Effect of CTLA-4 Inhibition on Inflammation and Apoptosis After Spinal Cord Injury.

Spinal cord injury (SCI) encompasses various pathological processes, notably neuroinflammation and apoptosis, both of which play significant roles. CTLA-4, a well-known immune molecule that suppresses T cell-mediated immune responses, is a key area of research and a focal point for targeted therapy development in treating tumors and autoimmune disorders. Despite its prominence, the impact of CTLA-4 inhibition on inflammation and apoptosis subsequent to SCI remains unexplored. This study aimed to investigate the influence of CTLA-4 on SCI. A weight-drop technique was used to establish a rat model of SCI. To examine the safeguarding effect of CTLA-4 on the restoration of motor function in rats with SCI, the Basso-Beattie-Bresnahan (BBB) scale and inclined plane test were employed to assess locomotion. Neuronal degeneration and apoptosis were assessed using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) and Fluoro-Jade B labeling, respectively, and the activity of microglial cells was examined by immunofluorescence. To evaluate the impact of CTLA4 on SCI, the levels of inflammatory markers were measured. After treatment with the CTLA-4 inhibitor ipilimumab, the rats showed worse neurological impairment and more severe neuroinflammation after SCI. Furthermore, the combination therapy with ipilimumab and durvalumab after SCI had more pronounced effects than treatment with either inhibitor alone. These findings indicate that CTLA-4 contributes to neuroinflammation and apoptosis after SCI, presenting a promising new therapeutic target for this traumatic condition.

Exploring the capacities of ChatGPT: A comprehensive evaluation of its accuracy and repeatability in addressing helicobacter pylori-related queries.

BACKGROUND: Educational initiatives on Helicobacter pylori (H. pylori) constitute a highly effective approach for preventing its infection and establishing standardized protocols for its eradication. ChatGPT, a large language model, is a potentially patient-friendly online tool capable of providing health-related knowledge. This study aims to assess the accuracy and repeatability of ChatGPT in responding to questions related to H. pylori. MATERIALS AND METHODS: Twenty-one common questions about H. pylori were collected and categorized into four domains: basic knowledge, diagnosis, treatment, and prevention. ChatGPT was utilized to individually answer the aforementioned 21 questions. Its responses were independently assessed by two experts on H. pylori. Questions with divergent ratings were resolved by a third reviewer. Cohen's kappa coefficient was calculated to assess the consistency between the scores of the two reviewers. RESULTS: The responses of ChatGPT on H. pylori-related questions were generally satisfactory, with 61.9% marked as "completely correct" and 33.33% as "correct but inadequate." The repeatability of the responses of ChatGPT to H. pylori-related questions was 95.23%. Among the responses, those related to prevention (comprehensive: 75%) had the best response, followed by those on treatment (comprehensive: 66.7%), basic knowledge (comprehensive: 60%), and diagnosis (comprehensive: 50%). In the "treatment" domain, 16.6% of the ChatGPT responses were categorized as "mixed with correct or incorrect/outdated data." However, ChatGPT still lacks relevant knowledge regarding H. pylori resistance and the use of sensitive antibiotics. CONCLUSIONS: ChatGPT can provide correct answers to the majority of H. pylori-related queries. It exhibited good reproducibility and delivered responses that were easily comprehensible to patients. Further enhancement of real-time information updates and correction of inaccurate information will make ChatGPT an essential auxiliary tool for providing accurate H. pylori-related health information to patients.

Effectiveness and Safety of Tenofovir Alafenamide Fumarate in the Prevention of Perinatal Hepatitis B Transmission: A Meta-Analysis.

