The Lactobacillus plantarum P-8 Probiotic Microcapsule Prevents DSS-Induced Colitis through Improving Intestinal Integrity and Reducing Colonic Inflammation in Mice.

Probiotics, recognized as beneficial and active microorganisms, often face challenges in maintaining their functionality under harsh conditions such as exposure to stomach acid and bile salts. In this investigation, we developed probiotic microcapsules and assessed their protective effects and underlying mechanisms in a murine model of dextran sulfate sodium (DSS)-induced colitis using male C57BL/6J mice. The administration of the probiotic microcapsules significantly mitigated body weight loss, prevented colon length shortening, decreased the disease activity index scores, and reduced histopathological scores in mice with DSS-induced colitis. Concurrently, the microencapsulated probiotics preserved intestinal barrier integrity by upregulating the expressions of tight junction proteins ZO-1 and occludin, as well as the mucus layer component MUC-2. Moreover, the treatment with probiotic microcapsules suppressed the activation of the NLRP3 inflammasome signaling pathway in the context of DSS-induced colitis. In conclusion, these findings support the utilization of probiotic microcapsules as a potential functional food ingredient to maintain the permeability of the intestinal barrier and alleviate colonic inflammation in UC.

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: The MARVEL Randomized Clinical Trial.

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.

Relation between LRG1 and CD4+ T cells, cognitive impairment and neurological function in patients with acute ischemic stroke.

Objective: To assess the relationship between LRG1 and CD4+ T cells, cognitive impairment and neurological function in acute ischemic stroke (AIS). Methods: Plasma LRG1 was detected by ELISA in 175 patients with AIS at baseline, day (D) 1, D7, month (M) 1 and M3. Results: LRG1 was negatively related to Th2 and Treg cells and positively linked to Th17 (all p < 0.05). LRG1 increased from baseline to D1, then decreased until M3 (p < 0.001). LRG1 at each assessment point was increased in patients with cognitive impairment or poor neurological function at M3 versus those without (all p < 0.05). Conclusion: LRG1 is linked to decreased Th2 and Tregs, increased Th17, cognitive impairment and nonideal neurological function recovery in patients with AIS.

The immunometabolic reprogramming of microglia in Alzheimer's disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder (NDD). In the central nervous system (CNS), immune cells like microglia could reprogram intracellular metabolism to alter or exert cellular immune functions in response to environmental stimuli. In AD, microglia could be activated and differentiated into pro-inflammatory or anti-inflammatory phenotypes, and these differences in cellular phenotypes resulted in variance in cellular energy metabolism. Considering the enormous energy requirement of microglia for immune functions, the changes in mitochondria-centered energy metabolism and substrates of microglia are crucial for the cellular regulation of immune responses. Here we reviewed the mechanisms of microglial metabolic reprogramming by analyzing their flexible metabolic patterns and changes that occurred in their metabolism during the development of AD. Further, we summarized the role of drugs in modulating immunometabolic reprogramming to prevent neuroinflammation, which may shed light on a new research direction for AD treatment.

3,6'-Disinapoyl sucrose alleviates cognitive deficits in APP/PS1 transgenic mice.

Alzheimer's disease (AD) is a neurodegenerative disorder with insidious onset and progressive development. There is an urgent need to find drugs that prevent and slow AD progression. We focus our attention on 3,6'-disinapoyl sucrose (DISS), an oligosaccharide with antidepressant and antioxidant activities. In this work, APP/PS1 transgenic mice were used to explore the neuroprotective impact of DISS to provide new applications for prevention and therapy of AD. This study aims to assess DISS's neuroprotective impact on learning and memory deficits in APP/PS1 transgenic mice using behavioral tests (Morris water maze, novel object recognition test, and passive avoidance test). Morphological alterations of hippocampus neurons were observed by Nissl staining and neuronal apoptosis was assessed by TUNEL assay. By using ELISA, the expressions of inflammatory factors were evaluated, and Western blotting was used to measure the protein expressions of neuron-related regulators in the hippocampus. DISS significantly ameliorated the cognitive disorder in APP/PS1 transgenic mice, reduced apoptosis by decreasing the ratio of Bax/B-cell lymphoma/leukemia-2 (Bcl-2) in hippocampal neurons, and restored the abnormal secretion of inflammatory factors (IL-2, TNF-α, IL-1ß, and IL-6). Moreover, the gavage of high-dose DISS can boost the expressions of CREB/brain-derived neurotrophic factor (BDNF). Overall, our results indicate that DISS improves cognitive function in APP/PS1 transgenic mice by inhibiting neural apoptosis and activating the CREB/BDNF signal pathway.NEW & NOTEWORTHY In this study, for the first time, DISS was used in APP/PS1 transgenic mice to explore its neuroprotective effect. After gavage DISS for 1 mo, the impairment of learning and spatial memory ability and the loss of neurons in APP/PS1 mice were alleviated. DISS reduced a neuroprotective effect in AD mice via decreasing neuronal apoptosis, enhancing the expressions of CREB phosphorylation and BDNF, pointing to DISS as a new therapeutic target for AD.

