Advancing towards practice: A novel LC-MS/MS method for detecting retinol in dried blood spots.

BACKGROUND: To date, clinical laboratories face challenges in quantifying retinol from DBS samples. Disputes arise throughout the whole detection process, encompassing the storage condition, the release strategy as well as the selection of internal standards. METHODS: We incubated DBS with ascorbic acid solution. Then, retinol-d4 in acetonitrile was introduced to incorporate isotopic internal standard and promote protein precipitation. Afterward, sodium carbonate solution was added to ionize cytochromes (such as bilirubin), which amplified the difference of their hydrophobicity to retinol. Subsequently, cold-induced phase separation could be facilitated to separate retinol from the impurities. In the end, the upper layer was injected for LC-MS/MS analysis. RESULTS: By comparing the detected retinol content in whole blood and DBS samples prepared from the same volume, we confirmed the established pretreatment was capable to extract most of retinol from DBS (recovery >90 %). Thereafter, we verified that within DBS, retinol possessed satisfying stability without antioxidation. Indoor-light exposure and storage duration would not cause obvious degradation (<10 %). Following systematic validation, the established method well met the criteria outlined in the relevant guidelines. After comparing with detected DBS results to the paired plasma samples, 54 out of 60 met the acceptance limit for cross-validation of ±20 %. CONCLUSIONS: We realized precise quantification of retinol from one 3.2 mm DBS disc. By circumventing conventional antioxidation, liquid-liquid/solid-phase extraction and organic solvent evaporation, the pretreatment could be completed within 15 min consuming only minimal amounts of low-toxicity chemicals (ascorbic acid, acetonitrile, and sodium carbonate). We expect this contribution holds the potential to significantly facilitate the evaluation of patients' vitamin A status by using DBS samples in the future.

Targeting Neuronal GPR65 With Delayed BTB09089 Treatment Improves Neurorehabilitation Following Ischemic Stroke.

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.

Pulmonary tumor thrombotic microangiopathy: Two case reports and literature review.

RATIONALE: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary hypertension with severe respiratory distress. More than 200 cases have been reported since it was first identified in 1990. PTTM accounts for approximately 0.9% to 3.3% of deaths due to malignancy, but only a minority of patients are diagnosed ante-mortem, with most patients having a definitive diagnosis after autopsy. PATIENT CONCERNS: Two middle-aged women both died within a short period of time due to progressive dyspnea and severe pulmonary hypertension. DIAGNOSES: One patient was definitively confirmed as a gastrointestinal malignant tumor by liver puncture biopsy pathology. Ultimately, the clinical diagnosis was pulmonary tumor thrombotic microangiopathy. INTERVENTIONS: The patient was treated symptomatically with oxygen, diuresis, and anticoagulation, while a liver puncture was perfected to clarify the cause. OUTCOMES: Two cases of middle-aged female patients with rapidly progressive pulmonary hypertension and respiratory failure resulted in death with malignant neoplasm. LESSONS: PTTM has a rapid onset and a high morbidity and mortality rate. Our clinicians need to be more aware of the need for timely diagnosis through a targeted clinical approach, leading to more targeted treatment and a better prognosis.

The association between diabetes mellitus and prostate cancer: a meta-analysis and Mendelian randomization.

BACKGROUND: Prostate cancer is one of the most common types of cancer in the US, and it has a high mortality rate. Diabetes mellitus is also a dangerous health condition. While some studies have examined the relationship between diabetes mellitus and the risk of prostate cancer, there is still some debate on the matter. This study aims to carefully assess the relationship between prostate cancer and diabetes from both real-world and genetic-level data. METHODS: This meta-analysis was conducted following the PRISMA 2020 reporting guidelines. The study searched three databases including Medline, Embase and Cochrane. The studies about the incidence risk of prostate cancer with diabetes mellitus were included and used to evaluate the association. The odds ratio (OR), risk ratio (RR) and 95% confidence intervals (95% CI) were estimated using Random Effects models and Fixed Effects models. Mendelian randomization study using genetic variants was also conducted. RESULTS: A total of 72 articles were included in this study. The results showed that risk of prostate cancer decreased in diabetes patients. And the influence was different in different regions. This study also estimated the impact of body mass index (BMI) in the diabetes populations and found that the risk decreased in higher BMI populations. The MR analysis found that diabetes mellitus exposure reduced the risk of prostate cancer in the European population and Asia populations. Conclusions The diabetes mellitus has a protective effect on prostate cancer. And the influence of obesity in diabetes mellitus plays an important role in this effect.

