Relationship between anterior segment biometry and primary angle-closure glaucoma in Hubei region: a retrospective case-control study.

Objective: To investigate the pathogenesis of Primary Angle-Closure Glaucoma (PACG) and its relationship with the anatomical structure of the anterior segment by obtaining biometric parameters using the IOL-Master 700. Methods: A retrospective case-control study was conducted. Clinical data from 39 PACG patients and 40 normal controls treated at the Aier Eye Hospital affiliated with Wuhan University from January to December 2022 were collected. Anterior chamber depth (AC), white-to-white (WTW), lens thickness (LT), central corneal thickness (CCT), axial length (AL), corneal curvature (K1), corneal curvature (K2), and lens position (LP) were measured using the IOL-Master 700 to analyze the characteristics and differences in the anterior segment structure of both groups. Statistical methods included independent sample t-tests and logistic regression analysis. Results: Significant differences were found in the anterior segment biometric parameters between PACG patients and normal controls (p < 0.05). Anterior chamber depth, white-to-white, lens thickness, central corneal thickness, axial length, and K2 were all related to the occurrence of PACG (p < 0.05). The occurrence of PACG was negatively correlated with ACD, CCT, and AL (OR = 0.12-0.64, p < 0.05), and positively correlated with LT. Conclusion: Compared to the normal control group, PACG patients in the Hubei region have a smaller anterior segment space, narrower angles, thicker lens, thinner cornea, shorter axial length, flatter cornea, and more anteriorly positioned lens.

Nitrogen-containing heterocyclic drug products approved by the FDA in 2023: Synthesis and biological activity.

This article profiles 13 newly approved nitrogen-containing heterocyclic drugs by the U.S. Food and Drug Administration (FDA) in 2023. These drugs target a variety of therapeutic areas including proteinuria in patients with IgA nephropathy, migraine in adults, Rett syndrome, PI3Kδ syndrome, vasomotor symptoms, alopecia areata, acute myeloid leukemia, postpartum depression, myelofibrosis, and various cancer and tumor types. The molecular structures of these approved drugs feature common aromatic heterocyclic compounds such as pyrrole, imidazole, pyrazole, isoxazole, pyridine, and pyrimidine, as well as aliphatic heterocyclic compounds like caprolactam, piperazine, and piperidine. Some compounds also contain multiple heteroatoms like 1,2,4-thiadiazole and 1,2,4-triazole. The article provides a comprehensive overview of the bioactivity spectrum, medicinal chemistry discovery, and synthetic methods for each compound.

Baseline CT radiomics features to predict pathological complete response of advanced esophageal squamous cell carcinoma treated with neoadjuvant chemotherapy using paclitaxel and cisplatin.

PURPOSE: To develop a CT radiomics model to predict pathological complete response (pCR) of advanced esophageal squamous cell carcinoma (ESCC) toneoadjuvant chemotherapy using paclitaxel and cisplatin. MATERIALS AND METHODS: 326 consecutive patients with advanced ESCC from two hospitals undergoing baseline contrast-enhanced CT followed by neoadjuvant chemotherapy using paclitaxel and cisplatin were enrolled, including 115 patients achieving pCR and 211 patients without pCR. Of the 271 cases from 1st hospital, 188 and 83 cases were randomly allocated to the training and test cohorts, respectively. The 55 patients from a second hospital were assigned as an external validation cohort. Region of interest was segmented on the baseline thoracic contrast-enhanced CT. Useful radiomics features were generated by dimension reduction using least absolute shrinkage and selection operator. The optimal radiomics features were chosen using support vector machine (SVM). Discriminating performance was assessed with area under the receiver operating characteristic curve (ROC) and F-1score. The calibration curves and Brier score were used to evaluate the predictive accuracy. RESULTS: Eight radiomics features were selected to create radiomics models related to pCR of advanced ESCC (P-values < 0.01 for both the training and test cohorts). SVM model showed the best performance (AUCs = 0.929, 0.868 and 0.866, F-1scores = 0.857, 0.847 and 0.737 in the training, test and external validation cohorts, respectively). The calibration curves and Brier scores indicated goodness-of-fit and its great predictive accuracy. CONCLUSION: CT radiomics models could well help predict pCR of advanced ESCC, and SVM model could be a suitable predictive model.