Protective effects of fisetin in an Aß1-42-induced rat model of Alzheimer's disease.

Alzheimer's disease (AD) is a chronic, neurodegenerative disorder that affects the central nervous system and is found predominantly in elderly populations. As amyloid b protein (Ab) is one of the key players responsible for the pathogenesis of AD, we sought to investigate the protective effects of fisetin in an Ab1-42-induced rat model of AD. In this model, the protective effects of fisetin on learning and memory impairment induced by Ab1-42 were determined via the Morris water maze and passive avoidance test. Furthermore, the antioxidant activity, anti-inflammation, and apoptosis effect of fisetin were investigated using biochemical and immunohistochemical methods. The results showed that intragastric (i.g.) administration of fisetin (100, 50, and 25 mg/kg) improved previous learning and memory impairments in Ab1-42-treated rats. Hippocampal tissue from these fisetin-treated rats revealed that the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) were markedly enhanced, and that the levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were significantly reduced. Meanwhile, fisetin also significantly attenuated Ab1-42-induced cholinergic dysfunction such as elevated the activity of choline acetyltransferase (ChAT) and reduced the activity of acetylcholine esterase (AChE). In addition, hippocampal tissue obtained from fisetin-treated rats revealed a reversal of Ab1-42-induced effects on apoptotic pathway protein (caspase-3) expression and inflammatory response of glial fibrillary acidic protein (GFAP). This indicated that the amount of degenerating hippocampal neurons with apoptotic features was dramatically reduced after treatment with fisetin. Collectively, these findings suggest that fisetin has potential as a treatment agent for Alzheimer's disease and that its effects occur through several mechanisms, including inhibition of oxidative stress, adjustments to previous cholinergic dysfunction, anti-inflammatory actions, and decreased apoptotic activity.

3,6'-Disinapoylsucrose alleviates the amyloid precursor protein and lipopolysaccharide induced cognitive dysfunction through upregulation of the TrkB/BDNF pathway.

The aim of this study is to explore the effect and mechanism of 3,6'-disinapoylsucrose (DISS) on an Alzheimer's disease (AD) mice model induced by APPswe695 lentivirus (LV) and intraperitoneal injection of lipopolysaccharide (LPS). The results show that DISS improves cognitive ability, decreases the levels of IL-2, IL-6, IL-1ß, and TNF-α, reduces the expression of NF-κB p65, and alleviates Aß deposition and nerve cell damage. DISS can regulate tyrosine kinase B (TrkB)/brain-derived neurotrophic factor (BDNF) signaling in the hippocampus. In summary, DISS can significantly alleviate neuroinflammation, spatial learning and memory disorders in AD model mice.

Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion.

