Supramolecular Hydrogel Dexamethasone-Diclofenac for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) severely affects patients' quality of life and is commonly treated with glucocorticosteroids injections, like dexamethasone, which may have side effects. This study aimed to create a novel low dose of twin-drug hydrogel containing dexamethasone and diclofenac and explore its potential as a drug delivery system for an enhanced anti-inflammatory effect. Its characterization involved rheology, transmission electron microscope (TEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Furthermore, the hydrogel demonstrated thixotropic properties. The hydrogel exhibited no cytotoxicity against RAW 264.7 macrophages. Furthermore, the hydrogel demonstrated a significant anti-inflammatory efficacy by effectively downregulating the levels of NO, TNF-α, and IL-6 in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The co-delivery approach, when intra-articularly injected in adjuvant-induced arthritis (AIA) rats, significantly alleviated chronic inflammation leading to reduced synovitis, delayed bone erosion onset, and the downregulation of inflammatory cytokines. The biocompatibility and adverse effect evaluation indicated good biological safety. Furthermore, the hydrogel demonstrated efficacy in reducing NF-κB nuclear translocation in LPS-induced RAW 264.7 macrophages and inhibited p-NF-kB, COX-2, and iNOS expression both in RAW 264.7 macrophages and the joints of AIA rats. In conclusion, the findings indicate that the hydrogel possesses potent anti-inflammatory activity, which effectively addresses the limitations associated with free forms. It presents a promising therapeutic strategy for the management of RA.

A p21-ATD mouse model for monitoring and eliminating senescent cells and its application in liver regeneration post injury.

Cellular senescence associates with pathological aging and tissue dysfunctions. Studies utilizing mouse models for cell lineage tracings have emphasized the importance of senescence heterogeneity in different organs and cell types. Here, we constructed a p21- (Akaluc - tdTomato - Diphtheria Toxin Receptor [DTR]) (ATD) mouse model to specifically study the undefined mechanism for p21-expressing senescent cells in the aged and liver injury animals. The successful expressions of these genes enabled in vitro flow cytometric sorting, in vivo tracing, and elimination of p21-expressing senescent cells. During the natural aging process, p21-expressing cells were found in various tissues of p21-ATD mice. Eliminating p21-expressing cells in the aged p21-ATD mice recovered their multiple biological functions. p21-ATD/Fah-/- mice, bred from p21-ATD mice and fumarylacetoacetate hydrolase (Fah)-/- mice of liver injury, showed that the majority of their senescent hepatocytes were the phenotype of p21+ rather than p16+. Furthermore, eliminating the p21-expressing hepatocytes significantly promoted the engraftment of grafted hepatocytes and facilitated liver repopulation, resulting in significant recovery from liver injury. Our p21-ATD mouse model serves as an optimal model for studying the pattern and function of p21-expressing senescent cells under the physical and pathological conditions during aging.

Plumbagin Regulates Snail to Inhibit Hepatocellular Carcinoma Epithelial-Mesenchymal Transition in vivo and in vitro.

Background/Aims: Plumbagin (PL) has been shown to effe ctively inhibit autophagy, suppressing invasion and migration of hepatocellular carcinoma (HCC) cells. However, the specific mechanism remains unclear. This study aimed to investigate the effect of PL on tumor growth factor (TGF)-ß-induced epithelial-mesenchymal transition (EMT) in HCC. Methods: Huh-7 cells were cultured, and in vivo models of EMT and HCC-associated lung metastasis were developed through tail vein and in situ injections of tumor cells. In vivo imaging and hematoxylin and eosin staining were used to evaluate HCC modeling and lung metastasis. After PL intervention, the expression levels of Snail, vimentin, E-cadherin, and N-cadherin in the liver were evaluated through immunohistochemistry and Western blot. An in vitro TGF-ß-induced cell EMT model was used to detect Snail, vimentin, E-cadherin, and N-cadherin mRNA levels through a polymerase chain reaction. Their protein levels were detected by immunofluorescence staining and Western blot. Results: In vivo experiments demonstrated that PL significantly reduced the expression of Snail, vimentin, and N-cadherin, while increasing the expression of E-cadherin at the protein levels, effectively inhibiting HCC and lung metastasis. In vitro experiments confirmed that PL up-regulated epithelial cell markers, down-regulated mesenchymal cell markers, and inhibited EMT levels in HCC cells. Conclusion: PL inhibits Snail expression, up-regulates E-cadherin expression, and down-regulates N-cadherin and vimentin expression, preventing EMT in HCC cells and reducing lung metastasis.

