Prevotella copri transplantation promotes neurorehabilitation in a mouse model of traumatic brain injury.

BACKGROUND: The gut microbiota plays a critical role in regulating brain function through the microbiome-gut-brain axis (MGBA). Dysbiosis of the gut microbiota is associated with neurological impairment in Traumatic brain injury (TBI) patients. Our previous study found that TBI results in a decrease in the abundance of Prevotella copri (P. copri). P. copri has been shown to have antioxidant effects in various diseases. Meanwhile, guanosine (GUO) is a metabolite of intestinal microbiota that can alleviate oxidative stress after TBI by activating the PI3K/Akt pathway. In this study, we investigated the effect of P. copri transplantation on TBI and its relationship with GUO-PI3K/Akt pathway. METHODS: In this study, a controlled cortical impact (CCI) model was used to induce TBI in adult male C57BL/6J mice. Subsequently, P. copri was transplanted by intragastric gavage for 7 consecutive days. To investigate the effect of the GUO-PI3K/Akt pathway in P. copri transplantation therapy, guanosine (GUO) was administered 2 h after TBI for 7 consecutive days, and PI3K inhibitor (LY294002) was administered 30 min before TBI. Various techniques were used to assess the effects of these interventions, including quantitative PCR, neurological behavior tests, metabolite analysis, ELISA, Western blot analysis, immunofluorescence, Evans blue assays, transmission electron microscopy, FITC-dextran permeability assay, gastrointestinal transit assessment, and 16 S rDNA sequencing. RESULTS: P. copri abundance was significantly reduced after TBI. P. copri transplantation alleviated motor and cognitive deficits tested by the NSS, Morris's water maze and open field test. P. copri transplantation attenuated oxidative stress and blood-brain barrier damage and reduced neuronal apoptosis after TBI. In addition, P. copri transplantation resulted in the reshaping of the intestinal flora, improved gastrointestinal motility and intestinal permeability. Metabolomics and ELISA analysis revealed a significant increase in GUO levels in feces, serum and injured brain after P. copri transplantation. Furthermore, the expression of p-PI3K and p-Akt was found to be increased after P. copri transplantation and GUO treatment. Notably, PI3K inhibitor LY294002 treatment attenuated the observed improvements. CONCLUSIONS: We demonstrate for the first time that P. copri transplantation can improve GI functions and alter gut microbiota dysbiosis after TBI. Additionally, P. copri transplantation can ameliorate neurological deficits, possibly via the GUO-PI3K/Akt signaling pathway after TBI.

Constructing Built-in-Electric Field for Boosting Electrocatalytic Water Splitting.

Electrocatalytic water splitting shows great potential for producing clean and green hydrogen, but it is hindered by slow reaction kinetics. Advanced electrocatalysts are needed to lower the energy barriers. The establishment of built-in electric fields (BIEF) in heterointerfaces has been found to be beneficial for speeding up electron transfer, increasing electrical conductivity, adjusting the local reaction environment, and optimizing the chemisorption energy with intermediates. Engineering and modifying the BIEF in heterojunctions offer significant opportunities to enhance the electronic properties of catalysts, thus improving reaction kinetics. This comprehensive review focuses on the latest advances in BIEF engineering in heterojunction catalysts for efficient water electrolysis. It highlights the fundamentals, engineering, modification, characterization, and application of BIEF in electrocatalytic water splitting. The review also discusses the challenges and future prospects of BIEF engineering. Overall, this review provides a thorough examination of BIEF engineering for the next generation of water electrolysis devices.

Neuronal regulation of bone and tendon injury repair: a focused review.

Beyond the sensation of pain, peripheral nerves have been shown to play crucial roles in tissue regeneration and repair. As a highly innervated organ, bone can recover from injury without scar formation, making it an interesting model in which to study the role of nerves in tissue regeneration. As a comparison, tendon is a musculoskeletal tissue that is hypo-innervated, with repair often resulting in scar formation. Here, we reviewed the significance of innervation in three stages of injury repair (inflammatory, reparative, and remodeling) in two commonly injured musculoskeletal tissues: bone and tendon. Based on this focused review, we conclude that peripheral innervation is essential for phases of proper bone and tendon repair, and that nerves may dynamically regulate the repair process through interactions with the injury microenvironment via a variety of neuropeptides or neurotransmitters. A deeper understanding of neuronal regulation of musculoskeletal repair, and the crosstalk between nerves and the musculoskeletal system, will enable the development of future therapies for tissue healing.