Heterogenetic mechanism in multidimensional pit mud with different fermentation years: From microbial structure dynamic succession to metabolism phenotypes.

Pit mud (PM) is fermenting agents in the strong-flavor baijiu (SFB) production. In this paper, the discrepancies in fermentation parameters, microbial community succession patterns and metabolic phenotypes were compared in multidimensional PMs. The results showed that pyruvic acid, succinic acid, S-Acetyldihydrolipoamide-E, glycerol and glyceric acid were the key metabolites responsible for the metabolic differences between the 2-, 30-,100- and 300-year multidimensional PMs, while the butanoic acid, heptyl, heptanoic acid, heptanoic acid ethyl ester, hexanoic acid and octanoic acid were the key differential flavor compounds in the 2-, 30-,100- and 300-year multidimensional PMs. Concurrently, the diversity and abundance of microbial community also exhibited significant differences between the new and old multidimensional PMs, the assembly pattern of bacterial communities changed from deterministic to stochasticity from lower (bottom of the pit and under the huangshui fluid) to upper PM (up the huangshui fluid and top of the pit). Key microorganisms related to the succession process of the lower PM were Clostridium, Methanobacterium, Petrimonas, Lactobacillus, Methanobrevibacter, Bellilinea, Longilinea, Bacillus. In contrast, the upper PM were Caproicibacter, Longilinea, Lactobacillus, Proteinphilum, Methanobrevibacter, Methanobacterium, Methanobacteriaceae, Petrimonas, Bellilinea and Atopobium. Redundancy analysis (RDA) indicated that the key environmental factors regulating the succession of microbial in upper PM were lactic acid, moisture, pH and available phosphorus. In contrast, the lower was lactic acid, acetic acid and ammonia N. Based on these results, heterogeneous mechanisms between new and old multidimensional PMs were explored, providing a theoretical support for improving the quality of new PM.

The effects of sleep quality on loneliness among older adults: cohort analysis from the life course perspective.

BACKGROUND: Using cohort analysis to examine the effects of sleep quality on loneliness among older adults from the life course perspective. METHODS: The hierarchical age-period-cohort growth curve model was used to analyze the data from the 2005-2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS). RESULTS: (1) Loneliness has a 'U' curve relationship with age, but with the rate of increase gradually slowing down. (2) There were significant differences in loneliness across birth cohorts, with younger cohorts having higher predicted loneliness than older cohorts at the same age. (3) The influence of different sleep quality on loneliness showed a trend of increasing with age. (4) There were no significant differences in the impact of sleep quality on loneliness in different cohorts. CONCLUSIONS: This study has identified heterogeneity in loneliness, emphasising the need for a diversified intervention approach. Sleep quality has a protective effect on loneliness and is easy to assess, making it an important intervention tool. In addition, it is imperative to account for the influences of age and cohort effects when formulating intervention strategies.

A customized self-assembled synergistic biocatalyst for plastic depolymerization.

The enzymatic degradation of plastic offers a green, sustainable strategy and scalable circular carbon route for solving polyester waste. Among the earlies discovered plastic-degrading enzymes are PET hydrolase (PETase) and MHET hydrolase (MHETase), which act synergistically. To promote the adsorption of enzymes on PET surfaces, increase their robustness, and enable directly depolymerization, we designed hydrophobin HFBI fused-PETase and MHETase. A customized self-assembled synergistic biocatalyst (MC@CaZn-MOF) was further developed to promote the two-step depolymerization process. The tailored catalysts showed better adhesion to the PET surface and desirable durability, retaining over 70% relative activity after incubation at pH 8.0 and 60 °C for 120 h. Importantly, MC@CaZn-MOF could directly decompose untreated AGf-PET to generate 9.5 mM TPA with weight loss over 90%. The successful implementation of a bifunctional customized catalyst makes the large-scale biocatalytic degradation of PET feasible, contributing to polymer upcycling and environmental sustainability.

