Rural Hospital Performance in Guideline-Recommended Ischemic Stroke Thrombolysis, Secondary Prevention, and Outcomes.

BACKGROUND: Existing data suggested a rural-urban disparity in thrombolytic utilization for ischemic stroke. Here, we examined the use of guideline-recommended stroke care and outcomes in rural hospitals to identify targets for improvement. METHODS: This retrospective cohort study included patients (aged ≥18 years) treated for acute ischemic stroke at Get With The Guidelines-Stroke hospitals from 2017 to 2019. Multivariable mixed-effect logistic regression was used to compare thrombolysis rates, speed of treatment, secondary stroke prevention metrics, and outcomes after adjusting for patient- and hospital-level characteristics and stroke severity. RESULTS: Among the 1 127 607 patients admitted to Get With The Guidelines-Stroke hospitals in 2017 to 2019, 692 839 patients met the inclusion criteria. Patients who presented within 4.5 hours were less likely to receive thrombolysis in rural stroke centers compared with urban stroke centers (31.7% versus 43.5%; adjusted odds ratio [aOR], 0.72 [95% CI, 0.68-0.76]) but exceeded rural nonstroke centers (22.1%; aOR, 1.26 [95% CI, 1.15-1.37]). Rural stroke centers were less likely than urban stroke centers to achieve door-to-needle times of ≤45 minutes (33% versus 44.7%; aOR, 0.86 [95% CI, 0.76-0.96]) but more likely than rural nonstroke centers (aOR, 1.24 [95% CI, 1.04-1.49]). For secondary stroke prevention metrics, rural stroke centers were comparable to urban stroke centers but exceeded rural nonstroke centers (aOR of 1.66, 1.94, 2.44, 1.5, and 1.72, for antithrombotics within 48 hours of admission, antithrombotics at discharge, anticoagulation for atrial fibrillation/flutter, statin treatment, and smoking cessation, respectively). In-hospital mortality was similar between rural and urban stroke centers (aOR, 1.11 [95% CI, 0.99-1.24]) or nonstroke centers (aOR, 1.00 [95% CI, 0.84-1.18]). CONCLUSIONS: Rural hospitals had lower thrombolysis utilization and slower treatment times than urban hospitals. Rural stroke centers provided comparable secondary stroke prevention treatment to urban stroke centers and exceeded rural nonstroke centers. These results reveal important opportunities and specific targets for rural health equity interventions.

Narrow-Band Imaging in Head and Neck Carcinomas: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study was to assess the diagnostic performance of narrow-band imaging (NBI) in monitoring patients with head and neck carcinomas posttreatment and to compare it with that of white light endoscopy (WLE). DATA SOURCES: PubMed, Embase, Web of Science (WOS), Cochrane Library, China Biology Medicine disc (CBM disc), China National Knowledge Internet (CNKI), Wanfang Data, China Science and Technology Journal Database (CSTJ), Chinese Clinical Trial Register. REVIEW METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), literature published before July 2024 was searched. Patients who underwent surgery, radiotherapy (RT), or chemo-RT for head and neck carcinomas with posttreatment follow-up using NBI were analyzed. The main outcomes were sensitivity, specificity, and diagnostic odds ratio (DOR) for NBI and WLE in posttreatment follow-up. RESULTS: The sensitivity, specificity, and DOR for NBI and WLE in posttreatment follow-up for head and neck carcinomas were 95% (95% confidence interval [CI]: 88%-98%), 96% (95% CI: 92%-98%), 433 (95% CI: 120-1560) and 72% (95% CI: 49%-87%), 72% (95% CI: 4%-99%), 7 (95% CI: 0-191). Additionally, the area under the curve (AUC) values for NBI and WLE were 0.99 (95% CI: 0.97-0.99) and 0.75 (95% CI: 0.71-0.79), respectively. The number of lesions and patients, treatment modality, follow-up time, disease, and endoscopic system might be sources of heterogeneity. CONCLUSION: Compared to WLE, NBI demonstrated superior diagnostic performance in follow-up patients with head and neck carcinoma posttreatment. NBI offers technical support and a clinical foundation for early detection of head and neck carcinoma recurrence. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

In acute ICH, minimally invasive surgery improved functional outcome at 180 d.

