Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke: current evidence and future perspectives.

Ischemic stroke is a leading cause of death and disability worldwide, with an increasing trend and tendency for onset at a younger age. China, in particular, bears a high burden of stroke cases. In recent years, the inflammatory response after stroke has become a research hotspot: understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment. This review summarizes several major cells involved in the inflammatory response following ischemic stroke, including microglia, neutrophils, monocytes, lymphocytes, and astrocytes. Additionally, we have also highlighted the recent progress in various treatments for ischemic stroke, particularly in the field of stem cell therapy. Overall, understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes. Stem cell therapy may potentially become an important component of ischemic stroke treatment.

Influencing factors and prediction of neutralizing antibodies in post-exposure rabies vaccine recipients.

To assess the factors that influencing the persistence of virus neutralizing antibody (VNA), and to establish prediction models to provide the appropriate timing for booster administration, a cohort of post-exposure rabies vaccine recipients was investigated. The VNA determined records from 2019 to 2023 and interrelated factors were analyzed, including gender, age, rabies immunoglobulin (RIG) administration, vaccine products, vaccination schedule, and vaccination intervals etc. The geometric mean of VNA titre within 1 month after primary vaccination with 2-1-1 schedule was statistically higher than that with 5-dose course (P = 0.031). The interaction between exposure and vaccination schedule was observed on primary vaccination, which showed that a decrease of 19.74 % (95 % CI: 5.99%-64.95 %, P = 0.008) of VNA titre among vaccinee with 5-dose and exposure III. Individuals with RIG administration produced lower VNA titres than those without RIG administration (P = 0.001). Vaccine products (Chengda, P = 0.015; human diploid cell, P = 0.026) and re-exposed time (P = 0.000) exhibited independent effects following booster vaccination. Based on the prediction model, the 99 % individual prediction intervals (IPI) of VNA titres were established at 3, 6, 12 and 18 months for the 12 characteristic populations respectively. The cases of VNA below 0.5 IU/ml first appeared at 6 months in group D of primary vaccinations and at 10 years in group F of boosters. We conclude that for primary vaccination 2-1-1 schedule is more efficient than 5-dose; the use of residual rabies immunoglobulin for distal intramuscular injection isn't recommended. The 99 % IPI of VNA titres could provide the appropriate timing for booster vaccination.

Construction of nomogram based on clinical factors for the risk prediction of postoperative complications in children with choledochal cyst.

Objective: The aim of the study was to develop a prediction nomogram based on clinical factors to assess the risk of postoperative complications in children with congenital choledochal cyst. Methods: The clinical data from 131 children who underwent choledochal cyst resection and Roux-en-Y hepaticojejunostomy in our hospital between January 2016 and December 2022 were retrospectively analyzed. The general information, clinical symptoms, procedure, biochemical indicators, and imaging data were recorded. A prolonged hospital stay induced by postoperative complications or a follow-up over 6 months was assessed as the event outcome. A logistics regression analysis was performed to screen for risk factors with statistical significance in inducing postoperative complications. Then, with the dataset split into the training group and internal validation group, the nomogram for the prediction of postoperative complications was developed based on a computer algorithm. In addition, the receiver operating characteristic (ROC) curve and calibration curve were performed for nomogram verification. Results: Of 131 children, the multivariate logistics regression analysis suggested that age ≤2 years [odds ratio (OR) 0.93; 95% confidence interval (CI) 0.15-5.65; p = 0.938], Todani classification type 1 (OR 36.58; 95% CI 4.14-871.74; p = 0.005), cyst wall thickness >0.4 cm (OR 10.82; 95% CI 2.88-49.13; p < 0.001), with chronic cholecystitis (OR 7.01; 95% CI 1.62-38.52; p = 0.014), and choledochal cyst diameter (OR 1.01; 95% CI 0.99-1.03; p = 0.370) were predictors associated with the postoperative complications of choledochal cysts. The data were randomly divided into the training group (n = 92) and internal validation group (n = 39) to build the prediction nomogram including the appeal factors. The accuracy and discrimination of the model were evaluated using a ROC curve and calibration curve. The results showed that the nomogram area under the ROC curve [area under the curve (AUC) = 0.894; 95% CI 0.822-0.966; p < 0.001], validation (AUC = 0.844; 95% CI 0.804-0.952; p < 0.001), and Brier = 0.120 (95% CI 0.077-0.163p; p < 0.001) were indicative of the good stability and calibration of the predictive nomogram. Conclusion: The prognosis of congenital choledochal cysts was associated with multiple aspects of clinical factors. Combined with the internal validation, the novel prediction nomogram was suitable for evaluating the individualized risk of postoperative complications of choledochal cysts. The prediction nomogram could provide a more accurate strategy of procedure and postoperative follow-up for children with choledochal cysts.