Optical detection of infectious SARS-CoV-2 virions by counting spikes.

Existing methods for the mass detection of viruses are limited to the registration of small amounts of a viral genome or specific protein markers. In spite of high sensitivity, the applied methods cannot distinguish between virulent viral particles and non-infectious viral particle debris. We report an approach to solve this long-standing challenge using the SARS-CoV-2 virus as an example. We show that wide-field optical microscopy with the state-of-the-art mesoscopic fluorescent labels, formed by a core-shell plasmonic nanoparticle with fluorescent dye molecules in the core-shell that are strongly coupled to the plasmonic nanoparticle, not only rapidly, i.e. in less than 20 minutes after sampling, detects SARS-CoV-2 virions directly in a patient sample without a pre-concentration step, but can also distinguish between infectious and non-infectious virus strains by counting the spikes on the lipid envelope of individual viral particles.

Menopausal hormone therapy decreases the likelihood of diabetes development in peri­menopausal individuals with prediabetes.

BACKGROUND: The influence of menopausal hormone therapy (MHT) on the probability of developing diabetes mellitus in individuals with prediabetes remains uncertain. METHODS: This retrospective cohort study, utilizing the TriNetX U.S. Collaborative Network, investigated cohorts, implemented propensity score matching, and analyzed outcomes associated with diabetes mellitus. The study focused on individuals aged 46-60 with prediabetes prior to menopause, categorizing them into MHT and non-MHT groups. Further stratified analyses, including variables such as age and race, were conducted to thoroughly examine potential variations in outcomes. RESULTS: The study involved 6566 individuals (MHT and non-MHT), with propensity score matching ensuring balanced cohorts. Over a 20-year follow-up, the MHT group demonstrated a lower incidence of diabetes mellitus compared to the non- MHT group, with a Hazard Ratio of 0.693 (95 % CI: 0.577, 0.832). Stratified analyses revealed age-specific nuances, with significant protective effects in individuals aged 46-50 and 55-60. Additionally, ethnicity played a role, with MHT demonstrating significant benefits in White individuals but not in the Black or Asian populations. BMI analysis indicated a significant risk reduction with MHT in individuals with BMI less than or equal to 24.9 and 25-29.9 kg/m 2, but not in those with BMI greater than or equal to 30 kg/m 2. CONCLUSION: In our study, we demonstrate a sustained 20-year decrease in the risk of diabetes among premenopausal individuals with prediabetes who undergo menopausal hormone therapy.

Novel thiosemicarbazide-based ß-carboline derivatives as α-glucosidase inhibitors: Synthesis and biological evaluation.

In the quest for potent α-glucosidase inhibitors to combat diabetes, a series of novel thiosemicarbazide-based ß-carboline derivatives (CTL1∼36) were synthesized and evaluated. CTL1∼36 exhibited remarkable inhibitory effects against α-glucosidase, with IC50 values ranging from 2.81 to 12.40 µM, significantly surpassing the positive control acarbose (IC50 = 564.28 µM). Notably, CTL26 demonstrated the most potent inhibition (IC50 = 2.81 µM) and was characterized as a non-competitive inhibitor. Through a combination assay with fluorescence quenching, 3D fluorescence spectra, CD spectra, and molecular docking, we elucidated that CTL26 formed a complex with α-glucosidase via hydrogen bondings and hydrophobic interactions, leading to α-glucosidase conformation changes that impaired enzymatic activity. In vivo studies revealed that oral administration of CTL26 (25 and 50 mg/kg/d) reduced fasting blood glucose levels, enhanced glucose tolerance, and ameliorated lipid abnormalities in diabetic mice. These findings positioned CTL26 as a promising candidate for the development of α-glucosidase inhibitors with anti-diabetic potential.

Associations Between Vitamin K and Suicide Attempts in Patients with Depression: A Case-Control Study.