SOURCE CITATION: Pradilla G, Ratcliff JJ, Hall AJ, et al; ENRICH trial investigators. Trial of early minimally invasive removal of intracerebral hemorrhage. N Engl J Med. 2024;390:1277-1289. 38598795.

[Phytic Acid Modification Enhanced Cadmium Sorption and Immobilization of Sludge-based Hydrochar].

Phytic acid-assisted sludge hydrothermal carbonization was employed to synthesize phytic acid-modified hydrochar via a one-step method. The surface morphology, pore structure, elemental composition, functional groups, and thermal stability of the phytic acid-modified hydrochar were characterized. Sorption kinetics and isotherm experiments were conducted to investigate the effects of humic acid, temperature, and pH on the sorption process of cadmium （Cd） onto the phytic acid-modified hydrochar. The Cd fixation ability was evaluated through soil passivation experiments. The results demonstrated that the surface of the phytic acid-modified hydrochar exhibited an abundance of phosphoric acid groups, enhanced electronegativity, and thermal stability. Furthermore, both the sorption rate and maximum sorption capacity for Cd increased by 1.88 times and 1.22 times compared to that in unmodified hydrochar, respectively, owing to the presence of phosphoric acid groups that enhanced complexation and electrostatic interaction with Cd. Elevated temperatures, higher pH values, and coexistence with humic acids were beneficial for enhancing Cd sorption onto phytic acid-modified hydrochar. When heavy metals such as Cu, Zn, and Pb coexisted, the sorption capacity of phytic acid-modified hydrochar for Cd was 0.77-6.88 times higher than that for other metals. Phyic acid-modified hydrochar exhibited excellent efficiency in fixing Cd （56.1%-81.l%）, mitigating the loss of available nutrients in soil and significantly increasing the AP content in the soil. In conclusion, the use of phytic acid-modified hydrochar could effectively remove Cd from water and serve as a promising soil amendment for stabilizing soil Cd content.

Comparison of learning curves and related postoperative indicators between endoscopic and robotic thyroidectomy: a systematic review and meta-analysis.

BACKGROUD: Endoscopic thyroidectomy (ET) and robotic thyroidectomy (RT) yield similar perioperative outcomes. This study investigated how the learning curve (LC) affects perioperative outcomes between ET and RT, identifying factors that influence the LC. MATERIALS AND METHODS: Two researchers individually searched PubMed, EMBASE, Web of Science, and Cochrane Library for relevant studies published until February 2024. The Newcastle-Ottawa Scale assessed study quality. Random effects model was used to compute the odds ratio and weighted mean difference (WMD). Poisson regression comparison of the number of surgeries (NLC) was required for ET and RT to reach the stable stage of the LC. Heterogeneity was measured using Cochran's Q. Publication bias was tested using funnel plots, and sensitivity analysis assessed findings robustness. Subgroup analysis was done by operation type and patient characteristics. RESULTS: This meta-analysis involved 33 studies. The drainage volume of ET was higher than that of RT (WMD=-17.56 [30.22, -4.49]). After reaching the NLC, the operation time of ET and RT was shortened (ET: WMD=28.15[18.04, 38.26]; RT: WMD=38.53[29.20, 47.86]). Other perioperative outcomes also improved to varying degrees. Notably, RT showed more refined central lymph node resection(5.67 vs. 4.71), less intraoperative bleeding (16.56 mL vs. 42.30 mL), and incidence of transient recurrent laryngeal nerve injury(24.59 vs. 26.77). The NLC of RT was smaller than that of ET(Incidence-rate ratios [IRR]=0.64[0.57, 0.72]). CUSUM analysis (ET: IRR=0.84[0.72, 0.99]; RT: IRR=0.55[0.44, 0.69]) or a smaller number of respondents (ET: IRR=0.26[0.15, 0.46]; RT: IRR=0.51[0.41, 0.63]) was associated with smaller NLC. In RT, transoral approach (IRR=2.73[1.96, 4.50]; IRR=2.48[1.61, 3.84]) and retroauricular approach (RAA) (IRR=2.13[1.26, 3.60]; IRR=1.78[1.04, 3.05]) had smaller NLC compared to bilateral axillo-breast and transaxillary approach (TAA). In ET, the NLC of RAA was smaller than that of TAA (IRR=1.61[1.04, 2.51]), breast approach(IRR=1.67[1.06, 2.64]), and subclavian approach(IRR=1.80[1.03, 3.14]). CONCLUSIONS: Rich surgical experience can improve surgical results of ET and RT. After reaching the NLC, the perioperative outcomes of RT are better than those of ET. Study subjects, surgical approaches, and analysis methods can affect NLC.