Serum Metabolomics and NF-κB Pathway Analysis Revealed the Antipyretic Mechanism of Ellagic Acid on LPS-Induced Fever in Rabbits.

Fever is one of the most common clinical conditions and is characterized by pyrogenic infection, malignancy, inflammation, and tissue damage, among others. Ellagic acid (EA) can inhibit the expression of related proteins on the pathway by blocking the nuclear factor kappa-B(NF-κB) signaling pathway, inhibit the levels of pro-inflammatory factors interleukin-1ß(IL-1ß), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), increase the level of anti-inflammatory factor IL-10, and effectively alleviate inflammatory symptoms. In addition, EA can also reduce the levels of malondialdehyde(MDA) and nitric oxide(NO) in the body, increase the activities of superoxide dismutase (SOD), glutathione (GSH), and catalase(CAT), scavenge oxidative free radicals, inhibit lipid oxidation, and achieve antipyretic and anti-inflammatory effects. The purpose of this study was to establish the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1ß, prostaglandin E2(PGE2), and cyclic adenosine monophosphate(cAMP), and clarify the mechanism of the cyclooxidase-2(COX-2)/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism. Compared to lipopolysaccharide (LPS)- treated animals, subsequent administration of EA significantly lowered the LPS-induced rectal temperature increase (p < 0.05 or p < 0.01), significantly increased serum SOD and GSH levels (p < 0.05 or p < 0.01), and significantly decreased serum MDA, IL-1ß, IL-6, and TNF-α levels (p < 0.05 or p < 0.01). In addition, compared to LPS-treated animals, subsequent administration of EA significantly decreased cerebrospinal fluid cAMP and PGE2 levels (p < 0.05 or p < 0.01), significantly decreased cAMP, significantly increased 5-HT levels (p < 0.05 or p < 0.01), and significantly down-regulated p-NF-κB p65 and COX-2 protein levels in the hypothalamus. Subsequent gas chromatography mass spectrometry(GC-MS) metabolite analysis indicated that 12 differential metabolites were detected in serum isolated 4 h after LPS treatment, and 10 differential metabolites were detected in serum collected 7 h after LPS treatment. Next, Pearson correlation analysis was used to systematically characterize the relationship between the identified metabolites and TNF-α, IL-6, MDA, SOD, PGE2, and cAMP. The levels of propionic acid, pyridine, and L-valine were up-regulated by EA, which inhibited the expression of MDA, IL-1ß, and TNF-α and increased the activity of GSH. The levels of inositol, urea, and 2-monopalmitin were down-regulated by EA, which inhibited the expression of MDA, IL-1ß, and TNF-α, increased the activity of SOD and GSH, reduced the inflammatory response, and alleviated the oxidative stress state. Combined with the results of the metabolic pathway analysis, we suggest that the pathways of the galactose metabolism, synthesis and degradation of ketone bodies, as well as ascorbic acid and aldehyde acid metabolism are closely related to the antipyretic and anti-inflammatory effects of EA. Our study established the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1ß, PGE2, and cAMP, and clarified the mechanism of the COX-2/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism.

Poly[[{µ2-5-[(di-methyl-amino)(thioxo)meth-oxy]benzene-1,3-di-carboxyl-ato-κ4 O 1,O 1':O 3,O 3'}(µ2-4,4'-di-pyridyl-amine-κ2 N 4:N 4')cobalt(II)] di-methyl-formamide hemisolvate monohydrate].

In the crystal structure of the title compound, {[Co(C11H9NSO5)(C10H9N3)]0.5C3H7NO·H2O} n or {[Co(dmtb)(dpa)]·0.5DMF·H2O} n (dmtb2- = 5-[(di-meth-yl-amino)-thioxometh-oxy]-1,3-benzene-dicarboxyl-ate and dpa = 4,4'-di-pyridyl-amine), an assembly of periodic [Co(C11H9NSO5)(C10H9N3)] n layers extending parallel to the bc plane is present. Each layer is constituted by distorted [CoO4N2] octa-hedra, which are connected through the µ 2-coordination modes of both dmtb2- and dpa ligands. Occupationally disordered water and di-meth-yl-formamide (DMF) solvent mol-ecules are located in the voids of the network to which they are connected through hydrogen-bonding inter-actions.

