Kidney targeting and modulating macrophage polarization through AMPK signaling: Therapeutic mechanism of berberine in uric acid nephropathy.

Uric acid nephropathy (UAN), caused by a common metabolic disorder resulting from hyperuricemia (HUA), has an increasing incidence. Previous studies have shown that berberine (BBR) has clear urate-lowering and anti-inflammatory effects in UAN mice, but its mechanism needs to be further clarified. Therefore, Potassium Oxonate (PO) combined with hypoxanthine (HX) induced UAN mice model and MSU induced THP-1 cells polarization model were adopted to investigate the mechanism of BBR on UAN in terms of tissue distribution and molecular pharmacology. Study unveiled that BBR was first found to bind to red blood cells (RBCs), which were recognized and phagocytosed by monocytes, then recruited by the injured kidney. Subsequently, BBR was enriched and functional in damaged kidney. The results of in vivo experiments revealed that, BBR reduced UA, BUN, CRE levels as well as the release of TNF-α, IL-1ß, IL-18 and IL-6, and alleviated renal injury in UAN mice, as consistent with previous studies. Additionally, BBR decreased MCP-1 expression, while diminishing macrophage infiltration and decreasing M1 proportion as determined by RT-qPCR. In vitro experiments, demonstrated that MSU promoted inflammatory polarization of THP-1 cells, while BBR reduced synthesis of inflammatory factors and inhibited MSU-induced inflammatory polarization. These effects of BBR were dependent on AMPK activation along with indirect inhibition of NF-κB signaling pathway mediated. However, the anti-inflammatory and macrophage polarization regulation effects of BBR were completely reversed upon administration of Compound C, an AMPK inhibitor. Therefore, BBR ameliorated kidney injury via regulating macrophage polarization through AMPK, which has therapeutic potential for UAN patients.

Hsa_Circ_002144 Promotes Glycolysis and Immune Escape of Breast Cancer Through miR-326/PKM Axis.

Background: Breast cancer is a leading cause of cancer-related deaths in women worldwide, posing a significant threat to female health. Therefore, it is crucial to search for new therapeutic targets and prognostic biomarkers for breast cancer patients. Method: Bioinformatics analysis, quantitative real-time PCR (qRT-PCR), and fluorescence in situ hybridization (FISH) were employed to investigate the expression of hsa_circ_002144 in breast cancer. Transwell assay, Western blotting, and cell viability assay were utilized to assess the impact of hsa_circ_002144 on the proliferation, migration, and invasion of breast cancer cells. Additionally, a mouse model was established to validate its functionality. Flow cytometry, WB analysis, enzyme-linked immunosorbent assay (ELISA), qRT-PCR, exosomes isolation, and co-culture system were employed to elucidate the molecular mechanism underlying macrophage polarization. Result: we have discovered for the first time that hsa_circ_002144 is highly expressed in breast cancer. It affected tumor growth and metastasis and could influence macrophage polarization through the glycolytic pathway. Conclusion: This finding provides a new direction for breast cancer treatment and prognosis assessment.

Patchouli alcohol alleviates metabolic dysfunction-associated steatohepatitis via inhibiting mitochondria-associated endoplasmic reticulum membrane disruption-induced hepatic steatosis and inflammation in rats.

Metabolic dysfunction-associated steatohepatitis (MASH) is a severe metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by abnormal hepatic steatosis and inflammation. Previous studies have shown that Patchouli alcohol (PA), the primary component of Pogostemonis Herba, can alleviate digestive system diseases. However, its protection against MASH remains unclear. This study explored the protective effects and underlying mechanism of PA against high-fat diet-induced MASH in rats. Results showed that PA considerably reduced body weight, epididymal fat, and liver index and attenuated liver histological injury in MASH rats. PA alleviated hepatic injury by inhibiting steatosis and inflammation. These effects are associated with the improvement of SREBP-1c- and PPARα-mediated lipid metabolism and inhibition of the STING-signaling pathway-mediated inflammatory response. Moreover, PA-inhibited hepatic endoplasmic reticulum (ER) stress and mitochondrial dysfunction, reducing SREBP-1c and STING expressions and enhance PPARα expression. PA treatment had the strongest effect on the regulation of mitogen fusion protein 2 (Mfn2) in inhibiting mitochondrial dysfunction. Mfn2 is an important structural protein for binding ERs and mitochondria to form mitochondria-associated ER membranes (MAMs). MASH-mediated disruption of MAMs was inhibited after PA treatment-induced Mfn2 activation. Therefore, the pharmacological effect of PA on MASH is mainly attributed to the inhibition of MAM disruption-induced hepatic steatosis and inflammation. The findings of this study may have implications for MASH treatment that do not neglect the role of Mfn2-mediated MAMs.