BACKGROUND: Data from trials investigating the effects and risks of endovascular thrombectomy for the treatment of stroke due to basilar-artery occlusion are limited. METHODS: We conducted a multicenter, prospective, randomized, controlled trial of endovascular thrombectomy for basilar-artery occlusion at 36 centers in China. Patients were assigned, in a 2:1 ratio, within 12 hours after the estimated time of basilar-artery occlusion to receive endovascular thrombectomy or best medical care (control). The primary outcome was good functional status, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]), at 90 days. Secondary outcomes included a modified Rankin scale score of 0 to 2, distribution across the modified Rankin scale score categories, and quality of life. Safety outcomes included symptomatic intracranial hemorrhage at 24 to 72 hours, 90-day mortality, and procedural complications. RESULTS: Of the 507 patients who underwent screening, 340 were in the intention-to-treat population, with 226 assigned to the thrombectomy group and 114 to the control group. Intravenous thrombolysis was used in 31% of the patients in the thrombectomy group and in 34% of those in the control group. Good functional status at 90 days occurred in 104 patients (46%) in the thrombectomy group and in 26 (23%) in the control group (adjusted rate ratio, 2.06; 95% confidence interval [CI], 1.46 to 2.91, P<0.001). Symptomatic intracranial hemorrhage occurred in 12 patients (5%) in the thrombectomy group and in none in the control group. Results for the secondary clinical and imaging outcomes were generally in the same direction as those for the primary outcome. Mortality at 90 days was 37% in the thrombectomy group and 55% in the control group (adjusted risk ratio, 0.66; 95% CI, 0.52 to 0.82). Procedural complications occurred in 14% of the patients in the thrombectomy group, including one death due to arterial perforation. CONCLUSIONS: In a trial involving Chinese patients with basilar-artery occlusion, approximately one third of whom received intravenous thrombolysis, endovascular thrombectomy within 12 hours after stroke onset led to better functional outcomes at 90 days than best medical care but was associated with procedural complications and intracerebral hemorrhage. (Funded by the Program for Innovative Research Team of the First Affiliated Hospital of USTC and others; ATTENTION ClinicalTrials.gov number, NCT04751708.).

Functional mechanism of EGR3 in cerebral ischemia/reperfusion injury in rats by modulating transcription of pri-miR-146a/146b to miR-146 and suppressing SORT1 expression.

OBJECTIVE: EGR3 is implicated in angiogenesis in rats with cerebral ischemia/reperfusion injury (CIRI). This research aimed to explore the effect and in vivo and ex vivo mechanisms of EGR3 in CIRI. METHODS: CIRI rat models were established via middle cerebral artery occlusion. Cell models were established via oxygen-glucose deprivation/reoxygenation (OGD/R). Brain injury was assessed by neurological scoring, HE, and TTC staining. Inflammatory factors and oxidative stress markers were measured using corresponding kits. Mitochondrial membrane potential and mitochondrial respiration were examined by flow cytometry and respirometry. EGR3-miR-146 network was predicted on TransmiR v2.0 database. Target genes of miR-146 were screened on Starbase, Targetscan, and miRDB databases. miR-146 expression was determined by RT-qPCR. Levels of EGR3 and SORT1 were determined by Western blot. Binding relationships among EGR3, miR-146, and SORT1 were validated by dual-luciferase assay. EGR3, miR-146, and SORT1 levels were altered by injection or cell transfection to observe their functions. RESULTS: EGR3 was poorly-expressed in CIRI rats and OGD/R-induced neurons. EGR3 overexpression reduced inflammatory factor levels and attenuated oxidative stress and mitochondrial injury in CIRI rats and OGD/R-induced neurons. EGR3 bound to miR-146b promoter region. EGR3 promoted pri-miR-146a/146b processing and stimulated miR-146 transcription. miR-146 overexpression ameliorated oxidative stress and mitochondrial injury and miR-146 downregulation abolished the effect of EGR3 overexpression in vitro. miR-146 targeted SORT1. SORT1 overexpression invalidated the protective function of miR-146 overexpression on oxidative stress and mitochondrial injury in vitro. CONCLUSION: EGR3 protected against CIRI by mitigating oxidative stress and mitochondrial injury via the miR-146/SORT1 axis.

Balloon Angioplasty vs. Stenting for Symptomatic Intracranial Arterial Stenosis.