Comparing the antioxidation and bioavailability of polysaccharides from extruded and unextruded Baijiu vinasses via in vitro digestion and fecal fermentation.

Extrusion has been proven to be a novel approach for modifying the physicochemical characteristic of Baijiu vinasses (BV) to extract polysaccharides, contributing to the sustainable development of brewing industry. However, the comparison of the bioactivity and bioavailability of extruded (EX) and unextruded (UE) BV polysaccharides was unclear, which impended the determination of the efficacy of extrusion in BV resourcing. In this study, in vitro digestion and fecal fermentation experiments were conducted to investigate the bioavailability, and the results showed that EX exhibited less variation in the monosaccharide composition and molecular weight, while exhibiting a stronger antioxidant capacity compared to UE. Moreover, during fermentation EX increased the abundance of Parasutterella and Lachnospiraceae, while UE promoted the proliferation of Bacteroides, Faecalibacterium, and Dialister, resulting in variation in short-chain fatty acids. These findings indicate that extrusion can enhance the capacity of antioxidants and bioavailability of BV polysaccharides.

Characterizing the Contribution of Functional Microbiota Cultures in Pit Mud to the Metabolite Profiles of Fermented Grains.

Elevating the flavor profile of strong flavors Baijiu has always been a focal point in the industry, and pit mud (PM) serves as a crucial flavor contributor in the fermentation process of the fermented grains (FG). This study investigated the influence of wheat flour and bran (MC and FC) as PM culture enrichment media on the microbiota and metabolites of FG, aiming to inform strategies for improving strong-flavor Baijiu flavor. Results showed that adding PM cultures to FG significantly altered its properties: FC enhanced starch degradation to 51.46% and elevated reducing sugar content to 1.60%, while MC increased acidity to 2.11 mmol/10 g. PM cultures also elevated FG's ester content, with increases of 0.36 times for MC-FG60d and 1.48 times for FC-FG60d compared to controls, and ethyl hexanoate rising by 0.91 times and 1.39 times, respectively. Microbial analysis revealed that Lactobacillus constituted over 95% of the Abundant bacteria community, with Kroppenstedtia or Bacillus being predominant among Rare bacteria. Abundant fungi included Rasamsonia, Pichia, and Thermomyces, while Rare fungi consisted of Rhizopus and Malassezia. Metagenomic analysis revealed bacterial dominance, primarily consisting of Lactobacillus and Acetilactobacillus (98.80-99.40%), with metabolic function predictions highlighting genes related to metabolism, especially in MC-FG60d. Predictions from PICRUSt2 suggested control over starch, cellulose degradation, and the TCA cycle by fungal subgroups, while Abundant fungi and bacteria regulated ethanol and lactic acid production. This study highlights the importance of PM cultures in the fermentation process of FG, which is significant for brewing high-quality, strong-flavor Baijiu.

The synergistic anti-nociceptive effects of nefopam and gabapentinoids in inflammatory, osteoarthritis, and neuropathic pain mouse models.

Pain is a common public health problem and remains as an unmet medical need. Currently available analgesics usually have limited efficacy or are accompanied by many adverse side effects. To achieve satisfactory pain relief by multimodal analgesia, new combinations of nefopam and gabapentinoids (pregabalin/gabapentin) were designed and assessed in inflammatory, osteoarthritis and neuropathic pain. Isobolographic analysis was performed to analyze the interactions between nefopam and gabapentinoids in carrageenan-induced inflammatory pain, mono-iodoacetate-induced osteoarthritis pain and paclitaxel-induced peripheral neuropathic pain in mice. The anti-inflammatory effect and motor performance of monotherapy or their combinations were evaluated in the carrageenan-induced inflammatory responses and rotarod test, respectively. Nefopam (1, 3, 5, 10, 30 mg/kg, p.o.), pregabalin (3, 6, 12, 24 mg/kg, p.o.) or gabapentin (25, 50, 75, 100 mg/kg, p.o.) dose-dependently reversed mechanical allodynia in three pain models. Isobolographic analysis indicated that the combinations of nefopam and gabapentinoids exerted synergistic anti-nociceptive effects in inflammatory, osteoarthritis, and neuropathic pain mouse models, as evidenced by the experimental ED50 (median effective dose) falling below the predicted additive line. Moreover, the combination of nefopam-pregabalin/gabapentin alleviated carrageenan-induced inflammation and edema, and also prevented gabapentinoids-related sedation or ataxia by lowering their effective doses. Collectively, the co-administration of nefopam and gabapentinoids showed synergistic analgesic effects and may result in improved therapeutic benefits for treating pain.

