamin D deficiency group (< 10 ng/mL), deficiency group (< 20 ng/mL), insufficient group (< 30 ng/mL) and normal group (≥30 ng/mL). We also retrospectively collected the data of 67 COPD patients admitted in our department from April and June, 2021, with 67 healthy individuals undergoing physical examination in the same period as the control group. Routine blood test results, body mass index (BMI) and other parameters were obtained from all the subjects, and logistic regression models were used to investigate the association between 25(OH)D levels and eosinophil count.@*RESULTS@#The overall abnormal rate of 25(OH)D level (< 30 ng/mL) in the healthy individuals was 85.31%, and the rate was significantly higher in women (89.29%) than in men. Serum 25(OH)D levels in June, July, and August were significantly higher than those in December, January, and February. In the healthy individuals, blood eosinophil counts were the lowest in severe 25(OH)D deficiency group, followed by the deficiency group and insufficient group, and were the highest in the normal group (P < 0.05). Multivariable regression analysis showed that an older age, a higher BMI, and elevated vitamin D levels were all risk factors for elevated blood eosinophils in the healthy individuals. The patients with COPD had lower serum 25(OH)D levels than the healthy individuals (19.66±7.87 vs 26.39±9.28 ng/mL) and a significantly higher abnormal rate of serum 25(OH)D (91% vs 71%; P < 0.05). A reduced serum 25(OH)D level was a risk factor for COPD. Blood eosinophils, sex and BMI were not significantly correlated with serum 25(OH)D level in patients with COPD.@*CONCLUSION@#Vitamin D deficiency is common in both healthy individuals and COPD patients, and the correlations of vitamin D level with sex, BMI and blood eosinophils differ obviously between healthy individuals and COPD patients.

Clinical characteristics and follow-up analysis of 12 patients of acute phosphine poisoning / 中华劳动卫生职业病杂志

Objective: To investigate the clinical characteristics of patients with acute phosphine poisoning, and to follow up and evaluate the prognosis of patients. Methods: In May 2022, 12 patients with phosphine poisoning by respiratory inhalation in Beijing Chao-Yang Hospital of Capital Medical University were analyzed. The patients were treated with symptomatic support therapy. Three months later, patients were re-evaluated the symptoms of poisoning, pulmonary function and magnetic resonance imaging (MRI) of the brain to understand the prognosis of the phosphine poisoning. Results: The main symptoms of 12 patients were respiratory and central nervous system symptoms with hypoxia. The symptoms of poisoning improved after treatment. Follow-up found that the patients had different degrees of residual symptoms. Pulmonary function showed increased airway resistance. Airway challenge test was positive in some patients. MRI of the head of some patients showed small ischemic focus in bilateral frontal lobes. Conclusion: Acute phosphine poisoning may cause persistent damage to the respiratory system and central system, and residual symptoms after 3 months.

Effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant in Guangdong Province / 中华预防医学杂志

