OBJECTIVE To explore the mechanism of action of Qingre huatan huoxue decoction against atherosclerosis （AS）based on macrophage polarization. METHODS Using atorvastatin served as the positive control， the drug-containing serum of the Qingre huatan huoxue decoction was prepared to treat RAW264.7 macrophages. Macrophage viability， apoptosis rate， and the fluorescence intensities of CD86 and CD206 were measured， along with the levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. Apolipoprotei n E-deficient （ApoE －/－ ） mice （AS model mice） fed with a high-fat diet were randomly assigned to model group， atorvastatin group （2.6 mg/kg）， and low-， medium- and high-dose groups of Qingre huatan huoxue decoction （90， 180， 360 mg/kg）， respectively. C57BL/6J mice fed with a standard diet served as the normal control group， with 10 mice per group. The treatment group mice were administered the corresponding drugs intragastrically， once daily， for 8 consecutive weeks. Serum levels of TNF-α and IL-1β were measured in all groups. Lipid deposition in the aorta （assessed by the percentage of plaque in the entire aorta and aortic root） and morphological changes in the aortic root were observed. Expression levels of CD86 and CD206 in aortic tissue， as well as the protein expression levels of inducible nitric oxide synthase （iNOS）， arginase-1 （Arg-1）， AMP-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， and peroxisome proliferator-activated receptor γ （PPAR-γ） in aortic tissues were all detected. RESULTS Cell experiment results showed that， at concentrations of 5-100 μg/mL， the drug-containing serum of the Qingre huatan huoxue decoction significantly increased RAW264.7 cell viability （ P ＜0.05）. The drug-containing serum of the Qingre huatan huoxue decoction at concentrations of 10， 50， and 100 μg/mL， along with atorvastatin， significantly reduced apoptosis rates， CD86 fluorescence intensity， and TNF-α and IL-1β levels in RAW264.7 cells， while markedly enhancing CD206 fluorescence intensity （ P ＜0.05）. Animal experiment results showed that， compared with the model group， all dosage groups of Qingre huatan huoxue decoction and the atorvastatin group showed significantly reduced/down-regulated levels of TNF-α and IL-1β in serum， along with decreased aortic total and root plaque percentages， CD86 expression， and iNOS protein expression. CD206 expression and Arg-1， p-AMPK/AMPK， PPAR-γ protein expression were significantly up-regulated （ P ＜0.05）. Pathological morphology of the aorta showed varying degrees of improvement. CONCLUSIONS The formula of Qingre huatan huoxue decoction exerts its anti-AS effects by regulating macrophage polarization， increasing the proportion of M2 macrophages， thereby effectively inhibiting AS plaque formation and reducing inflammatory responses.

The interaction of gut microbiota and its metabolites with the host not only plays an important role in maintaining gut homeostasis and host health, but also is a key link in responding to pathogen infections. A thorough understanding of the changes in gut microbiota and its metabolites during infection, as well as their role and mechanism in host defense against infection, is helpful to guide anti-infection treatment. This review focuses on the role of gut microbiota and their metabolites in host defense against bacterial, fungal, and viral infections, and reveals that they can exert anti-infection effects through resistance mechanisms (inducing antimicrobial substances, training immunity, inhibiting pathogen respiration, directly neutralizing pathogens, immune regulation) and tolerance mechanisms (altering energy metabolism patterns of microbiota, cell proliferation and tissue damage repair, maintaining physiological signal transduction in extraintestinal organs, inflammation regulation, maintaining the integrity of the intestinal barrier), and also summarizes measures to regulate gut microbiota against pathogen infections, in order to provide more ideas for novel anti-infection prevention and treatment strategies targeting gut microbiota and its metabolites.

Objective To investigate the changes in blood microbiota in patients with high altitude polycythemia(HAPC)and the correlation with the risk of HAPC.Methods A cross-sectional trial was carried out among 41 HAPC patients(HAPC group)and 41 healthy plateau individuals(control group)who took physical examination in the Health Management Department of No.953 Hospital of PLA Army in 2021.High-throughput sequencing technology was used to detect the V3-V4 variable region of the 16S ribosomal RNA(16S rRNA)gene in the blood smaples,and the composition and difference of the blood microbiota were compared and analyzed between the 2 groups.Results All the participants were male and Han people,and there were no significant differences in baseline data such as age,body mass index and plateau migration time between the 2 groups(P＞0.05).The α-diversity of blood microbiota in the HAPC group,including the Simpson index(0.931±0.005 vs 0.907±0.008,P＜0.05),Goods Coverage index(0.998±0.001 vs 0.997±0.001,P＜0.001)and Pielou index(0.597±0.011 vs 0.567±0.009,P＜0.05)were significantly higher than those in the control group.Meanwhile,obvious difference was observed in the β diversity between the 2 groups(P＜0.01).The relative abundance analysis of bacteria showed that Pelomonas(0.046±0.004 vs 0.033±0.003,P＜0.05),Azospirillum(0.046±0.006 vs 0.021±0.003,P＜0.01),Acidovorax(0.032± 0.003 vs 0.019±0.002,Azospirillum(0.046±0.006 vs 0.021±0.003,P＜0.01)and Acidovorax(0.032± 0.003 vs 0.019±0.002,P＜0.05)were statistically higher in the HAPC group than the control group.LEfSe analysis showed that the characteristic blood microbiota of the HAPC group were α-Proteobacteria,and those of control group were Trichospiridae.Conclusion Significant changes are found in diversity,relative abundance and characteristic bacteria of the blood microbiota between the HAPC patients and healthy people at the high altitude,which might be closely associated with the occurrence and development of HAPC.