AIM: This study aimed to assess the effectiveness and safety of tenofovir alafenamide fumarate (TAF) in the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: We performed a meta-analysis of studies from the Cochrane Library, PubMed, ClinicalTrials.gov, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), China Medical Information Network, and Wanfang databases. The databases were searched from inception to January 7, 2023, for cohort studies and randomized controlled trials (RCTs) comparing the use of TAF antivirals to other antivirals during pregnancy. We combined the data by means of a random-effect DerSimonian-Laird model and risk ratios (RRs) or a random-effect inverse variance model and standardized mean differences (SMDs) to determine the influence on mothers and infants. Our primary outcomes were infant weight, height, head size, birth defects, and Apgar scores. Additionally, we assessed whether newborns tested positive for hepatitis B surface antigen (HBsAg) at birth and at six months of age. The secondary outcomes of our investigation were alterations in levels of HBV deoxyribonucleic acid (DNA), alanine aminotransferase (ALT), total bilirubin (TBIL), blood creatinine, and urine ß2-microglobulin (ß2-M) in mothers. RESULTS: An extensive literature search identified 216 relevant publications; three cohort studies and two RCTs were included in this study. A total of 341 mothers were treated with TAF, and 342 were treated with other antiviral agents. TAF was as effective as other antiviral medications at lowering HBV MTCT rates at birth and at 6 months of age and ALT, TBIL, and HBV DNA levels. Moreover, compared with other antiviral drugs, TAF did not affect infant weight, height, head size, Apgar scores, and birth defects or maternal blood creatinine or ß2-M levels. CONCLUSIONS: TAF antiviral therapy during pregnancy was found to be safe for both mothers and fetuses.

Helicobacter pylori Infection and Serum Pepsinogen Level With the Risk of Gastric Precancerous Conditions: A Cross-sectional Study of High-risk Gastric Cancer Population in China.

BACKGROUND AND AIM: Gastric precancerous conditions are generally considered to play an essential role in the gastric carcinogenesis cascade. This study identified risk factors of gastric precancerous conditions in a nationwide multicenter cross-sectional study. METHODS: Individuals who made their visit to 115 hospitals in China for gastric cancer screening were recruited. Lifestyle habits and personal information were collected through a series of questionnaires. Serum biomarker test (pepsinogen I, pepsinogen II, gastrin-17, and anti-Helicobacter pylori immunoglobulin G antibody) and endoscopy were then performed. Risk factors for gastric precancerous conditions were identified by univariate and multivariate analyses. RESULTS: Of 14,929 subjects eligible for analysis, 4477 (30.0%) developed gastric precancerous conditions and 405 (2.71%) developed gastric cancer. In multiple logistic regression, precancerous conditions were associated with advanced age [odds ratio (OR)=1.027; 95% confidence interval (Cl), 1.023-1.032; P<0.001], male gender (OR=1.303; 95% Cl, 1.188-1.429; P<0.001), H. pylori infection (OR=1.377; 95% Cl, 1.272-1.490, P<0.001), and smoking (OR=1.142; 95% Cl, 1.005-1.298, P=0.004), whereas they were inversely correlated with white meat intake (OR=0.731; 95% Cl, 0.673-0.794; P<0.001) and pepsinogen I level (30 to 70 subgroup OR=1.536; 95% Cl, 1.163-2.028; P=0.002; <30 subgroup OR=1.354; 95% Cl, 1.206-1.520; P<0.001). Also, the authors observed a statistically lower prevalence of reflux esophagitis (2.8% vs. 4.7%) and of gastric polyps (11.0% vs. 13.7%) in H. pylori-infected population. CONCLUSIONS: Patients with H. pylori have a 1.4-fold higher risk of having gastric precancerous conditions. Besides, precancerous conditions were associated with advanced age, male gender, H. pylori infection, and smoking in a large population. However, regular white meat intake and higher pepsinogen I level were associated with reduced risk of having precancerous lesions.