Background: Hypovitaminosis K has been linked to depression and suicide, but epidemiological research is scarce. This study aimed to explore the association among vitamin K with depression and suicidal attempts. Methods: This was a retrospective cross-sectional study involving 146 cases with a history of suicidal attempts and 149 subjects without a lifetime history of suicidal attempts. The levels of thyroid hormones, lipid profile, inflammatory cytokines, and vitamins were measured. Results: Subjects who had suicidal attempts presented with a significant decrease in FT4, TC, vitamin D, and vitamin K but increased CRP levels. In these variables, vitamin K has a better diagnostic value for suicidal attempts in depressed patients, with a sensitivity of 0.842 and a specificity of 0.715. Correlation analysis suggested that vitamin K was significantly and positively related to FT4, TC, LDL, and sdLDL. Multivariate analysis showed that serum vitamin K level predicts suicidal attempts in depressive patients (OR = 0.614, P = 0.004, 95% CI 0.153-0.904). Moreover, a negative correlation between vitamin K and suicidal attempts was also noted for partial FT4, CRP, and vitamin D strata analysis. Conclusion: Our study suggests that low vitamin K levels were correlated with suicidal attempts in patients with depression, indicating that vitamin K deficiency might be a biological risk factor for depression.

Steering Geometric Reconstruction of Bismuth with Accelerated Dynamics for CO2 Electroreduction.

Bismuth-based materials have emerged as promising catalysts in the electrocatalytic reduction of CO2 to formate. However, the reasons for the reconstruction of Bi-based precursors to form bismuth nanosheets are still puzzling, especially the formation of defective bismuth sites. Herein, we prepare bismuth nanosheets with vacancy-rich defects (V-Bi NS) by rapidly reconstructing Bi19Cl3S27 under negative potential. Theoretical analysis reveals that the introduction of chlorine induces the generation of intrinsic electric field in the precursor, thereby increasing the electron transfer rate and further promoting the metallization of trivalent bismuth. Meanwhile, in situ Raman and ex situ XRD tests verify that Bi19Cl3S27 has a faster reconstruction rate than Bi2S3. The formed V-Bi NS exhibits up to 96% HCOO- Faraday efficiency and 400 mA cm-2 HCOO- partial current densities, and its ECSA normalized formate current density and yield are 2.2 times higher than those of intact bismuth nanosheets (I-Bi NS). Density functional theory (DFT) calculations indicate that bismuth vacancies with electron-rich aggregation reduce the activation energy of CO2 to *CO2- radicals and stabilize the adsorption of the key intermediate *OCHO, thus facilitating the reaction kinetics of formate production.

Tannic acids and proanthocyanidins in tea inhibit SARS-CoV-2 variants infection.

The COVID-19 pandemic has caused hundreds million cases and millions death as well as continues to infect human life in the world since late of 2019. The breakthrough infection caused from mutation of SARS-CoV-2 is rising even the vaccinated population has been increasing. Currently, the severe threat posed by SARS-CoV-2 has been alleviated worldwide, and the situation has transitioned to coexisting with the virus. The dietary food with antiviral activities may improve to prevent virus infection for living with COVID-19 pandemic. Teas containing enriched phenolic ingredients such as tannins have been reported to be antitumor agents as well as be good inhibitors for coronavirus. This study developed a highly sensitive and selective ultra-high performance liquid chromatography-high resolution mass spectrometric method for quantification of tannic acids, a hydrolysable tannin, and proanthocyanidins, a condense tannin, in teas with different levels of fermentation. The in vitro pseudoviral particles (Vpp) infection assay was used to evaluate the inhibition activities of various teas. The results of current research demonstrate that the tannins in teas are effective inhibitors against infection of SARS-CoV-2 and its variants.

Advances and prospects of biomarkers for immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) activate anti-cancer immunity by blocking T cell checkpoint molecules such as programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Although ICIs induce some durable responses in various cancer patients, they also have disadvantages, including low response rates, the potential for severe side effects, and high treatment costs. Therefore, selection of patients who can benefit from ICI treatment is critical, and identification of biomarkers is essential to improve the efficiency of ICIs. In this review, we provide updated information on established predictive biomarkers (tumor programmed death-ligand 1 [PD-L1] expression, DNA mismatch repair deficiency, microsatellite instability high, and tumor mutational burden) and potential biomarkers currently under investigation such as tumor-infiltrated and peripheral lymphocytes, gut microbiome, and signaling pathways related to DNA damage and antigen presentation. In particular, this review aims to summarize the current knowledge of biomarkers, discuss issues, and further explore future biomarkers.

Histological Features of Uterine Myometrial Dysfunction: Possible Involvement of Localized Inflammation.