Accumulating evidence has shown that, across organs systems, peripheral nerves regulate the process of tissue repair and regeneration. This is particularly relevant in the context of musculoskeletal injuries such as those affecting the bone and tendon. The question then arises: what is the function of peripheral innervation in the repair of bone and tendon injuries? This review offers an in-depth look at the ways in which nerves regulate the healing of bone and tendon injuries at various stages of recovery. A deeper comprehension of the influence of nerves on the repair of these tissues could pave the way for the development of future therapeutic strategies for tissue healing.

Endotherapy for the proximal migration of pancreatic stents: A systematic review.

OBJECTIVES: Proximal migration is one of the complications after pancreatic duct stenting. This study aimed to determine the incidence of proximal migration and to analyze the rescue methods. METHODS: A search was performed in MEDLINE/EMBASE database. The literatures included were reviewed and analyzed. Retrieval tools were classified into 3 classes: Class A works by indirectly contacting the outer surface of the stent. Class B works by directly contacting the outer surface. Class C works by directly contacting the inner surface. RESULTS: 416 literatures were retrieved from 1983 to 2021. 15 literatures were included. The incidence of proximal migration of pancreatic stents was 4.7% (106/2246). The success rate of endotherapy was 86.6% (214/247), and the surgical conversion rate of it was 9.3%. Among the 214 cases in which the displaced stents were successfully removed under endoscopy, 49 cases (22.9%) used Class A methods, 154 cases (72.0%) used Class B methods and 11 cases (5.1%) used Class C methods. The overall rate of postoperative complication was 12.1%, including postprocedure pancreatitis (9.1%, 18/247), followed by bleeding (1.5%), perforation (1.0%) and biliary infection (0.5%). CONCLUSIONS: Endoscopy is an effective method for the treatment of proximal displacement of pancreatic stents with acceptable complication rate.

Nomogram for the prediction of infected pancreatic necrosis in moderately severe and severe acute pancreatitis.

OBJECTIVES: As a serious complication of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), infected pancreatic necrosis (IPN) can lead to a prolonged course of interventional therapy. Most predictive models designed to identify such patients are complex or lack validation. The aim of this study was to develop a predictive model for the early detection of IPN in MSAP and SAP. METHODS: A total of 594 patients with MSAP or SAP were included in the study. To reduce dimensionality, least absolute shrinkage and selection operator regression analysis was used to screen potential predictive variables, a nomogram was then constructed using logistic regression analysis. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical efficacy of the model. External data were also obtained to further validate the constructed model. RESULTS: There were 476, 118, and 82 patients in the training, internal validation, and external validation cohorts, respectively. Platelet count, hematocrit, albumin/globulin, severity of acute pancreatitis, and modified computed tomography severity index score were independent factors for predicting IPN in MSAP and SAP. The area under the ROC curves were 0.923, 0.940, and 0.817, respectively, in the three groups. There was a good consistency between the actual probabilities and the predicted probabilities. DCA revealed excellent clinical utility. CONCLUSION: The constructed nomogram is a simple and feasible model that has good clinical predictive value and efficacy in clinical decision-making for IPN in MSAP and SAP.

AvrSr27 is a zinc-bound effector with a modular structure important for immune recognition.

Effector proteins are central to the success of plant pathogens, while immunity in host plants is driven by receptor-mediated recognition of these effectors. Understanding the molecular details of effector-receptor interactions is key for the engineering of novel immune receptors. Here, we experimentally determined the crystal structure of the Puccinia graminis f. sp. tritici (Pgt) effector AvrSr27, which was not accurately predicted using AlphaFold2. We characterised the role of the conserved cysteine residues in AvrSr27 using in vitro biochemical assays and examined Sr27-mediated recognition using transient expression in Nicotiana spp. and wheat protoplasts. The AvrSr27 structure contains a novel ß-strand rich modular fold consisting of two structurally similar domains that bind to Zn2+ ions. The N-terminal domain of AvrSr27 is sufficient for interaction with Sr27 and triggering cell death. We identified two Pgt proteins structurally related to AvrSr27 but with low sequence identity that can also associate with Sr27, albeit more weakly. Though only the full-length proteins, trigger Sr27-dependent cell death in transient expression systems. Collectively, our findings have important implications for utilising protein prediction platforms for effector proteins, and those embarking on bespoke engineering of immunity receptors as solutions to plant disease.

