Oroxyloside protects against dextran sulfate sodium-induced colitis by inhibiting ER stress via PPARγ activation.

Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), may result from immune system dysfunction, leading to the sustained overproduction of reactive oxygen species (ROS) and subsequent cellular oxidative stress damage. Recent studies have identified both peroxisome proliferator-activated receptor-γ (PPARγ) and endoplasmic reticulum (ER) stress as critical targets for the treatment of IBD. Oroxyloside (C22H20O11), derived from the root of Scutellariabaicalensis Georgi, has traditionally been used in treating inflammatory diseases. In this study, we investigated the molecular mechanisms by which oroxyloside mitigates dextran sulfate sodium (DSS)-induced colitis. We examined the effects of oroxyloside on ROS-mediated ER stress in colitis, including the protein expressions of GRP78, p-PERK, p-eIF2α, ATF4, and CHOP, which are associated with ER stress. The beneficial impact of oroxyloside was reversed by the PPARγ antagonist GW9662 (1 mg·kg-1, i.v.) in vivo. Furthermore, oroxyloside decreased pro-inflammatory cytokines and ROS production in both bone marrow-derived macrophages (BMDM) and the mouse macrophage cell line RAW 264.7. However, PPARγ siRNA transfection blocked the anti-inflammatory effect of oroxyloside and even abolished ROS generation and ER stress activation inhibited by oroxyloside in vitro. In conclusion, our study demonstrates that oroxyloside ameliorates DSS-induced colitis by inhibiting ER stress via PPARγ activation, suggesting that oroxyloside might be a promising effective agent for IBD.

Percutaneous mechanical thrombectomy using the Rotarex®S device for the treatment of acute lower limb artery embolism: A retrospective single-center, single-arm study.

Objective: Acute limb embolism (ALE) is a challenging, highly morbid, and frequently fatal vascular emergency. Percutaneous mechanical thrombectomy (PMT) devices are an alternative treatment to restore perfusion by removing emboli in the limb arterial system. We evaluated the outcomes of treatment of ALE patients using PMT devices in our center. Methods: A retrospective review of ALE patients treated with Rotarex S (Straub Medical) at a single institution from 2018 to 2022 was performed. The primary outcome was technical success, defined as complete recanalization of the occluded segment with satisfactory outflow and good capillary filling of the distal parts of the foot without any major or obstructing residual emboli or thrombi either in the treated segment or in the outflow tract without the need for additional catheter-directed thrombolysis (CDT) or conversion to open surgery. Embolized segments treated, treatment outcomes, and perioperative complications were reviewed. Results: A total of 17 ALE patients (29% men, 71% women; mean age, 73 years) underwent PMT procedures. The femoral arteries and popliteal arteries are the most commonly treated vessels, with both present in 59% of the patients. The technical success rate was 100%, but the majority of cases (82%) had concurrent percutaneous transluminal angioplasty or stent grafting, and two patients were treated with urokinase during the operation. There was one thrombotic recurrence that required amputation. There were no 30-day deaths. Complications included extravasation after PMT (two), intraoperative embolization of the outflow tract (one), access site hematoma (one), target artery thrombosis (one), and acute kidney injury (one). There were no severe bleeding complications. Conclusions: The Rotarex S device has a satisfactory success rate, although complementary use of various adjunctive techniques is frequently required. It seems to be a moderately effective tool for treating ALE to avoid CDT or open surgery. The device appears safe, with low risks of amputation and mortality rates, but special attention should be given to the potential for extravasation and distal embolism.

Effect of transcutaneous electrical acupoint stimulation on bone metabolism in patients with immobilisation after foot and ankle fracture surgery: a randomised controlled trial study protocol.