Alpha oscillation mediates the interaction between suicide risk and symptom severity in Major Depressive Disorder.

Objective: The aim of our study was to explore the relationship between changes in neural oscillatory power in the EEG, the severity of depressive-anxiety symptoms, and the risk of suicide in MDD. Methods: 350 MDD patients' demographic and clinical data were collected, and their depressive and anxious symptoms were evaluated using HDRS-17 and HAMA-14, along with a suicide risk assessment using the Nurses' Global Assessment of Suicide Risk (NGASR). EEG data were captured, processed, and analyzed to study brain activity patterns related to MDD. The participants were divided based on suicide risk levels, and statistical analyses, including chi-square, t-tests, Pearson's correlations were used to explore the associations between brain activity, symptom severity, and suicide risk. Closely related variables were identified and ultimately the optimal model was screened using stepwise regression analysis with a forward strategy, and mediation effects were further used to determine the possible interactions between the variables in the regression model. Results: The regression model showed a significant effect of HDRS-17 and alpha power of Medial Occipital Cortex (MOC) on suicide risk, with elevated HDRS-17 increasing suicide risk and elevated alpha power decreasing suicide risk. Mediation effect analyses showed that MOC alpha power partially mediated the effect of depression level on suicide risk, and that an increase in depression severity may lead to a decrease in MOC alpha power, while a decrease in MOC alpha power may lead to an increase in suicide risk. Conclusion: The severity of depression directly increases suicide risk, whereas higher alpha power in the MOC serves as a protective factor, reducing this risk. Notably, MOC alpha power not only directly impacts suicide risk but also mediates the effects of both depression severity and anxiety levels on this risk. Limitations: The relatively small sample size of this study may limit the representativeness of the overall MDD patient population and the detailed analysis of different subgroups. This study did not delve into the relationship between the severity of cognitive symptoms in MDD patients and suicide risk.

Surgical outcomes of sacrospinous hysteropexy and hysteropreservation for pelvic organ prolapse: a systematic review of randomized controlled trials.

Objective: In several randomized controlled trials (RCTs), sacrospinous hysteropexy and other forms of hysteropreservation have been compared. Nevertheless, there is no definitively best treatment. This study summarized RCT evidence for various uterine preservation surgical procedures. Methods: From each database inception to August 2023, we searched PubMed, Embase, Cochrane Library, and Web of Science for eligible RCTs. A comparison was made between sacrospinous hysteropexy and other hysteropreservation, including vaginal and abdominal surgery. For categorical and continuous variables, relative risks (RRs) and mean differences (MDs) were calculated using random-effects models. Results: We reviewed a total 1,398 studies and ultimately included five RCTs that met all inclusion criteria. These five studies included a total of 1,372 uterine POP cases all of whom received transvaginal surgery and had a follow-up period for assessment of recurrence from 12 months to 5 years. There were no significant differences between sacrospinous hysteropexy and other hysteropreservation for the incidences of recurrence (RR,1.24; 95% CI, 0.58 to 2.63; p = 0.58) or hematoma (RR,0.70; 95% CI, 0.17 to 2.92; p = 0.62). Moreover, neither sacrospinous hysteropexy nor hysteropreservation had any significant effect on the risk of mesh exposure (RR,0.34; 95% CI, 0.03 to 4.31; p = 0.41), dyspareunia (RR,0.45; 95% CI, 0.13 to1.6; p = 0.22), urinary tract infection (RR,0.66; 95% CI, 0.38 to 1.15; p = 0.15), bothersome bulge symptoms (RR,0.03; 95% CI, -0.02 to 0.08; p = 0.24), operative time (MD, -4.53; 95% CI, -12.08 to 3.01; p = 0.24), and blood loss (MD, -25.69; 95% CI, -62.28 to 10.91; p = 0.17). However, sacrospinous hysteropexy was associated with a lower probability of pain (RR,4.8; 95% CI, 0.79 to 29.26; p = 0.09) compared with other hysteropreservation. Conclusion: There was no difference between sacrospinous hysteropexy and hysteropreservation in terms of recurrence, hematoma, mesh exposure, dyspareunia, urinary tract infection, bothersome bulge symptoms, operative time, pain, and blood loss. Systematic Review Registration: PROSPERO [CRD42023470025].