Carboxymethyl chitosan composited poly(ethylene oxide) electrolyte with high ion conductivity and interfacial stability for lithium metal batteries.

Low ionic conductivity and poor interface stability of poly(ethylene oxide) (PEO) restrict the practical application as polymeric electrolyte films to prepare solid-state lithium (Li) metal batteries. In this work, biomass-based carboxymethyl chitosan (CMCS) is designed and developed as organic fillers into PEO matrix to form composite electrolytes (PEO@CMCS). Carboxymethyl groups of CMCS fillers can promote the decomposition of Lithium bis(trifluoromethane sulfonimide) (LiTFSI) to generate more lithium fluoride (LiF) at CMCS/PEO interface, which not only forms ionic conductive network to promote the rapid transfer of Li+ but also effectively enhances the interface stability between polymeric electrolyte and Li metal. The enrichment of carboxyl, hydroxyl, and amidogen functional groups within CMCS fillers can form hydrogen bonds with ethylene oxide (EO) chains to improve the tensile properties of PEO-based electrolyte. In addition, the high hardness of CMCS additives can also strengthen mechanical properties of PEO-based electrolyte to resist penetration of Li dendrites. LiLi symmetric batteries can achieve stable cycle for 2500 h and lithium iron phosphate full batteries can maintain 135.5 mAh g-1 after 400 cycles. This work provides a strategy for the enhancement of ion conductivity and interface stability of PEO-based electrolyte, as well as realizes the resource utilization of biomass-based CMCS.

Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss.

Clonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A mutations with a higher prevalence of periodontitis and gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice with the heterozygous loss-of-function mutation R878H, equivalent to the human hotspot mutation R882H. Partial transplantation with Dnmt3aR878H/+ bone marrow (BM) cells resulted in clonal expansion of mutant cells into both myeloid and lymphoid lineages and an elevated abundance of osteoclast precursors in the BM and osteoclastogenic macrophages in the periphery. DNMT3A-driven clonal hematopoiesis in recipient mice promoted naturally occurring periodontitis and aggravated experimentally induced periodontitis and arthritis, associated with enhanced osteoclastogenesis, IL-17-dependent inflammation and neutrophil responses, and impaired regulatory T cell immunosuppressive activity. DNMT3A-driven clonal hematopoiesis and, subsequently, periodontitis were suppressed by rapamycin treatment. DNMT3A-driven CHIP represents a treatable state of maladaptive hematopoiesis promoting inflammatory bone loss.

Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers: A case report and review of literature.