Synthesis of iridium-based nanocomposite with catalase activity for cancer phototherapy.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted attention due to its enhanced tumor therapy effect. This study proposes a novel nanoenzyme-based theranostic nanoplatform, IrO2@MSN@PDA-BSA(Ce6), for the combined PTT and PDT of tumors. IrO2 was prepared by a simple hydrolysis method and coated with a thin layer of mesoporous silica (MSN) to facilitate the physical adsorption of Chlorin e6 (Ce6). The PDA coating and IrO2 NPs of the nanoplatform demonstrated an improved photothermal conversion efficiency of 29.8% under NIR irradiation. Further, the Ce6 loading imparts materials with the ability to produce reactive oxygen species (ROS) under 660 nm NIR laser irradiation. It was also proved that the IrO2 NPs could catalyze the hydrogen peroxide (H2O2) in the tumor microenvironment (TME) to generate endogenous oxygen (O2), thereby enhancing the efficiency of PDT. The in vitro and in vivo experiments indicated that the nanocomposite was highly biocompatible and could produce a satisfactory tumor therapeutic effect. Thus, the findings of the present study demonstrate the viability of using theranostic nanoenzymes for translational medicine.

Development and validation of a prediction rule for estimating gastric cancer risk in the Chinese high-risk population: a nationwide multicentre study.

OBJECTIVE: To develop a gastric cancer (GC) risk prediction rule as an initial prescreening tool to identify individuals with a high risk prior to gastroscopy. DESIGN: This was a nationwide multicentre cross-sectional study. Individuals aged 40-80 years who went to hospitals for a GC screening gastroscopy were recruited. Serum pepsinogen (PG) I, PG II, gastrin-17 (G-17) and anti-Helicobacter pylori IgG antibody concentrations were tested prior to endoscopy. Eligible participants (n=14 929) were randomly assigned into the derivation and validation cohorts, with a ratio of 2:1. Risk factors for GC were identified by univariate and multivariate analyses and an optimal prediction rule was then settled. RESULTS: The novel GC risk prediction rule comprised seven variables (age, sex, PG I/II ratio, G-17 level, H. pylori infection, pickled food and fried food), with scores ranging from 0 to 25. The observed prevalence rates of GC in the derivation cohort at low-risk (≤11), medium-risk (12-16) or high-risk (17-25) group were 1.2%, 4.4% and 12.3%, respectively (p<0.001).When gastroscopy was used for individuals with medium risk and high risk, 70.8% of total GC cases and 70.3% of early GC cases were detected. While endoscopy requirements could be reduced by 66.7% according to the low-risk proportion. The prediction rule owns a good discrimination, with an area under curve of 0.76, or calibration (p<0.001). CONCLUSIONS: The developed and validated prediction rule showed good performance on identifying individuals at a higher risk in a Chinese high-risk population. Future studies are needed to validate its efficacy in a larger population.

Poor sleep and reduced quality of life were associated with symptom distress in patients receiving maintenance hemodialysis.

BACKGROUND: The quality of life in patients receiving chronic hemodialysis is compromised despite of the substantial achievements in treatments. Quality of life in hemodialysis patients have been shown to be associated with decreased survival and increased hospitalization. Therefore, it is necessary to incorporate the managements of symptoms and patient self-perceived well-being as measurements of effective treatments for these patients. METHODS: A survey of symptom distress, quality of sleep and quality of life was performed in 301 maintenance hemodialysis patients using Dialysis Symptom Index, Short Form-36, and Pittsburgh Quality of Sleep Index table. Patients were recruited from five hospitals in Guangdong area of China by convenience sampling. RESULTS: The prevalence of various symptoms in maintenance hemodialysis patients was between 23.3 and 80.4 %. These patients had compromised sleep and poor quality of life. Moreover, poor quality of sleep and impaired quality of life were associated with high symptom burden of these patients. CONCLUSION: The patients receiving chronic hemodialysis generally have heavy symptom distress, which could contribute to the disturbed sleep and impaired quality of life of these patients. Measurements of clinical outcomes for hemodialysis patients should include the management of symptoms and morbidity. The ultimate goal of treatments is to improve patient self-perceived quality of life.

Secondary radial nerve palsy after internal fixation of humeral shaft fractures.

