An Unusual Cause of Intestinal Ulcers Masquerading as Inflammatory Bowel Disease: A Case Report of Allied Disorders of Hirschsprung's Disease.

Background: Allied disorders of Hirschsprung's disease (ADHD) exhibit symptoms akin to those of Hirschsprung's disease, primarily characterized by intestinal obstruction, bowel dilatation, and chronic constipation. The occurrence of amyloid complications in patients with ADHD is infrequent. In this report, we present a case of ADHD with intestinal ulcers as the initial gastrointestinal manifestation, and subsequent pathological examination revealed the presence of amyloid deposits in the colonic mucosa. Case Report: A male patient, aged 20, exhibited recurring abdominal distension and intestinal obstruction for a duration of three years. Multiple colonoscopies revealed the presence of recurrent colonic ulcers, with pathological examination indicating the existence of amyloid deposits within the mucosal layer of the colon. Abdominal CT scans suggested colonic dilatation. Following a multidisciplinary consultation, a subtotal resection of the colon was performed, and subsequent postoperative pathology confirmed a decrease and absence of myenteric plexus ganglion cells. Considering the patient's symptoms and the findings from the postoperative pathology, a diagnosis of ADHD was made. The patient's symptoms resolved postoperatively and he was discharged from the hospital and followed up for 1 year in stable condition. Conclusion: Our study highlights the potential association between ADHD and the initial presentation of recurrent colonic ulcers, accompanied by amyloid deposition in the intestinal mucosa. This finding suggests a possible pathogenic mechanism for ADHD and offers a novel perspective on its diagnosis.

Hypoxia-Induced Myocardial Hypertrophy Companies with Apoptosis Enhancement and p38-MAPK Pathway Activation.

Li, Xiaoxu, Zhijun Pu, Gang Xu, Yidong Yang, Yu Cui, Xiaoying Zhou, Chenyuan Wang, Zhifeng Zhong, Simin Zhou, Jun Yin, Fabo Shan, Chengzhong Yang, Li Jiao, Dewei Chen, and Jian Huang. Hypoxia-induced myocardial hypertrophy companies with apoptosis enhancement and p38-MAPK pathway activation. High Alt Med Biol. 00:00-00, 2024. Background: Right ventricular function and remodeling are closely associated with symptom severity and patient survival in hypoxic pulmonary hypertension. However, the detailed molecular mechanisms underlying hypoxia-induced myocardial hypertrophy remain unclear. Methods: In Sprague-Dawley rats, hemodynamics were assessed under both normoxia and hypobaric hypoxia at intervals of 7 (H7), 14 (H14), and 28 (H28) days. Morphological changes in myocardial tissue were examined using hematoxylin and eosin (HE) staining, while myocardial hypertrophy was evaluated with wheat germ agglutinin (WGA) staining. Apoptosis was determined through TUNEL assays. To further understand the mechanism of myocardial hypertrophy, RNA sequencing was conducted, with findings validated via Western blot analysis. Results: The study demonstrated increased hypoxic pulmonary hypertension and improved right ventricular diastolic and systolic function in the rat models. Significant elevations in pulmonary arterial systolic pressure (PASP), mean pulmonary arterial pressure (mPAP), right ventricular mean pressure (RVMP), and the absolute value of +dp/dtmax were observed in the H14 and H28 groups compared with controls. In addition, right ventricular systolic pressure (RVSP), -dp/dtmax, and the mean dp/dt during isovolumetric relaxation period were notably higher in the H28 group. Heart rate increased in the H14 group, whereas the time constant of right ventricular isovolumic relaxation (tau) was reduced in both H14 and H28 groups. Both the right heart hypertrophy index and the heart weight/body weight ratio (HW/BW) were elevated in the H14 and H28 groups. Myocardial cell cross-sectional area also increased, as shown by HE and WGA staining. Western blot results revealed upregulated HIF-1α levels and enhanced HIF-2α expression in the H7 group. In addition, phosphorylation of p38 and c-fos was augmented in the H28 group. The H28 group showed elevated levels of Cytochrome C (Cyto C), whereas the H14 and H28 groups exhibited increased levels of Cleaved Caspase-3 and the Bax/Bcl-2 ratio. TUNEL analysis revealed a rise in apoptosis with the extension of hypoxia duration in the right ventricle. Conclusions: The study established a link between apoptosis and p38-MAPK pathway activation in hypoxia-induced myocardial hypertrophy, suggesting their significant roles in this pathological process.