INTRODUCTION: Fracture is a disease with a high incidence worldwide. Foot and ankle fractures are common among fractures of the lower extremities. Foot and ankle fractures usually require surgical fixation and a period of fixed treatment, which can lead to decreased bone density. Although transcutaneous electrical acupoint stimulation (TEAS) is widely used for movement system diseases, there is minimal evidence to show the effectiveness of TEAS on patients after surgical fixation of ankle and foot fractures. This trial aims to evaluate whether TEAS can reduce bone loss in patients with immobilisation after ankle and foot fractures. METHODS AND ANALYSIS: A randomised controlled trial will be conducted in which 60 patients will be randomly divided into two groups: (a) the control group will be treated according to the routine procedures of basic orthopaedics treatment; (b) in the treatment group, bilateral SP36, BL23 and ST36 will be performed on the basis of the control group, and the test will be performed for 30 min every other day for a total of 8 weeks. Bone turnover markers will be used as primary outcome. Secondary outcomes are composed of blood phosphorus, blood calcium and bone mineral density. Treatment safety will be monitored and recorded. ETHICS AND DISSEMINATION: This trial is approved by the Ethics Committee of Beijing University of Chinese Medicine (2020BZYLL0611) and the Ethics Committee of Beijing Luhe Hospital (2020-LHKY-055-02), and inpatients who meet the following diagnostic and inclusion criteria are eligible to participate in this study. TRIAL REGISTRATION NUMBER: ChiCTR 2000039944.

Effects of Compound Centella on Oxidative Stress and Keap1-Nrf2-ARE Pathway Expression in Diabetic Kidney Disease Rats.

The formula of Compound Centella mainly contains 3 traditional Chinese herbs: Centella asiatica (L.) Urb. (JiXueCao), Astragalus Membranaceus Fish. (HuangQi), and Tripterygium wilfordii Hook. f. (LeiGongTeng). Though this formula is effective for treating diabetic kidney disease (DKD) in clinic, the exact mechanism is still unclear. This study aims to investigate the effect and antioxidant mechanism of Compound Centella on DKD rats. High-performance liquid chromatography (HPLC) was applied to analyse 3 herbs in Compound Centella. Sprague-Dawley rats were divided into the normal group (NG), DKD group (DKDG), Compound Centella group (CCG), and losartan group (LG), with 8 rats in each group. On the first day of the experiment, rats in the NG were fed with ordinary -feed, while the other groups were fed with high-fat and high-sugar feed. On the 29th day, except the NG, the other 3 groups received a single intraperitoneal injection of streptozocin (STZ, 35 mg/kg). Fasting blood glucose (FBG) was measured on the 1st day, 32nd day, 46th day, 56th day, 84th day, and 112th day. Total protein/creatinine ratio of urine was determined by the phenol red assay on the 1st day and 112th day. Serum creatinine (Scr) was determined by an automatic biochemical analyser on the 112th day. Kidneys were collected on the 112th day for analysis and evaluation. Periodic acid-Schiff (PAS) staining, hematoxylin-eosin (HE) staining, and transmission electron microscopy were used to observe kidney pathological changes. The mRNA and protein expressions of Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor-erythroid 2-related factor 2 (Nrf2) in renal tissues were detected by RT-qPCR, Western blot, and immunohistochemistry. Oxidative stress was evaluated by detecting the levels of malondialdehyde (MDA) and heme oxidase-1 (HO-1). The results showed that the content of asiaticoside, astragaloside, and triptolide in the herb was 5960, 809, and 2.42 µg/g and in the Compound Centella was 340, 64, and 0.1403 µg/mL by HPLC. Compound Centella reduced the urine protein/creatinine ratio and improved renal pathology in the kidneys of DKD rats. In addition, the mRNA and protein expressions of Keap1 and Nrf2 in kidneys were upregulated by Compound Centella. The expressions of MDA were downregulated but HO-1 were upregulated by Compound Centella. Therefore, the protective effect of Compound Centella in the kidney of DKD rats may be related to regulating the Keap1-Nrf2-ARE pathway under oxidative stress, suggesting Compound Centella as a promising treatment against DKD.

[Effect of Zhenwu Tang on regulating of "AVP-V2R-AQP2" pathway in NRK-52E cells].