Objective:To compare the effect of a 3D-printed ankle and foot orthosis (AFO) with that of a traditional AFO on the recovery of walking function after a stroke.Methods:Thirty-four hemiplegic stroke survivors were randomly divided into an observation group and a control group, each of 17. Both groups were taught good limb placement and given joint mobility, standing and walking training for 4 weeks wearing either a 3D-printed or a conventional AFO. Walking speed, walking endurance, and dynamic balance were evaluated before and after the experiment using the 10-metre walk test (10MWT), the 6-minute walk test (6MWT), and the timed up and go test (TUGT). Integrated electromyography (iEMG) was also performed on each subject′s bilateral rectus femoris, anterior tibialis, and gastrocnemius muscles during walking, and their healthy and affected side iEMG results were compared to assess the activation of the affected lower limb muscles.Results:After treatment, the 10MWT, 6MWT, and TUGT results of both groups had improved significantly, but the observation group′s average results were then significantly better than those in the control group. The iEMG disparities between the healthy and affected sides had also decreased significantly, but on average the disparities in the observation group were significantly smaller than in the control group.Conclusion:Both types of AFO can effectively improve the walking speed, walking endurance, and dynamic balance of hemiplegic stroke survivors and promote muscle activation in the affected lower limb. A 3D-printed AFO is relatively more effective.

Background:The core circadian clock gene Bmal1 has been shown to be involved in the formation of visceral sensitization in irritable bowel syndrome(IBS)by affecting the tryptophan hydroxylase 1(TPH1)-5-hydroxytryptamine(5-HT)pathway,but the exact mechanism of its regulation is unknown.Aims:To investigate the molecular mechanism by which Bmal1 regulates the TPH1-5-HT pathway through the clock-controlled gene Piezo1.Methods:Dexamethasone was used to synchronize the expression of the circadian clock genes in RIN-14B cells.Bmal1 expression was up-regulated or down-regulated in RIN-14B cells by plasmid and siRNA transfection of the enterochromaffin cell(EC)model.The expression levels of target genes and proteins were detected by immunofluorescence staining,RT-qPCR,and Western blotting.5-HT content was detected by ELISA method.Results:(1)This study was the first to report the oscillation characteristics of RIN-14B circadian clock genes in EC model,among which the oscillation of Bmal1 was the most significant.Immunofluorescence showed that RIN-14B cells expressed CGA,Bmal1 and Piezo1.(2)After transfected with the Bmal1 overexpression plasmid,the mRNA and protein expression of Bmal1 were significantly up-regulated in RIN-14B cells compared with the negative control group(all P<0.001);while transfected with Bmal1 siRNA significantly decreased the mRNA and protein expression of Bmal1 in RIN-14B cells compared with the negative control group(all P<0.05).(3)After transfected with Bmal1 overexpression plasmid,the mRNA and protein expression of Piezo1,the protein expression of TPH1,and the intracellular content of 5-HT were significantly increased(all P<0.051).(4)After transfected with Bmal siRNA,mRNA expression of Piezo1 and TPH1 in RIN-14B cells was significantly down-regulated(all P<0.05),and the protein expression of Piezo1,TPH1,the intracellular 5-HT content tended to be decreased by 21%,31%,and 10%,respectively.Conclusions:RIN-14B cells have the characteristics of rhythmic oscillation of circadian clock genes,and Bmal1 overexpression and underexpression EC models can be successfully established by using RIN-14B cells.Overexpression and underexpression of Bmal1 can lead to significant changes in the clock-controlled Piezo1-TPH1-5-HT signaling pathway,suggesting that Bmal1 can be expressed by clock-control signals through the Piezo1-TPH1 pathway.This suggests that Bmal1 may be involved in the development of visceral hypersensitivity in IBS through regulation of 5-HT synthesis by the clock-controlled gene Piezo1.