Assessment of Acute Mountain Sickness: Comparing the Chinese AMS Score to the Lake Louise Score.

Wu, Yu, Wenqi Zhao, Bao Liu, Jianyang Zhang, Zhifeng Zhong, Simin Zhou, Jiaxin Xie, Yuqi Gao, Peng Li, and Jian Chen. Assessment of Acute Mountain Sickness: Comparing the Chinese Ams Score to the Lake Louise Score. High Alt Med Biol 00:000-000, 2024. Objective: To compare the ability of the Chinese AMS Score (CAS) to detect acute mountain sickness (AMS) using the 2018 version of the Lake Louise Score (LLS) as reference. Methods: After flying from Chengdu (altitude: 500 m) to Lhasa (3,658 m), 2,486 young men completed a questionnaire. The questionnaire contained LLS and CAS items. An LLS ≥3 and/or a CAS ≥cutoff were used as the criteria for AMS. Hierarchical cluster analysis and two-step cluster analysis were used to investigate relationships between the symptoms. Results: AMS incidence rates were 33.8% (n = 840) with the LLS and 59.3% (n = 1,473) with the CAS (χ2 = 872.5, p < 0.001). The LLS and CAS had a linear relationship (orthogonal regression, Pearson r = 0.91, p < 0.001). With the LLS as the standard, the CAS had high diagnostic accuracy (area under the curve = 0.95, 95% confidence interval: 0.94-0.96). However, with the CAS, 25.5% (n = 633) more participants were labeled as having AMS than with the LLS (false positives). Two clusters were identified: one with headache only (419 participants, 66.2%) and one without headache but with other symptoms (214 participants, 33.8%). Reducing the weight of headache in the CAS allowed to align CAS and LLS. Conclusion: In comparison to the LLS, the CAS has a sensitivity close to 100% but lacks specificity given the high rate of false positives. The different weight of headaches may be the main reason for the discrepancy.

Hypoxic preacclimatization combining intermittent hypoxia exposure with physical exercise significantly promotes the tolerance to acute hypoxia.

Background: Both hypoxia exposure and physical exercise before ascending have been proved to promote high altitude acclimatization, whether the combination of these two methods can bring about a better effect remains uncertain. Therefore, we designed this study to evaluate the effect of hypoxic preacclimatization combining intermittent hypoxia exposure (IHE) and physical exercise on the tolerance to acute hypoxia and screen the optimal preacclimatization scheme among the lowlanders. Methods: A total of 120 Han Chinese young men were enrolled and randomly assigned into four groups, including the control group and three experimental groups with hypoxic preacclimatization of 5-day rest, 5-day exercise, and 3-day exercise in a hypobaric chamber, respectively. Main physical parameters for hypoxia acclimatization, AMS incidence, physical and mental capacity were measured for each participant in the hypobaric chamber simulated to the altitude of 4500 m in the effect evaluation stage. The effect was compared between different schemes. Results: During the effect evaluation stage, SpO2 of the 5-day rest group and 5-day exercise group was significantly higher than that of the control group (p = 0.001 and p = 0.006, respectively). The participants with 5-day rest had significantly lower HR than the controls (p = 0.018). No significant differences of AMS incidence were found among the four groups, while the proportion of AMS headache symptom (moderate and severe vs. mild) was significantly lower in the 3-day exercise group than that in the control group (p = 0.002). The 5-day exercise group had significantly higher VO2max, than the other three groups (p = 0.033, p < 0.001, and p = 0.023, respectively). The 5-day exercise group also had significantly higher digital symbol and pursuit aiming test scores, while shorter color selection reaction time than the control group (p = 0.005, p = 0.005, and p = 0.004, respectively). Conclusion: Hypoxic preacclimatization combining IHE with physical exercise appears to be efficient in promoting the tolerance to acute hypoxia. Hypoxia duration and physical exercise of moderate intensity are helpful for improvement of SpO2 and HR, relief of AMS headache symptoms, and enhancement of mental and physical operation capacity.

4D DIA-PRM proteomic study identifying modulated pathways and biomarkers associated with pelvic organ prolapse.