OBJECTIVE: The latest perspective suggests that elevated levels of inflammation and cytokines are implicated in atonic postpartum hemorrhage. Lipopolysaccharide (LPS) has been widely used to induce inflammation in animal models. Therefore, this study aimed to induce uterine inflammation using LPS to investigate whether local inflammation triggers dysfunction and atrophy in the myometrium, as well as the potential underlying molecular mechanisms involved. METHODS: In vivo, an animal model was established by intraperitoneal injection of 300 µg/ kg LPS in rats on gestational day 21. Hematoxylin-eosin (H&E) staining and Masson staining were employed to determine morphological changes in the rat uterine smooth muscle. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory cytokines. Immunohistochemistry, tissue fluorescence, and Western blotting were conducted to assess the expression levels of the uterine contraction-related proteins Toll-like receptor 4 (TLR4) and the nuclear factor kappa-B (NF-κB) signaling pathway. In vitro, human uterine smooth muscle cells (HUtSMCs) were exposed to 2 µg/mL LPS to further elucidate the involvement of the TLR4/NF-κB signaling pathway in LPS-mediated inflammation. RESULTS: In this study, LPS induced uterine myometrial dysfunction in rats, leading to a disorganized arrangement, a significant increase in collagen fiber deposition, and widespread infiltration of inflammatory cells. In both in vivo animal models and in vitro HUtSMCs, LPS elevated IL-6, IL-1ß, and TNF-α levels while concurrently suppressing the expression of connexin 43 (Cx43) and oxytocin receptor (OXTR). Mechanistically, the LPS-treated group exhibited TLR4 activation, and the phosphorylation levels of p65 and IκBα were notably increased. CONCLUSION: LPS triggered the TLR4/NF-κB signaling pathway, inducing an inflammatory response in the myometrium and leading to uterine myometrial dysfunction and uterine atony.

Incidence of cardiovascular mortality among head and neck cancer patients.

BACKGROUND: While treatment advancements have prolonged the lives of patients with head and neck cancer, the subgroups of these patients at higher risk for cardiovascular disease (CVD) mortality remain unclear. METHODS: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with head and neck cancer from 2000 to 2019. We compared their CVD mortality against the general US population using standardized mortality ratios (SMRs). RESULTS: Our analysis included 474,366 patients, identifying that 14% of deaths were due to CVD, with an SMR of 1.19. Notably, patients under the age of 39 had a CVD SMR increase of over 100-fold. Those with distant tumor stages showed the highest CVD SMR of 1.52 (95% CI 1.50-1.54). An upward trend in SMR to 2.53 (95% CI 2.51-2.56) was observed from 2011 to 2019. Within the initial 5-year post-diagnosis, the SMR for CVD was 3.17 (95% CI 3.14-3.20), which exceeded the general population's rates but declined in the 5-20-year range after diagnosis. Patients who did not any therapy had the greatest CVD SMR of 2.26 (95% CI 2.24-2.28). Hypopharyngeal cancer patients exhibited the highest CVD SMR of 1.54 (95% CI 1.52-1.56). CONCLUSIONS: The study highlights that head and neck cancer patients, especially younger individuals and those with advanced disease stages, face substantial CVD mortality risks. The CVD SMR peaks within 5 years following diagnosis. Patients abstaining from treatment bear the highest risk of CVD mortality. Cardioprotective measures should be considered critical for this patient population.

Different biomarker ratios in peripheral blood have limited value in diagnosing periprosthetic joint infection after total joint arthroplasty: a single-center, retrospective study.

BACKGROUND: Periprosthetic joint infection (PJI) is a severe complication that can occur after total joint arthroplasty (TJA). The timely and accurate diagnosis of PJI is the key to treatment. This study investigated the diagnostic value of platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in PJI after total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: We performed a retrospective analysis of the patients who underwent revision hip or knee arthroplasty at our Institute between June 2015 and June 2020. Of the 187 patients reviewed, 168 were included in the study. According to the diagnostic criteria of the Musculoskeletal Infection Society (MSIS), 58 patients were in the PJI group, and 110 patients were in the aseptic loosening (AL) group. We recorded and compared the preoperative peripheral blood white blood cell (WBC) count, platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), PLR, PVR, NLR, and MLR in both groups. The diagnostic performance of the WBC, PLT, PLR, PVR, NLR, and MLR individually and in combination with the ESR and CRP for PJI diagnosis was evaluated by receiver operating characteristic (ROC) curves, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Compared to those in the AL group, the mean WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR in the peripheral blood of the PJI group were significantly greater (P < 0.05). The analysis of the ROC curve revealed that the ESR, CRP, PLR, PVR, NLR, and MLR in peripheral blood had moderate effectiveness in diagnosing PJI, with area under the curve (AUC) values of 0.760 (95% CI: 0.688-0.823), 0.758 (95% CI: 0.687-0.821), 0.714 (95% CI: 0.639-0.781), 0.709 (95% CI: 0.634-0.777), 0.723 (95% CI: 0.649-0.789), and 0.728 (95% CI: 0.654-0.793), respectively. Conversely, the WBC and PLT counts demonstrated poor diagnostic value for PJI, with AUC values of 0.578 (95% CI: 0.499-0.653) and 0.694 (95% CI: 0.619-0.763), respectively. The results of the prediction model calculations revealed that the combined AUC of the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR was the highest at 0.853 (95% CI, 0.790-0.909), indicating good value in the diagnosis of PJI, with a sensitivity of 82.8% and a specificity of 72.7%. Moreover, the novel composite of parameters improved the accuracy and reliability in diagnosing PJI compared to the traditional biomarkers ESR and CRP (P = 0.015). CONCLUSION: Our study suggested that the diagnostic value of the peripheral blood biomarkers PLR, PVR, NLR, and MLR for diagnosing PJI is limited and not superior to that of the ESR or CRP. However, when the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR are combined, the diagnostic performance of PJI in TJA patients can be improved.

