BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells

Ureteral stricture in renal allografts is one of the common postoperative complications in kidney transplant recipients. Due to short ureter in renal allografts, endovascular treatment should be adopted before reconstruction surgery to avoid irreversible injury. Alleviating renal allograft injury, easing obstruction or establishing drainage channel are the key measures to treat ureteral stricture. In endovascular treatment, balloon dilatation and internal incision yield high recurrence rate, and long-term indwelling of self-expanding metallic ureteral stents may be a better option. Compared with traditional stents, metallic stents may maintain urinary tract patency for a long time and mitigate the irritation of lower urinary tract symptoms,with different indications and efficacy. Although all metallic stents may be displaced and occluded, it still plays a positive role in the treatment of ureteral stricture in renal allografts. In this article, the application of self-expanding metallic ureteral stent in ureteral stricture of renal allografts was mainly illustrated, aiming to provide reference for optimizing the treatment of ureteral stricture in renal allografts.

Objective:To explore the diagnostic value of color Doppler ultrasonography for transplanted pancreatic venous thrombosis after simultaneous pancreas-kidney transplantation(SPK).Methods:From June 2019 to September 2022, retrospective analysis was conducted for the relevant clinical data of 181 recipients of SPK.Based upon a presence or absence of clinical high-risk factors, such as a sudden decline of blood/urine amylase, elevated fasting blood glucose and D-dimer, they were assigned into two groups of high-risk(n=48)and non-high-risk(n=133). Color Doppler ultrasonography was performed for evaluating the status of transplanted pancreas and reconstructed blood vessels and diagnosing pancreatic thrombosis post-SPK.Also they were divided into two groups of donor splenic vein thrombosis(n=6)and non-thrombosis(n=39)based upon the presence or absence of splenic vein thrombosis.Various laboratory parameters(fasting blood glucose, blood/urine amylase, fatty acids & D-dimer)and transplanted pancreatic ultrasonic measurements(thickness of transplanted pancreatic head/body/tail, inner diameter & blood flow velocity of donor splenic vein, transplanted pancreatic parenchymal arterial blood flow velocity and resistance index)were recorded.Measurement data were tested for normal distribution and homogeneity of variances.Group comparisons for measurement data fulfilling the criteria of normal distribution and homogeneity of variances were conducted by t-test.For data not fulfilling these criteria, Mann-Whitney U test was utilized.Results:Among 9 cases of pancreatic thrombosis as diagnosed by color Doppler ultrasonography, pancreatic venous thrombosis(n=6)occurred in donor splenic vein.The proportion of transplanted pancreatic thrombosis occurring within Week 2 was 88.9%(8/9)and the proportion of transplanted pancreatic venous thrombosis occurring within Week 2 3.3%(5/6). Fasting blood glucose, blood amylase, urine amylase and D-dimer of high-risk group were(14.7±1.9)U/L, (92.6±15.4)mmol/L, (9.7±1.7)U/L and(6.1±2.2)mg/L.The corresponding values for non-high-risk group were(4.9±0.6)U/L, (209.4±34.4)mmol/L, (168.2±95.7)U/L and(1.3±0.6)mg/L respectively.Statistically significant inter-group differences existed( P=0.021, 0.035, 0.001, 0.017). Pancreatic thrombosis was diagnosed by color Doppler ultrasonography in 9 patients in high-risk group and 8 cases occurred within Week 2 post-SPK.Among 6 cases of pancreatic venous thrombosis, 5 cases occurred in donor splenic veins within Week 2 post-SPK.No significant differences existed in the above parameters between group with donor splenic vein thrombosis and group without donor splenic vein thrombosis( P>0.05). Inner diameters of splenic veins in groups with and without splenic vein thrombosis were(11.7±0.5)and(3.9±0.2)mm.Blood flow velocities in splenic veins were(18.3±8.4)and(40.3±16.6)cm/s respectively.The inter-group differences were statistically significant( P=0.001, 0.006). No significant differences existed in thickness of transplanted pancreatic head/body/tail, as well as blood flow velocity or resistance index in transplant pancreatic artery( P>0.05). Conclusions:Fasting blood glucose, blood amylase, urine amylase, fatty acid and D-dimer are important and yet non-specific biochemical parameters in the diagnosis of pancreatic transplantation thrombosis.Color Doppler ultrasonography may provide valuable imaging diagnostic rationales for making an early diagnosis and providing timely interventions of transplanted pancreatic venous thrombosis post-SPK.It is imperative to enhance dynamic monitoring using color Doppler ultrasound within 1-2 weeks post-SPK.Greater attention should be paid to internal diameter and blood flow velocity of donor splenic vein.