Rumen Microbiota Transplantation Alleviates Gossypol Diet-Induced Reproductive, Liver, and Intestinal Damage in Male Mice.

Ruminants exhibit stronger tolerance to gossypol, an anti-nutritional factor, compared to monogastric animals. We transplanted Hu sheep rumen microbiota into male mice to investigate the role of rumen microbiota in animal gossypol tolerance. Thirty specific-pathogen-free (SPF) male C57BL/6 mice were randomly divided into three groups: normal diet (CK group), gossypol diet (FG group), and rumen microbiota transplantation (FMT group, gossypol diet). The pathological changes in the liver and small intestine of the mice, the organ coefficient, and sperm parameters were analyzed. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the blood and lactate dihydrogen-X (LDH-X) levels in the testicular tissue were also measured. The results showed that body weight, feed intake, sperm concentration, sperm motility, and LDH-X levels in the FMT group increased (p < 0.05) compared with the FG group, while the enzyme activities of ALT, AST, and AST/ALT decreased (p < 0.05). In the FMT group, the injury to liver cells was alleviated, the structure of the small intestine was intact, and the villus height and the ratio of villus height to crypt depth (V/C) were higher than those in the FG group (p < 0.05). And there were no differences in various organ coefficients and sperm deformity rates among the three groups (p > 0.05), but compared with the FG group, mice in the FMT group showed tendencies closer to those in the CK group. Rumen microbiota transplantation relieved the reproductive toxicity and liver damage induced by gossypol in male mice and improved the tolerance of recipient animals to gossypol. Additionally, rumen microbes improved the intestinal structural integrity of recipients.

Two-stage deep neural network for diagnosing fungal keratitis via in vivo confocal microscopy images.

Timely and effective diagnosis of fungal keratitis (FK) is necessary for suitable treatment and avoiding irreversible vision loss for patients. In vivo confocal microscopy (IVCM) has been widely adopted to guide the FK diagnosis. We present a deep learning framework for diagnosing fungal keratitis using IVCM images to assist ophthalmologists. Inspired by the real diagnostic process, our method employs a two-stage deep architecture for diagnostic predictions based on both image-level and sequence-level information. To the best of our knowledge, we collected the largest dataset with 96,632 IVCM images in total with expert labeling to train and evaluate our method. The specificity and sensitivity of our method in diagnosing FK on the unseen test set achieved 96.65% and 97.57%, comparable or better than experienced ophthalmologists. The network can provide image-level, sequence-level and patient-level diagnostic suggestions to physicians. The results show great promise for assisting ophthalmologists in FK diagnosis.

Association between dietary niacin intake and risk of Parkinson's disease in US adults: cross-sectional analysis of survey data from NHANES 2005-2018.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases and involves various pathogenic mechanisms, including oxidative stress and neuroinflammation. Niacin, an important cofactor in mitochondrial energy metabolism, may play a key role in the pathogenesis of PD. An in-depth exploration of the relationship between niacin and mitochondrial energy metabolism may provide new targets for the treatment of PD. The present study was designed to examine the association between dietary niacin intake and the risk of PD in US adults. Data from adults aged 40 years and older collected during cycles of the United States (US) National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 were used. A multiple logistic regression model was used to analyze the relationship between dietary niacin intake and the risk of PD. Further linear tests using restricted cubic splines (RCS) were performed to explore the shape of the dose-response relationship. Subgroup stratification and interaction analyses were conducted according to years of education, marital status, smoking, and hypertension to evaluate the stability of the association between different subgroups. A total of 20,211 participants were included in this study, of which 192 were diagnosed with PD. In the fully adjusted multiple logistic regression model, dietary niacin intake was negatively associated with the risk of PD (OR: 0.77, 95%CI: 0.6-0.99; p = 0.042). In the RCS linear test, the occurrence of PD was negatively correlated with dietary niacin intake (nonlinearity: p = 0.232). In stratified analyses, dietary niacin intake was more strongly associated with PD and acted as an important protective factor in patients with fewer years of education (OR: 0.35, 95%CI: 0.13-0.93), married or cohabitating (OR: 0.71, 95%CI: 0.5-0.99), taking dietary supplements (OR: 0.6, 95%CI: 0.37 0.97), non-smokers (OR: 0.57, 95%CI: 0.39-0.85), those with hypertension (OR: 0.63, 95%CI: 0.63-0.95), coronary artery disease (OR: 0.77, 95%CI: 0.6-1), and stroke (OR: 0.75, 95%CI: 0.88-0.98), but the interaction was not statistically significant in all subgroups. Dietary niacin intake was inversely associated with PD risk in US adults, with a 23% reduction in risk for each 10 mg increase in niacin intake.