Pelvic organ prolapse (POP) is a highly disabling condition that negatively affects the quality of life of millions of women worldwide. However, the underlying mechanisms associated with the development and progression of the disease remain poorly understood. Here, an untargeted four-dimensional data-independent acquisition (4D DIA)-based proteomics approach was applied to vaginal wall tissue samples from POP (n = 19) and control (n = 8) patients to identify potential diagnostic biomarker(s) for POP and examine the molecular mechanisms underlying the disease. Of the 5713 tissue proteins that were detected, 1957 proteins were significantly changed in POP patients. Further bioinformatics analysis revealed that multiple biological processes including protein digestion & absorption, retrograde endocannabinoid signaling, tyrosine metabolism, and nucleotide metabolism were significantly enriched and associated with the pathogenesis of POP. Interestingly, 16 of these differentially expressed proteins associated with four pathways were also identified by targeted parallel reaction monitoring (PRM) proteomics analysis on the same 27 tissue samples. Changes in 94 % (15/16) of these proteins were consistent with the 4D DIA data. Furthermore, most proteins displayed good diagnostic accuracy with high area under the curve (AUC) values (AUC＞0.8). Specifically, five proteins including ELN, COL6A2, ENTPD1, AOC3, and COX7A2 distinguished between POP and control patients with very high accuracy (AUC ≥ 0.95) in both 4D DIA and PRM analyses, and may therefore be potential diagnostic biomarkers for POP. In summary, the present study not only provided several potential biomarker(s) for effective POP diagnosis, but extended our knowledge of the key regulatory pathways associated with the disease.

Metabolomic and Proteomic Identification of Serum Exosome for Hypoxic Preconditioning Participants.

Background: In high-altitude areas, hypoxic stress can elicit a series of physiological responses in humans. Exosomes play important roles in both local and distal cellular communications. Methods: We used ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) studies to analyze the differentially expressed metabolomics and proteomics in serum exosome of hypoxic preconditioning participants and control subjects in the hypoxic conditions. Results: Fifty-seven military personnel were divided into hypoxic preconditioning group (n = 27) and control group (n = 30). One hundred thirty-six differentially expressed serum exosomal metabolites were found between the hypoxic preconditioning and control groups in the hypoxic conditions, and these differentially expressed metabolites were enriched in pathways related to lysine degradation, butanoate metabolism, GABAergic synapse, histidine metabolism, and linoleic acid metabolism. In addition, hypoxic preconditioning participants showed 102 excellent differential expressions of proteomics compared to controls, which involved actin cytoskeleton organization, hemostasis, complement and coagulation cascades, vesicle-medicated transport, wound healing, etc. Conclusions: We revealed that the expression of exosomal metabolites and proteomics in hypoxic preconditioning participants was significantly different compared to controls in hypoxic conditions.

Identification of serum exosomal metabolomic and proteomic profiles for remote ischemic preconditioning.

BACKGROUND: Remote ischemic preconditioning (RIPC) refers to a brief episode of exposure to potential adverse stimulation and prevents injury during subsequent exposure. RIPC has been shown to increase tolerance to ischemic injury and improve cerebral perfusion status. Exosomes have a variety of activities, such as remodeling the extracellular matrix and transmitting signals to other cells. This study aimed to investigate the potential molecular mechanism of RIPC-mediated neuroprotection. METHODS: Sixty adult male military personnel participants were divided into the control group (n = 30) and the RIPC group (n = 30). We analyzed the differential metabolites and proteins in the serum exosomes of RIPC participants and control subjects. RESULTS: Eighty-seven differentially expressed serum exosomal metabolites were found between the RIPC and control groups, which were enriched in pathways related to tyrosine metabolism, sphingolipid metabolism, serotonergic synapses, and multiple neurodegeneration diseases. In addition, there were 75 differentially expressed exosomal proteins between RIPC participants and controls, which involved the regulation of insulin-like growth factor (IGF) transport, neutrophil degranulation, vesicle-mediated transport, etc. Furthermore, we found differentially expressed theobromine, cyclo gly-pro, hemopexin (HPX), and apolipoprotein A1 (ApoA1), which are associated with neuroprotective benefits in ischemia/reperfusion injury. In addition, five potential metabolite biomarkers, including ethyl salicylate, ethionamide, piperic acid, 2, 6-di-tert-butyl-4-hydroxymethylphenol and zerumbone, that separated RIPC from control individuals were identified. CONCLUSION: Our data suggest that serum exosomal metabolites are promising biomarkers for RIPC, and our results provide a rich dataset and framework for future analyses of cerebral ischemia‒reperfusion injury under ischemia/reperfusion conditions.