BACKGROUND: Genetic factors of chronic intestinal ulcers are increasingly garnering attention. We present a case of chronic intestinal ulcers and bleeding associated with mutations of the activin A receptor type II-like 1 (ACVRL1) and phospholipase A2 group IVA (PLA2G4A) genes and review the available relevant literature. CASE SUMMARY: A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain, diarrhea, and dark stools. At the onset 6 years ago, the patient had received treatment at a local hospital for abdominal pain persisting for 7 d, under the diagnosis of diffuse peritonitis, acute gangrenous appendicitis with perforation, adhesive intestinal obstruction, and pelvic abscess. The surgical treatment included exploratory laparotomy, appendectomy, intestinal adhesiolysis, and pelvic abscess removal. The patient's condition improved and he was discharged. However, the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge. On the basis of these features and results of subsequent colonoscopy, the clinical diagnosis was established as inflammatory bowel disease (IBD). Accordingly, aminosalicylic acid, immunotherapy, and related symptomatic treatment were administered, but the symptoms of the patient did not improve significantly. Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes. ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation, respectively. This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes. Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms. CONCLUSION: Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD. Orally administered Kangfuxin liquid may have therapeutic potential.

To explore the pathogenesis of anterior resection syndrome by magnetic resonance imaging rectal defecography.

BACKGROUND: Over 90% of rectal cancer patients develop low anterior resection syndrome (LARS) after sphincter-preserving resection. The current globally recognized evaluation method has many drawbacks and its subjectivity is too strong, which hinders the research and treatment of LARS. AIM: To evaluate the anorectal function after colorectal cancer surgery by quantifying the index of magnetic resonance imaging (MRI) defecography, and pathogenesis of LARS. METHODS: We evaluated 34 patients using the standard LARS score, and a new LARS evaluation index was established using the dynamic images of MRI defecography to verify the LARS score. RESULTS: In the LARS score model, there were 10 (29.41%) mild and 24 (70.58%) severe cases of LARS. The comparison of defecation rate between the two groups was 29.36 ± 14.17% versus 46.83 ± 18.62% (P = 0.004); and MRI-rectal compliance (MRI-RC) score was 3.63 ± 1.96 versus 7.0 ± 3.21 (P = 0.001). Severe and mild LARS had significant differences using the two evaluation methods. There was a significant negative correlation between LARS and MRI-RC score (P < 0.001), and they had a negative correlation with defecation rate (P = 0.028). CONCLUSION: MRI defecography and standard LARS score can both be used as an evaluation index to study the pathogenesis of LARS.

Role of Prognostic Marker PRR11 in Immune Infiltration for Facilitating Lung Adenocarcinoma Progression.

The PRR11 gene (Proline Rich 11) has been implicated in lung cancer; however, relationship between PRR11 and immune infiltration is not clearly understood. In this study, we used The Cancer Genome Atlas (TCGA) data to analyze the lung adenocarcinoma patients; PRR11 gene expression, clinicopathological findings, enrichment, and immune infiltration were also studied. PRR11 immune response expression assays in lung adenocarcinoma (LUAD) were performed using TIMER, and statistical analysis and visualization were conducted using R software. All data were verified using Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). We found that PRR11 was an important prognostic factor in patients with LUAD. PRR11 expression was correlated with tumor stage and progression. Gene Set Enrichment Analysis (GSEA) showed that PRR11 was enriched in the cell cycle regulatory pathways. Immune infiltration analysis revealed that the number of T helper 2 (Th2) cells increased when PRR11 was overexpressed. These results confirm the role of PRR11 as a prognostic marker of lung adenocarcinoma by controlling the cell cycle and influencing the immune system to facilitate lung cancer progression.

Pan-Immune-Inflammatory Value in Patients with Non-Small-Cell Lung Cancer Undergoing Neoadjuvant Immunochemotherapy.