miR-203-3p promotes senescence of mouse bone marrow mesenchymal stem cells via downregulation of Pbk.

The senescence of bone marrow mesenchymal stem cells (BMSCs) contributes to the development of degenerative skeletal conditions. To date, the molecular mechanism resulting in BMSC senescence has not been fully understood. In this study, we identified a small non-coding RNA, miR-203-3p, the expression of which was elevated in BMSCs from aged mice. On the other hand, overexpression of miR-203-3p in BMSCs from young mice reduced cell growth and enhanced their senescence. Mechanistically, PDZ-linked kinase (PBK) is predicted to be the target of miR-203-3p. The binding of miR-203-3p to Pbk mRNA could decrease its expression, which in turn inhibited the ubiquitination-mediated degradation of p53. Furthermore, the intravitreal injection of miR-203-3p-inhibitor into the bone marrow cavity of aged mice attenuated BMSC senescence and osteoporosis in aged mice. Collectively, these findings suggest that targeting miR-203-3p to delay BMSC senescence could be a potential therapeutic strategy to alleviate age-related osteoporosis.

The splicing factor SF3B1 confers ferroptosis resistance and promotes lung adenocarcinoma progression via upregulation of SLC7A11.

This study aimed to investigate the expression of SF3B1 in non-small cell lung cancer, and its clinical significance, biological function, and molecular mechanisms. SF3B1 mRNA and protein levels were elevated in both lung squamous cell carcinoma and lung adenocarcinoma (LUAD) tissues based on TCGA data and immunohistochemistry. Notably, high SF3B1 expression in LUAD was significantly associated with increased lymph node metastasis. Functional experiments involving SF3B1 knockdown and overexpression demonstrated that SF3B1 facilitated the proliferation, invasion, and migration of LUAD cells. Additionally, the SF3B1 inhibitor pladienolide-B attenuated the aggressive behavior of LUAD cells both in vitro and in vivo. RNA sequencing analysis indicated that differentially expressed genes in the SF3B1 knockdown and SF3B1 inhibitor groups were enriched in ferroptosis-related pathways compared to their respective control groups. The antiferroptotic role of SF3B1 in LUAD cells was validated by detecting glutathione depletion, lipid peroxidation, and observing morphological changes using transmission electron microscopy. This process was confirmed to be independent of apoptosis and autophagy, as evidenced by the effects of the ferroptosis inducer erastin, the apoptosis inhibitor Z-VAD-FMK, and the autophagy inhibitor 3-methyladenine. Rescue experiments indicated that the antiferroptotic role of SF3B1 in LUAD is partially mediated by upregulating the expression of SLC7A11.

Potential therapeutic targets for pelvic organ prolapse: insights from key genes related to blood vessel development.