Mutant androgen receptor induces neurite loss and senescence independently of ARE binding in a neuronal model of SBMA.

Spinal and bulbar muscular atrophy (SBMA) is a slowly progressing neuromuscular disease caused by a polyglutamine (polyQ)-encoding CAG trinucleotide repeat expansion in the androgen receptor (AR) gene, leading to AR aggregation, lower motor neuron death, and muscle atrophy. AR is a ligand-activated transcription factor that regulates neuronal architecture and promotes axon regeneration; however, whether AR transcriptional functions contribute to disease pathogenesis is not fully understood. Using a differentiated PC12 cell model of SBMA, we identified dysfunction of polyQ-expanded AR in its regulation of neurite growth and maintenance. Specifically, we found that in the presence of androgens, polyQ-expanded AR inhibited neurite outgrowth, induced neurite retraction, and inhibited neurite regrowth. This dysfunction was independent of polyQ-expanded AR transcriptional activity at androgen response elements (ARE). We further showed that the formation of polyQ-expanded AR intranuclear inclusions promoted neurite retraction, which coincided with reduced expression of the neuronal differentiation marker ß-III-Tubulin. Finally, we revealed that cell death is not the primary outcome for cells undergoing neurite retraction; rather, these cells become senescent. Our findings reveal that mechanisms independent of AR canonical transcriptional activity underly neurite defects in a cell model of SBMA and identify senescence as a pathway implicated in this pathology. These findings suggest that in the absence of a role for AR canonical transcriptional activity in the SBMA pathologies described here, the development of SBMA therapeutics that preserve this activity may be desirable. This approach may be broadly applicable to other polyglutamine diseases such as Huntington's disease and spinocerebellar ataxias.

Supersaturated Drug Delivery System of Oxyberberine Based on Cyclodextrin Nanoaggregates: Preparation, Characterization, and in vivo Application.

Propose: Oxyberberine (OBB), one of the main metabolites of berberine derived from intestinal and erythrocyte metabolism, exhibits appreciable anti-hyperuricemic activity. However, the low water solubility and poor plasma concentration-effect relationship of OBB hamper its development and utilization. Therefore, an OBB-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) supersaturated drug delivery system (SDDS) was prepared and characterized in this work. Methods: OBB-HP-ß-CD SDDS was prepared using the ultrasonic-solvent evaporation method and characterized. Additionally, the in vitro and in vivo release experiments were conducted to assess the release kinetics of OBB-HP-ß-CD SDDS. Subsequently, the therapeutic efficacy of OBB-HP-ß-CD SDDS on hyperuricemia (HUA) was investigated by means of histopathological examination and evaluation of relevant biomarkers. Results: The results of FT-IR, DSC, PXRD, NMR and molecular modeling showed that the crystallized form of OBB was transformed into an amorphous OBB-HP-ß-CD complex. Dynamic light scattering indicated that this system was relatively stable and maintained by formation of nanoaggregates with an average diameter of 23 nm. The dissolution rate of OBB-HP-ß-CD SDDS was about 5 times higher than that of OBB raw material. Furthermore, the AUC0-t of OBB-HP-ß-CD SDDS (10.882 µg/mL*h) was significantly higher than that of the raw OBB counterpart (0.701 µg/mL*h). The oral relative bioavailability of OBB-HP-ß-CD SDDS was also enhanced by 16 times compared to that of the raw material. Finally, in vivo pharmacodynamic assay showed the anti-hyperuricemic potency of OBB-HP-ß-CD SDDS was approximately 5-10 times higher than that of OBB raw material. Conclusion: Based on our findings above, OBB-HP-ß-CD SDDS proved to be an excellent drug delivery system for increasing the solubility, dissolution, bioavailability, and anti-hyperuricemic potency of OBB.

Sources and formation characteristics of particulate nitrate in the Pearl River Delta region of China: Insights from three-year online observations.