Enhancing Electron/Ion Transport in SnO2 Quantum Dots Decorated Polyaniline/Graphene Hybrid Fibers for Wearable Supercapacitors with High Energy Density.

Fiber-based supercapacitors are the potential power sources in the field of wearable electronics and energy storage textiles due to their unique advantages of electrochemical properties and mechanical flexibility, but achieving high energy density and practical energy supply still presents some challenges. In this study, we reported an approach of microfluidic assisted wet-spinning to fabricate SnO2 quantum dots encapsulated polyaniline/graphene hybrid fibers (SnO2 QDs@PGF) by incorporating uniformly polyaniline into graphene fibers and covalently bridging SnO2 quantum dots. The assembled SnO2 QDs@PGF fiber-typed flexible supercapacitors exhibit an ultralarge specific areal capacitance of 925 mF cm-2 in PVA/H2SO4, superior rate capabilities, and capacitance retention of 88% after 8000 cycles, indicating that the SnO2 QDs@PGF possess near-ideal capacitance properties, efficient ion transfer rate, and good cycling stability. In the EMITFSI/PVDF-HFP electrolyte system, SnO2 QDs@PGF realize a wide operating potential window of 2.5 V, a specific areal capacitance of 678.4 mF cm-2, and an energy density of 147.2 µWh cm-2 at 500 µW cm-2, which can be utilized to power an alarm clock, an electronic timer, and a desk lamp with a requirement of a 3 V battery. The exceptional performance of the SnO2 QDs@PGF can be attributed to the molecular-level homogeneous composite of granular polyaniline and graphene nanosheets and the interfacial C-O-Sn covalent coupling strategy employed between SnO2 QDs and PGF. These avenues not only effectively prevent the undesirable restacking of graphene nanosheets but also increase the interlayer electroactive sites, ordered ion diffusion channels, and strong interfacial charge transfer.

A Mouse Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Procedure Aided by Microscopy.

Hepatectomy is widely regarded as the primary treatment for hepatic malignancies; yet, postoperative liver failure remains a major cause of perioperative mortality, severely impacting patient outcomes. In a robust hepatic environment, the future liver remnant (FLR) must exceed 25%, and in cases of cirrhosis, this requirement increases to over 40%. The inadequacy of FLR is currently a major obstacle in the progression of hepatic surgery. Traditional methods to enhance FLR hypertrophy mainly focus on portal vein embolization (PVE), but its effectiveness is considerably limited. In recent years, there have been numerous reports on a novel biphasic hepatectomy method involving hepatic partitioning and portal vein ligation, known as associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). ALPPS surpasses PVE in efficiently and considerably inducing FLR hypertrophy. However, the detailed mechanisms driving ALPPS-facilitated hepatic regeneration are not fully understood. Thus, replicating ALPPS in animal models is crucial to thoroughly investigate the molecular mechanisms of hepatic regeneration, offering valuable theoretical and practical insights.

Inhaled delivery of cetuximab-conjugated immunoliposomes loaded with afatinib: A promising strategy for enhanced non-small cell lung cancer treatment.