OBJECTIVE AND BACKGROUND: There was no agreement with regard to the treatment for secondary radial nerve palsy. This study aimed to investigate at what point should exploration of the nerve be considered. METHODS: One hundred and twenty-five patients with fracture of the diaphyseal humerus treated with internal fixation at our hospital from February 2000 to February 2010 were reviewed retrospectively. There were six cases of secondary radial nerve palsy occurred soon after humeral internal fixation. No recognized intraoperative injuries to the radial nerve were recorded. Initial conservative observation was carried out in all six cases. RESULTS: Follow-up period averaged 28 months (range 24-37 months). In four cases, the beginning of electromyography recovery averaged 3.5 months (range 1-5 months), the meantime of onset of clinical recovery was 4.8 months (range 1-6 months), and the average time to full recovery of wrist and finger extension was 8.5 months (range 3-12 months). In other two cases, nerve exploration was made when there was no nerve recovery 3 months after internal fixation of humeral fracture at the request of patients. There were no macroscopic lesions of the radial nerve. At 2-year follow-up, extension of wrist and finger recovered to nearly normal in these two cases. CONCLUSIONS: For treatment for secondary radial nerve palsy, it seems reasonable to consider watchful waiting for about 5 months before nerve exploration if the decision as to the period of waiting was based on the clinical recovery onset time.

Risk factors for gastrointestinal bleeding in patients with intracerebral hemorrhage: A propensity score matching analysis.

BACKGROUND: Gastrointestinal bleeding (GIB) is a common complication of intracerebral hemorrhage (ICH). Rate pressure product (RPP) is an objective hemodynamic index that is closely related to the prognosis of cardia-cerebrovascular disease. The purpose of this study was to investigate the relationship between RPP and GIB in ICH patients. METHODS: We retrospectively analyzed data from ICH patients admitted to the neurosurgery department of Nanchang University affiliated with Ganzhou Hospital from January 2019 to December 2021. The patients were divided into a GIB group and a non-GIB group according to whether they had GIB. Propensity score matching was used to match between the two groups. Univariate analysis was used to select factors affecting GIB, and multivariate conditional logistic regression was used to analyze the independent factors associated with GIB. RESULTS: There were 1232 patients included in the study, including 182 in the GIB group and 1050 in the non-GIB group, and 182 pairs of patients were successfully matched through propensity score matching. The univariate analysis showed that high RPP, low Glasgow coma score (GCS), fibrinogen, D-dimer and PPIs were factors associated with GIB. Multivariate conditional logistic regression showed that high RPP, low GCS and urokinase were independent risk factors for GIB, and PPIs was a protective factor for GIB. CONCLUSIONS: High RPP, low GCS and urokinase were independent risk factors for GIB, and PPIs was a protective factor for GIB. Patients with a high risk of developing GIB should be monitored closely. Nevertheless, multicenter prospective studies with more patients are needed to further validate the results.

An antibiotic-free platform for eliminating persistent Helicobacter pylori infection without disrupting gut microbiota.

Helicobacter pylori (H. pylori) infection remains the leading cause of gastric adenocarcinoma, and its eradication primarily relies on the prolonged and intensive use of two antibiotics. However, antibiotic resistance has become a compelling health issue, leading to H. pylori eradication treatment failure worldwide. Additionally, the powerlessness of antibiotics against biofilms, as well as intracellular H. pylori and the long-term damage of antibiotics to the intestinal microbiota, have also created an urgent demand for antibiotic-free approaches. Herein, we describe an antibiotic-free, multifunctional copper-organic framework (HKUST-1) platform encased in a lipid layer comprising phosphatidic acid (PA), rhamnolipid (RHL), and cholesterol (CHOL), enveloped in chitosan (CS), and loaded in an ascorbyl palmitate (AP) hydrogel: AP@CS@Lip@HKUST-1. This platform targets inflammatory sites where H. pylori aggregates through electrostatic attraction. Then, hydrolysis by matrix metalloproteinases (MMPs) releases CS-encased nanoparticles, disrupting bacterial urease activity and membrane integrity. Additionally, RHL disperses biofilms, while PA promotes lysosomal acidification and activates host autophagy, enabling clearance of intracellular H. pylori. Furthermore, AP@CS@Lip@HKUST-1 alleviates inflammation and enhances mucosal repair through delayed Cu2+ release while preserving the intestinal microbiota. Collectively, this platform presents an advanced therapeutic strategy for eradicating persistent H. pylori infection without inducing drug resistance.