Nitrate (NO3-) has been identified as a key component of particulate matter (PM2.5) in China. However, there is still a lack of understanding regarding its sources and how it forms, especially in the context of high-frequency and long-term data. In this study, NO3- levels were observed on an hourly basis over an almost three-year period at an urban site in the Pearl River Delta (PRD) region, China, from January 2019 to December 2021. The results reveal an average daily NO3- concentration ranging from 0.08 µg m-3 to 61.69 µg m-3, constituting 11.9 ± 12.5 % of PM2.5. This percentage rose to as high as 57 % during pollution episodes, highlighting NO3-'s significant role in pollution formation. The ammonia-rich environment was found to be the most important factor in promoting NO3- formation. Positive Matrix Factorization (PMF) analysis indicates that the primary sources of NO3- in the PRD region were vehicle emissions (43.8 ± 21.2 %) and coal combustion (39.1 ± 21.5 %), with shipping emissions, sea salt, soil dust and industrial emissions + biomass burning following in importance. Regarding source areas, the primary contributor of vehicle emissions was predominantly from the PRD region, whereas the coal combustion, aside from local contributions, also originates from the northern region. From a long-term perspective, NO3- pollution has remained relatively stable since the summer of 2020. Concurrently, coal combustion source has shown a localization trend. These insights derived from the extensive, high-frequency observation presented in this study serve as a valuable reference for devising strategies to control NO3- and PM2.5 in the PRD region and China.

Patient derived cancer organoids model the response to HER2-CD3 bispecific antibody (BsAbHER2) generated from hydroxyapatite gene delivery system.

HER2-positive cancer is a prevalent subtype of malignancy with poor prognosis, yet current targeted therapies, like Trastuzumab and pyrotinib, have resulted in remission in patients with HER2-positive cancer. This study provides a novel approach for immunotherapy based on a hydroxyapatite (HA) gene delivery system producing a bispecific antibody for HER2-positive cancer treatment. An HA nanocarrier has been synthesized by the classical hydrothermal method. Particularly, the HA-nanoneedle system was able to mediate stable gene expression of minicircle DNA (MC) encoding a humanized anti-CD3/anti-HER2 bispecific antibody (BsAbHER2) in vivo. The produced BsAbs exhibited a potent killing effect not only in HER2-positive cancer cells but also in patient-derived organoids in vitro. This HA-nanoneedle gene delivery system features simple large-scale preparation and clinical applicability. Hence, the HA-nanoneedle gene delivery system combined with minicircle DNA vector encoding BsAbHER2 reported here provides a potential immunotherapy strategy for HER2-positive tumors.

A self-healing thermogelling polymer with tunable transparency based on biomolecule alginate grafting phenylboronic acid.

Thermogelling polymers with transparency, structure stability and biocompatibility are promising for biomedicine application. In this study, a thermogelling polymer P-C5PEG with tunable transparency was developed by the reaction between alternating copolymer C5PEG and chemically modified biomolecule Alg-PBA via boronic ester bonds. The sol-to-gel transition of P-C5PEG aqueous solution sensitively responded to changes in temperature, and the critical value could be adjusted between 15 and 40 °C by varying the content of C5PEG and Alg-PBA. As the weight ratio of Alg-PBA to C5PEG was over 0.3, the transparency of as-synthesized hydrogel kept above 75 % at 37 °C. Meanwhile, immersion P-C5PEG hydrogel in CaCl2 solution significantly increased its mechanical strength by 3 times due to chelation effect. The shear-resistance and self-healing properties were ensured by dynamic boronic ester bonds due to the protective effect of hydrophobic gel network. As a drug delivery, P-C5PEG hydrogel had a swelling rate of 3748.7 ± 103 % in PBS and could continuously release fluorescein sodium within 24 h. Moreover, the in vitro degradability and cytotoxicity of P-C5PEG was confirmed. Finally, the mechanisms behind the thermogelling property and tunable transparency were revealed. Overall, this thermogelling P-C5PEG polymer, with tunable transparency and thermo-responsiveness, exhibits great potential for biomedicine application.

Extraction, purification, structural characteristics, and pharmacological activities of the polysaccharides from corn silk: A review.