Afatinib (AT), an FDA-approved aniline-quinazoline derivative, is a first-line treatment for metastatic non-small cell lung cancer (NSCLC). Combining it with cetuximab (CX), a chimeric human-murine derivative immunoglobulin-G1 monoclonal antibody (mAb) targeting the extracellular domain of epidermal growth factor receptor (EGFR), has shown significant improvements in median progression-free survival. Previously, we developed cetuximab-conjugated immunoliposomes loaded with afatinib (AT-MLP) and demonstrated their efficacy against NSCLC cells (A549 and H1975). In this study, we aimed to explore the potential of pulmonary delivery to mitigate adverse effects associated with oral administration and intravenous injection. We formulated AT-MLP dry powders (AT-MLP-DPI) via freeze drying using tert-butanol and mannitol as cryoprotectants in the hydration medium. The physicochemical and aerodynamic properties of dry powders were well analyzed firstly. In vitro cellular uptake and cytotoxicity study revealed concentration- and time-dependent cellular uptake behavior and antitumor efficacy of AT-MLP-DPI, while Transwell assay demonstrated the superior inhibitory effects on NSCLC cell invasion and migration. Furthermore, in vivo pharmacokinetic study showed that pulmonary delivery of AT-MLP-DPI significantly increased bioavailability, prolonged blood circulation time, and exhibited higher lung concentrations compared to alternative administration routes and formulations. The in vivo antitumor efficacy study carried on tumor-bearing nude mice indicated that inhaled AT-MLP-DPI effectively suppressed lung tumor growth.

An Interpretable Screening Approach Derived Through XGBoost Regression for the Discovery of Hypolipidemic Contributors in Chinese Hawthorn Leaf and its Counterfeit Malus Doumeri Leaf.

The active ingredient group is a prominent feature reflecting the inherent characteristics of plant-based functional foods. Chinese hawthorn leaf (CHL), a tea substitute possessing intrinsic nutritional properties in anti-hyperlipidemia, was first found to be adulterated with Malus doumeri leaf (MDL) owing to similar commercial labels. In this context, the above-mentioned two contrasting species were explored through phytochemical profiling and activity assessment. The amelioration effect of CHL on free fatty acids-elicited lipid deposition in HepG2 cells was significantly better than that of MDL. Molecular networking-based metabolic profiles identified 68 and 67 components in CHL and MDL, with 33 shared components. Extreme gradient boosting (XGBoost) algorithm with outstanding performance was selected to screen candidate components contributing to hypolipidemic activity, and the output was later interpreted by Shapley additive explanations (SHAP) method. Twelve and eight components were separately screened as hyperlipidemic inhibitors in CHL and MDL, while only four constituents were shared. The bioactivity evaluation of selected ingredients and combinations further confirmed their anti-hyperlipidemia capacity. These findings emphasized the feasibility of filtering bioactivity-related compounds using interpretable machine learning approaches and illustrated that related species may contain different hypolipidemic contributors, even if shared constituents existed.

Single-Plane Retroperitoneoscopic Adrenalectomy Guided by Indocyanine Green Dye: An Optimized Step.

Background: The objective of this study was to explore the perioperative outcomes of single-plane posterior retroperitoneoscopic adrenalectomy (SPRA) guided by indocyanine green dye (ICG) fluorescence imaging. Methods: A retrospective analysis of patients who underwent SPRA from April to September 2023 in our center was conducted. Patients were divided into the ICG group and the non-ICG group, based on whether they received intraoperative ICG fluorescence guided or not. Baseline and perioperative data were recorded and analyzed by R software (R 4.3.1). Results: A total of 23 patients were enrolled in the study, with 12 in the ICG group and 11 in the non-ICG group. The demographics including age, gender, body mass index, or American Society of Anesthesiologists classification showed no significant differences between groups. There were obvious advantages in shortening adrenal gland localization time and total operative time, as well as reducing estimated blood loss in the ICG group compared with the non-ICG group (5.58 ± 0.36 minutes vs 7.55 ± 0.62 minutes, p < 0.001; 27.50 ± 5.46 minutes vs 45.00 ± 10.99 minutes, p < 0.001; 22.91 ± 7.57 mL vs 54.54 ± 18.90 mL, p < 0.001; respectively). Furthermore, patients in the ICG group exhibited significantly lower visual analog pain scale scores at 24 hours postoperatively and at discharge (p = 0.001 and p = 0.006, respectively). The oral intake intervals, hospital stays, and perioperative complications were comparable between groups. Conclusions: ICG-guided SPRA could be a safe and effective procedure for patients with adrenal tumors. This technique improves the accuracy and efficacy of adrenal gland localization and has shown benefits in perioperative outcomes. The use of ICG fluorescence guidance represents a promising clinical application.