Remote ischemic preconditioning improves spatial memory and sleep of young males during acute high-altitude exposure.

OBJECTIVE: The high-altitude hypoxia environment will cause poor acclimatization in a portion of the population. Remote ischemic preconditioning（RIPC）has been demonstrated to prevent cardiovascular and cerebrovascular diseases under ischemic or hypoxic conditions. However, its role in improving acclimatization and preventing acute mountain sickness (AMS) at high altitude has been undetermined. This study aims to estimate the effect of RIPC on acclimatization of individuals exposed to high altitude. METHODS: The project was designed as a randomized controlled trial with 82 healthy young males, who received RIPC training once a day for 7 consecutive days. Then they were transported by aircraft to a high altitude (3680 m) and examined for 6 days. Lake Louise Score(LLS) of AMS, physiological index, self-reported sleep pattern, and Pittsburgh Sleep Quality Index（PSQI）score were applied to assess the acclimatization to the high altitude. Five neurobehavioral tests were conducted to assess cognitive function. RESULTS: The result showed that the RIPC group had a significantly lower AMSscore than the control group (2.43 ± 1.58 vs 3.29 ± 2.03, respectively; adjusted mean difference-0.84, 95% confidence interval-1.61 to -0.06, P = 0.036). and there was no significant difference in AMS incidence between the two groups (25.0% vs 28.57%, P = 0.555). The RIPC group performed better than the control group in spatial memory span score (11[9-12] vs 10[7.5-11], P=0.025) and the passing digit (7[6-7.5] vs 6[5-7], P= 0.001). Spatial memory was significantly higher in the high-altitude RIPC group than in the low-altitude RIPC group (P＜0.01). And the RIPC group obtained significantly lower self-reported sleep quality score (P = 0.024) and PSQI score (P = 0.031). CONCLUSIONS: The RIPC treatment improved spatial memory and sleep quality in subjects exposed to acute hypoxic exposure and this may lead to improved performance at high altitude.

Remote ischemic preconditioning enhances aerobic performance by accelerating regional oxygenation and improving cardiac function during acute hypobaric hypoxia exposure.

Remote ischemic preconditioning (RIPC) may improve exercise performance. However, the influence of RIPC on aerobic performance and underlying physiological mechanisms during hypobaric hypoxia (HH) exposure remains relatively uncertain. Here, we systematically evaluated the potential performance benefits and underlying mechanisms of RIPC during HH exposure. Seventy-nine healthy participants were randomly assigned to receive sham intervention or RIPC (4 × 5 min occlusion 180 mm Hg/reperfusion 0 mm Hg, bilaterally on the upper arms) for 8 consecutive days in phases 1 (24 participants) and phase 2 (55 participants). In the phases 1, we measured the change in maximal oxygen uptake capacity (VO2max) and muscle oxygenation (SmO2) on the leg during a graded exercise test. We also measured regional cerebral oxygenation (rSO2) on the forehead. These measures and physiological variables, such as cardiovascular hemodynamic parameters and heart rate variability index, were used to evaluate the intervention effect of RIPC on the changes in bodily functions caused by HH exposure. In the phase 2, plasma protein mass spectrometry was then performed after RIPC intervention, and the results were further evaluated using ELISA tests to assess possible mechanisms. The results suggested that RIPC intervention improved VO2max (11.29%) and accelerated both the maximum (18.13%) and minimum (53%) values of SmO2 and rSO2 (6.88%) compared to sham intervention in hypobaric hypoxia exposure. Cardiovascular hemodynamic parameters (SV, SVRI, PPV% and SpMet%) and the heart rate variability index (Mean RR, Mean HR, RMSSD, pNN50, Lfnu, Hfnu, SD1, SD2/SD1, ApEn, SampEn, DFA1and DFA2) were evaluated. Protein sequence analysis showed 42 unregulated and six downregulated proteins in the plasma of the RIPC group compared to the sham group after HH exposure. Three proteins, thymosin ß4 (Tß4), heat shock protein-70 (HSP70), and heat shock protein-90 (HSP90), were significantly altered in the plasma of the RIPC group before and after HH exposure. Our data demonstrated that in acute HH exposure, RIPC mitigates the decline in VO2max and regional oxygenation, as well as physiological variables, such as cardiovascular hemodynamic parameters and the heart rate variability index, by influencing plasma Tß4, HSP70, and HSP90. These data suggest that RIPC may be beneficial for acute HH exposure.