Corn silk is widely used as a traditional Chinese medicine possessing multiple beneficial effects, whose active ingredient is corn silk polysaccharide (CSP). CSP is abundant in corn silk, and has a variety of bioactivities, such as antioxidant, hypoglycemic, hypolipidemic, hepatorenal-protective, antitumor, anti-fatigue, immunomodulating, and anti-ischemia-reperfusion injury effects. Moreover, CSP ameliorates diabetes, diabetes nephropathy, and hyperlipidemia. This review aimed to comprehensively and systematically summarize recent information on the extraction, purification, structural characterization, biological activity, potential mechanism, and toxicity of CSP. Thus, it could provide a reference for the further use of CSP and discuss the future prospects of CSP research and development.

Effect of intraocular pressure reduction on progressive high myopia (PHM study): study protocol of a randomised controlled trial.

BACKGROUND: In adult patients with high myopia (HM), progressive axial elongation poses a significant risk for the development of subsequent ocular complications that may lead to visual impairment. Effective strategies to reduce or prevent further axial elongation in highly myopic adult patients have not been available so far. Recent studies suggested that medically lowering intraocular pressure (IOP) may reduce axial elongation. OBJECTIVE: This clinical randomised controlled trial (RCT) aims to evaluate the efficacy of medical IOP reduction in adult patients with progressive HM (PHM). TRIAL DESIGN: Single-centre, open-label, prospective RCT. METHODS: This RCT will recruit 152 participants with PHM at the Zhongshan Ophthalmic Center (ZOC). Randomised in a ratio of 1:1, participants will receive IOP-lowering eyedrops (intervention group) or will be followed without treatment (control group) for 12 months. Follow-up visits will be conducted at 1, 6 and 12 months after baseline. Only one eye per eligible participant will be included for analysis. The primary outcome is the change in axial length (AL) within the study period of 12 months. Secondary outcomes include the incidence and progression of visual field (VF) defects, changes in optic disc morphology and incidence and progression of myopic maculopathy. Difference in AL changes between the two groups will be analysed using linear regression analysis. For the secondary outcomes, a multifactor Poisson regression within a generalised linear model will be used to estimate the relative risk of progression in VF defects and myopic maculopathy, and the rate of thinning in retinal nerve fibre layer and ganglion cell-inner plexiform will be assessed through Kaplan-Meier curves and log-rank tests. ETHICS AND DISSEMINATION: Full ethics approval for this trial has been obtained from the Ethics Committee of ZOC, Sun Yat-sen University, China (ID: 2023KYPJ110). Results of this trial will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05850936.

Knowledge, Attitudes, and Practices about Hyperuricemia and Gout in Community Health Workers and Patients with Diabetes.

Hyperuricemia exhibits a high incidence among individuals with diabetes; however, the significance of hyperuricemia and gout is often underestimated. This study aimed to assess the knowledge, attitude, and practice of hyperuricemia and gout among community health workers and patients with diabetes. Two questionnaires were designed to investigate knowledge, attitudes, and practices of hyperuricemia and gout among community health workers and patients with diabetes in Chenghua District, Chengdu, from August 2021 to January 2022. A total of 709 community health workers were included, whose average score was 17.74/30. Approximately half of general practitioners (GPs) demonstrated knowledge regarding the target serum uric acid levels for hyperuricemia and gout. Only 11.2% of GPs were fully aware of the preferred medicine for acute gout. The majority of GPs (86.7%) demonstrated limited awareness regarding the contraindications associated with colchicine, while a significant proportion (65.1%) lacked knowledge about the specific classes of drugs that inhibit uric acid synthesis. Among the 508 patients with diabetes included in this survey, 32.3% demonstrated awareness of hyperuricemia, while 60.8% exhibited knowledge regarding gout. The average score attained by these individuals was recorded at 7.21 out of a total of 26 points. The majority of patients with diabetes (87.8%) held the mistaken belief that hyperuricemia definitely led to the development of gout. Almost 66% agreed that a massage or a hot compress could be used when acute gouty arthritis attacks. The knowledge rate of hyperuricemia and gout among community health workers was moderate, while it was low in patients with diabetes.

PRG ameliorates cognitive impairment in Alzheimer's disease mice by regulating ß-amyloid and targeting the ERK pathway.