Tumor necrosis factor mediates the impact of PM2.5 on bone mineral density: Inflammatory proteome Mendelian randomization and colocalization analyses.

To assess the causal effect of particulate matter 2.5 (PM2.5) on human bone mineral density (BMD) and to explore the possible mechanism and proportion mediated by inflammation-related protein. The genetic correlation between PM2.5 and BMD was assessed using the Linkage Disequilibrium Score (LDSC), and the causal effect between PM2.5 and BMD was assessed by two-sample Mendelian randomization (TSMR). A 2-step Mendelian randomization (MR) approach was employed to evaluate the potential role of inflammation-associated protein as the mediator in the causal association between PM2.5 and BMD. The multivariate Mendelian randomization (MVMR) study was designed to perform mediation analyses, exclude possible confounders and calculate the proportion of mediation. Subsequently, we used Bayesian colocalization analysis to consolidate the MR results. Finally, using drug-target MR design, we evaluated the potential repurposing of tumor necrosis factor (TNF) inhibitors for the treatment of osteoporosis (OP). The results of the analyses show that BMD is negatively influenced by PM2.5 (Inverse variance weighted [IVW] beta [ß] = -0.288, 95% confidence interval [CI]: -0.534 - -0.042, P < 0.05). PM2.5 has a positive causal association with TNF (IVW ß = 1.564, 95% CI: 0.155 - 2.973, P < 0.05) and a negative causal association with protachykinin-1 (TAC-1) (IVW ß = -1.654, 95% CI: -3.063 - -0.244, P < 0.05). TNF has a negative causal association with BMD (Wald ratio ß = -0.082, 95% CI: -0.165 - 0.000, P < 0.05) and TAC-1 has a positive causal association with BMD (IVW ß = 0.042, 95% CI: 0.007 - 0.077, P < 0.05). After adjusting TNF and TAC-1, PM2.5 has no causal association with BMD (IVW ß = -0.200, 95% CI: -0.579 - 0.179, P > 0.05). After adjusting PM2.5 and TAC-1, there was still a negative causal association between TNF and BMD (IVW ß = -0.089, 95% CI: -0.166 - -0.012, P < 0.05). In the final drug-target MR study, the protective effect of TNF/TNF receptor 1 (TNFR1) inhibition on BMD was observed. For every 10% decrease of circulating C-reactive protein (CRP) achieved by TNF/TNF receptor 1 (TNFR1) blockade, ß was 0.540 (95% CI: 0.040-1.040) for BMD. We found a negative causal association between PM2.5 and BMD and that causal association was mediated by TNF. The results of drug-target MR do support TNFR1 as a promising target for OP prevention among the general population.

Bladder neck contracture following transurethral surgery of prostate: a retrospective single-center study.

PURPOSE: Bladder neck contracture (BNC) is a rare but intolerant complication after transurethral surgery of prostate. The present study aims to investigate the incidence and risk factors of BNC in patients diagnosed benign prostate hyperplasia (BPH) and following transurethral resection or enucleation of the prostate (TURP/TUEP). METHODS: This retrospective study included 1008 BPH individuals who underwent transurethral surgery of the prostate between January 2017 and January 2022. Patients' demographics, medical comorbidities, urologic characteristics, perioperative parameters, and the presence of BNC were documented. Univariate and multivariate analyses were conducted to identify the risk factors. RESULTS: A total of 2% (20/1008) BPH patients developed BNC postoperatively and the median occurring time was 5.8 months. Particularly, the incidences of BNC were 4.7% and 1.3% in patients underwent Bipolar-TURP and TUEP respectively. Preoperative urinary tract infection (UTI), elevated PSA, smaller prostate volume (PV), bladder diverticulum (BD), and B-TURP were significantly associated with BNC in the univariate analysis. Further multivariate logistic regression demonstrated preoperative UTI (OR 4.04, 95% CI 2.25 to 17.42, p < 0.001), BD (OR 7.40, 95% CI 1.83 to 31.66, p < 0.001), and B-TURP (OR 3.97, 95% CI 1.55 to 10.18, p = 0.004) as independent risk factors. All BNC patients were treated with transurethral incision of the bladder neck (TUIBN) combined with local multisite injection of betamethasone. During a median follow-up of 35.8 months, 35% (7/20) of BNC patients recurred at a median time of 1.8 months. CONCLUSION: BNC was a low-frequency complication following transurethral surgery of prostate. Preoperative UTI, BD, and B-TURP were likely independent risk factors of BNC. TUIBN combined with local multisite injection of betamethasone may be promising choice for BNC treatment.