Relationship between preoperative high triglyceride-glucose index and myocardial injury following non-cardiac surgery in advanced-age patients: a retrospective cohort study.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a common and insidious postoperative complication. This study aimed to evaluate the relationship between the triglyceride-glucose index (TyG) and MINS in advanced-age patients. METHODS: We performed a single-center retrospective study including patients ≥ 65 years of age who underwent non-cardiac surgery. The relationship between TyG and MINS was investigated using univariate and multivariate logistic regression analyses. Multivariate logistic regression analysis involved three models: Model I adjusted for preoperative factors, Model II adjusted for surgery-related factors, and Model III adjusted for both preoperative and surgery-related factors. Propensity score matching (PSM) was used to reduce the confounding effects of covariates. Subgroup analyses were then performed to evaluate the relationship between TyG and MINS in various subsamples. RESULTS: A total of 7789 patients were studied, among whom 481 (6.2%) developed MINS. A cut-off value of TyG of 8.57 was determined using a receiver operating characteristic (ROC) curve to be associated with the best predictive performance. Participants with TyG ≥ 8.57 were at a higher risk of developing MINS than those with TyG < 8.57 [n = 273 (7.6%) vs. n = 208 (4.9%), respectively; p < 0.001]. The univariate analysis showed that TyG ≥ 8.57 was significantly associated with MINS in elderly patients [odds ratio (OR): 1.58; 95% confidence interval (95%CI): 1.32-1.91; p < 0.001)]. In multivariate logistic regression, adjustments were made for risk factors including age, sex, body mass index (BMI), hypertension, coronary heart disease, and duration of surgery, etc. The adjusted ORs for TyG ≥ 8.57 were 1.46 (95%CI: 1.17-1.82), p = 0.001; 1.46 (95%CI: 1.19-1.77), p < 0.001; and 1.43 (95%CI: 1.13-1.81), p = 0.003, in the three multivariate models, respectively. The relationship remained after PSM (adjusted OR: 1.35, 95% CI: 1.03-1.78, p = 0.029). Furthermore, the relationship between TyG and MINS remained in a number of subgroups in the sensitivity analyses, but not in participants with peripheral vascular stenosis. CONCLUSIONS: A preoperative high TyG (≥ 8.57) is associated with a higher risk of MINS in advanced-age patients undergoing non-cardiac surgery.

Highly Efficient and Stable Organic Solar Cells Enabled by a Commercialized Simple Thieno[3,2-b]thiophene Additive.

Delicately manipulating nanomorphology is recognized as a vital and effective approach to enhancing the performance and stability of organic solar cells (OSCs). However, the complete removal of solvent additives with high boiling points is typically necessary to maintain the operational stability of the device. In this study, two commercially available organic intermediates, namely thieno[3,2-b]thiophene (TT) and 3,6-dibromothieno[3,2-b]thiophene (TTB) are introduced, as solid additives in OSCs. The theoretical simulations and experimental results indicate that TT and TTB may exhibit stronger intermolecular interactions with the acceptor Y6 and donor PM6, respectively. This suggests that the solid additives (SAs) can selectively intercalate between Y6 and PM6 molecules, thereby improving the packing order and crystallinity. As a result, the TT-treated PM6:Y6 system exhibits a favorable morphology, improved charge carrier mobility, and minimal charge recombination loss. These characteristics contribute to an impressive efficiency of 17.75%. Furthermore, the system demonstrates exceptional thermal stability (T80 > 2800 h at 65 °C) and outstanding photostability. The universal applicability of TT treatment is confirmed in OSCs employing D18:L8-BO, achieving a significantly higher PCE of 18.3%. These findings underscore the importance of using appropriate solid additives to optimize the blend morphology of OSCs, thereby improving photovoltaic performance and thermal stability.

Analysis of risk factors for the recurrence of osteomyelitis of the limb after treatment with antibiotic-loaded calcium sulfate and autologous bone graft.

