The 3,3'-dimethoxy-4,4'-dihydroxy-stilbene Triazole (STT) Inhibits Liver Cancer Cell Growth by Targeting Akt/mTOR Pathway.

The present study was aimed to investigate the proliferation inhibitory ability of 3,3'-dimethoxy-4,4'-dihydroxy-stilbene triazole (STT) on SNU449 and Huh7 cells. Moreover, the mechanism associated with the suppression of liver cancer cell proliferation by STT was also studied. The results revealed that STT suppresses proliferation of SNU449 and Huh7 cells to 28 and 21%, respectively treatment with 20 µM. The clonogenic survival of SNU449 and Huh7 cells was also significantly reduced after incubation with STT compared to the control cultures. In comparison to the control, STT treatment significantly decreased the invasive potential of SNU449 cells. Treatment with STT led to a prominent suppression in p62 and increase in LC3B protein expression in SNU449 cells compared to the control cells. The STT treatment dramatically decreased p-Akt and p-mTOR protein expression in SNU449 cells. Docking study revealed that STT interacts via traditional hydrogen bonding with the glutamine, phenylalanine, leucine, serine, arginine, aspartic acid, and lysine residues of Akt protein. In summary, the current study demonstrates that STT effectively suppresses the viability of SNU449 and Huh7 liver cancer cells. Moreover, STT treatment of the liver cancer cells also significantly reduces the clonogenic survival and invasive potential of SNU449 cells. Treatment of liver cancer cells with STT increases the expression of autophagic, targets anti-autophagic protein expression and down-regulates Akt/mTOR pathway to inhibit cancer growth and proliferation. Thus, STT exhibits prominent anticancer effect and needs to be investigated further as a potential candidate for the treatment of liver cancer.

Clinical application of transcranial neuroendoscopy combined with supraorbital keyhole approach in minimally invasive surgery of the anterior skull base.

To explore the techniques, safety, and feasibility of minimally invasive neurosurgery through the supraorbital eyebrow arch keyhole approach by neuroendoscopy. Retrospective analysis of clinical data of patients with various cranial diseases treated by transcranial neuroendoscopic supraorbital eyebrow keyhole approach in our hospital from March 2021 to October 2023. A total of 39 complete cases were collected, including 21 cases of intracranial aneurysms, 9 cases of intracranial space occupying lesions, 5 cases of brain trauma, 3 cases of cerebrospinal fluid rhinorrhea, and 1 case of cerebral hemorrhage. All patients' surgeries were successful. The good prognosis rate of intracranial aneurysms was 17/21 (81%), and the symptom improvement rate of intracranial space occupying lesions was 8/9 (88.9%). Among them, the initial symptoms of one patient with no improvement were not related to space occupying, while the total effective rate of the other three types of patients was 9/9 (100%). The average length of the craniotomy bone window of the supraorbital eyebrow arch keyhole is 3.77 ± 0.31 cm, and the average width is 2.53 ± 0.23 cm. The average postoperative hospital stay was 14.77 ± 6.59 days. The average clearance rate of hematoma by neuroendoscopy is 95.00% ± 1.51%. Our results indicate that endoscopic surgery through the supraorbital eyebrow arch keyhole approach is safe and effective for the treatment of anterior skull base lesions and cerebral hemorrhage. However, this retrospective study is a single center, small sample study, and the good surgical results do not exclude the subjective screening of suitable patients by clinical surgeons, which may have some bias. Although the clinical characteristics such as indications and contraindications of this surgical method still require further prospective and multicenter clinical research validation, our study still provides a new approach and choice for minimally invasive surgical treatment of anterior skull base lesions.

Activation of peroxydisulfate by zero valent iron-carbon composites prepared by carbothermal reduction: Enhanced non-radical and radical synergies.