Impact of innovative immunization strategy on PCV13 vaccination coverage among children under 5 years in Weifang city, China: A retrospective study.

BACKGROUND: Pneumococcal Diseases (PDs) remains a serious public health problem around the world and in China. Pneumococcal vaccination is the most cost-effective measure to prevent PDs. In 2021, the government of Weifang City, Shandong Province, China introduced a free dose of domestic 13-valent Pneumococcal Conjugate Vaccine (PCV 13) to vaccinate registered children aged 6 months-2 years. This study aimed to evaluate the vaccination rate of PCV13 in children aged under 5 years before and after the vaccination program to provide evidences for further improving the prevention and control strategy for PDs. METHODS: We collected data from the children's vaccination information management system in Weifang City and analyzed the PCV13 vaccination coverage and characteristics in all vaccination clinics of Weifang City for children aged under 5 years. We compared the differences in vaccination rates by gender, birth year, manufacturer, and county before and after innovative immunization strategy. RESULTS: Among the included 593,784 children aged under 5 years, the PCV13 vaccination rate in Weifang was generally low before the innovative immunization strategy. Urban children had a higher PCV13 coverage than rural children (P < 0.001), and parents tended to vaccinate their children with imported PCV13.The full vaccination rate for domestic and imported PCV13 was 0.67 % and 1.70 %, respectively. After the vaccination program, the PCV13 coverage of children increased significantly in all counties within Weifang City (P < 0.001), especially for children above 12 months of age. Most parents preferred to vaccinate their children with domestic PCV13, and the full vaccination rate of domestic and imported PCV13 was 6.59 % and 0.16 %, respectively. CONCLUSIONS: The vaccination rate of PCV13 in children is still much lower than the global average, posting a severe health challenge that needs to be addressed thoroughly. To improve the prevention and control strategy for PDs, it is recommended to continue to explore other relevant incentives based on the innovative immunization strategy. Furthermore, it is also recommended that China should incorporate PCV13 into the National Immunization Programs (NIP) as soon as possible.

Involvement of CD44 and MAPK14-mediated ferroptosis in hemorrhagic shock.

To elucidate the induction of ferroptotic pathways and the transcriptional modulation of pivotal genes in the context of hemorrhagic shock. The R software was used to analyze the GSE64711 dataset, isolating genes relevant to ferroptosis. Enrichment analyses and protein interaction networks were assembled. Using WGCNA hub genes were identified and intersected with ferroptosis-related genes, highlighting hub genes CD44 and MAPK14. In a rat hemorrhagic shock model, cardiac ROS, Fe2+, MDA, and GSH levels were assessed. Key ferroptotic proteins (SLC7A11/GPX4) in myocardial tissues were examined via western blot. Hub genes, CD44 and MAPK14, expressions were confirmed through immunohistochemistry. Analyzing the GSE64711 dataset revealed 337 differentially expressed genes, including 12 linked to ferroptosis. Enrichment analysis highlighted pathways closely related to ferroptosis. Using Genemania, we found these genes mainly affect ROS metabolism and oxidative stress response. WGCNA identified CD44 and MAPK14 as hub genes. Rat myocardial tissue validation showed significant cardiac damage and elevated ROS and MDA levels, and decreased GSH levels in the hemorrhagic shock model. The ferroptotic pathway SLC7A11/GPX4 was activated, and immunohistochemistry showed a significant increase in the expression levels of CD44 and MAPK14 in the hemorrhagic shock rat model. We demonstrated the presence of tissue ferroptosis in hemorrhagic shock by combining bioinformatics analysis with in vivo experimentation. Specifically, we observed the activation of the SLC7A11/GPX4 ferroptotic pathway. Further, CD44 and MAPK14 were identified as hub genes in hemorrhagic shock.