Objective: We aimed to evaluate the efficacy of antibiotic-loaded calcium sulfate combined with autologous iliac bone transplantation in the treatment of limb-localized osteomyelitis (Cierny-Mader type III) and analyze the causes and risk factors associated with infection recurrence. Methods: Clinical data of 163 patients with localized osteomyelitis of the extremities treated with antibiotic-loaded calcium sulfate combined with autologous iliac bone transplantation in Xi'an Honghui Hospital from January 2017 to December 2022 were retrospectively analyzed. All patients were diagnosed with localized osteomyelitis through clinical examination and treated with antibiotic-loaded calcium sulfate combined with autologous iliac bone. Based on the infection recurrence status, the patients were divided into the recurrence group and the non-recurrence group. The clinical data of the two groups were compared using univariate analysis. Subsequently, the distinct datasets were included in the binary logistic regression analysis to determine the risk and protective factors. Results: This study included 163 eligible patients, with an average age of 51.0 years (standard deviation: 14.9). After 12 months of follow-up, 25 patients (15.3%) experienced infection recurrence and were included in the recurrence group; the remaining 138 patients were included in the non-recurrence group. Among the 25 patients with recurrent infection, 20 required reoperation, four received antibiotic treatment alone, and one refused further treatment. Univariate analysis showed that education level, smoking, hypoproteinemia, open injury-related infection, and combined flap surgery were associated with infection recurrence (p < 0.05). Logistic regression analysis showed that open injury-related infection (odds ratio [OR] = 35.698; 95% confidence interval [CI]: 5.997-212.495; p < 0.001) and combined flap surgery (OR = 41.408; 95% CI: 5.806-295.343; p < 0.001) were independent risk factors for infection recurrence. Meanwhile, high education level (OR = 0.009; 95% CI: 0.001-0.061; p < 0.001) was a protective factor for infection recurrence. Conclusion: Antibiotic-loaded calcium sulfate combined with autologous iliac bone transplantation is an effective method for treating limb-localized osteomyelitis. Patients without previous combined flap surgery and non-open injury-related infections have a relatively low probability of recurrence of infection after treatment with this surgical method. Additionally, patients with a history of smoking and hypoproteinemia should pay attention to preventing the recurrence of infection after operation. Providing additional guidance and support, particularly in patients with lower education levels and compliance, could contribute to the reduction of infection recurrence.

Regorafenib plus programmed death­1 inhibitors vs. regorafenib monotherapy in second­line treatment for advanced hepatocellular carcinoma: A systematic review and meta­analysis.

The present study compared the efficacy and safety of regorafenib plus programmed death-1 inhibitors (R-P) with regorafenib monotherapy as second-line therapies for advanced hepatocellular carcinoma (HCC). A systematic search of relevant literature published in PubMed, Embase, Web of Science and Cochrane Library databases until October 2023 was conducted. Two authors independently performed data extraction and screening using standardized protocols. Stata/MP 17.0 was used for the meta-analysis to evaluate the impact of R-P treatment on major outcome indicators, including overall survival, progression-free survival (PFS), tumor response and adverse reactions, in patients with advanced HCC. The results indicated that five cohort studies involving 444 patients with advanced HCC were included. The results revealed that R-P treatment improved overall survival [hazard ratio (HR), 0.61; 95% confidence interval (CI) 0.48-0.77; I2=0.0%; P=0.663] and PFS (HR, 0.51; 95% CI 0.41-0.63; I2=17.5%; P=0.303). Additionally, it increased the objective response rate (risk ratio, 2.33; 95% CI, 1.49-3.64; I2=0.0%; P=0.994) and disease control rate (HR, 1.40; 95% CI, 1.20-1.63; I2=0.0%; P=0.892) compared with those of regorafenib. However, R-P treatment was associated with an increased incidence of adverse events, such as hypothyroidism, thrombocytopenia and rash, compared with that in regorafenib. In conclusion, R-P is superior to regorafenib monotherapy in terms of survival benefits and tumor response.

Capture of single Ag atoms through high-temperature-induced crystal plane reconstruction.

The "terminal hydroxyl group anchoring mechanism" has been studied on metal oxides (Al2O3, CeO2) as well as a variety of noble and transition metals (Ag, Pt, Pd, Cu, Ni, Fe, Mn, and Co) in a number of generalized studies, but there is still a gap in how to regulate the content of terminal hydroxyl groups to influence the dispersion of the active species and thus to achieve optimal catalytic performance. Herein, we utilized AlOOH as a precursor for γ-Al2O3 and induced the transformation of the exposed crystal face of γ-Al2O3 from (110) to (100) by controlling the calcination temperature to generate more terminal hydroxyl groups to anchor Ag species. Experimental results combined with AIMD and DFT show that temperature can drive the atomic rearrangement on the (110) crystal face, thereby forming a structure similar to the atomic arrangement of the (100) crystal face. This resulted in the formation of more terminal hydroxyl groups during the high-temperature calcination of the support (Al-900), which can capture Ag species to form single-atom dispersions, and ultimately develop a stable and efficient single-atom Ag-based catalyst.