Remote ischemic preconditioning improves cognitive control in healthy adults: Evidence from an event-related potential study.

It is suggested that remote ischemic preconditioning (RIPC) may be a promising treatment for improving healthy adults' cognitive control. However, direct empirical evidence was absent. Therefore, this study aims to provide evidence for the impact of RIPC on cognitive control. Sixty healthy young male volunteers were recruited, and 30 of them received 1-week RIPC treatment (RIPC group), while the rest did not receive RIPC (control group). Their cognitive control before and after RIPC treatment was evaluated using the classic Stroop task, and the scalp electricity activity was recorded by event-related potentials (ERPs). The behavioral results showed a conventional Stroop interference effect of both reaction times (RTs) and the accuracy rate (ACC), but the Stroop interference effect of RTs significantly decreased in the posttest compared to the pretest. Furthermore, at the electrophysiological level, ERP data showed that N450 and SP for incongruent trials were larger than that for congruent trials. Importantly, the SP differential amplitude increased after RIPC treatment, whereas there was no significant change in the control group. These results implied that RIPC treatment could improve cognitive control, especially conflict resolving in the Stroop task.

The anxiolytic effect of koumine on a predatory sound stress-induced anxiety model and its associated molecular mechanisms.

BACKGROUND: Koumine is the most abundant alkaloid extracted from Gelsemium elegans Benth.. Preliminary studies by our research group have shown that koumine has significant anxiolytic effect, but this needs to be further confirmed. HYPOTHESIS/PURPOSE: To investigate the potential anxiolytic effect of koumine on predatory sound (PS) stress-induced anxiety models and preliminarily explore its therapeutic targets and molecular mechanisms. STUDY DESIGN AND METHODS: The anxiolytic effect of koumine in an animal model of acute PS stress-induced anxiety were determined. Then, neurosteroids levels in the main brain regions involved in anxiety disorders, as well as plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels, were determinated. Finally, to clarify the effect of koumine on translocator protein 18 kDa (TSPO), the affinity between koumine and TSPO was evaluated by surface plasmon resonance (SPR) technology. RESULTS: Koumine treatment mitigated anxiety-like behavior following acute PS stress in the open field test and elevated plus maze test. PS exposure significantly decreased progesterone and allopregnanolone levels in the PFC, Hip, and Amy and increased ACTH and CORT levels in plasma, and koumine administration significantly reversed these effects. Finally, the reliable SPR results showed that the KD of koumine with TSPO was 155.33 ± 11.0 µM, indicating that koumine is a human TSPO high-affinity ligand that has an affinity comparable to typical TSPO ligands. CONCLUSION: Our results show that koumine has obvious anxiolytic effect in the PS-induced anxiety model. Targeting TSPO-neurosteroids-HPA axis may be an important mechanism by which koumine exerts its anxiolytic effect.

IL-6/STAT3 Induced Neuron Apoptosis in Hypoxia by Downregulating ATF6 Expression.