Borate bonds-containing pH-responsive chitosan hydrogel for postoperative tumor recurrence and wound infection prevention.

Chitosan has been widely used in biomedical fields due to its good antibacterial properties, excellent biocompatibility, and biodegradability. In this study, a pH-responsive and self-healing hydrogel was synthesized from 3-carboxyphenylboronic acid grafted with chitosan (CS-BA) and polyvinyl alcohol (PVA). The dynamic boronic ester bonds and intermolecular hydrogen bonds are responsible for the hydrogel formation. By changing the mass ratio of CS-BA and PVA, the tensile stress and compressive stress of hydrogel can controlled in the range of 0.61 kPa - 0.74 kPa and 295.28 kPa - 1108.1 kPa, respectively. After doping with tannic acid (TA)/iron nanocomplex (TAFe), the hydrogel successful killed tumor cells through the near infrared laser-induced photothermal conversion and the TAFe-triggered reactive oxygen species generation. Moreover, the photothermal conversion of the hydrogel and the antibacterial effect of CS and TA give the hydrogel a good antibacterial effect. The CS-BA/PVA/TAFe hydrogel exhibit good in vivo and in vitro anti-tumor recurrence and antibacterial ability, and therefore has the potential to be used as a powerful tool for the prevention of local tumor recurrence and bacterial infection after surgery.

The status quo of short videos as a health information source of Helicobacter pylori: a cross-sectional study.

Background: Health education about Helicobacter pylori (H. pylori) is one of the most effective methods to prevent H. pylori infection and standardize H. pylori eradication treatment. Short videos enable people to absorb and remember information more easily and are an important source of health education. This study aimed to assess the information quality of H. pylori-related videos on Chinese short video-sharing platforms. Methods: A total of 242 H. pylori-related videos from three Chinese short video-sharing platforms with the most users, TikTok, Bilibili, and Kwai, were retrieved. The Global Quality Score (GQS) and the modified DISCERN tool were used to assess the quality and content of videos, respectively. Additionally, comparative analyzes of videos based on different sources and common H. pylori issues were also conducted. Results: The median GQS score and DISCERN score was 2 for H. pylori-related videos analyzed in this study. Non-gastroenterologists posted the most H. pylori-related videos (136/242, 56.2%). Videos from gastroenterologists (51/242, 21.0%) had the highest GQS and DISCERN scores, with a median of 3. Few videos had content on family-based H. pylori infection control and management (5.8%), whether all H. pylori-positive patients need to undergo eradication treatment (27.7%), and the adverse effects of H. pylori eradication therapy (16.1%). Conclusion: Generally, the content and quality of the information in H. pylori-related videos were unsatisfactory, and the quality of the video correlated with the source of the video. Videos from gastroenterologists provided more correct guidance with higher-quality information on the prevention and treatment of H. pylori infection.

Silencing lncRNA GAS5 alleviates apoptosis and fibrosis in diabetic cardiomyopathy by targeting miR-26a/b-5p.