Objective: To evaluate the effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant. Methods: A total of 1 403 Omicron-infected patients admitted to 20 designated hospitals in Guangdong Province from January 1 to May 31, 2022, were selected as subjects in this study. A case-control study was conducted to collect the demographic data, underlying disease, vaccination status, last exposure date, gene sequencing of infected strains and clinical outcomes from the China Disease Prevention and Control Information System and Guangdong telemedicine platform. Pneumonia (common, severe and critical) and non-pneumonia (asymptomatic and mild) were selected as the case group and control group. The effect of inactivated SARS-CoV-2 vaccine on the clinical outcomes of patients infected with the Omicron variant was analyzed. Results: The median age [M (Q1, Q3)] of the subjects was 36 (27-47) years old, with males accounting for 52.25% (733 cases). The main outcome of the infection was non-pneumonia, accounting for 92.09% (1 292 cases), and the duration [M (Q1, Q3)] of the disease was 18 (14-22) days. There were 134 (9.55%), 39 (2.78%), 403 (28.72%), 437 (31.15%) and 390 (27.80%) cases with no or partial vaccination, within 90 days of primary vaccination, over 90 days of primary vaccination, within 90 days of booster vaccination and over 90 days of booster vaccination, respectively. Multivariate logistic regression analysis showed that after adjusting for gender, age, underlying disease, and location of the report, compared with those with no or partial vaccination, the risk of developing pneumonia was lower in those with over 90 days of primary vaccination, within 90 days of booster vaccination and over 90 days of booster vaccination [OR (95%CI) values were 0.52 (0.28-0.98), 0.39 (0.21-0.73) and 0.40 (0.21-0.77), respectively]. Cox proportional hazard regression model analysis showed that after adjusting for gender, age, underlying disease and location of the report, the duration of the disease was shorter in those who received booster vaccinated for more than 90 days compared with that in those who had no or partial vaccination [HR (95%CI): 1.26 (1.03-1.55)]. Conclusion: The inactivated SARS-CoV-2 vaccine affects the clinical outcomes of patients infected with the Omicron variant.

Integrated Metagenomics and UPLC-Q-TOF-MS/MS to Explore the Mechanism of Dexamethasone on Pneumonia in Rats / 中山大学学报(医学科学版)

ObjectiveUsing multi-omics technology， we conducted the present study to determine whether dexamethasone has therapeutic effect on pneumonia rats through the regulation of intestinal flora and metabolites. MethodsTotally 18 Sprague-Dawley rats were randomly divided into 3 groups （n = 6 each）： Control group， Model group and Dexamethasone （Dex） group. Lipopolysaccharide （LPS） was continuously injected intraperitoneally into rats at a dose of 4 mg/kg for 7 days to induce pneumonia except the Control group. Then the Dex group was given Dex at a dose of 2 mg/kg via oral gavage for 12 days， and both the other two groups received continuously equal volume of sterile PBS buffer for 12 days. On the 19th day， lung， plasma， feces and intestinal contents of rat were collected. Hematoxylin-eosin （H&E） staining and Bio-plex suspension chip system were applied to evaluate the effect of Dex on pneumonia. Furthermore， metagenomic sequencing and UPLC-Q-TOF-MS/MS technology were employed to determine the intestinal flora and metabolites of rats， respectively. ResultsH&E staining results showed that the lung tissue of the Model group was infiltrated with inflammatory cells， the alveolar septum was increased， alveolar hemorrhage， and histological lesions were less severe in Dex group than in the model group. The levels of 3 inflammatory cytokines including TNF-α （P < 0.000 1）， IL-1α （P = 0.009 6） and IL-6 （P < 0.000 1） in the Model group were increased compared with the Control group， while Dex treatment reduced the levels of the three inflammatory factors. Taken together， Dex treatment effectively reversed the features of pneumonia in rats. Metagenomic analysis revealed that the intestinal flora structure of the three groups of rats was changed. In contrast with the Model group， an increasing level of the Firmicutes and an elevated proportion of Firmicutes/Bacteroidetes were observed after Dex treatment. Dex-treated rats possessed notably enrichment of Bifidobacterium， Lachnospiraceae and Lactobacillus. Multivariate statistical analysis showed a great separation between Model group and Dex group， indicating metabolic profile changes. In addition， 69 metabolites （P < 0.05） were screened， including 38 up-regulated in the Model group and 31 elevated in the Dex group， all of which were mainly involved in 3 metabolic pathways： linoleic acid metabolism， tryptophan metabolism and primary bile acid biosynthesis. ConclusionsIn summary， we demonstrate the beneficial effects of Dex on the symptoms of pneumonia. Meanwhile， integrated microbiome-metabolome analysis reveals that Dex improves LPS-induced pneumonia in rats through regulating intestinal flora and host metabolites. This study may provide new insights into the mechanism of Dex treatment of pneumonia in rats.