Aims: We performed a meta-analysis to indirectly compare the treatment effectiveness of balloon angioplasty and stenting for patients with intracranial arterial stenosis. Methods: Literature searches were performed in well-known databases to identify eligible studies published before January 04, 2021. The incidence of restenosis, transient ischemic attack (TIA), stroke, death, and dissection after balloon angioplasty or stenting were pooled. An indirect comparison of balloon angioplasty vs. stenting was performed, and the ratios of incidence (RIs) with 95% confidence intervals (CIs) were calculated using the random-effects model. Results: 120 studies that recruited 10,107 patients with intracranial arterial stenosis were included. The pooled incidence of restenosis after balloon angioplasty and stenting were 13% (95%CI: 8-17%) and 11% (95%CI: 9-13%), respectively, with no significant difference between them (RI: 1.18; 95%CI: 0.78-1.80; P = 0.435). Moreover, the pooled incidence of TIA after balloon angioplasty and stenting was 3% (95%CI: 0-6%) and 4% (95%CI: 3%-5%), and no significant difference was observed (RI: 0.75; 95%CI: 0.01-58.53; P = 0.897). The pooled incidence of stroke after balloon angioplasty and stenting was 7% (95%CI: 5-9%) and 8% (95%CI: 7-9%), respectively, and the difference between groups was found to be statistically insignificant (RI: 0.88; 95%CI: 0.64-1.20; P = 0.413). Additionally, the pooled incidence of death after balloon angioplasty and stenting was 2% (95%CI: 1-4%) and 2% (95%CI: 1-2%), with no significant difference between groups (RI: 1.00; 95%CI: 0.44-2.27; P = 1.000). Finally, the pooled incidence of dissection after balloon angioplasty and stenting was 13% (95%CI: 5-22%) and 3% (95%CI: 2-5%), respectively, and balloon angioplasty was associated with a higher risk of dissection than that with stenting for patients with intracranial arterial stenosis (RI: 4.33; 95%CI: 1.81-10.35; P = 0.001). Conclusion: This study found that the treatment effectiveness of balloon angioplasty and stenting were similar for patients with symptomatic intracranial arterial stenosis.

Endovascular Treatment Versus Best Medical Management in Acute Basilar Artery Occlusion Strokes: Results From the ATTENTION Multicenter Registry.

BACKGROUND: The authors compare the effectiveness and safety of endovascular treatment (EVT) versus best medical management (BMM) in strokes attributable to acute basilar artery occlusion (BAO). METHODS: The present analysis was based on the ongoing, prospective, multicenter ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion) trial registry in China. Our analytic sample comprised 2134 patients recruited at 48 sites between 2017 and 2021 and included 462 patients who received BMM and 1672 patients who received EVT. We performed an inversed probability of treatment weighting analysis. Qualifying patients had to present within 24 hours of estimated BAO. The primary clinical outcome was favorable functional outcome (modified Rankin Scale score, 0-3) at 90 days. We also performed a sensitivity analysis with the propensity score matching-based and the instrumental variable-based analysis. RESULTS: In our primary analysis using the inversed probability of treatment weighting-based analysis, there was a significantly higher rate of favorable outcome at 90 days among EVT patients compared with BMM-treated patients (adjusted relative risk, 1.42 [95% CI, 1.19-1.65]; absolute risk difference, 11.8% [95% CI, 6.9-16.7]). The mortality was significantly lower (adjusted relative risk, 0.78 [95% CI, 0.69-0.88]; absolute risk difference, -10.3% [95% CI, -15.8 to -4.9]) in patients undergoing EVT. Results were generally consistent across the secondary end points. Similar associations were seen in the propensity score matching-based and instrumental variable-based analysis. CONCLUSIONS: In this real-world study, EVT was associated with significantly better functional outcomes and survival at 90 days. Well-designed randomized studies comparing EVT with BMM in the acute BAO are needed. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR2000041117.

Screening of Siderophore-Producing Bacteria and Their Effects on Promoting the Growth of Plants.

Iron deficiency is a major global agricultural problem. Siderophores can help organisms to uptake iron in form of siderophore-Fe3+ complexes and then in the cell cytosol, iron is reducted and released in ferrous form. This research aimed to obtain some efficient siderophore-producing bacterial strains and evaluate their plant growth-promoting effects in the iron-deficit environment. Two strains, Brucella sp. E7 and Pseudomonas brassicae W7, were isolated from rhizosphere soil. Both strains could produce maximum siderophores under the optimal conditions. Plant promoting experiment showed that many indicators of Vigna radiata seedling were all increased significantly by strain E7/W7 or the consortium of E7 + W7. Under no-iron and high iron stress, the inoculation treatment also showed growth promotion effects on both Vigna radiata and Lolium multiflorum. These results indicated that the potential ability of strain E7 and W7 in increasing agricultural production as a growth-promoting agent in iron-deficit soil.

Clinical study on the effectiveness and safety of loose combined cutting seton in the treatment of high perianal abscess: a randomized controlled trial protocol.