Vascular endothelial growth factor-D plasma levels in fluid overload and cardiac function evaluation of elderly patients with cardiovascular disease.

This study aimed to investigate the clinical significance of vascular endothelial growth factor (VEGF) subtypes and growth differentiation factor-15 (GDF-15) plasma levels in evaluating the fluid overload and cardiac function of elderly patients with cardiovascular disease. The plasma levels of VEGF-C, VEGF-D, and GDF-15 were measured using ELISA. Their correlations with N-terminal pro B-type natriuretic peptide (NT-Pro BNP) and echocardiography data were analyzed. 1. Higher plasma levels of VEGF-D and GDF-15 were observed in elderly patients with cardiovascular disease and heart failure(P < .01). VEGF-D plasma levels were higher in patients with chronic heart failure than those with acute myocardial infarction (P < .01). VEGF-D plasma levels were positively correlated with amino-terminal pro-B type natriuretic peptide (NT-pro BNP) (P < .001). VEGF-D plasma levels were positively correlated with echocardiographic parameters, including left atrial diameter, left ventricular end-diastolic diameter and left ventricular ejection fraction, in patients with cardiovascular disease (P < .01). 2. VEGF-C plasma levels were higher in acute myocardial infarction group (P < .05). The plasma levels of VEGF-C were not correlated with either VEGF-D or NT-pro BNP plasma levels. VEGF-C plasma levels had no correlation with echocardiographic parameters. 3. GDF-15 plasma levels were positively correlated with sera biomarkers of cardiac injury (creatine kinase isoenzyme MB and cardiac troponin I). GDF-15 plasma levels were positively correlated with urinary biomarkers of tubular injury (N-acetyl-ß-galactosidase and α1-microglobulin). Both GDF-15 and NT-pro BNP plasma levels were correlated with age, estimated glomerular filtration rate (eGFR), and nutritional biomarkers (albumin and hemoglobin plasma levels). VEGF-D plasma levels is a potential biomarker of fluid overload and cardiac function in elderly patients with cardiovascular disease. Age, nutrition, and kidney injury are factors influencing both GDF-15 and NT-pro BNP plasma levels in estimating cardiac function and fluid overload.

Predictive value of machine learning for the risk of acute kidney injury (AKI) in hospital intensive care units (ICU) patients: a systematic review and meta-analysis.

Background: Recent studies suggest machine learning represents a promising predictive option for patients in intensive care units (ICU). However, the machine learning performance regarding its actual predictive value for early detection in acute kidney injury (AKI) patients remains uncertain. Objective: This study represents the inaugural meta-analysis aiming to investigate the predictive value of machine learning for assessing the risk of AKI among ICU patients. Methods: PubMed, Web of Science, Embase, and the Cochrane Library were all thoroughly searched from inception to June 25, 2022. Eligible studies for inclusion were those concentrating on the predictive value and the development, validation, or enhancement of a prediction model for AKI patients in the ICU. Measures of effects, including c-index, sensitivity, specificity, and their corresponding 95% confidence intervals (CIs), were employed for analysis. The risk of bias in the included original studies was assessed using Probst. The meta-analysis in our study was carried out using R version 4.2.0. Results: The systematic search yielded 29 articles describing 13 machine-learning models, including 86 models in the training set and 57 in the validation set. The overall c-index was 0.767 (95% CI [0.746, 0.788]) in the training set and 0.773 (95% CI [0.741, 0.804]) in the validation set. The sensitivity and specificity of included studies are as follows: sensitivity [train: 0.66 (95% CI [0.59, 0.73]), validation: 0.73 (95% CI [0.68, 0.77])]; and specificity [train: 0.83 (95% CI [0.78, 0.87])], validation: 0.75 (95% CI [0.71, 0.79])]. Conclusion: The machine learning-based method for predicting the risk of AKI in hospital ICU patients has excellent predictive value and could potentially serve as a prospective application strategy for early identification. PROSPERO Registration number ID: CRD42022362838.