Objective:To investigate the effectiveness of mindfulness training on the emotional regulation and resilience of college students.Methods:Eighty one college students were recruited and randomly divided into mindfulness training group and control group, of which 74 completed the study (36 in mindfulness training group and 38 in control group). Participants in mindfulness training group received an 8-week mindfulness training, while participants in control group received no intervention. Participants were assessed with the Five Facet Mindfulness Questionnaire (FFMQ, measuring mindfulness level), Profile of Mood State (POMS, measuring emotion) and the Resilience Scale for Chinese Adolescent(RSCA, measuring resilience) before and after intervention (4 and 8 weeks).Results:Before and after the intervention, the interaction effects of total score of five factors mindfulness, scores of observing, actaware, non-judging, total score of resilience, scores of goal planning, help-seeking and the fatigue score were significant(all P<0.05). There were significant differences in mindfulness level, mood state and resilience scores in mindfulness training group before and after intervention(all P<0.05). There were significant differences of scores of FFMQ , POMS and RSCA post-training compared with baseline( P<0.05). The total score of FFMQ was improved significantly after 4 weeks of intervention ((114.92±11.70) vs(110.36±11.24), P<0.05), while the scores of observing((26.19±5.21) vs(24.00±5.34)), describing((23.36±4.82) vs(21.19±4.76)), non-judging((23.75±4.20) vs(22.06±4.99)) and non-reacting((19.72±3.16) vs(18.58±3.61)) were improved significantly after 8 weeks of intervention. There were significant differences of the scores of fatigue, depression-dejection, panic, vigor-activity and total mood disturbance before and after the intervention in mindfulness training group (all P<0.05). The scores of fatigue((12.31±4.08) vs(13.39±5.12)), panic((12.08±3.57) vs(13.67±4.35)) and total mood disturbance((132.94±17.71) vs(145.75±22.68)) were reduced significantly after 8 weeks of intervention (all P<0.05), while the scores of vigor-activity were improved significantly after 8 weeks of intervention ((18.31±4.61) vs (15.39±4.99), P<0.01). The participants in mindfulness training group got significantly higher total score, scores of goal planning, help-seeking, and affect control of RSCA after intervention compared with baseline (all P<0.05). Conclusion:Mindfulness training can enhance the mindfulness level and resilience of college students, decrease negative affect such as fatigue, depression, panic, and increase positive affect such as activity.

Cardiomyocyte hypertrophy is a major cause of morbidity and mortality worldwide. The aim of this study is to determine the effects of sodium tanshinone IIA sulfonate (STS) on cardiomyocyte hypertrophy induced by angiotensin II (Ang II) in vivo and in vitro. In long-term treatment, adult Wistar rats were infused with Ang II for three weeks via osmotic mini-pumps and some of them were given intragastrically of STS. Left ventricle was isolated; the ratio of left ventricular weight to body weight and systolic blood pressure (SBP) were determined and heart morphometry was assessed after hematoxylin and eosin staining. Results indicated STS inhibited Ang II-induced increases in myocyte diameter and decreased the LVW/BW ratio independent of decreasing systolic blood pressure. In vitro, treatment of cultured cardiomyocytes with STS inhibited Ang II-induced increase in cell size, protein synthesis, ANP expression, activation of extracellular signal-regulated kinase (ERK) and ERK kinase (MEK). Then we reexamined the mechanism of STS-induced anti-hypertrophic effects. Results revealed MEK inhibitor U0126 (20 microM) markedly enhanced STS-induced depressions in [3H]leucine incorporation and ANP expression. In conclusion, MEK/ERK pathway plays a significant role in the anti-hypertrophic effects of STS.
Rats, Wistar ; Rats ; Phenanthrenes/chemistry/*pharmacology ; Myocytes, Cardiac/*drug effects/enzymology/pathology ; Molecular Structure ; Mitogen-Activated Protein Kinase Kinases/*metabolism ; MAP Kinase Signaling System/*drug effects ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Enzyme Activation/drug effects ; Cardiomegaly/chemically induced/enzymology/*metabolism/pathology ; Animals ; Angiotensin II/*antagonists & inhibitors/pharmacology

AIMTo investigate whether chronic bacterial prostatitis might increase oxidative stress and oxidative damage in chronic bacterial prostatitis patients (CBPP), and to explore its possible mechanism.

METHODSEnrolled in a case-control study were 70 randomly sampled CBPP and 70 randomly sampled healthy adult volunteers (HAV), on whom plasma nitric oxide (NO), vitamin C (VC), vitamin E (VE) and beta-carotene (beta-CAR) level, erythrocyte malondialdehyde (MDA) level, as well as erythrocyte superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities were determined by spectrophotometry.

RESULTSCompared with the HAV group, values of plasma NO and erythrocyte MDA in the CBPP group were significantly increased (P < 0.001); those of plasma VC, VE and beta-CAR as well as erythrocyte SOD, CAT and GPX activities in the CBPP group were significantly decreased (P < 0.001). Findings from partial correlation for the 70 CBPP showed that with prolonged course of disease, values of NO and MDA were gradually increased (P < 0.001), and those of VC, VE, beta-CAR, SOD, CAT and GPX were gradually decreased (P < 0.05-0.001). The findings from stepwise regression for the 70 CBPP suggested that the model was Y = -13.2077 + 0.1894MDA + 0.0415NO - 0.1999GPX, F = 18.2047, P < 0.001, r = 0.6729, P < 0.001.

CONCLUSIONThe findings suggest that there exist increased oxidative stress and oxidative damage induced by chronic bacterial prostatitis in the patients, and such phenomenon was closely related to the course of disease.

Adult ; Ascorbic Acid ; blood ; Bacterial Infections ; blood ; physiopathology ; Case-Control Studies ; Catalase ; blood ; Erythrocytes ; metabolism ; Glutathione Peroxidase ; blood ; Humans ; Male ; Malondialdehyde ; blood ; Nitric Oxide ; blood ; Oxidative Stress ; physiology ; Prostatitis ; blood ; microbiology ; physiopathology ; Reference Values ; Superoxide Dismutase ; blood ; Vitamin E ; blood ; beta Carotene ; blood