Background: We aimed to investigate the predictive value of a systematic serum inflammation index, pan-immune-inflammatory value (PIV), in pathological complete response (pCR) of patients treated with neoadjuvant immunotherapy to further promote ideal patients' selection. Methods: The clinicopathological and baseline laboratory information of 128 NSCLC patients receiving neoadjuvant immunochemotherapy between October 2019 and April 2022 were retrospectively reviewed. We performed least absolute shrinkage and selection operator (LASSO) algorithm to screen candidate serum biomarkers for predicting pCR, which further entered the multivariate logistic regression model to determine final biomarkers. Accordingly, a diagnostic model for predicting individual pCR was established. Kaplan-Meier method was utilized to estimate curves of disease-free survival (DFS), and the Log rank test was analyzed to compare DFS differences between patients with and without pCR. Results: Patients with NSCLC heterogeneously responded to neoadjuvant immunotherapy, and those with pCR had a significant longer DFS than patients without pCR. Through LASSO and the multivariate logistic regression model, PIV was identified as a predictor for predicting pCR of patients. Subsequently, a diagnostic model integrating with PIV, differentiated degree and histological type was constructed to predict pCR, which presented a satisfactory predictive power (AUC, 0.736), significant agreement between actual and our nomogram-predicted pathological response. Conclusion: Baseline PIV was an independent predictor of pCR for NSCLC patients receiving neoadjuvant immunochemotherapy. A significantly longer DFS was achieved in patients with pCR rather than those without pCR; thus, the PIV-based diagnostic model might serve as a practical tool to identify ideal patients for neoadjuvant immunotherapeutic guidance.

Effectiveness of the recurrent laryngeal nerve monitoring during endoscopic thyroid surgery: systematic review and meta-analysis.

BACKGROUND: Thyroid disease is a common endocrine disorder, and thyroid surgeries and postoperative complications have increased recently. This study aimed to explore the effectiveness of intraoperative nerve monitoring (IONM) in endoscopic thyroid surgery using subgroup analysis and determine confounding factors. MATERIALS AND METHODS: Two researchers individually searched for relevant studies published till November 2022 in the PubMed, Embase, Web of Science and Cochrane Library databases. Eventually, eight studies met the inclusion criteria. Heterogeneity was assessed using the Cochran's Q test, and a funnel plot was implemented to evaluate publication bias. The odds ratio or risk difference were calculated using fixed-effects models. The weighted mean difference of continuous variables was calculated. Subgroup analysis was performed according to the disease type. RESULTS: Eight eligible papers included 915 patients and 1242 exposed nerves. The frequencies of transient, permanent and total recurrent laryngeal nerve (RLN) palsy were 2.64, 0.19 and 2.83%, respectively, in the IONM group and 6.15, 0.75 and 6.90%, respectively, in the conventional exposure group. In addition, analysis of the secondary outcome indicators for the average total length of surgery, localisation time of the RLN, recognition rate of the superior laryngeal nerve and length of incision revealed that IONM reduced the localisation time of the RLN and increased the identification rate of the superior laryngeal nerve. Subgroup analysis showed that IONM significantly reduced the incidence of RLN palsy in patients with malignancies. CONCLUSIONS: The use of IONM significantly reduced the incidence of transient RLN palsy during endoscopic thyroid surgery, but it did not significantly reduce the incidence of permanent RLN palsy. However, the reduction in the total RLN palsy was statistically significant. In addition, IONM can effectively reduce the location time of the RLN and increase the recognition rate of the superior laryngeal nerve. Therefore, the application of IONM for malignant tumours is recommended.

[Shaofu Zhuyu Decoction attenuates fibrosis in endometriosis through regulating PTEN/Akt/mTOR signaling pathway].