BACKGROUND: PRG is derived from Phellinus ribis and is a homogeneous polysaccharide with well-defined structural information. PRG was found to have significant in vitro neurotrophic and neuroprotective activities. Thus, PRG might be a potential treatment for Alzheimer's disease. However, the related mechanisms of action are still unclear, so deeper in vivo experimental validation and the potential mechanisms need to be investigated. PURPOSE: The effects of PRG on AD mice were investigated using Senescence-accelerated SAMP8 mice as an AD model to elucidate the crucial molecular mechanisms. METHODS: PRG was obtained from Phellinus ribis by water-alcohol precipitation, column chromatography, and ultrafiltration. The Morris water maze and novel object recognition behavioral assays were used to evaluate the effects of PRG in AD mice. Nissl staining, the TUNEL apoptosis assay, and Golgi staining were used to assess brain neuronal cell damage, apoptosis, and neuronal status. Enzyme-linked immunosorbent assays, Western blotting, and immunofluorescence were used to explore the impacts of correlated factors and protein pathways under relevant mechanisms. RESULTS: The findings suggest that PRG improved learning ability and spatial memory capacity in SAMP8 mice. PRG hastened the disintegration of ß-amyloid, reduced the content and abnormal accumulation of the toxic Aß1-42 protein, and decreased apoptosis. PRG activated the BDNF/ERK/CREB signaling pathway through a cascade, exerted neurotrophic effects, regulated cell proliferation and differentiation, increased neuronal dendritic branching and spine density, and improved synaptic plasticity. CONCLUSION: PRG promoted ß-amyloid degradation to reduce neuronal damage and apoptosis. It exerted neurotrophic effects by activating the BDNF/ERK/CREB pathway, promoting neuronal dendritic branching and dendritic spine growth, regulating cell proliferation and differentiation, and improving synaptic plasticity, which improved AD. Taken together, as a novel natural active polysaccharide with a well-defined structure, PRG affected AD symptoms in senescence-accelerated mice by interacting with multiple targets. The results indicate that PRG is a promising potential anti-AD drug candidate.

A Mean Field to Capture Asynchronous Irregular Dynamics of Conductance-Based Networks of Adaptive Quadratic Integrate-and-Fire Neuron Models.

Mean-field models are a class of models used in computational neuroscience to study the behavior of large populations of neurons. These models are based on the idea of representing the activity of a large number of neurons as the average behavior of mean-field variables. This abstraction allows the study of large-scale neural dynamics in a computationally efficient and mathematically tractable manner. One of these methods, based on a semianalytical approach, has previously been applied to different types of single-neuron models, but never to models based on a quadratic form. In this work, we adapted this method to quadratic integrate-and-fire neuron models with adaptation and conductance-based synaptic interactions. We validated the mean-field model by comparing it to the spiking network model. This mean-field model should be useful to model large-scale activity based on quadratic neurons interacting with conductance-based synapses.

Association of Overweight and Inflammatory Indicators with Breast Cancer: A Cross-Sectional Study in Chinese Women.

Objective: This cross-sectional study aimed to explore the association of overweight and inflammatory indicators with breast cancer risk in Chinese patients. Methods: Weight, height, and peripheral blood inflammatory indicators, including white blood cell count (WBC), neutrophil count (NE), lymphocyte count (LY), platelet count (PLT) and the concentration of hypersensitivity C-reactive protein (hsCRP), were collected in 383 patients with benign breast lumps (non-cancer) and 358 patients with malignant breast tumors (cancer) at the First Affiliated Hospital of Soochow University, China, from March 2018 to July 2020. Body mass index (BMI), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were determined according to the ratio equation. The correlations among overweight, inflammatory indicators, and the proportion of non-cancer or cancer cases were analyzed. Results: BMI is associated with an increased breast cancer risk. Compared with non-cancer patients, the average WBC count, NE count, NLR, and level of hsCRP were significantly higher in cancer patients. The level of hsCRP was closely associated with the size of malignant breast tumors. Conclusion: We conclude that overweight and high levels of hsCRP may serve as putative risk factors for malignant breast tumors in Chinese women.

DDID: a comprehensive resource for visualization and analysis of diet-drug interactions.