Hydrogen­rich saline promotes neuronal recovery in mice with cerebral ischemia through the AMPK/mTOR signal­mediated autophagy pathway.

This study explored the protective effect and mechanism of hydrogen­rich saline (HRS) on the neurological function of mice with cerebral ischemia. Effects of HRS on neurological function in mice with cerebral ischemia were evaluated by neurological function scores. Infarct volume and histological damage were evaluated by 2,3,5­triphenyl tetrazolium chloride staining (TTC staining). Golgi­Cox staining was conducted to measure the morphological changes of neuronal dendrites and dendritic spines. The expression of neuronal markers was detected by immunofluorescence. Western blot was used to detect protein expression. The infarct volume of mice in the HRS­H group decreased significantly compared to that of the distal middle cerebral artery occlusion (dMCAO) group. Mice in the HRS­H group had a lower neurological deficit score than that in the dMCAO group. Compared to the dMCAO group, the activity of superoxide dismutase (SOD) and the level of glutathione (GSH) significantly increased in the HRS­H group. Compared with the dMCAO group, the number of apoptotic cells in the HRS­H group decreased. Administration of HRS was shown to be able to decrease cavitation of the brain cortex after ischemia. The spine density in the HRS­H group increased compared to that of the dMCAO group. In the in vitro experiment, compared with the oxygen­glucose deprivation (OGD) group, the active oxygen content in the 75% HRM group decreased, and the mitochondrial membrane potential and adenosine triphosphate (ATP) content increased. Compared with the OGD group, the ratio of P­AMPK and the levels of LC3II/LC3I in the hydrogen­rich medium (HRM) group was upregulated, and P­mTOR levels and P62 levels in the HRM group were down­regulated. HRS can enhance neuroplasticity after ischemia and promote neurological recovery in mice with cerebral ischemia, which may involve the autophagy pathway mediated by the AMPK/mTOR signaling pathway.

A modified triangular flap suture method used for inferior third molar extraction: A three-arm randomized clinical trial for the assessment of quality of life

Background: The purpose of this study is to explore whether decreasing the number of sutures can improve the quality of life after inferior third molar extraction. Material and methods: This study used a three-arm randomized design that included 90 individuals. Patients were randomized and divided into three groups-the airtight suture group (traditional), the buccal drainage group, and the no-suture group. Postoperative measurements, including treatment time, visual analog scale, questionnaire on postoperative patient quality of life, and details about trismus, swelling, dry socket, and other postoperative complications were obtained twice and the mean values were recorded. To verify the normal distribution of the data, the Shapiro-Wilk test was performed. The statistical differences were evaluated using the one-way ANOVA and the Kruskal-Wallis test with Bonferroni post-hoc correction. Results: The buccal drainage group showed a significant decrease in postoperative pain and better speech ability than the no-suture group on the 3st day, with a mean of 1.3 and 0.7 (P < 0.05). The airtight suture group also showed similar eating and speech ability, which was better than the no-suture group, with a mean of 0.6 and 0.7 (P < 0.05). However, no significant improvements were noted on the 1st and 7th days. The surgical treatment time, postoperative social isolation, sleep impairment, physical appearance, trismus, and swelling showed no statistical difference between the three groups at all measured times (P > 0.05). Conclusions: Based on the above findings, the triangular flap without a buccal suture may be superior to the traditional group and no-suture group in less pain, and better postoperative patient satisfaction in the first 3 days and may be a simple and viable option in clinical practice. (AU)

Articles on hemorrhagic shock published between 2000 and 2021: A CiteSpace-Based bibliometric analysis.