The present study aimed to investigate the protective role of Shaofu Zhuyu Decoction(SFZY) against endometriosis fibrosis in mice, and decipher the underlying mechanism through the phosphatase and tensin homolog deleted on chromosome ten(PTEN)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) pathway. Eighty-five BALB/c female mice were randomly assigned into a blank group, a model group, high-, medium, and low-dose SFZY(SFZY-H, SFZY-M, and SFZY-L, respectively) groups, and a gestrinone suspension(YT) group. The model of endometriosis was induced by intraperitoneal injection of uterine fragments. The mice in different groups were administrated with corresponding groups by gavage 14 days after modeling, and the blank group and model group with equal volume of distilled water by gavage. The treatment lasted for 14 days. The body weight, paw withdrawal latency caused by heat stimuli, and total weight of dissected ectopic focus were compared between different groups. The pathological changes of the ectopic tissue were observed via hematoxylin-eosin(HE) and Masson staining. Real-time PCR was employed to measure the mRNA levels of α-smooth muscle actin(α-SMA) and collagen type Ⅰ(collagen-Ⅰ) in the ectopic tissue. The protein levels of PTEN, Akt, mTOR, p-Akt, and p-mTOR in the ectopic tissue were determined by Western blot. Compared with the blank group, the modeling first decreased and then increased the body weight of mice, increased the total weight of ectopic focus, and shortened the paw withdrawal latency. Compared with the model group, SFZY and YT increased the body weight, prolonged the paw withdrawal latency, and decreased the weight of ectopic focus. Furthermore, the drug administration, especially SFZY-H and YT(P<0.01), recovered the pathological and reduced the area of collagen deposition. Compared with the blank group, the modeling up-regulated the mRNA levels of α-SMA and collagen-Ⅰ in the ectopic focus, and such up-regulation was attenuated after drug intervention, especially in the SFZY-H and YT groups(P<0.05,P<0.01). Compared with the blank group, the modeling down-regulated the protein level of PTEN and up-regulated the protein levels of Akt, mTOR, p-Akt, and p-mTOR(P<0.01, P<0.001). Drug administration, especially SFZY-H and YT, restored such changes(P<0.01). SFZY may significantly attenuate the focal fibrosis in the mouse model of endometriosis by regulating the PTEN/Akt/mTOR signaling pathway.

[Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction].

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

Retinoic acid protects against lipopolysaccharide-induced ferroptotic liver injury and iron disorders by regulating Nrf2/HO-1 and RARß signaling.

Acute liver injury (ALI) can progress to severe liver diseases, making its prevention and treatment a focus of research. Retinoic acid (RA) has been shown to have anti-oxidative and iron-regulatory effects on organs. In this study, we investigated the effect of RA on lipopolysaccharide (LPS)-induced ALI in both in vivo and in vitro experiments. We found that RA significantly reduced LPS-induced serum iron and red blood cell-associated disorders, as well as decreased serum ALT and AST levels. RA also reversed the accumulation of non-heme iron and labile iron in LPS-induced mice and hepatocytes by increasing the expression of FTL/H and Fpn. Furthermore, RA inhibited tissue reactive oxygen species (ROS) and malondialdehyde (MDA) production and improved the expression of Nrf2/HO-1/GPX4 in mice and Nrf2 signaling in hepatocytes. In vitro experiments employing RAR agonists and antagonists have revealed that retinoic acid (RA) can effectively inhibit cell ferroptosis induced by lipopolysaccharide (LPS), erastin, and RSL3. The mechanism underlying this inhibition may involve the activation of retinoic acid receptors beta (RARß) and gamma (RARγ). Knocking down the RARß gene in Hepatocytes cells significantly diminished the RA's protective effect, indicating that the anti-ferroptotic role of RA was partially mediated by RARß signaling. Overall, our study demonstrated that RA inhibited ferroptosis-induced liver damage by regulating Nrf2/HO-1/GPX4 and RARß signaling.

Risk of type 2 diabetes after diagnosed gestational diabetes is enhanced by exposure to PM2.5.