Multidimensional combinatorial screening for high-level production of erythritol in Yarrowia lipolytica.

Yarrowia lipolytica was successfully engineered to synthesize erythritol from crude glycerol, a cheap by-product of biodiesel production, but the yield remained low. Here, a biosensor-guided adaptive evolution screening platform was constructed to obtain mutant strains which could efficiently utilize crude glycerol to produce erythritol. Erythrose reductase D46A (M1) was identified as a key mutant through whole-genome sequencing of the strain G12, which exhibited higher catalytic activity (1.6-fold of the wild-type). M1 was further modified to obtain a combinatorial mutant with 4.1-fold enhancement of catalytic activity. Finally, the metabolic network was reconfigured to redirect carbon fluxes toward erythritol synthesis. The erythritol titer of the engineered strain G31 reached 220.5 g/L with a productivity of 1.8 g/L/h in a 5-L bioreactor. The study provides valuable guidance for biosensor-based ultra-high-throughput screening strategies in Y. lipolytica, as well as presenting a new paradigm for the sustainable valorization of crude glycerol.

Safety and effectiveness of tunneled peripherally inserted central catheters versus conventional PICC in adult cancer patients.

OBJECTIVES: This study aimed to compare the safety and effectiveness of tunneled peripherally inserted central catheters (T-PICC) vs. conventional PICCs (C-PICC) in adult cancer patients. METHODS: A multicentre randomized controlled trial was conducted between April 2021 and January 2022 in seven hospitals in China. 564 participants were randomly assigned to T-PICC or C-PICC. These data were collected and compared: the baseline characteristics and catheterization-related characteristics, periprocedural complications, and long-term complications. RESULTS: Five-hundred fifty-three participants (aged, 52.6 ± 12.3 years; female, 39.1%) were ultimately analyzed. No significant differences in periprocedural complications were found between the T-PICC and C-PICC groups (all p > 0.05). Compared with C-PICC, T-PICC significantly reduced the incidence of long-term complications (26.4% vs. 39.9%, p < 0.001). Specifically, reduced complications were found in central line-associated bloodstream infection (1.8% vs. 5.1%, p = 0.04), thrombosis (1.1% vs. 4.0%, p = 0.03), catheter dislodgement (4.7% vs. 10.1%, p = 0.01), non-infectious oozing (17.3% vs. 28.6%, p = 0.002), local infection (3.6% vs. 7.6%, p = 0.04), skin irritation (6.1% vs. 10.9%, p = 0.046), and reduced unplanned catheter removal (2.2% vs. 7.2%, p = 0.005). No significant differences were found between T-PICC and C-PICC regarding catheter occlusion (6.5% vs. 5.8%, p = 0.73) or skin damage (2.2% vs. 2.9%, p = 0.58). CONCLUSION: T-PICC is safe and effectively reduces long-term complications. CLINICAL RELEVANCE STATEMENT: The tunneled technique is effective in reducing PICC-related long-term complications. Thus, it is recommended for cancer patients at high risk of PICC-related complications. TRIAL REGISTRATION: The registration number on https://www.chictr.org.cn/ is ChiCTR2100044632. The name of the trial registry is "A multicenter randomized controlled study of clinical use of tunneled vs. non-tunneled PICC". KEY POINTS: Cather-related complications are associated with the technique of catheterization. Compared with conventional PICC, tunneled PICC reduced catheter-related long-term complications. Tunneled PICC placement provides an alternative catheterization method for cancer patients.