Optimal Glycated Hemoglobin Cutoff for Diagnosis of Diabetes and Prediabetes in Chinese Breast Cancer Women.

Purpose: Glycated hemoglobin (HbA1c) is widely used in diabetes management and now recommended for diagnosis and risk assessment. Our research focused on investigating the optimal cutoff points of HbA1c for diagnosis of diabetes and prediabetes in Chinese breast cancer women, aiming to enhance early detection and tailor treatment strategies. Patients and Methods: This study involved 309 breast cancer women without diabetes history in China. Patients were categorized into groups of newly diagnosed diabetes, prediabetes, and normal glucose tolerance using oral glucose tolerance test (OGTT) according to the 2010 ADA criteria. HbA1c data were collected from all patients. Receiver operating characteristic (ROC) curve analysis was used to assess the effectiveness of the HbA1c screening. Results: Among the 309 breast cancer women without diabetes history, 96 (31.0%) were identified with diabetes and 130 (42.1%) had prediabetes according to OGTT, and the incidence of normal glucose tolerance was only 26.9% (83). ROC curve analysis, using OGTT as a reference, revealed that the area under the curve of 0.903 (P<0.001, 95% CI, 0.867-0.938) for HbA1c alone, indicating high accuracy. The optimal HbA1c cutoff for identifying diabetes was determined to be 6.0%, with a sensitivity of 78.1% and specificity of 86.4%. For prediabetes, the ROC curve for HbA1c alone showed that the area under the ROC curve of 0.703 (P<0.001, 95% CI, 0.632-0.774), with an optimal cutoff of 5.5% (sensitivity of 76.9% and specificity of 51.8%). Conclusion: The prevalence of undiagnosed diabetes is very high in breast cancer women without diabetes history in China. The optimal cutoff points of HbA1c for identifying diabetes and prediabetes are 6.0% and 5.5% in Chinese breast cancer women, respectively.

Efficacy of non-pharmacological interventions for individuals with amyotrophic lateral sclerosis: systematic review and network meta-analysis of randomized control trials.

This network meta-analysis (NMA) aimed to compare the efficacy of five non-pharmacological interventions, including exercise intervention (EI), nutritional intervention (NI), respiratory intervention (RI), psychological intervention (PSI), and integrated physical intervention (IPI), on functional status, quality of life, muscle strength, pulmonary function, and safety in patients with amyotrophic lateral sclerosis (ALS). We searched nine databases, PubMed, Cochrane, Embase, Scopus, Web of Science, CNKI, CBM, WFPD, and CSTJ, for randomized controlled trials of ALS patients. The primary outcome was the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score. Secondary outcomes were the McGill Quality of Life Questionnaire (McGill-QoL), Medical Research Council (MRC)-sum score, Forced Vital Capacity (FVC), and Fatigue Severity Scale (FSS) score. This NMA was conducted using random-effect models to calculate the standard mean difference (SMD) and 95% confidence interval (CI). All types of supplemental interventions had some benefit for patients with ALS. EI had a beneficial effect on the ALSFRS-R score (SMD: 1.01; 95% CI 0.50-1.51), FVC (SMD: 0.78; 95% CI 0.02-1.55), McGill-QoL (SMD: 0.71 95% CI 0.33-1.08), and MRC (SMD: 1.11; 95% CI 0.08-2.14). RI had a beneficial effect on the ALSFRS-R score (SMD: 0.83 95% CI 0.12-1.55). IPI had a beneficial effect on the ALSFRS-R score (SMD: 0.65 95% CI 0.06-1.24). NI had a beneficial effect on the McGill-QoL (SMD: 0.63 95% CI 0.02-1.23). The current study findings support a multimodal intervention strategy with an emphasis on EI for slowing disease progression in patients with ALS.

Naringin attenuates Actinobacillus pleuropneumoniae-induced acute lung injury via MAPK/NF-κB and Keap1/Nrf2/HO-1 pathway.

Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PCP), which is clinically characterized by acute hemorrhagic, necrotizing pneumonia, and chronic fibrinous pneumonia. Although many measures have been taken to prevent the disease, prevention and control of the disease are becoming increasingly difficult due to the abundance of APP sera, weak vaccine cross-protection, and increasing antibiotic resistance in APP. Therefore, there is an urgent need to develop novel drugs against APP infection to prevent the spread of APP. Naringin (NAR) has been reported to have an excellent therapeutic effect on pulmonary diseases, but its therapeutic effect on lung injury caused by APP is not apparent. Our research has shown that NAR was able to alleviate APP-induced weight loss and quantity of food taken and reduce the number of WBCs and NEs in peripheral blood in mice; pathological tissue sections showed that NAR was able to prevent and control APP-induced pathological lung injury effectively; based on the establishment of an in vivo/in vitro model of APP inflammation, it was found that NAR was able to play an anti-inflammatory role through inhibiting the MAPK/NF-κB signaling pathway and exerting anti-inflammatory effects; additionally, NAR activating the Nrf2 signalling pathway, increasing the secretion of antioxidant enzymes Nqo1, CAT, and SOD1, inhibiting the secretion of oxidative damage factors NOS2 and COX2, and enhancing the antioxidant stress ability, thus playing an antioxidant role. In summary, NAR can relieve severe lung injury caused by APP by reducing excessive inflammatory response and improving antioxidant capacity.

Ultrasonography screening of hepatic cystic echinococcosis in sheep flocks used for evaluating control progress in a remote mountain area of Hejing County, Xinjiang.

BACKGROUND: Although ultrasonography (US) has been widely used in the diagnosis of human diseases to monitor the progress of cystic echinococcosis (CE) control, the screening method for hepatic CE in sheep flocks requires adjustment. In this study, we used a US scanner to screen sheep flocks and evaluated the efficacy of dosing dogs once a year with praziquantel for 7 years from 2014 to 2021. METHODS: All sheep in the three flocks were screened using an ultrasound scanner in 2014 and compared with the prevalence of infection in 2021 in Bayinbuluke, Xinjiang, China. Sheep age was determined using incisor teeth. Cyst activity and calcification were determined using US images. The dogs were dewormed with praziquantel once a year to control echinococcosis in the community. RESULTS: Three flocks had 968 sheep in 2014, with 13.22%, 22.62%, 18.7%, 27.27%, 11.88%, and 6.3% of sheep aged 1, 2, 3, 4, 5, and ≥ 6 years old, respectively. US scanning revealed that the overall CE prevalence was 38.43% (372/968), with active cysts and calcified cysts present in 9.40% (91/968) and 29.02% (281/968) of the sheep, respectively. For the young sheep aged 1 and 2 years, the prevalence of active and calcified cysts was: 1.56% and 0.91%, and 10.94% and 18.72%, respectively. Approximately 15.15% and 16.52% of the 4- and 5-year-old sheep, respectively, harbored active cysts. There was no significant difference in the infection rates of sheep between 2014 and 2021 (P > 0.05). CONCLUSIONS: US is a practical tool for the field screening of CE in sheep flocks. One-third of the sheep population in the flocks was 1-2 years old, and these sheep played a very limited role in CE transmission, as most of the cysts were calcified. Old sheep, especially culled aged sheep, play a key role in the transmission of CE. Dosing dogs once a year did not affect echinococcosis control.

Adverse events in endoscopic ultrasound-guided choledochoduodenostomy with lumen-apposing metal stents: A systematic review and meta-analysis.

BACKGROUND AND AIM: Several meta-analyses have analyzed the technical and clinical success of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) by using lumen-apposing metal stents (LAMS) in malignant biliary obstruction, but those concerning adverse events (AEs) are scarce. The current systematic review and meta-analysis was conducted to evaluate the AEs after EUS-CDS with LAMS. METHODS: A comprehensive literature search of PubMed, Embase, Scopus, Web of Science, and the Cochrane Library was conducted for studies reporting the outcomes of EUS-CDS with LAMS. The main endpoints were the incidence of overall and specific AEs. Moreover, the stent dysfunction, and reintervention rates were evaluated independently. RESULTS: A total of 21 studies (n = 1438) were included in the final meta-analysis. The pooled rate of technical and clinical success was 93.5% (95% confidence interval [CI]: 91.3-95.1) and 88.0% (95% CI: 83.9-91.1), respectively. After EUS-CDS with LAMS, the pooled incidence of overall AEs was 20.1% (95% CI: 16.0-24.9). The estimated rate of early AEs was 10.6% (95% CI: 7.9-14.2), and late AEs was 11.2% (95% CI: 8.2-15.2). Infection/cholangitis was the commonest AE, with a pooled incidence of 6.1% (95% CI: 3.7-10.1). The estimated incidence of stent dysfunction and reintervention was 10.5% (95% CI: 7.5-14.4), and 12.1% (95% CI: 9.3-15.7), respectively. CONCLUSION: Despite with a high technical and clinical success rate, EUS-CDS with LAMS may be associated with overall AEs and stent dysfunction in one-fifth and one-tenth of cases, respectively. Further efforts are required to optimize its safety and long-term stent patency.