BACKGROUND: Air pollution and gestational diabetes mellitus (GDM) are both associated with increased diabetes mellitus (DM) occurrence. However, whether air pollutants modify the effects of GDM on the occurrence of DM has been unknown. This study aims to determine whether the effect of GDM on DM development can be modified by exposure to ambient air pollutants. METHODS: Women with one singleton birth delivery during 2004-14 according to the Taiwan Birth Certificate Database (TBCD) were included as the study cohort. Those newly diagnosed as having DM 1 year or later after childbirth were identified as DM cases. Controls were selected among women without DM diagnosis during follow-up. Personal residence was geocoded and linked with interpolated concentrations of air pollutants into township levels. Conditional logistic regression was used to determine the odds ratio (OR) of pollutant exposure and GDM, adjusting for age, smoking and meteorological variables. RESULTS: There were 9846 women who were newly diagnosed as having DM over a mean follow-up period of 10.2 years. We involved them and the 10-fold matching controls involved in our final analysis. The OR (odds ratio) (95% confidence interval, 95% CI) of DM occurrence per interquartile range increased in particulate matter (PM) smaller than or equal to 2.5 µm (PM2.5) and ozone (O3) was 1.31 (1.22-1.41) and 1.20 (1.16-1.25), respectively. The effects of PM exposure on DM development were significantly higher in the GDM group (OR: 2.46, 95% CI: 1.84-3.30) than in the non-GDM group (OR: 1.30, 95% CI: 1.21-1.40). CONCLUSIONS: Exposure to high levels of PM2.5 and O3 elevates the risk of DM. GDM acted synergistically in DM development with exposure to PM2.5 but not with that to O3.

Marein reduces lipid levels via modulating the PI3K/AKT/mTOR pathway to induce lipophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: The capitulum of Coreopsis tinctoria Nutt. (CT, Xue-Ju in Chinese) is a precious medicine in Xinjiang Uygur Autonomous region of China. The Coreopsis tinctoria Nutt. is used to prevent and treat dyslipidemia, coronary heart disease, etc. Recent studies have shown that its extract has a pharmacological effect on hyperlipidemia and hyperglycemia. AIM OF THE STUDY: The study aimed to systematically evaluate the lipid-lowering activity of CT through a mice model of hyperlipidemia and a human hepatoma G2 (HepG2) cells model of lipid accumulation, and to investigate its main active components and mechanism. MATERIALS AND METHODS: Biochemical analysis of blood/liver lipids and liver histopathology were used to evaluate the effect of the aqueous extract of Coreopsis tinctoria Nutt. (AECT) on hyperlipidemia mice. High-performance liquid chromatography (HPLC) analysis was used to identify the main components in the AECT. Oil red O staining, immunofluorescence, western blotting, and determination of the total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were used to further study the effect and potential mechanism of the AECT main components on sodium oleate-induced lipid accumulation in HepG2 cells. RESULTS: We confirmed the lipid-lowering activity of the aqueous extract and further identified flavonoids as its main components. Among them, five Coreopsis tinctoria Nutt. flavonoids mixture (FM) significantly reduced lipid droplet area, lipid content, TC, TG, and LDL-C levels, and elevated HDL-C levels in HepG2 cells induced by sodium oleate. Furthermore, they increased lipophagy in HepG2 lipid-accumulating cells, while decreasing the ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Most importantly, marein may be a key component. CONCLUSIONS: Our study demonstrated that AECT, with flavonoids as the main component, can improve diet-induced hyperlipidemia in obese mice. Among the main five flavonoids, marein plays a key role in promoting lipophagy by regulating the PI3K/AKT/mTOR pathway, resulting in a lipid-lowering effect.

Lymph Node Follicle-Targeting STING Agonist Nanoshells Enable Single-Shot M2e Vaccination for Broad and Durable Influenza Protection.