A new perspective on prostate cancer treatment: the interplay between cellular senescence and treatment resistance.

The emergence of resistance to prostate cancer (PCa) treatment, particularly to androgen deprivation therapy (ADT), has posed a significant challenge in the field of PCa management. Among the therapeutic options for PCa, radiotherapy, chemotherapy, and hormone therapy are commonly used modalities. However, these therapeutic approaches, while inducing apoptosis in tumor cells, may also trigger stress-induced premature senescence (SIPS). Cellular senescence, an entropy-driven transition from an ordered to a disordered state, ultimately leading to cell growth arrest, exhibits a dual role in PCa treatment. On one hand, senescent tumor cells may withdraw from the cell cycle, thereby reducing tumor growth rate and exerting a positive effect on treatment. On the other hand, senescent tumor cells may secrete a plethora of cytokines, growth factors and proteases that can affect neighboring tumor cells, thereby exerting a negative impact on treatment. This review explores how radiotherapy, chemotherapy, and hormone therapy trigger SIPS and the nuanced impact of senescent tumor cells on PCa treatment. Additionally, we aim to identify novel therapeutic strategies to overcome resistance in PCa treatment, thereby enhancing patient outcomes.

Employing Graph Neural Networks for Predicting Electrode Average Voltages and Screening High-Voltage Sodium Cathode Materials.

For many years, humans have been relentlessly focused on enhancing battery longevity and boosting energy storage capacities. The performance and durability of a battery depend significantly on the material used for its electrodes. In this context, merging machine learning with density functional theory (DFT) calculations has emerged as a pivotal approach to advancing the exploration of battery crystal structures. We present a new method that combines a graph convolutional neural network (GNN) with a Transformer convolutional layer, which we call Transformer-GNN. To underscore its efficacy, we benchmarked Transformer-GNN against three established statistical machine learning models: Support Vector Machine, Random Forest, and XGBoost. We also developed a standard GNN, which we refer to as Basic-GNN. Additionally, we compared Basic-GNN with Transformer-GNN to highlight the improvements brought about by incorporating the Transformer convolutional layer. The Transformer-GNN model outperforms the other models, achieving the highest R2 value of 0.82 and the lowest mean squared error of 0.3161. Our findings demonstrate that the Transformer-GNN can profoundly understand battery crystal structures, thus forging the path toward more sophisticated and durable battery systems. Leveraging the GNN model's voltage predictions in tandem with the capacity data sourced from the database, we screened and pinpointed Na(NiO2)2 as a high-voltage (higher than 5 V), high-capacity sodium cathode material. We conducted DFT calculations on Na(NiO2)2 and revealed the migration mechanism of the Na ions.

Identification of 1,3,4-Thiadiazolyl-Containing Thiazolidine-2,4-dione Derivatives as Novel PTP1B Inhibitors with Antidiabetic Activity.