Electroacupuncture enhances cerebral blood perfusion by inhibiting HIF-1α in rat subarachnoid hemorrhage.

OBJECTIVE: Cerebral blood perfusion (CBP) reduction is a prevalent complication following subarachnoid hemorrhage (SAH) in clinical practice, often associated with long-term cognitive impairment and prognosis. Electroacupuncture (EA), a widely utilized traditional Chinese therapy for central nervous system disorders, has demonstrated promising therapeutic effects. This study aims to investigate the therapeutic potential of EA in restoring CBP in SAH rats and to explore the mechanisms involving HIF-1α in this process. METHODS: Rats were randomly assigned to one of five groups, including Sham, SAH, EA, EA + Saline, and EA + dimethyloxallyl glycine (DMOG) groups. EA treatment was administered for 10 min daily, while DMOG were intraperitoneally injected. Behavioral tests, cerebral blood flow monitoring, vascular thickness measurement, western blotting, and immunofluorescence staining were conducted to assess the therapeutic effects of EA on cerebral blood flow. RESULTS: SAH resulted in elevated levels of HIF-1α, endothelin (ET), ICAM-1, P-SELECTIN, E-SELECTIN, and decreased level of eNOS in the brain. This led to cerebral vasospasm, decreased CBF, and cognitive deficits in the rat SAH model. EA intervention downregulated the expression of HIF-1α, ET, ICAM-1, P-SELECTIN, and E-SELECTIN, while increasing eNOS expression. This alleviated cerebral vasospasm, restored CBF, and improved cognitive function. However, the administration of the HIF-1α stabilizer (DMOG) counteracted the therapeutic effects of EA. CONCLUSION: EA promotes the recovery of cerebral blood flow after SAH injury, attenuates cerebral vasospasm, and accelerates the recovery of cognitive dysfunction, and its mechanism of action may be related to the inhibition of the HIF-1α signaling pathway.

Altered gut microbiota and metabolite profiles provide clues in understanding resistant hypertension.

BACKGROUND: Resistant hypertension is a severe phenotype in hypertension that may be driven by interactions between genetic and environmental factors. Specific changes in gut microbiota and metabolites have been shown to influence cardiovascular disease progression. However, microbial and metabolomic changes associated with resistant hypertension remain elusive. METHODS: In this study, the gut microbiome of 30 participants with resistant hypertension, 30 with controlled hypertension, and 30 nonhypertension was characterized using 16S rRNA amplicon sequencing. In addition, the serum metabolome of the same population was assessed by untargeted metabolomics. RESULTS: The alpha diversity of microbiome in the resistant hypertension decreased, and changes were also observed in the composition of the gut microbiota. The resistant hypertension group was characterized by elevated levels of Actinobacteitia and Proteobacteria. Twenty-three genera were found to have significantly different abundances between resistant hypertension and controlled hypertension, as well as 55 genera with significantly different abundances between resistant hypertension and nonhypertension. Compared with the controlled hypertension group, the genera Rothia and Sharpea in resistant hypertension were more abundant. Compared with the nonhypertension group, the genera Escherichia-Shigella , Lactobacillus , Enterococcus were more abundant. Untargeted metabolomics provided distinctly different serum metabolic profiles for the three groups and identified a range of differential metabolites. These metabolites were mainly associated with the pathway of glycerophospholipid metabolism. Furthermore, correlation analysis provided evidence of new interactions between gut microbiota and metabolites in the resistant hypertension. CONCLUSION: In conclusion, our study provides a comprehensive understanding of the resistant hypertension gut microbiota and metabolites, suggesting that treatment resistance in resistant hypertension patients may be related to the gut microbiota and serum metabolites.