Objective: Pelvic organ prolapse (POP) is a disease in which pelvic floor support structures are dysfunctional due to disruption of the extracellular matrix (ECM). The vascular system is essential for maintaining ECM homeostasis. Therefore, this study explored the potential mechanism of blood vessel development-related genes (BVDRGs) in POP. Methods: POP-related datasets and BVDRGs were included in this study. Differentially expressed genes (DEGs) between the POP and control groups were first identified in the GSE12852 and GSE208271 datasets, and DE-BVDRGs were identified by determining the intersection of these DEGs and BVDRGs. Subsequently, the feature genes were evaluated by machine learning. Feature genes with consistent expression trends in the GSE12852 and GSE208271 datasets were considered key genes. Afterward, the overall diagnostic efficacy of key genes in POP was evaluated through receiver operating characteristic (ROC) curve analysis. Based on the key genes, enrichment analysis, immune infiltration analysis and regulatory network construction were performed to elucidate the molecular mechanisms underlying the functions of the key genes in POP. Results: A total of 888 DEGs1 and 643 DEGs2 were identified in the GSE12852 and GSE208271 datasets, and 26 candidate genes and 4 DE-BVDRGs were identified. Furthermore, Hyaluronan synthase 2 (HAS2), Matrix metalloproteinase 19 (MMP19) and Plexin Domain Containing 1 (PLXDC1) were identified as key genes in POP and had promising value for diagnosing POP (AUC > 0.8). Additional research revealed that the key genes were predominantly implicated in immune cell activation, chemotaxis, and cytokine release via the chemokine signaling pathway, the Nod-like receptor signaling pathway, and the Toll-like receptor signaling pathway. Analysis of immune cell infiltration confirmed a decrease in the proportion of plasma cells in POP, and MMP19 expression showed a significant negative correlation with plasma cell numbers. In addition, regulatory network analysis revealed that MALAT1 (a lncRNA) targeted hsa-miR-503-5p, hsa-miR-23a-3p and hsa-miR-129-5p to simultaneously regulate three key genes. Conclusion: We identified three key BVDRGs (HAS2, MMP19 and PLXDC1) related to the ECM in POP, providing markers for diagnostic studies and investigations of the molecular mechanism of POP.

Preparation of magnetic activated carbon fibers@Fe3O4 by electrostatic self-assembly method and adsorption properties for methylene blue.

Nano-Fe3O4 was loaded onto coconut-based activated carbon fibres (CACF) using an electrostatic self-assembly method. The effects of the mass ratio of CACF to nano-Fe3O4, loading time, pH and temperature on the loading effect were investigated and ideal loading conditions were determined. To study the adsorption performance of MACF@Fe3O4 for methylene blue, the effects of the initial concentration, pH and time on the adsorption were investigated and the working conditions of adsorption were established. MACF@Fe3O4 was systematically characterized. Adsorption kinetics were investigated under ideal conditions. The ideal loading conditions for MACF@Fe3O4 were as follows: mass ratio of 1:1, 20 min, pH 9.36, 22.5°C. The saturation magnetization of MACF@Fe3O4 was 48.2263 emu·g-1, which could be quickly separated under an external magnetic field. When the dosage was 0.010 g, the adsorption rate reached 97.29% and the maximum adsorption capacity was 12.1616 mg·g-1. The adsorption process conformed to pseudo-first-order kinetics during the first 15 min and pseudo-second-order kinetics during 20-120 min. The equations were ln( Q e - Q t )=2.2394-0.0689t and t Q t =0.0774 + 0.5295t , respectively. The isothermal adsorption model showed that MACF@Fe3O4 was more in line with the Langmuir model, indicating that the adsorption process was mainly monolayer adsorption. The thermodynamic analysis results showed that the adsorption process of MB by MACF@Fe3O4 was an endothermic process. In this study, MACF@Fe3O4 with high adsorption capacity and easy separation from coconut palm fibres has good application prospects in the field of adsorption, which can promote the high-value utilization of coconut palms.

Molecular cloning and functional characterization of mitochondrial RNA splicing 2 in fish Megalobrama amblycephala, and its potential roles in magnesium homeostasis and mitochondrial function.

Mitochondrial function can be regulated by ion channels. Mitochondrial RNA splicing 2 (Mrs2) is a magnesium ion (Mg2+) channel located in the inner mitochondrial membrane, thereby mediating the Mg2+ influx into the mitochondrial matrix. However, its potential role in regulating the Mg homeostasis and mitochondrial function in aquatic species is still unclear. This study molecularly characterizes the gene encoding Mrs2 in fish M. amblycephala with its functions in maintaining the Mg homeostasis and mitochondrial function verified. The mrs2 gene is 2133 bp long incorporating a 1269 bp open reading frame, which encodes 422 amino acids. The Mrs2 protein includes two transmembrane domains and a conserved tripeptide Gly-Met-Asn, and has a high homology (65.92-97.64%) with those of most vertebrates. The transcript of mrs2 was relatively high in the white muscle, liver and kidney. The inhibition of mrs2 reduces the expressions of Mg2+ influx/efflux-related proteins, mitochondrial Mg content, and the activities of mitochondrial complex I and V in hepatocytes. However, the over-expression of mrs2 increases the expressions of Mg2+ influx/efflux-related proteins, mitochondrial Mg content, and the complex V activity, but decreases the activities of mitochondrial complex III and IV and citrate synthase in hepatocytes. Collectively, Mrs2 is highly conserved among different species, and is prerequisite for maintaining Mg homeostasis and mitochondrial function in fish.