Forty-one 1,3,4-thiadiazolyl-containing thiazolidine-2,4-dione derivatives (MY1-41) were designed and synthesized as protein tyrosine phosphatase 1B (PTP1B) inhibitors with activity against diabetes mellitus (DM). All synthesized compounds (MY1-41) presented potential PTP1B inhibitory activities, with half-maximal inhibitory concentration (IC50) values ranging from 0.41 ± 0.05 to 4.68 ± 0.61 µM, compared with that of the positive control lithocholic acid (IC50 = 9.62 ± 0.14 µM). The most potent compound, MY17 (IC50 = 0.41 ± 0.05 µM), was a reversible, noncompetitive inhibitor of PTP1B. Circular dichroism spectroscopy and molecular docking were employed to analyze the binding interaction between MY17 and PTP1B. In HepG2 cells, MY17 treatment could alleviate palmitic acid (PA)-induced insulin resistance by upregulating the expression of phosphorylated insulin receptor substrate and protein kinase B. In vivo, oral administration of MY17 could reduce the fasting blood glucose level and improve glucose tolerance and dyslipidemia in mice suffering from DM.

Vertebral Artery Stenting for Acute Multiple Cerebral Infarctions Caused by Vertebral Artery Dissection After Massage: A Case Report.

Vertebral artery dissection is a rare pathology that causes ischemic stroke in young people. Cervical massage, especially improper pulling manipulation, is a cause of vertebral artery dissection. We present a case of 32-year-old woman who developed acute multiple posterior circulation ischemic cerebral infarctions as a result of left vertebral artery V4 segment dissection after receiving neck massage. She underwent emergency vertebral artery stent implantation at the site of the dissection. Symptoms were relieved the day after treatment. The patient recovered without adverse complications or endovascular restenosis in the following year.

Mechanisms of the Masquelet technique to promote bone defect repair and its influencing factors.

The Masquelet technique, also known as the induced membrane technique, is a surgical technique for repairing large bone defects based on the use of a membrane generated by a foreign body reaction for bone grafting. This technique is not only simple to perform, with few complications and quick recovery, but also has excellent clinical results. To better understand the mechanisms by which this technique promotes bone defect repair and the factors that require special attention in practice, we examined and summarized the relevant research advances in this technique by searching, reading, and analysing the literature. Literature show that the Masquelet technique may promote the repair of bone defects through the physical septum and molecular barrier, vascular network, enrichment of mesenchymal stem cells, and high expression of bone-related growth factors, and the repair process is affected by the properties of spacers, the timing of bone graft, mechanical environment, intramembrane filling materials, artificial membrane, and pharmaceutical/biological agents/physical stimulation.

The prognostic impact of tumor location in non-muscle-invasive bladder cancer patients undergoing transurethral resection: insights from a cohort study utilizing chinese multicenter and SEER registries.

OBJECTIVE: Most bladder cancers are non-muscle invasive bladder cancer (NMIBC), and transurethral resection of bladder tumors (TURBT) is the standard treatment. However, postoperative recurrence remains a significant challenge, and the influence of bladder tumor location on prognosis is still unclear. This study aims to investigate how tumor location affects the prognosis of NMIBC patients undergoing TURBT and to identify the optimal surgical approach. METHODS: A multicenter study was conducted, which included Chinese NMIBC data from 15 hospitals (1996-2019) and data from 17 registries of the Surveillance, Epidemiology, and End Results database (SEER) (2000-2020). Patients initially diagnosed with NMIBC and undergoing TURBT or partial cystectomy were analyzed, with cases lost to follow-up or with missing data excluded. The study investigated the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) among patients with different tumor locations. Kaplan-Meier, Cox regression, and propensity score matching methods were employed to explore the association between tumor location and prognosis. Stratified populations were analyzed to minimize bias. RESULTS: This study included 118,477 NMIBC patients and highlighted tumor location as a crucial factor impacting post-TURBT prognosis. Both anterior wall and dome tumors independently predicted adverse outcomes in two cohorts. For anterior wall tumors, the Chinese cohort showed hazard ratios (HR) for OS of 4.35 (P < 0.0001); RFS of 2.21 (P < 0.0001); SEER cohort OS HR of 1.10 (P = 0.0001); DSS HR of 1.13 (P = 0.0183). Dome tumors displayed similar trends (Chinese NMIBC cohort OS HR of 7.91 (P < 0.0001); RFS HR of 2.12 (P < 0.0001); SEER OS HR of 1.05 (P = 0.0087); DSS HR of 1.14 (P = 0.0006)). Partial cystectomy significantly improved the survival of dome tumor patients compared to standard TURBT treatment (P < 0.01). CONCLUSION: This study reveals the significant impact of tumor location in NMIBC patients on the outcomes of TURBT treatment, with tumors in the anterior wall and bladder dome showing poor post-TURBT prognosis. Compared to TURBT treatment, partial cystectomy improves the prognosis for bladder dome tumors. This study provides guidance for personalized treatment and prognosis management for NMIBC patients.