Background: High perianal abscess is an emergency in the anorectal department. It can result in long-term pain and a huge psychological burden to patients, and seriously affects the quality of life of patients. At present, the effect of antibiotics alone for high perianal abscess is not satisfactory. Loose combined cutting seton (LCCS) can effectively treat high anal fistulas and high perianal abscesses in our clinical practice, but there is no sufficient evidence for its effectiveness in the treatment of high perianal abscesses. The purpose of this study is to observe the effectiveness and safety of LCCS in the treatment of high perianal abscess. Methods: This study is a single-center, prospective, single-blind, randomized, controlled, non-inferiority clinical study. This study will include patients who are diagnosed with high perianal abscesses and hospitalized for surgery in the Department of Proctology in China-Japan Friendship Hospital (enrollment time: from January 2022 through December 2024). Patients in the experimental group will be treated with LCCS, while patients in the control group will be treated with incision and drainage. Follow-ups will be performed at 1, 3, 7, 14, 21, 28, 90, and 180 days after the operation. The main outcome measures are as follows: (I) cure rate; (II) half-year recurrence rate; (III) postoperative pain visual analog scale (VAS) score; (IV) wound healing time; (V) postoperative anal function evaluation by the Wexner scale; (VI) pressure measurement of the anal canal and rectum before and at half a year after surgery; and (VII) the incidence of adverse events. Discussion: This study will assess the effectiveness and safety of LCCS in the treatment of high perianal abscess through a strictly designed randomized controlled study, and provides evidence for treatment in clinical practice, thereby improving the treatment effect and improving patients' quality of life. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100049198.

Simplified dressing change after loose combined cutting seton surgery for high anal fistula: a prospective, single center randomized controlled study.

BACKGROUND: High anal fistula (HAF) is a refractory infectious disease. Surgery is the most effective way to treat HAF. Dressing change is an indispensable part of the rehabilitation process after surgery. The purpose of this study is to provide feasibility and evidence of safety for the implementation of a simplified dressing change after loose combined cutting seton (LCCS) surgery and to offer a better method for clinical treatment and postoperative rehabilitation of HAF. METHODS: In this single-blind randomized controlled trial, 76 patients diagnosed with HAF will be randomly divided into two groups: the simplified dressing change group (n=38) or the traditional debridement and dressing change group (n=38). Compared with traditional debridement and dressing change, simplified dressing change was conducted without mechanical debridement and disinfection. All patients were treated surgically with the LCCS and dressing change. Postoperative follow-up will be carried out on the 3rd, 7th, 14th, 21st, and 180th day after the operation. The primary outcomes will be: complete healing rate of wound and fistula, long-term recurrence rate, poor wound healing rate, and complete wound healing time. The following secondary outcomes will be evaluated: postoperative pain using a visual analogue scale (VAS) score, wound secretions, edema, granulation shape, depth of wound, duration of each dressing change, and incidence of adverse events. DISCUSSION: Dressing change after HAF surgery is a necessary stage of recovery after anorectal surgery. Effective dressing change can reduce false healing and increase the cure rate. However, traditional dressing change takes a long time, and the patient endures severe pain. We have found that the dressing change process can be simplified in the clinic for patients treated with LCCS. In particular, simplification of the dressing change process may be related to the unobstructed drainage provided by the combination of LCCS and the separation of the dotted line. We will treat HAF using LCCS and compare the simplified dressing change method after the operation with traditional routine debridement and dressing change to demonstrate whether the simplified dressing change can be used in patients with HAF treated with LCCS. TRIAL REGISTRATION: ChiCTR2100047312.

[Full-zirconia single-tooth molar implant-supported restorations with angulated screw channel abutments: evaluation of short-term outcomes].