An immunosensor for the near real-time and site of inflammation detections of multiple proinflammatory cytokines.

Diseases mediated by cytokine storms are often characterized by an overexuberant pace of pathogenesis accompanied by significant morbidity and mortality. Thus, near real-time (NRT) detections via a site-of-inflammation (SOI) sampling of proinflammatory cytokines are essential to ensure a timely and effective treatment of acute inflammations, which up to now, has not been fully possible. In this work, we proposed a novel NRT and SOI immunosensor using ZIF-8 signal amplification together with an off-on strategy. To achieve NRT detections via a SOI sampling, the body fluid of choice is the dermal interstitial fluid (ISF). The significant merits of ISF over blood are the quality, quantity and diversity of ISF-based biomarkers; the fluid is non-coagulating, making it feasible to perform multiple or continuous samplings and the sampling is minimally invasive. Our immunosensor requires only 5 µL of ISF to achieve a simultaneous detection of five highly potent proinflammatory cytokines: IL-6, IFN-γ, IL-1ß, TNF-α, IP-10. We employed a microneedle array patch (MAP) together with a trifurcated nozzle pump to extract a mean volume of between 30 and 60 µL of ISF in 20 min. Under optimal conditions, the biosensor is capable of high-quality performance that exhibits a lower limit of detection (LOD) of 5.761 pg/mL over a wide linear range of 5.761-3 ‒ 20.00 ng/mL. We believe our immunosensor for NRT detections via a SOI sampling of ISF-biomarkers offers new theranostic opportunities that may not be possible with blood-based biomarkers.

Hierarchically Micro-, Meso-, and Macro-Porous MOF Nanosystems for Localized Cross-Scale Dual-Biomolecule Loading and Guest-Carrier Cooperative Anticancer Therapy.

Mass transfer of bulky molecules, e.g., bioenzymes, particularly for cross-scale multibiomolecules, imposes serious challenges for microporous metal-organic frameworks (MOFs). Here, we create a hierarchically porous MOF heterostructure featuring highly region-ordered micro-, meso-, and macro-pores by growing a microporous ZIF-8 shell onto a hollow Prussian blue core through an epitaxial growth strategy. This allows for localized loading of large bioenzyme glucose oxidase (GOx) and small drug 5-fluorouracil (5-FU) within specific pores simultaneously and triggers unique guest-carrier cooperative anticancer capabilities. The stable ZIF-8 outer layer effectively blocks the core pores, preventing the undesired leakage of GOx into normal tissues. The acidity-induced ZIF-8 degradation gradually releases Zn2+ and loaded 5-FU for chemotherapy under acidic tumor microenvironments. With the loss of the shielding effect of the ZIF-8 coating, the released GOx depletes intratumoral glucose (Glu) for starvation therapy. Notably, an accelerated cascade reaction occurs between ZIF-8 decomposition and GOx release, facilitated by the modulator factor of Glu. This culminates in the realization of synergistic cancer therapy, as comprehensively demonstrated by in vitro and in vivo experiments, as well as transcriptome sequencing analyses. Our work not only introduces a hierarchically porous MOF heterostructure with highly region-ordered pores but also provides a perspective for guest-carrier cooperative anticancer therapy.

Metformin relieves bone cancer pain by reducing TGFßRI-TRPV1 signaling in rats.