Production of 17α-hydroxyprogesterone using an engineered biocatalyst with efficient electron transfer and improved 5-aminolevulinic acid synthesis coupled with a P450 hydroxylase.

17α-Hydroxyprogesterone (17α-OH-PROG) is an important intermediate with a wide range of applications in the pharmaceutical industry. Strategies based on efficient electron transfer and cofactor regeneration were used for the production of 17α-OH-PROG. Here, CYP260A1, Fpr and Adx were expressed using a double plasmid system, resulting in higher biotransformation efficiency. Further optimization of reaction conditions and addition of polymyxin B increased the production of 17α-OH-PROG from 12.52 mg/L to 102.37 mg/L after 12 h of biotransformation. To avoid the addition of external 5-aminolevulinic acid (ALA) as a heme precursor for the P450 enzyme, a modified C5 pathway was introduced into the engineered strain, further reducing the overall process cost. The resulting whole-cell biocatalyst achieved the highest biotransformation yield of 17α-OH-PROG reported to date, offering a promising strategy for commercial application of P450 enzymes in industrial production of hydroxylated intermediates.

Integrated toxicity of secondary, tertiary, wetland effluents on human stem cells triggered by ERα and PPARγ agonists.

Residual pollutants in discharged and reused water pose both direct and indirect human exposure. However, health effects caused by whole effluent remain largely unknown due to the lack of human relevant model for toxicity test. Effluents from four secondary wastewater treatment plants (SWTPs), a tertiary wastewater treatment plant (TWTP) and a constructed wetland (CW) were evaluated for the integrated toxicity of the organic extractions. Multiple-endpoint human mesenchymal stem cells (MSCs) assay was used as an in vitro model relevant to human health. The effluents caused cytotoxicity, oxidative stress and genotoxicity in MSCs. The osteogenic and neurogenic differentiation were inhibited and the adipogenic differentiation were stimulated by some of the effluent extractions. The SWTP, TWTP and CW treatments reduced integrated biomarker response (IBR) by 26.3 %, 17.5 % and 33.3 % respectively, where the IBR values of final CW (8.3) and TWTP (8.2) effluents were relatively lower than SWTPs (9.1). Among multiple biomarkers, the inhibition of osteogenesis was the least reduced by wastewater treatment. Besides, ozone disinfection in tertiary treatment increased cytotoxicity and differentiation effects suggesting the generation of toxic products. The mRNA expressions of estrogen receptor alpha (ERα) and peroxisome proliferator-activated receptor gamma (PPARγ) were significantly upregulated by effluents. The inhibitory effects of effluents on neural differentiation were mitigated after antagonizing ERα and PPARγ in the cells. It is suggested that ERα and PPARγ agonists in effluents were largely accountable for the impairment of stem cell differentiation. Besides, the concentrations of n-C29H60, o-cresol, fluorene and phenanthrene in the effluents were significantly correlated with the intergrated stem cell toxicity. The present study provided toxicological evidence for the relation between water contamination and human health, with an insight into the key toxicity drivers. The necessity for deep water treatment and the potential means were suggested for improving water quality.

Real-world setting comparison of bridging therapy versus direct mechanical thrombectomy for acute ischemic stroke: A meta-analysis.

BACKGROUND AND PURPOSE: Intravenous Thrombolysis (IVT) prior to Mechanical Thrombectomy (MT) for Acute Ischaemic Stroke (AIS) due to Large-Vessel Occlusion (LVO) remains controversial. Therefore, the authors performed a meta-analysis of the available real-world evidence focusing on the efficacy and safety of Bridging Therapy (BT) compared with direct MT in patients with AIS due to LVO. METHODS: Four databases were searched until 01 February 2023. Retrospective and prospective studies from nationwide or health organization registry databases that compared the clinical outcomes of BT and direct MT were included. Odds Ratios (ORs) and 95 % Confidence Intervals (CIs) for efficacy and safety outcomes were pooled using a random-effects model. RESULTS: Of the 12 studies, 86,695 patients were included. In patients with AIS due to LVO, BT group was associated with higher odds of achieving excellent functional outcome (modified Rankin Scale score 0-1) at 90 days (OR = 1.48, 95 % CI 1.25-1.75), favorable discharge disposition (to the home with or without services) (OR = 1.33, 95 % CI 1.29-1.38), and decreased mortality at 90 days (OR = 0.62, 95 % CI 0.56-0.70), as compared with the direct MT group. In addition, the risk of symptomatic intracranial hemorrhage did not increase significantly in the BT group. CONCLUSION: The present meta-analysis indicates that BT was associated with favorable outcomes in patients with AIS due to LVO. These findings support the current practice in a real-world setting and strengthen their validity. For patients eligible for both IVT and MT, BT remains the standard treatment until more data are available.