Diet-drug interactions (DDIs) are pivotal in drug discovery and pharmacovigilance. DDIs can modify the systemic bioavailability/pharmacokinetics of drugs, posing a threat to public health and patient safety. Therefore, it is crucial to establish a platform to reveal the correlation between diets and drugs. Accordingly, we have established a publicly accessible online platform, known as Diet-Drug Interactions Database (DDID, https://bddg.hznu.edu.cn/ddid/), to systematically detail the correlation and corresponding mechanisms of DDIs. The platform comprises 1338 foods/herbs, encompassing flora and fauna, alongside 1516 widely used drugs and 23 950 interaction records. All interactions are meticulously scrutinized and segmented into five categories, thereby resulting in evaluations (positive, negative, no effect, harmful and possible). Besides, cross-linkages between foods/herbs, drugs and other databases are furnished. In conclusion, DDID is a useful resource for comprehending the correlation between foods, herbs and drugs and holds a promise to enhance drug utilization and research on drug combinations.

Superior Rectal Artery Preservation in Laparoscopically Assisted Subtotal Colectomy and Ileorectal Anastomosis for Slow-Transit Constipation.

Our previous retrospective observational study demonstrated the safety of laparoscopically assisted subtotal colectomy with ileorectal anastomosis and preservation of the superior rectal artery (SRA), without instances of leakage, in patients with slow-transit constipation (STC). Thus, we extended the enrollment period and enlarged the sample size to detect the differences in the postoperative complications and surgical and functional outcomes between patients who underwent laparoscopically assisted subtotal colectomy with and without SRA preservation. We conducted a retrospective single-center analysis of patients with STC who underwent laparoscopically assisted subtotal colectomy between 2016 and 2020. The diagnosis of STC was based on the colonic transit and anal functional tests and barium enema to exclude secondary causes. Patients were divided into group A, which underwent surgery with SRA preservation, and group B, which underwent ligation of the SRA during surgery. Outcome assessments for both groups included the incidence of anastomotic breakdown, intraoperative complications, length of hospital stay, estimated blood loss, time to first flatus, and complications. Propensity score matching allocated 34 patients to groups A and B each. Postoperative bowel function, including time to first flatus, stool, and oral intake, recovered better in group A than in group B. Anastomotic leakage, a significant postoperative complication, was less frequent in patients with SRA preservation. In conclusion, preservation of the SRA in patients undergoing laparoscopically assisted subtotal colectomy with ileorectal anastomosis for STC is associated with favorable postoperative bowel function recovery and lower anastomotic leakage rates.

Analysis of care-seeking and diagnosis delay among pulmonary tuberculosis patients in Beijing, China.

Background: Tuberculosis (TB) remains a significant public health challenge in China. Early detection and diagnosis of TB cases are crucial to interrupt disease transmission and prevent its progression. This study aims to describe the delay in seeking care and diagnosis among patients with pulmonary tuberculosis (PTB) and identify the influencing factors in two counties in Beijing. Methods: A retrospective analysis was carried out to investigate care-seeking and diagnosis delay in two counties in Beijing. Basic information of PTB patients from January 1 to December 31, 2021, was extracted from the Tuberculosis Information Management System of China (TBIMS), and all enrolled patients were interviewed via telephone using a standard questionnaire. Statistical description was performed using the median and interquartile range (IQR). Chi-square test and multivariate logistic regression model were used to analyze the influencing factors. Results: 537 patients were enrolled. The median duration of care-seeking and diagnosis delay was 11 (IQR: 5-26) days and 8 (IQR: 0-18) days, with 41.71 and 35.20% of patients experiencing delays (>14 days). The study found that being asymptomatic (OR = 2.791, 95%CI: 1.710-4.555) before seeking medical care and not attending work during treatment (OR = 2.990, 95%CI: 1.419-6.298) were identified as risk factors for care-seeking delay. Patients who were tracked (OR = 2.632, 95%CI: 1.062-6.521) and diagnosed at tuberculosis control and prevention institutions (OR = 1.843, 95%CI: 1.061-3.202) had higher odds of diagnostic delays. 44.69% of patients presented a total delay (>28 days), with a median duration of 25 (IQR: 13-39) days. A multivariate logistic regression analysis showed that healthy examination (OR = 0.136, 95%CI: 0.043-0.425) was a protective factor for total delay. Conclusion: Public interventions are necessary to improve the efficiency of PTB patients detection and treatment in Beijing. Medical services should focus on the target population and improve access to medical care to further reduce delays for PTB patients.