PURPOSE: To evaluate the effect of full-zirconia single-tooth molar implant-supported restorations with angulated screw channel abutments. METHODS: Seventy-six patients with a single missing tooth in the posterior region of the maxilla and mandible underwent dental implants from March 2016 to March 2018 were enrolled. After 3 months, each patient received a full-contour screw-retained zirconia restoration with angulated screw channel abutment. Modified sulcus bleeding index (MSBI), modified plaque index (mPLI), periodontal probing depth (PD), marginal bone levels (MBLs) and mid-buccal mucosal levels (MBMLs) were recorded at the implantation moment (T0), four weeks (T1), one year (T2) and two years (T3) after treatment. During the follow-up period, the incidence of implant defects, survival rate and porcelain fracture were recorded. The data were processed using SPSS 23.0 software package. RESULTS: Of the 76 patients, 9 did not have a complete follow-up record (two of the implants failed before restoration, two patients had bilateral first molars missing, and five were lost to follow-up), and the remaining 67 patients with a total of 67 implants had a complete follow-up record. The success rate of implant was 97.01%(65/67) during one-year follow-up, and the initial success rate was 100% at an interval of three months. Compared with indexes at T0, mSBI and mPLI were significantly reduced at T1, T2 and T3 (P<0.05). There was no significant difference in PD level at T0, T1, T2 and T3(P>0.05), and the effective depth averaged 1.75 mm. Compared with indexes at T0, MBLs and MBMLs were significantly increased at T1(P<0.05). A total of 4 cases had implant reconstruction at T1 due to concerns about framework fracture, veneering fracture and aesthetics. At T2 and T3, there was no implant problems and loosening of restoration. There were 2 cases of peri-implant inflammation, one case of implant loss and one case of abutment pain, which were all improved after corresponding treatments. Two cases of porcelain fracture occurred in 67 zirconia restorations (2.63%), and the implant survival rate was 100%. CONCLUSIONS: Full-zirconia single-tooth molar implant-supported restorations with angulated screw channel abutments can effectively improve the implant stability in early phase, with high success rate, good short-term effect and few complications.

Endovascular Recanalization and Standard Medical Management for Symptomatic Non-acute Intracranial Artery Occlusion: Study Protocol for a Non-randomized, 24-Month, Multicenter Study.

Background: The management of patients with symptomatic non-acute intracranial artery occlusion (sNA-ICAO), which is a special subset with high morbidity and a high probability of recurrent serious ischemic events despite standard medical therapy (SMT), has been clinically challenging. A number of small-sample clinical studies have also discussed endovascular recanalization (ER) for sNA-ICAO; however, there is currently a lack of evidence from multicenter, prospective, large-sample cohort trials. The purpose of our present study was to evaluate the technical feasibility and safety of ER for sNA-ICAO. Methods: Our group is currently undertaking a multisite, non-randomized cohort, prospective registry study enrolling consecutive patients presenting with sNA-ICAO at 15 centers in China between January 1, 2020 and December 31, 2022. A cohort of patients who received SMT and a cohort of similar patients who received ER plus SMT were constructed and followed up for 2 years. The primary outcome is any stroke from enrollment to 2 years of follow-up. The secondary outcomes are all-cause mortality, mRS score, NIHSS score and cognitive function from enrollment to 30 days, 3 months, 8 months, 12 months, 18 months, and 2 years of follow-up. Descriptive statistics and linear/logistic multiple regression models will be generated. Clinical relevance will be measured as relative risk reduction, absolute risk reduction and the number needed to treat. Discussion: The management of patients with sNA-ICAO has been clinically challenging. The current protocol aims to evaluate the technical feasibility and safety of ER for sNA-ICAO. Trial Registration Number: www.ClinicalTrials.gov, identifier: NCT04864691.

Loose combined cutting seton for patients with suprasphincteric anal fistula: a randomized clinical trial protocol.

BACKGROUND: Suprasphincteric anal fistula is a type of high anal fistula. The traditional method of cutting seton (CS) has a high recurrence rate and can cause severe damage to the anal sphincter and anal incontinence. The combination of loose and cutting seton is a novel method developed on the basis of the traditional cutting seton technique, and has already been adopted by some clinicians in China. This study will examine the effectiveness and safety of the loose combined cutting seton (LCCS) technique for the treatment of suprasphincteric anal fistulas. METHODS: This is a single-blinded randomized controlled trial conducted in the Anorectal Department of the China-Japan Friendship Hospital. A total of 76 patients diagnosed with suprasphincteric anal fistula will be randomly divided into two groups. One group will be treated with the LCCS method (the LCCS group; n=38) and the other group will be treated with the traditional CS method (the CS group; n=38). There will be 3 intervention periods, including the screening period, the surgical treatment period, and the postoperative follow-up period. Postoperative follow-up will be carried out on days 3, 5, 7, 14, 21, 28, 90, 180, and 365 after the operation. The main outcome measures are the complete cure rate of postoperative wounds and fistulas, the long-term recurrence rate, and evaluation of postoperative anal function (Wexner anal function assessment and anal function questionnaire). The secondary outcomes are the visual analogue scale (VAS) score for postoperative pain, pressure measurements of the anal canal and rectum before and after treatment, and the incidence of adverse events. All statistical results will be analyzed using the SPSS software 21.0 version. P values <0.05 will be considered statistically significant. DISCUSSION: This research introduces a novel method for the treatment of suprasphincteric anal fistulas. The LCCS method will be compared with the traditional CS method in terms of safety and efficacy. If the LCCS technique is a safe and effective treatment for suprasphincteric anal fistula, its clinical application should be promoted. TRIAL REGISTRATION: ClinicalTrials, Registration number: ChiCTR2100045450; pre-results. PROTOCOL VERSION: 2020-09-10 1.0 version.