BACKGROUND: LncRNA GAS5 is associated with high glucose-induced cardiomyocyte injury, but its role in diabetic cardiomyopathy (DCM) remains unclear. METHODS: Mice were administered with streptozotocin to construct the diabetic model (DM). Primary mouse cardiomyocytes were isolated and treated with 30 mmol/L high glucose to mimic the diabetic condition in vitro. GAS5 expression was detected by quantitative reverse transcription polymerase chain reaction. The relationship between GAS5 and miR-26a/b-5p was determined by bioinformatic prediction, luciferase reporter assay and RNA immunoprecipitation assay. The cardiac function of diabetic mice was evaluated by two-dimensional echocardiography. RESULTS: GAS5 was significantly upregulated in diabetic cardiomyopathy both in vitro and in vivo. GAS5 knockdown and miR-26a/b-5p overexpression not only effectively attenuated myocardial fibrosis of diabetic mice in vivo but also inhibited high glucose-induced cardiomyocyte injury in vitro. miR-26a/b-5p was identified as a target of GAS5. GAS5 knockdown efficiently attenuated myocardial fibrosis and high glucose-induced cardiomyocyte injury through negatively regulating miR-26a/b-p. CONCLUSION: Our study showed that GAS5 promotes DCM progression by regulating miR-26a/b-5p, suggesting that GAS5 might be a potential therapeutic target for DCM.

Oxidation triggered formation of polydopamine-modified carboxymethyl cellulose hydrogel for anti-recurrence of tumor.

In this research, a hydrogel that combined the tumor photodynamic therapy (PDT) and photothermal therapy (PTT) ability was designed, using dopamine-modified sodium carboxymethyl cellulose (CMC-DA) as the matrix and Chlorin e6 (Ce6) as the photosensitizer. The gel formation was initiated by adding the oxidizing agent sodium periodate (NaIO4) to the CMC-DA solution, during which the dopamine was simultaneously oxidized to polydopamine (PDA) and NaIO4 was reduced to sodium iodide (NaI). The formed NaI was encapsulated in the hydrogel and endowed the hydrogel with computerized tomography (CT) imaging ability to monitor the hydrogel degradation and the tumor therapy process. Moreover, the photosensitizer Ce6 can be loaded by the gel system via directly soaking the hydrogel in the Ce6 solution. Under the near-infrared light irradiation, Ce6 can produce cytotoxic reactive oxygen species and the PDA can produce heat to trigger the tumor PDT and PTT respectively to eradicate the tumor recurrence. In general, the designed hydrogel is biocompatible and biodegradable, has a good photothermal conversion, drug loading and CT imaging ability, which laid the foundation for the rational design of biodegradable hydrogels for multifunctional applications.

Clinical Analysis of Patients with Ipsilateral Coexistence of Hemifacial Spasm and Trigeminal Neuralgia.

OBJECTIVE: We sought to analyze the clinical data of patients with ipsilateral coexistence of hemifacial spasm (HFS) and trigeminal neuralgia (TN) and their treatment by microvascular decompression. METHODS: We retrospectively analyzed the clinical data, imaging examination, offending vessels, surgical methods, and efficacy in 40 patients with ipsilateral coexistence of HFS and TN from January 2009 to January 2018. The posterior cranial fossa was measured using ITK-SNAP 3.0, which counted the cerebrospinal fluid volume on the basis of the region of interest. Preoperative and postoperative status was based on visual analog scale pain scores and Cohen evaluation scale. RESULTS: Preoperative visual analog scale pain scores were 10 for 30 patients, 9 for 8 patients, and 8 for 2 patients. Preoperative Cohen scores were 4 and 3 for 14 and 26 patients, respectively. A big looped vertebral basilar artery (VBA) was identified in the operative field in 18 patients (45%), which was regarded as the direct offending vessel. Postoperative the Barrow Neurological Institute scores were excellent (T = 2) for 30 patients (75%). The HFS completely disappeared in 28 patients (70%). In the follow-up period (12-110 months), no recurrence or any dysfunction of cranial nerves was found. When patients were grouped as per the responsible artery, the mean size of the posterior cranial fossa was significantly lower in the patients with VBA involved, compared with the patients in the noninvolved VBA group. In the VBA-involved group, HFS symptoms first appeared in all 18 patients, while in the non-VBA-involved group, HFS symptoms first appeared in 6/22 patients (P < 0.05). The preoperative Cohen score of the 4 patients in the VBA involved group, as well as that of 22 patients in the non-VBA-involved group, was 3 (P < 0.05). CONCLUSIONS: Our study suggests that patients with ipsilateral coexistence of HFS and TN usually have a narrower and smaller posterior fossa and have a large looped VBA as the responsible artery. In addition, patients with VBA involvement often develop HFS symptoms first and are more severe than those with non-vertebral artery involvement. Microvascular decompression is effective for patients with ipsilateral coexistence of HFS and TN.