Objective: To conduct a bibliometric analysis of literature on hemorrhagic shock published between 2000 and 2021 with the help of Citespace to explore the current status, hotspots and research trends in this regard, with the results presented in a visualized manner. Methods: The data over the past 22 years were retrieved from the Web of Science (WOS) Core Collection database and downloaded as the "Full Record and Cited References". Cooperative analysis, cluster analysis, co-citation analysis, and burst analysis were performed based on the data on countries/regions, institutions, journals, authors, and keywords through Citespace. Results: A total of 2027 articles were retrieved. The number of annual publications fluctuated but was generally on an upward trend. The United States stands out as the most productive country (989 articles), the University of Pittsburgh the most productive publishing institution (109 articles), SHOCK the most cited journal (1486 articles), TAO LI the most productive author (40 articles), DEITCH EA the most cited author (261 times of citation), hemorrhagic shock the most frequent keyword (725 times of occurrence), and "traumatic brain injury" the most covered article in keyword clustering (29 articles). The burst analysis revealed Harvard University as the institution with the highest strength value and the Journal of Trauma and Acute Care Surgery the most important journal. It was also concluded that HASAN B ALAM, AARON M WILLIAMS, and LIMIN ZHANG may continue to publish high-quality articles in the future. In the meanwhile, both "protect" and "transfusion" were considered the hotspots and trends in current research. Conclusions: The United States has been a major contributor to the publication of the articles over the past 22 years, with the most productive publishing institution, the most cited journal, and the most cited author all coming from the US. Hemorrhagic shock, injury, resuscitation, trauma, models, activation, expression, fluid resuscitation, rats, and nitric oxide are hot topics in relevant research. According to the keyword burst analysis, the areas related to "protect" and "transfusion" may rise as the research directions in the future. However, since the hotspots in the research of hemorrhagic shock are short-lived and fast-changing, the researchers should pay more attention to the development trend in this field.

Association between serum complement 1q and the associated factors of acute ischemic stroke in patients with type 2 diabetes.

OBJECTIVE: The aim of this study was to examine the association between serum complement 1q (C1q) and the associated factors of acute ischemic stroke in patients with type 2 diabetes (T2DM). METHODS: The baseline clinical variables of the participants were collected, and the levels of blood lipids, blood sugar, inflammatory cytokines, and C1q in the three groups were then compared. The variables which affected the associated factors of acute ischemic stroke in T2DM cases were determined. RESULTS: The levels of C1q in the DAIS group were increased significantly compared with those in the T2DM group. Receiver operating characteristic curve analyses showed that the AUC for C1q and the combined diagnosis of acute ischemic stroke were 0.830 (95%CI 0.747-0.914), with a sensitivity of 0.854 and specificity of 0.780. The results of Pearson's correlation analyses demonstrated that C1q was associated positively with low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (PBG), 2-h postprandial blood glucose (2h PG), and high-sensitive C reaction protein (hs-CRP) (all p < .05). Stratified analysis showed that there was a positive relationship between C1q and the associated factors of acute ischemic stroke for partial LDL-C, and hs-CRP strata. Logistic model analysis suggested that C1q was an independent risk factor for acute ischemic stroke in patients with T2DM. After adjusting for potential confounders, a one-standard deviation (SD) increase in C1q level was strongly related to an approximately 1.5-fold increased risk of acute ischemic stroke in cases with a hs-CRP ≥1.78 mg/L. CONCLUSION: In DAIS patients, the levels of C1q were increased significantly and were an independent associated factor which affected the occurrence of acute ischemic stroke.

Development of a green fermentation strategy with resource cycle for the docosahexaenoic acid production by Schizochytrium sp.

The fermentation production of docosahexaenoic acid (DHA) is an industrial process with huge consumption of freshwater resource and nutrient, such as carbon sources and nitrogen sources. In this study, seawater and fermentation wastewater were introduced into the fermentation production of DHA, which could solve the problem of fermentation industry competing with humans for freshwater. In addition, a green fermentation strategy with pH control using waste ammonia, NaOH and citric acid as well as FW recycling was proposed. It could provide a stable external environment for cell growth and lipid synthesis while alleviating the dependence on organic nitrogen sources of Schizochytrium sp. It was proved that this strategy has good industrialization potential for DHA production, and the biomass, lipid and DHA yield reached to 195.8 g/L, 74.4 g/L and 46.4 g/L in 50 L bioreactor, respectively. This study provides a green and economic bioprocess technology for DHA production by Schizochytrium sp.