The highly conserved matrix protein 2 ectodomain (M2e) of influenza viruses presents a compelling vaccine antigen candidate for stemming the pandemic threat of the mutation-prone pathogen, yet the low immunogenicity of the diminutive M2e peptide renders vaccine development challenging. A highly potent M2e nanoshell vaccine that confers broad and durable influenza protectivity under a single vaccination is shown. Prepared via asymmetric ionic stabilization for nanoscopic curvature formation, polymeric nanoshells co-encapsulating high densities of M2e peptides and stimulator of interferon genes (STING) agonists are prepared. Robust and long-lasting protectivity against heterotypic influenza viruses is achieved with a single administration of the M2e nanoshells in mice. Mechanistically, molecular adjuvancy by the STING agonist and nanoshell-mediated prolongation of M2e antigen exposure in the lymph node follicles synergistically contribute to the heightened anti-M2e humoral responses. STING agonist-triggered T cell helper functions and extended residence of M2e peptides in the follicular dendritic cell network provide a favorable microenvironment that induces Th1-biased antibody production against the diminutive antigen. These findings highlight a versatile nanoparticulate design that leverages innate immune pathways for enhancing the immunogenicity of weak immunogens. The single-shot nanovaccine further provides a translationally viable platform for pandemic preparedness.

Electrochemical Single-Cell Protein Therapeutics Using a Double-Barrel Nanopipette.

Single-cell protein therapeutics is expected to promote our in-depth understanding of how a specific protein with a therapeutic dosage treats the cell without population averaging. However, it has not yet been tackled by current single-cell nanotools. We address this challenge by the use of a double-barrel nanopipette, in which one lumen was used for electroosmotic cytosolic protein delivery and the other was customized for ionic evaluation of the consequence. Upon injection of protein DJ-1 through the delivery lumen, upregulation of the antioxidant protein could protect neural PC-12 cells against oxidative stress from phorbol myristate acetate exposure, as deduced by targeting of the cytosolic hydrogen peroxide by the detecting lumen. The nanotool developed in this study for single-cell protein therapeutics provides a perspective for future single-cell therapeutics involving different therapeutic modalities, such as peptides, enzymes and nucleic acids.

Transcutaneous electrical acupoint stimulation for reducing cognitive dysfunction in lumbar spine surgery: A randomized, controlled trail.

Objective: This study aimed to evaluate the effect of perioperative transcutaneous electrical acupoint stimulation (TEAS) on postoperative cognitive dysfunction (POCD) in older patients with lumbar spine surgery. Methods: Older patients (aged 60-80 years old) receiving lumbar spine surgery under general anesthesia were randomly divided into group A, 3-day intervention group; group B, 7-day intervention group; control group C, sham TEAS group, selected "Baihui" (GV 20) and "Dazhui" (GV 14) point was intervened once 30 min before operation with "HANS" transcutaneous electrical stimulation device, and then once a day after operation for 30 min each time. The primary outcome was the incidence of postoperative cognitive impairment assessed by the use of the Mini Mental Rating Scale (MMSE), patients developed POCD according to the Z score method. The secondary outcome was serum interleukin-6 (IL-6), tumor Necrosis factor α (TNF-α), neuron-specific enolase (NSE), and S100ß protein levels. Results: Three days after surgery, the incidence of POCD in groups A((22.4%)) and B ((18.3%)) were lower than those in group C ((42.9%)) (P < 0.05). There was no significant difference between groups A and B (P > 0.05). Seven days after surgery, the incidence of POCD in group B (18.3%) was lower than that in groups A (26.5%) and B (42.9%), and the comparison between groups B and C was statistically significant (P < 0.05). On the 3rd and 7th days after surgery, the levels of IL-6, TNF-α, NSE, and S100ß in the two TEAS groups were lower than those in the sham TEAS group (P < 0.01), but higher than the preoperative levels in the three groups (P < 0.01). Conclusion: It seems that Perioperative TEAS intervention could reduce the level of inflammatory factors IL-6, TNF-α in the blood of older patients with lumbar spine surgery, and reduce the incidence of POCD. Clinical trial registration: www.chictr.org.cn, identifier ChiCTR2200063030.