Background: Neuron apoptosis, regulated by endoplasmic reticulum (ER) stress in the hippocampus, is an essential factor influencing the cognitive impairment induced by hypobaric hypoxia. Hypoxia mainly changes the activating transcription factor (ATF6) pathway of ER stress. However, the role of ATF6 in neuron survival, apoptosis, and upstream regulation is still controversial. Methods: We established a hypobaric hypoxia-induced C57BL/6 murine model and cell lines exposed to 1% hypoxia, including PC12 and HT22. First, we tested the expressions of interleukin 6 (IL-6), IL-1ß, and IL-10 in C57BL/6 mice's hippocampus under hypoxia using enzyme-linked immunosorbent assay (ELISA). We determined the signal transducer and activator of transcription 3 (STAT3) phosphorylation at tyrosine (Tyr)705 by western blot and the expression of ATF6, 78-kDa glucose-regulated protein (GRP78), and C/-EBP homologous protein (CHOP) related to ER stress by immunofluorescence (IF), western blot, and qRT-PCR; they were then verified on the cell model. Additionally, IL-6 (40 ng/mL) and STAT3 siRNA were used to treat the PC12 cells for 48 and 4 h to activate or silence STAT3, respectively. Subsequently, the cells of siRNA group were exposed to 1% hypoxia for 48 h. Furthermore, the ATF6 and CHOP expressions were detected with western blot and qRT-PCR. Finally, we examined the binding of STAT3 to the ATF6 promoter by chromatin immunoprecipitation (ChIP)-seq. Results: The results showed that IL-6 increased, IL-10 decreased in the hypoxia group, and IL-1ß showed no difference between the hypoxia and the normoxia groups. Neuron apoptosis was significantly elevated by exposure to hypoxia for 48h in PC12 cells. The hypobaric hypoxia-induced ER stress proteins, ATF6, GRP78, and CHOP, and the p-STAT3 (Tyr705) expressions increased both in in vivo and in vitro. Besides, STAT3 silencing significantly promoted the ATF6 expression and inhibited CHOP, while STAT3 activation downregulated the expression of ATF6 and upregulated CHOP in PC12 cells. The ChIP-seq assay demonstrated that p-STAT3 (Tyr705) protein could bind to the ATF6 promoter region in HT22 cells. Conclusion: Phosphorylation of STAT3 at the Tyr705 site contributes to hypoxia-induced neuron apoptosis by downregulating ATF6, which might explain the inflammatory reaction and apoptosis of the hippocampal neurons induced by ER stress.

Association of Peripheral Plasma Neurotransmitters with Cognitive Performance in Chronic High-altitude Exposure.

Long-term living at high altitude causes significant impairment of cognitive function. Central neurotransmitters are potential mediators of cognitive performance. We aimed to determine whether there were significant associations between select peripheral plasma neurotransmitters and cognitive performance in humans with chronic high-altitude (HA) exposure and to determine the association between peripheral plasma neurotransmitters and brain neurotransmitters in rats after chronic hypobaric hypoxia (HH) exposure. We demonstrated that 3,4-dihydroxy-L-phenylalanine (DOPA), dopamine, serotonin, 5-hydroxyindole-3-acetic acid (5-HIAA) and GABA in the peripheral plasma were associated with cognitive performance in humans with HA exposure. Consistent with this result, peripheral plasma DOPA, dopamine, serotonin, 5-HIAA and glutamate were associated with brain neurotransmitter levels after chronic HH exposure in rats. These results provide experimental data indicating that neurotransmitter levels and cognitive performance are modified in chronic high-altitude exposure, with a possible causal effect.

Higher Circulating miR-199a-5p Indicates Poor Aerobic Exercise Capacity and Associates With Cardiovascular Dysfunction During Chronic Exposure to High Altitude.

BACKGROUND: Hypoxia-induced decline in exercise capacity is ubiquitous among lowlanders who immigrated to high altitudes, which severely reduces their work efficiency and quality of life. Although studies have revealed that hypoxia-induced cardiovascular dysfunction limits exercise capacity at high altitudes, the mechanisms have not been well explored at the molecular level. miR-199a-5p is hypoxia-sensitive and serves as an important regulator in cardiovascular pathophysiology. However, whether miR-199a-5p is involved in cardiovascular dysfunction at high altitudes and contributes to subsequent reductions in exercise capacity remains unknown. Thus, this study aimed at exploring these relationships in a high altitude population. METHODS: A total of 175 lowlanders who had immigrated to an altitude of 3,800 m 2 years previously participated in the present study. The level of plasma miR-199a-5p and the concentration of serum myocardial enzymes were detected by qRT-PCR and ELISA, respectively. Indices of cardiovascular function were examined by echocardiography. The exercise capacity was evaluated by Cooper's 12-min run test and the Harvard Step Test. Furthermore, we explored the biological functions of miR-199a-5p with silico analysis and a biochemical test. RESULTS: The level of miR-199a-5p was significantly higher in individuals with poor exercise capacity at 3,800 m, compared with those with good exercise capacity (p < 0.001). miR-199a-5p accurately identified individuals with poor exercise capacity (AUC = 0.752, p < 0.001). The level of miR-199a-5p was positively correlated with cardiovascular dysfunction indices (all, p < 0.001). Furthermore, miR-199a-5p was involved in the oxidative stress process. CONCLUSION: In this study, we reported for the first time that the level of circulating miR-199a-5p was positively associated with exercise capacity during chronic hypoxia at high altitudes. Moreover, higher miR-199a-5p was involved in hypoxia-induced cardiovascular dysfunctions, thus contributing to poorer exercise endurance at high altitudes.