Characterization of bronchoalveolar lavage fluid microbiota in acute exacerbations of bronchiectasis with non-tuberculous mycobacterial detection.

OBJECTIVES: Non-tuberculous mycobacteria (NTM) frequently colonize the airways of patients with bronchiectasis; however, there has been limited research into airway microbiota composition and predisposing factors for NTM detection during acute bronchiectasis exacerbations. METHODS: This study enrolled 34 patients with bronchiectasis experiencing acute exacerbations. Metagenomic next-generation sequencing was used to detect microbiota in bronchoalveolar lavage fluid (BALF), and bioinformatics methods were used for the comparative analysis of meaningful microbiota in the BALF of patients with acute exacerbations of bronchiectasis. A correlation analysis was conducted to identify susceptibility factors for NTM in patients with bronchiectasis. RESULTS: Compared with patients with community-acquired pneumonia, patients with bronchiectasis had higher detection rates of NTM (38.2%), Pseudomonas aeruginosa, and Haemophilus influenzae. Patients with NTM-positive bronchiectasis had lower body mass index and lipid profiles than patients who were NTM-negative. Metagenomic next-generation sequencing of BALF revealed patients who were NTM-positive had increased relative abundance of Rothia and other anaerobic genera compared with patients who were NTM-negative. Patients who were NTM-positive also showed higher levels of Streptococcus parasanguinis at the species level. Elevated Rothia mucilaginosa and S. parasanguinis correlated with decreased percentages of clusters of differentiation 3+ T lymphocytes and clusters of differentiation 3+ T-cell subgroups in peripheral blood. CONCLUSIONS: NTM colonization increases the risk of acute bronchiectasis exacerbations. Low body mass index, lipid levels, and isolation of R. mucilaginosa and S. parasanguinis in BALF are susceptibility factors for NTM colonization in patients with bronchiectasis.

Novel drug-drug salt crystals of metformin with ibuprofen or naproxen: Improved solubility, dissolution rate, and synergistic antinociceptive effects.

As the monotherapy of available analgesics is usually accompanied by serious side effects or limited efficacy in the management of chronic pain, multimodal analgesia is widely used to achieve improved benefit-to-risk ratios in clinic. Drug-drug salts are extensively researched to optimize the physicochemical properties of active pharmaceutical ingredients (APIs) and achieve clinical benefits compared with individual APIs or their combination. New drug-drug salt crystals metformin-ibuprofen (MET-IBU) and metformin-naproxen (MET-NAP) were prepared from metformin (MET) and two poorly water-soluble anti-inflammatory drugs (IBU and NAP) by the solvent evaporation method. The structures of these crystals were confirmed by single crystal and powder X-ray diffraction, Hirshfeld surface, Fourier transform infrared spectroscopy and thermal analysis. Both MET-IBU and MET-NAP showed significantly improved solubility and intrinsic dissolution rate than the pure IBU or NAP. The stability test indicated that MET-IBU and MET-NAP have excellent physical stability under stressing test (10 days) and accelerated conditions (3 months). Moreover, isobolographic analysis suggested that MET-IBU and MET-NAP exerted potent and synergistic antinociceptive effects in λ-Carrageenan-induced inflammatory pain in mice, and both of them had an advantage in rapid pain relief. These results demonstrated the potential of MET-IBU and MET-NAP to achieve synergistic antinociceptive effects by developing drug-drug salt crystals.