Background:The core circadian clock gene Bmal1 has been shown to be involved in the formation of visceral sensitization in irritable bowel syndrome(IBS)by affecting the tryptophan hydroxylase 1(TPH1)-5-hydroxytryptamine(5-HT)pathway,but the exact mechanism of its regulation is unknown.Aims:To investigate the molecular mechanism by which Bmal1 regulates the TPH1-5-HT pathway through the clock-controlled gene Piezo1.Methods:Dexamethasone was used to synchronize the expression of the circadian clock genes in RIN-14B cells.Bmal1 expression was up-regulated or down-regulated in RIN-14B cells by plasmid and siRNA transfection of the enterochromaffin cell(EC)model.The expression levels of target genes and proteins were detected by immunofluorescence staining,RT-qPCR,and Western blotting.5-HT content was detected by ELISA method.Results:(1)This study was the first to report the oscillation characteristics of RIN-14B circadian clock genes in EC model,among which the oscillation of Bmal1 was the most significant.Immunofluorescence showed that RIN-14B cells expressed CGA,Bmal1 and Piezo1.(2)After transfected with the Bmal1 overexpression plasmid,the mRNA and protein expression of Bmal1 were significantly up-regulated in RIN-14B cells compared with the negative control group(all P<0.001);while transfected with Bmal1 siRNA significantly decreased the mRNA and protein expression of Bmal1 in RIN-14B cells compared with the negative control group(all P<0.05).(3)After transfected with Bmal1 overexpression plasmid,the mRNA and protein expression of Piezo1,the protein expression of TPH1,and the intracellular content of 5-HT were significantly increased(all P<0.051).(4)After transfected with Bmal siRNA,mRNA expression of Piezo1 and TPH1 in RIN-14B cells was significantly down-regulated(all P<0.05),and the protein expression of Piezo1,TPH1,the intracellular 5-HT content tended to be decreased by 21%,31%,and 10%,respectively.Conclusions:RIN-14B cells have the characteristics of rhythmic oscillation of circadian clock genes,and Bmal1 overexpression and underexpression EC models can be successfully established by using RIN-14B cells.Overexpression and underexpression of Bmal1 can lead to significant changes in the clock-controlled Piezo1-TPH1-5-HT signaling pathway,suggesting that Bmal1 can be expressed by clock-control signals through the Piezo1-TPH1 pathway.This suggests that Bmal1 may be involved in the development of visceral hypersensitivity in IBS through regulation of 5-HT synthesis by the clock-controlled gene Piezo1.

Humans ; Asthma/drug therapy* ; Biological Therapy

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

Background::Patients with pneumoconiosis have an elevated risk of contracting pulmonary tuberculosis (PTB) and need particular attention. However, extensive population-based studies on the prevalence of PTB in patients with pneumoconiosis have not been reported in China since 1992. This study aimed to investigate the epidemiological characteristics of PTB in patients with pneumoconiosis based on its social determinants and risk factors in China.Methods::Based on the Commission on Social Determinants of Health (CSDH) framework, data were obtained from a questionnaire survey of patients with pneumoconiosis from China’s 27 provinces (autonomous regions, municipalities) from December 2017 to June 2021. By chi-square and multivariate logistic regression analyses, the epidemiological characteristics of PTB in the patients were identified based on its prevalence and odds ratio (OR) and associated social determinants and risk factors. The population attributable fractions (PAFs) of significant risk factors were also calculated.Results::The prevalence of PTB in patients with pneumoconiosis ( n = 10,137) was 7.5% (95% confidence interval [CI]: 7.0-8.0%). Multivariate logistic regression analysis showed that risk factors included in-hospital exposure to patients with PTB (OR = 3.30, 95% CI: 2.77-3.93), clinically diagnosed cases (OR = 3.25, 95% CI: 2.42-4.34), and northeastern regions (OR = 2.41, 95% CI: 1.76-3.31). In addition, lack of work-related injury insurance (WRII), being born in a rural area, being unemployed, living in western regions, household exposure to patients with PTB, smoking, being underweight, complications of pulmonary bullae or pneumothorax, hospitalization history, and former drinkers among the rural patients were also statistically significant risk factors. Being born in a rural area, lack of WRII and in-hospital exposure to patients with PTB had higher PAFs, which were 13.2% (95% CI: 7.9-18.5%), 12.5% (95% CI: 8.3-16.7%), and 11.6% (95% CI: 8.8-14.3%), respectively. Conclusion::The prevalence of PTB in pneumoconiosis remains high in China; it is basically in line with the CSDH models and has its characteristics.