A new isoflavone glycoside from flowers of Pueraria Montana var. lobata (Willd.) Sanjappa & Pradeep.

A new isoflavone glycoside, named 3'-hydroxytectorigenin-7-O-ß-D-xylosyl-(1→6)-ß-D-glucopyranoside (1) was isolated from the flowers of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep. The structure of compound 1 was characterised by HR-ESI-MS and NMR spectroscopic methods. In radical scavenging activity test using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), compound 1 showed moderate activity with IC50 value of 42 ± 4.2 µg/mL.

Thermosonication-induced structural changes and solution properties of mung bean protein.

Mung bean protein is considered a highly nutritive food ingredient, but its solution properties are not well defined. In this study, suspensions of mung bean protein isolate (MPI, 10%, w/v) were subjected to high intensity ultrasound (20 kHz, 30% amplitude) at varied durations (5, 10, 20, and 30 min) with controlled temperatures (30, 50, and 70 °C) to determine the effects of thermosonication treatment on physical properties of the protein solution. Results showed that thermosonication treatment significantly reduced the particle size and free sulfhydryl content of MPI in a time-dependent manner. Ultrasound increased surface hydrophobicity, and the exposure of nonpolar groups led to the formation of soluble aggregates. Changes in secondary structure of MPI were minimal at 30 and 50 °C but were significant at 70 °C. The dissociation of native components followed by reaggregation into soluble particles following ultrasound treatment at 70 °C resulted in remarkable improvements of protein solubility (>2 fold), clarity, and stability of the MPI suspensions. The findings indicated that thermosonication could be a promising technology for the processing of mung bean protein beverage.

Efficacy of continuous intravenous pumping of insulin for patients with diabetes complicated with perianal abscess and the effect on inflammatory cytokines.

Efficacy of insulin with different administrations for patients with diabetes complicated with perianal abscess and the effect on serum inflammatory cytokines were investigated. One hundred and sixty-seven patients with type 2 diabetes who underwent radical operation of perianal abscess in Jinhua Hospital of Zhejiang University from January 2014 to December 2016 were analyzed. Before and after the operation, 89 patients who received continuous intravenous pumping of insulin for blood glucose control were set as an observation group, and 78 patients who received intermittent subcutaneous injection of insulin as a control group. The operative efficacy, wound healing time and 1-week postoperative growth of the granulation tissue were scored and compared. Fasting blood glucose (FBG) and 2 h postprandial blood glucose (2hPBG) before and after treatment were recorded and compared. Fasting venous blood was extracted before and on the 3rd and 7th days after operation to detect and compare serum inflammatory cytokines including tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Patients in the observation group had significantly higher total effective rate of the operation than that in the control group (P<0.05), and significantly shorter wound healing time and significantly lower growth score of the granulation tissue (P<0.05). Before treatment, there was no significant difference between the two groups in FBG and 2hPBG (P>0.05). After treatment, FBG and 2hPBG were significantly lower than those before treatment (P<0.050), and FBG and 2hPBG after treatment in the observation group were significantly lower than those in the control group (P<0.05). In conclusion, insulin pumps for injection during the perioperative period of patients with diabetes complicated with perianal abscess can better control the patients' blood glucose, improve the operative efficacy and promote the patients' postoperative healing. Moreover, continuous intravenous pumping of insulin is significantly better than traditional intermittent subcutaneous injection of it in controlling inflammation, so it is worthy of application.

Neuroprotective Effects of Salidroside on Cerebral Ischemia/Reperfusion-Induced Behavioral Impairment Involves the Dopaminergic System.