Paeoniflorin Inhibits Hepatocyte Growth Factor- (HGF-) Induced Migration and Invasion and Actin Rearrangement via Suppression of c-Met-Mediated RhoA/ROCK Signaling in Glioblastoma.

Paeoniflorin (PF), as one of the important valid natural compounds of the total glucosides of peony, has displayed a potential effect in cancer prevention and treatment. Aggressive migration and invasion, as an important process, can contribute to tumor progression through infiltrating the surround normal tissue. Actin cytoskeleton rearrangement plays a key role in cells migration and invasion, involving multiple signal pathways. HGF/c-Met signal, as an important couple of oncoprotein, has been demonstrated to regulate actin cytoskeleton rearrangement. In our study, we aim to explore whether paeoniflorin can inhibit migration and invasion and actin cytoskeleton rearrangement via regulation of HGF/c-Met/RhoA/ROCK signal. Various approaches were applied to demonstrate the mechanism of paeoniflorin-mediated anticancer effect, including cell wound healing assay, invasion assay, immunofluorescence staining and transfection, and western blotting. We observed that paeoniflorin inhibited HGF-induced migration and invasion and actin cytoskeleton rearrangement in glioblastoma cells. Furthermore, the inhibition of HGF-induced migration and invasion and actin cytoskeleton rearrangement involved c-Met-mediated RhoA/ROCK signaling in glioblastoma. Thus, our study proved that paeoniflorin could inhibit migration and invasion and actin cytoskeleton rearrangement through inhibition of HGF/c-Met/RhoA/ROCK signaling in glioblastoma, suggesting that paeoniflorin might be a candidate compound to treat glioblastoma.

Effect of Blood Pump Flow and Arteriovenous Fistula Blood Flow on the Blood Pressure and Cardiac Function in Patients Undergoing Maintenance Hemodialysis.

The effect of blood pump flow rate on the cardiac functions of hemodialysis patients with arteriovenous fistula (AVF) is largely unknown. This study aimed to investigate if blood pump flow rate (Qb) and AVF access flow rate (Qa) can affect the cardiac function of Chinese hemodialysis patients. A total of 72 patients undergoing AVF hemodialysis were included from March 2010 to June 2014 and dichotomized into the high- and low-flow groups using the medians of Qb (220 mL/min) and Qa (1000 mL/min) as the cutoffs. The cardiac function parameters were measured by ultrasound dilution technique within the first (t + 30) and the last (t - 30) 30 min of dialysis. At t + 30, Qb-high group had significantly higher systolic blood pressure (SBP) and mean arterial pressure (MAP) than Qb-low group. At t - 30, Qb-high group had higher SBP, diastolic blood pressure (DBP), and MAP than Qb-low group. Qa-high group had higher SBP, MAP, cardiac output (CO), cardiac index (CI), central blood volume (CBV), and lower peripheral resistance than Qa-low group. Multiple linear regression showed that at t - 30, Qb was positively correlated with SBP and MAP. Qa was positively correlated with CO, CI, CBV, and PR but negatively correlated with heart rate. Although Qb > 220 mL/min and Qa >1000 mL/min would elevate some parameters, the means of SBP, DBP, MAP remain within the normal range, indicating that appropriate increase in blood pump flow rate has little effect on the cardiac function of hemodialysis patients.

Linderane protects pancreatic ß cells from streptozotocin (STZ)-induced oxidative damage.