Elucidating the Molecular Mechanism of Ischemic Stroke Using Integrated Analysis of miRNA, mRNA, and lncRNA Expression Profiles.

Objective: This study aimed to investigate the possible molecular mechanisms associated with ischemic stroke through the construction of a lncRNA-miRNA-mRNA network. miRNA expression profile in GSE55937, mRNA and lncRNA expression profiles in GSE122709, and mRNA expression profile in GSE146882 were downloaded from the NCBI GEO database. After the identification of the differentially expressed miRNA, lncRNA, and mRNA using GSE55937 and GSE122709 in ischemic stroke vs. control groups, a protein-protein interaction (PPI) network was constructed. The lncRNA-miRNA, lncRNA-mRNA, and miRNA-mRNA pairs were predicted, and a lncRNA-miRNA-mRNA network was constructed. Additionally, the gene-drug interactions were predicted. Characteristic genes were used to construct a support vector machine (SVM) model and verified using quantitative reverse transcription polymerase chain reaction. In total 38 miRNAs, 115 lncRNAs, and 990 mRNAs were identified between ischemic stroke and control groups. A PPI network with 371 nodes and 2306 interaction relationships was constructed. The constructed lncRNA-miRNA-mRNA network contained 7 mRNAs, 14 lncRNAs, such as SND1-IT1, NAPA-AS1, LINC01001, LUCAT1, and ASAP1-IT2, and 8 miRNAs, such as miR-93-3p and miR-24-3p. The drug action analysis of the seven differential mRNAs included in the lncRNA-miRNA-mRNA network showed that four genes (GPR17, ADORA1, OPRM1 and LPAR3) were predicted as molecular targets of drugs. The area under the curve of the constructed SVM model was 0.886. The verification results of the relative expression of RNA by qRT-PCR were consistent with the results of bioinformatics analysis. LPAR3, ADORA1, GPR17, and OPRM1 may serve as therapeutic targets of ischemic stroke. lncRNA-miRNA-mRNA regulatory axis such as SND1-IT1/NAPA-AS1/LINC01001-miR-24-3p-LPAR3/ADORA1 and LUCAT1/ASAP1-IT2-miR-93-3p-GPR17 may play important roles in the progression of ischemic stroke.

MicroRNA-532-5p upregulation protects neurological deficits after ischemic stroke through inhibition of BTB and CNC homology 1.

OBJECTIVE: MicroRNA (miR)-532-5p has been reported to protect against ischemic stroke (IS), while the underlying mechanism of miR-532-5p targeting BTB and CNC homology 1 (BACH1) in IS remains unknown. Thus, we aim to detect the role of miR-532-5p in IS via targeting BACH1. METHODS: Blood samples were collected from IS patients and healthy controls. Rat middle cerebral artery occlusion (MCAO) models were established and intracerebrally injected with altered miR-532-5p or BACH1 plasmid vectors to reveal their roles in neurological function, brain tissue pathology and inflammation in MCAO. Expression of miR-532-5p and BACH1 in patients' blood samples and rat brain tissues was assessed, and the targeting relationship between miR-532-5p and BACH1 was confirmed. RESULTS: MiR-532-5p was downregulated and BACH1 was upregulated in IS. BACH1 was targeted by miR-532-5p. Restored miR-532-5p or inhibited BACH1 improved neurological function and inhibited inflammation and apoptosis in MCAO rats. On the contrary, miR-532-5p reduction or BACH1 overexpression had totally opposite effects on MCAO rats. The protective role of miR-532-5p for MCAO rats was reversed by upregulated BACH1. CONCLUSION: MiR-532-5p upregulation protects against neurological deficits after IS through inhibition of BACH1.