Common cancer complications include bone cancer pain (BCP), which was not sufficiently alleviated by traditional analgesics. More safe and effective therapy was urgent needed. Metformin relieved osteoarthritis pain, but the analgesia of Metformin in BCP was not well studied. The study aimed to explore the Metformin-mediated analgesic effect and its molecular mechanisms in BCP rats. We demonstrated that Walker 256 cell transplantation into the medullary cavity of the tibia worsened mechanical allodynia in BCP rats, increased the expression of TGFß1 in the metastatic bone tissue, and raised the expression of TGFßRI and TRPV1 in the L4-6 dorsal root ganglion (DRG) of BCP rats. While, selectively blockade of TGFßRI by SD208 could obviously elevated the paw withdraw threshold (PWT) of BCP rats, together with decreased TRPV1 expression in L4-6 DRG. Notably, continuous Metformin treatment reduced TGFß1, TGFßRI and TRPV1 expression, and relieved mechanical allodynia of BCP rats in a long-term effect. In conclusion, these results illustrated that Metformin ameliorated bone cancer pain, and the downregulation of TGFß1-TGFßRI-TRPV1 might be a potential mechanism of Metformin-mediated analgesia in BCP.

Protein A immunoadsorption for anti-glomerular basement membrane nephritis.

Anti-glomerular basement membrane (GBM) nephritis is a rare autoimmune disorder characterized by acute and rapidly progressive glomerulonephritis. In this report, we present the case of a 52-year-old woman with anti-GBM nephritis who was treated with Staphylococcus Protein A immunoadsorption in combination with glucocorticoids and cyclophosphamide. After 8 cycles of immunoadsorption, the patient's anti-GBM antibodies decreased from 363 AU/mL to less than 20 AU/mL, accompanied by a dropped immunoglobin G level, although renal impairment persisted. We reviewed the therapeutic options for anti-GBM nephritis and compared plasma exchange, double filtration plasmapheresis, and immunoadsorption with regard to plasma consumption, allergic events, and plasma components loss. Protein A immunoadsorption appears to be a promising treatment modality for anti-GBM nephritis.

Ablation of myocardial autonomic ganglion plexus in the treatment of bradyarrhythmia A one-arm interventional study.

OBJECTIVES: To study the complications and effectiveness of the treatment of chronic arrhythmias with cardiac Ganglion Plexus (GP) ablation, and to explore the value of the treatment of chronic arrhythmias with GP ablation. METHODS: This study was a one-arm interventional study of patients from the first hospital of Xinjiang Medical University and the People's Hospital of Xuancheng City admitted (09/2018-08/2021) because of bradyarrhythmia. The left atrium was modeled using the Carto3 mapping system. The ablation endpoint was the absence of a vagal response under anatomically localized and high-frequency stimulation guidance. Postoperative routine follow-up was conducted. Holter data at 3-, 6-, and 12-months were recorded. RESULTS: Fifty patients (25 male, mean age 33.16 ± 7.89 years) were induced vagal response by either LSGP, LIGP, RAGP, or RIGP. The heart rate was stable at 76 bpm, SNRT 1.092s. DC, DR, HR, SDNN, RMSSD values were lower than that before ablation. AC, SSR, TH values were higher than those before ablation, mean heart rate and the slowest heart rate were significantly increased. There were significant differences in follow-up data between the preoperative and postoperative periods (all p < 0.05). All the patients were successfully ablated, and their blood pressure decreased significantly. No complications such as vascular damage, vascular embolism and pericardial effusion occurred. CONCLUSIONS: Left Atrial GP ablation has good long-term clinical results and can be used as a treatment option for patients with bradyarrhythmia.

ent-Kaurane diterpenoids from Isodon henryi and their anti-inflammatory activities.

Phytochemical investigation of the 70% ethanol extract of Isodon henryi Kudô afforded fifteen ent-kaurane diterpenoids, including nine previously undescribed compounds, named isohenolides C-K (1-9). Compounds 1-6 featured an unusual 6,7;8,15-diseco-7,20-olide ent-kaurane diterpenoid scaffold, in which 1 also possessed an 11,15-lactone ring while 2-6 all contained a free α-methylene-γ-carboxylic acid. Compound 6 was also a rare 6,8-cyclo-7,20-olide ent-kauranoid. Their structures were elucidated primarily by HRESIMS, 1D and 2D NMR spectroscopy, electronic circular dichroism and X-ray diffraction (Cu Kα) methods. Additionally, most compounds were also screened for anti-inflammatory actions against lipopolysaccharide-induced RAW 264.7 cells, and compounds 9 and 13 exhibited stronger nitric oxide inhibition, with IC50 values of 15.99 ± 0.75 and 18.19 ± 0.42 µM, respectively.