This study was aimed to investigate the effect and mechanism of Zhenwu Tang on AVP-V2R-AQP2 pathway in NRK-52E cells in vitro. Forty eight male SD rats were randomly divided into eight groups with 6 animals in each group. Distilled water or 22.68 g·kg⁻¹·d⁻¹ Zhenwu Tang(calculated by raw drug dosage meter) was given by gavage. Blood samples were collected by cardiac puncture， and the medicated serum was centrifuged from the blood by 3 000 r·min⁻¹. NRK-52E cells were treated with different medicated serum or dDAVP. The condition of cell proliferation was detected by RTCA. The distribution of V2R and AQP2 in cells were detected by immunofluorescence. The expression of V2R， PKA and AQP2 were detected by Western blot and AQP2 mRNA level was detected by real-time PCR. Results showed that the level of AQP2 mRNA(P<0.01) and protein expression of V2R， PKA and AQP2(P<0.05， P<0.01， P<0.05) of Z7d group which was treated with Zhenwu Tang medicated serum for 24 h were significantly higher than that of normal rat serum group. And the expression level of V2R， p-AQP2 and AQP2(P<0.01， P<0.05， P<0.01) of Z7d+dDAVP group were significantly increased comparing to normal rat serum group. The results indicate that the applying of Zhenwu Tang medicated serum could increase the expression level of V2R， PKA and AQP2 which exist in AVP-V2R-AQP2 pathway in NRK-52E， and there is synergistic effect between Zhenwu Tang medicated serum and dDAVP. So the pathway of AVP-V2R-AQP2 may be one of the mechanism for which Zhenwu Tang regulate balance of water transportation.

Unraveling microbial structure and diversity of activated sludge in a full-scale simultaneous nitrogen and phosphorus removal plant using metagenomic sequencing.

Activated sludge contains highly complex microbial communities, which play crucial roles in pollutant removal performance in wastewater treatment plants (WWTPs). Metagenomic sequencing was applied to characterize microbial community and functional profiles within activated sludge from a full-scale municipal WWTP carrying out simultaneous nitrogen and phosphorous removal (SNPR). We applied the assembled contigs (N90 of 591bp) and predicted genes to conduct taxonomic and function annotations, respectively. Results revealed the extraordinary microbial diversity of activated sludge, which included detection of minority populations that are difficult to be explored by traditional molecular methods. Taxonomic analysis indicated that the dominant bacterial phyla were Proteobacteria, Nitrospirae, Bacteroidetes, Actinobacteria and Firmicutes. The abundance of the key organisms involved in nitrogen and phosphorous removal were qualified. Aerobic ammonia-oxidizing bacteria distinctly dominate over ammonia-oxidizing archaea and anaerobic ammonium oxidation bacteria. Various key enzymes involved in the global nitrogen cycle were annotated in the activated sludge. High abundance of the known polyphosphate accumulating organisms was detected (approximately 4.89% of the overall population reads), supporting good phosphorous removal performance. This study provides a comprehensive insight into the community structure and diversity of the SNPR system, and will provide foundation for optimal operation of nutrient removal systems.

Mathematical Modeling of Nitrous Oxide Production during Denitrifying Phosphorus Removal Process.

A denitrifying phosphorus removal process undergoes frequent alternating anaerobic/anoxic conditions to achieve phosphate release and uptake, during which microbial internal storage polymers (e.g., Polyhydroxyalkanoate (PHA)) could be produced and consumed dynamically. The PHA turnovers play important roles in nitrous oxide (N2O) accumulation during the denitrifying phosphorus removal process. In this work, a mathematical model is developed to describe N2O dynamics and the key role of PHA consumption on N2O accumulation during the denitrifying phosphorus removal process for the first time. In this model, the four-step anoxic storage of polyphosphate and four-step anoxic growth on PHA using nitrate, nitrite, nitric oxide (NO), and N2O consecutively by denitrifying polyphosphate accumulating organisms (DPAOs) are taken into account for describing all potential N2O accumulation steps in the denitrifying phosphorus removal process. The developed model is successfully applied to reproduce experimental data on N2O production obtained from four independent denitrifying phosphorus removal study reports with different experimental conditions. The model satisfactorily describes the N2O accumulation, nitrogen reduction, phosphate release and uptake, and PHA dynamics for all systems, suggesting the validity and applicability of the model. The results indicated a substantial role of PHA consumption in N2O accumulation due to the relatively low N2O reduction rate by using PHA during denitrifying phosphorus removal.