AIMS: Linderane, an important bioactive compound in Linderae, improved glucose and lipid metabolism in ob/ob mice. However, the effect of linderane on streptozotocin (STZ)-induced oxidative damage in INS-1 cells remains unclear. MAIN METHODS: INS-1 cells were pre-treated with different doses of linderane for 2 h and then treated with 3 mM STZ for 12 h. Cell viability was determined by MTT assay. Cell apoptosis was detected using an Annexin V-FITC Apoptosis Detection Kit. The level of intracellular ROS was determined using dichlorofluorescein-diacetate (DCFH-DA). The activities of insulin secretion, SOD, catalase (CAT) and GPx were measured using ELISA kits. The expression levels of bax, bcl-2, p38, p-p38, nuclear Nrf2 and HO-1 were measured using western blot. KEY FINDINGS: The results showed that STZ-caused inhibitory effects on cell viability and insulin secretion were mitigated by linderane. Furthermore, linderane inhibited apoptosis and oxidative stress in STZ-induced INS-1 cells. Finally, linderane suppressed the activation of p38 MAPK pathway, as well as enhanced the activation of Nrf2 pathway in STZ-induced INS-1 cells. Activation of p38 MAPK pathway or inhibition of Nrf2 significantly reversed the protective effects of linderane against STZ-induced ROS production and cell apoptosis. SIGNIFICANCE: The protective effects of linderane on STZ-induced INS-1 cells might be attributed to the inhibition of p38 MAPK and activation of Nrf2 pathway.

The Reperfusion Delay in Finger Replantation by Vein Arterialization.

BACKGROUND: Extensive arterial damage of arteries that were too small in diameter precluded finger replantation. Venous arterialization in which arterial blood inflows through a proximal arterial-to-distal venous anastomosis, allows performing replantation that was previously considered as impossible and has resulted in a successful outcome. The aim is to introduce the distinctive phenomenon of the reperfusion delay in finger replantation by vein arterialization and to analyze its clinical significance. MATERIALS AND METHODS: In 2012-2015, vein arterialization was involved in 18 digits of 13 patients. The duration that the replants restore reperfusion following the release of tourniquet, defined as revascularization time, was recorded. RESULTS: The results showed that revascularization time ranged from 0 to 540 min, with an average of 54.5 min. The revascularization time was shorter than 20 min in 8 digits, between 20 and 120 min in 9 digits, and 540 min in one digit. CONCLUSION: The study findings have shown that reperfusion delay is usual during vein arterialization. Failing to understand it would result in the premature endings of the procedure. It is worth maintaining further observation, thus rescue otherwise possibly abandoned replantation.

Fe3+-Induced Synchronous Formation of Composite Hydrogels for Effective Synergistic Tumor Therapy in NIR-I/II Biowindows.

Alginate-Ca2+ hydrogel has been used to immobilize photothermal materials as well as chemotherapy drugs at lesion sites to prevent their entry into the bloodstream. However, the alginate-Ca2+ gelation mechanism may result in hardening of the blood vessels because of Ca2+ migration to the lesion site. In this study, a unique and facile one-pot formation of chemotherapeutic (doxorubicin, DOX) and polypyrrole-containing alginate hydrogel was designed by introducing Fe3+, which can synchronously induce the polymerization of pyrrole and gelatinization of alginate, into the DOX/pyrrole/alginate solution. The formed composite hydrogel was endowed with superior photothermal conversion properties in both the NIR-I (650-950 nm) and NIR-II (1000-1700 nm) biowindows and light-to-heat conversion efficiency higher than 50%, which enabled effective tumor hyperthermia treatment. Besides, near-infrared (NIR) irradiation could be used as a remote controller to trigger the DOX-release because of the heat generation, thus achieving continuous and on-demand tumor chemotherapy. The composite polymer hydrogels exhibited favorable hemo-, cyto-, and histocompatibility, as well as simple and cost-effective preparation and good clinical prospects.