Preparation, structural characteristics and pharmacological activity of polysaccharides from Polygala tenuifolia: A review.

Polygala tenuifolia is a traditional Chinese medicine with a long history of application, with the efficacy of suppressing cough, calming asthma, tranquilizing the mind, and benefiting the intellect. It is classified as a top-quality medicine in Shennong's Classic of Materia Medica. Polysaccharide is an important active ingredient in Polygala tenuifolia, which consists of several monosaccharides, including Ara, Gal, Glc, and so on. In this review, the preparation methods, structural characteristics, and biological activities of polysaccharides from Polygala tenuifolia are summarized, and the problems in the current studies are discussed to support further research, development, and utilization.

Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis.

BACKGROUND: Acute liver failure (ALF) has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis. The silent information regulator sirtuin 1 (SIRT1)-mediated deacetylation affects multiple biological processes, including cellular senescence, apoptosis, sugar and lipid metabolism, oxidative stress, and inflammation. AIM: To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms. METHODS: This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) testing. C57BL/6 mice were also intraperitoneally pretreated with SIRT1, p53, or glutathione peroxidase 4 (GPX4) inducers and inhibitors and injected with lipopolysaccharide (LPS)/D-galactosamine (D-GalN) to induce ALF. Gasdermin D (GSDMD)-/- mice were used as an experimental group. Histological changes in liver tissue were monitored by hematoxylin and eosin staining. ALT, AST, glutathione, reactive oxygen species, and iron levels were measured using commercial kits. Ferroptosis- and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction. SIRT1, p53, and GSDMD were assessed by immunofluorescence analysis. RESULTS: Serum AST and ALT levels were elevated in patients with ALF. SIRT1, solute carrier family 7a member 11 (SLC7A11), and GPX4 protein expression was decreased and acetylated p5, p53, GSDMD, and acyl-CoA synthetase long-chain family member 4 (ACSL4) protein levels were elevated in human ALF liver tissue. In the p53 and ferroptosis inhibitor-treated and GSDMD-/- groups, serum interleukin (IL)-1ß, tumour necrosis factor alpha, IL-6, IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated. In mice with GSDMD knockout, p53 was reduced, GPX4 was increased, and ferroptotic events (depletion of SLC7A11, elevation of ACSL4, and iron accumulation) were detected. In vitro, knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels, the cytostatic rate, and GSDMD expression, restoring SLC7A11 depletion. Moreover, SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group, accompanied by reduced p53, GSDMD, and ACSL4, and increased SLC7A11 and GPX4. Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalN-induced in vitro and in vivo models. CONCLUSION: SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.

Severity of COVID-19 infection in patients with COVID-19 combined with diabetes.

PURPOSE: This study aimed to analyse the correlation between blood glucose control and the severity of COVID-19 infection in patients with diabetes. METHODS: Clinical and imaging data of a total of 146 patients with diabetes combined with COVID-19 who visited our hospital between December 2022 and January 2023 were retrospectively collected. The patients were divided into the 'good blood glucose control' group and the 'poor blood glucose control' group based on an assessment of their blood glucose control. The clinical data, computed tomography (CT) appearance and score and the severity of COVID-19 infection of the two groups were compared, with the severity of COVID-19 infection being the dependent variable to analyse other influencing factors. RESULTS: The group with poor blood glucose control showed a higher lobar involvement degree and total CT severity score (CTSS) than the group with good blood glucose control (13.30 ± 5.25 vs. 10.38 ± 4.84, p < 0.05). The two groups exhibited no statistically significant differences in blood lymphocyte, leukocyte, C-reaction protein, pleural effusion, consolidation, ground glass opacity or crazy-paving signs. Logistic regression analysis showed that the total CTSS significantly influences the clinical severity of patients (odds ratio 1.585, p < 0.05), whereas fasting plasma glucose and blood glucose control are not independent factors influencing clinical severity (both p > 0.05). The area under the curve (AUC) of CTSS prediction of critical COVID-19 was 0.895 with sensitivity of 79.3% and specificity of 88.1% when the threshold value is 12. CONCLUSION: Blood glucose control is significantly correlated with the CTSS; the higher the blood glucose is, the more severe the lung manifestation. The CTSS can also be used to evaluate and predict the clinical severity of COVID-19.