A multiscale attribution framework for separating the effects of cascade and individual reservoirs on runoff.

Climate change and human activities have great impacts on runoff. With the gradual development of cascade hydropower in the watershed, the reservoirs have increasingly impacted runoff. However, the current study mainly focuses on quantifying the impacts of human activities and climate change on runoff, lacking the exploration of the impacts of cascade reservoirs, and the attribution results are relatively rough. Therefore, this study utilized data-driven models to establish a runoff attribution framework with the basic steps of "interval runoff prediction and scheduling rule extraction", which achieved the spatial scale separation of the impacts of cascade and individual reservoirs on the runoff, and the analysis of the impacts of each factor at multiple time scales. Taking the upper reaches of the Yangtze River mainstem as an example, we verified the applicability and accuracy of the framework, explored the impacts of climate change, human activities (without reservoir scheduling), and reservoir scheduling on runoff during the period 1980-2018. The research found: (1) Compared to the base period 1980-2005, the average multi-year runoff changes at Pingshan Station (during 2013-2018), Yichang Station (during 2006-2012) and Yichang Station (during 2013-2018) were - 2.61 %, -4.33 % and - 0.89 %, respectively, with decreasing, increasing, and flattening trends over time. (2) Reservoir scheduling is the main factor leading to runoff change, showing negative impacts during flood season and positive impacts during non-flood season. (3) Under the control domain of single and cascade reservoirs, the annual scale impacts of climate change, human activities, and reservoir scheduling on runoff accounted for approximately 1:1:8 and 2:2:6, respectively, showing a complex nonlinear relationship between the impacts of single and cascade reservoirs on runoff. This study provides ideas for quantitatively assessing the impacts of cascade reservoirs on runoff and provide a basis for comprehensively assessing the ecosystem and socio-economic impacts of reservoirs on future runoff changes.

Systematic review and network meta-analysis of different non-steroidal anti-inflammatory drugs for juvenile idiopathic arthritis.

BACKGROUND: Various non-steroidal anti-inflammatory drugs (NSAIDs) have been used for juvenile idiopathic arthritis (JIA). However, the optimal method for JIA has not yet been developed. AIM: To perform a systematic review and network meta-analysis to determine the optimal instructions. METHODS: We searched for randomized controlled trials (RCTs) from PubMed, EMBASE, Google Scholar, CNKI, and Wanfang without restriction for publication date or language at August, 2023. Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis. The surface under the cumulative ranking curve (SUCRA) analysis was used to rank the treatments. P value less than 0.05 was identified as statistically significant. RESULTS: We included 8 RCTs (1127 patients) comparing 8 different instructions including meloxicam (0.125 qd and 0.250 qd), Celecoxib (3 mg/kg bid and 6 mg/kg bid), piroxicam, Naproxen (5.0 mg/kg/d, 7.5 mg/kg/d and 12.5 mg/kg/d), inuprofen (30-40 mg/kg/d), Aspirin (60-80 mg/kg/d, 75 mg/kg/d, and 55 mg/kg/d), Tolmetin (15 mg/kg/d), Rofecoxib, and placebo. There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response. The SUCRA shows that celecoxib (6 mg/kg bid) ranked first (SUCRA, 88.9%), rofecoxib ranked second (SUCRA, 68.1%), Celecoxib (3 mg/kg bid) ranked third (SUCRA, 51.0%). There were no significant differences between any two NSAIDs regarding adverse events. The SUCRA shows that placebo ranked first (SUCRA, 88.2%), piroxicam ranked second (SUCRA, 60.5%), rofecoxib (0.6 mg/kg qd) ranked third (SUCRA, 56.1%), meloxicam (0.125 mg/kg qd) ranked fourth (SUCRA, 56.1%), and rofecoxib (0.3 mg/kg qd) ranked fifth (SUCRA, 56.1%). CONCLUSION: In summary, celecoxib (6 mg/kg bid) was found to be the most effective NSAID for treating JIA. Rofecoxib, piroxicam, and meloxicam may be safer options, but further research is needed to confirm these findings in larger trials with higher quality studies.