Combined common femoral artery endarterectomy with superficial femoral artery stenting plus Shuxuening Injection infusion for chronic lower extremity ischemia: 3-year results.

OBJECTIVE: To investigate the efficacy and safety of combined common femoral artery (CFA) endarterectomy with superficial femoral artery (SFA) stenting plus Shuxuening Injection infusion in patients with complex multifocal arterial steno-obstructive lesions of the lower extremities. METHODS: From March 2006 to March 2011, 104 lower limbs in 96 patients with multilevel peripheral arterial steno-occlusive disease, involving SFA as well as CFA and deep femoral artery (DFA) orifice, were treated by combined surgical with endovascular therapy, such as SFA stenting as an adjunct to CFA endarterectomy and patch angioplasty with the great saphenous vein. Before the end of the operation, 20 mL of Shuxuening Injection was infused through the catheter located in the treated artery. Technical and hemodynamic success, as well as primary and primary-assisted patency, was determined according to the Society for Vascular Surgery Guidelines. During follow-up, clinical status assessment, ankle-brachial index (ABI) test, and duplex Doppler ultrasound were administered every 6 months, and computed tomography angiography or magnetic resonance angiography was performed at 12, 24, and 36 months after discharge. RESULTS: All patients underwent successful combined CFA endarterectomy with SFA stenting treatment. The average ABI after the combination treatment increased from pretreatment of 0.32±0.21 to 0.82±0.24 (P<0.01). No perioperative death and major limb amputations occurred. The mean duration of follow-up for 104 limbs from 96 patients was 1,180 days (range, 196-2,064 days). During follow-up, 5 patients died due to myocardial infarction, cerebral infarction, or pneumonia, and 5 patients were lost to follow-up. There were 21 cases (21.4%) of restenosis, with 15 that occurred in-stent and 6 near the distal end of the stent. A total of 18 (18.3%) reinterventions were performed, including 6 balloon angioplasty, 8 restenting procedures, 2 bypass surgeries, and 2 major limb amputations. The primary patency rates were 92.2%, 76.8%, and 61.3% at 12, 24, and 36 months, respectively, while the primary-assisted patency rates were 94.4%, 83.2%, and 75.6% at 12, 24, and 36 months, respectively. CONCLUSION: The combined CFA endarterectomy with SFA stenting plus Shuxuening Injection infusion appears to offer a safe, less invasive, and effective treatment option to patients with chronic lower extremity ischemia due to complex multifocal peripheral artery disease.

[Investigation on the frequency specificity of the auditory brainstem response to tone burst in three different conditions].

OBJECTIVE: This study investigated and compared the effects of tone burst in three different conditions (linear-gated tone burst, linear-gated tone burst in broadband noise masking and Blackman-gated tone burst) on the frequency specificity of ABR. METHOD: The latencies of ABR wave V were recorded respectively on sixteen normal-hearing adults using 1, 2 and 4 kHz tone bursts in three types of stimuli at different intensities. RESULT & CONCLUSION: 1. Three types of tone bursts may evoke similar frequency-specific ABR when stimulus intensity was lower than 70 dB nHL for 1 kHz and any intensity for 2, 4 kHz. At the high-intensity(> or = 70 dB nHL) for lower frequency (1 kHz), however, linear-gated tone burst had poor frequency specificity due to the increased effects of spectral splatter. To improve the frequency specificity, linear-gated tone burst should be mixed with masking noise or using Blackman-gated tone burst directly. 2. Both linear-gated tone burst in broadband noise masking and Blackman-gated tone burst of 1 kHz, 2 kHz and 4 kHz at any intensity can produce frequency-specific ABR, but response amplitudes were smaller for the broadband noise masking condition than for the Blackman-gated one. Therefore the Blackman-gated tone burst is prefered.