Salidroside, a phenylpropanoid glycoside, is the main bioactive component of Rhodiola rosea L. Salidroside has prominent anti-stroke effects in cerebral ischemia/reperfusion models. However, the underlying mechanisms of its actions are poorly understood. This study examined the anti-stroke effects of salidroside in middle cerebral artery occlusion (MCAO)-induced rat model of stroke and its potential mechanisms involving the dopaminergic system. Salidroside administration increased the levels of dopamine (DA), homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) in the ipsilateral striatum after induction of transient ischemia, which were assessed using microdialysis with high-performance liquid chromatography coupled with electrochemical detection (HPLC-ECD). Furthermore, treatment with salidroside ameliorated neurobehavioral impairment, assessed with the modified neurological severity scores (mNSS), the balance beam test, and the foot fault test. Moreover, enzyme-linked immunosorbent assay (ELISA) suggested that MCAO-induced reduction in monoamine oxidase (MAO) was inhibited by salidroside. Immunohistochemical and immunofluorescence analyses revealed high level of tyrosine hydroxylase (TH) in the ipsilateral striatal caudate putamen (CPu) after cerebral ischemia/reperfusion, which could be further elevated by salidroside. In addition, salidroside could reverse the decreased immunoreactivity of TH in the substantia nigra pars compacta (SNpc). These results suggest that the anti-stroke effects of salidroside in MCAO-induced cerebral ischemia/reperfusion may involve the modulation of monoamine metabolism in the striatum and SNpc, which may be related to the function of the dopaminergic system in the rat brain.

Role of interleukin-17 in the pathogenesis of perianal abscess and anal fistula: a clinical study on 50 patients with perianal abscess.

BACKGROUND: To investigate the role of interleukin (IL)-17 in tissue and peripheral blood of perianal abscess and anal fistula. METHODS: Patients with primary perianal abscess (n = 50) admitted to Jinhua Municipal Central Hospital between March 2003 and August 2004 were enrolled. Fifty patients with mixed haemorrhoids, who showed no perianal abscess or anal fistula, were also recruited as the control. After surgery, patients were followed up for 6 months. Protein and gene expression of IL-17 was determined in surgically harvested anal tissues and peripheral blood, respectively. The relationship between IL-17 and clinical pathological features were analysed. RESULTS: As shown by immunohistochemistry of anorectal tissues, the positive rate of IL-17 protein was higher in the perianal abscess group than in the control group. In patients with perianal abscess, the expression of IL-17 significantly correlated with the diameter of the abscess (P = 0.013), the wound surface healing time (P = 0.010) and the progression into anal fistula (P = 0.003). For the gene expression of IL-17 in peripheral blood cells, the level was significantly higher in patients with perianal abscess comparing to the control group (0.4350 ± 0.1190 versus 0.1785 ± 0.1230, P ≤ 0.001). Comparing to the recovery group, patients with their perianal abscess progressed to anal fistula showed higher levels of IL-17 gene expression (P = 0.014). CONCLUSIONS: Expression of IL-17 was increased in the anorectal tissues and peripheral blood of patients with perianal abscess and anal fistula. IL-17 may play an important role in the pathogenesis of perianal abscess and anal fistula.

Loop Transverse Colostomy - A Modified Technique.

BACKGROUND: Transverse colostomy is commonly performed to create temporary stoma in rectal cancer patients after neoadjuvant chemoradiotherapy. Conventional methods are either difficult to implement or to care for. To resolve these problems, we herein describe a modified transverse colostomy method. MATERIAL AND METHODS: Two sutures of peritoneum were made as "bridges" to support the stoma. Absorbable sutures were utilized to reinforce the stoma. Once the stoma was created, the stoma bag was immediately placed on the skin. 120 patients who received conventional or modified transverse colostomy between 2008 and 2014 were selected. Then, the two groups of patients were compared for stoma-related complications. RESULTS: The operation time of stoma construction was 34±10 minutes for the conventional method and 28±7 minutes for the modified method (P= 0.009). There were no significant differences between the two groups with respect to postoperative bleeding, bowel obstruction or stoma retraction. Patients with conventional transverse colostomy were remarkably more likely to experience parastoma hernia (P= 0.048) and stoma prolapse (P= 0.038). CONCLUSION: In comparison with conventional methods, the modified transverse colostomy is a safe and effective diverting technique. It can be readily performed by all kinds of surgeons, especially those in underdeveloped areas. The technique represents a preferred method for constructing temporary stoma in rectal cancer patients treated with neoadjuvant chemoradiotherapy.