Since its application in environmental remediation, nano zero-valent iron (nZVI) has gained wide attention for its environmental friendliness, strong reducing ability, and wide range of raw materials. However, its high preparation cost and difficulty in preservation remain the bottlenecks for their application. Carbothermal reduction is a promising method for the industrial preparation of nZVI. Micronized zero-valent iron/carbon materials (Fe0/CB) were produced in one step by co-pyrolysis of carbon and iron. The performance of the Fe0/CB is comparable to that of nZVI. In addition, Fe0/CB overcomed the disadvantages of agglomeration and oxidative deactivation of nZVI. Experiments on the Fenton-like reaction of its activated PDS showed that metronidazole (MNZ) was efficiently removed through the synergistic action of radicals and non-radicals, which were mainly superoxide radicals (·O2-), monoclinic oxygen (1O2), and high-valent iron (FeIVO). Moreover, the degradation process showed better generalization, making it suitable for a wide range of applications in the degradation of antibiotics.

Helicobacter pylori infection induces POU5F1 upregulation and SPP1 activation to promote chemoresistance and T cell inactivation in gastric cancer cells.

Infection with Helicobacter pylori (H. pylori or Hp) is associated with an increased susceptibility to gastric diseases, notably gastric cancer (GC). This study investigates the impact of Hp infection on chemoresistance and immune activity in GC cells. Hp infection in AGS and MKN-74 cells promoted proliferation, migration and invasion, apoptosis resistance, and tumorigenic activity of cells under cisplatin (DDP) plus gemcitabine (GEM) treatment. Additionally, it dampened activity of the co-cultured CD8+ T cells. Hp infection increased POU class 5 homeobox 1 (POU5F1) level, which further activated secreted phosphoprotein 1 (SPP1) transcription to increase its expression. Silencing of either SPP1 or POU5F1 enhanced the GEM sensitivity in GC cells, and it increased the populations of CD8+ T cells and the secretion of immune-active cytokines both in vitro and in xenograft tumors in immunocompetent mice. However, the effects of POU5F1 silencing were counteracted by SPP1 overexpression. Furthermore, the POU5F1/SPP1 axis activated the PI3K/AKT signaling pathway. This study demonstrates that Hp infection induces POU5F1 upregulation and SPP1 activation, leading to increased DDP/GEM resistance and T cell inactivation in GC cells.

Inhibition of Liver Cancer Cell Viability by Triazole through Up-regulation of p38 Phosphorylation and Targeting the Activation of p-ERK1/2 and Akt Protein Expression.

The present study was aimed to explore the effect of triazole on growth and viability of liver cancer cells. Cell growth was examined using the MTT test and expression of several proteins was assessed by western blotting assay. The Matrigel-coated Transwell assay was employed to examine the infiltration of cells. The data from MTT assay showed that MHCC97H and H4TG liver cancer cell viability was inhibited by triazole in a concentration-dependent manner. After treatment with 0.5, 1.0, 2.0, 4, 8, and 16 µM doses of triazole, the rate of H4TG cell viability was decreased to 96, 73, 58, 39, 29, and 28%, respectively. Treatment of MHCC97H cells with 0.5, 1.0, 2.0, 4, 8, and 16 µM doses of triazole resulted in a reduction in cell viability to 94, 70, 53, 35, 22, and 21%, respectively. Triazole treatment also led to a significant reduction in MHCC97H cell invasiveness compared to the control cells. In MHCC97H cells treated with triazole, there was a noticeable decrease in the levels of p-ERK1/2, and p-Akt protein expression. Treatment of MHCC97H cells with triazole resulted in a prominent increase in p-p38 level. In summary, triazole inhibits growth and viability of liver cancer cells through targeting the activation of p-ERK1/2 and Akt proteins. Therefore, triazole may be investigated further as a therapeutic agent for the treatment of liver cancer.

A fully biodegradable spherical nucleic acid nanoplatform for self-codelivery of doxorubicin and miR122 for innate and adaptive immunity activation.

Facile construction of a fully biodegradable spherical nucleic acid (SNA) nanoplatform is highly desirable for clinical translations but remains rarely explored. We developed herein the first polycarbonate-based biodegradable SNA nanoplatform for self-codelivery of a chemotherapeutic drug, doxorubicin (DOX), and a human liver-specific miR122 for synergistic chemo-gene therapy of hepatocellular carcinoma (HCC). Ring-opening polymerization (ROP) of a carbonate monomer leads to a well-defined polycarbonate backbone for subsequent DOX conjugation to the pendant side chains via acidic pH-cleavage Schiff base links and miR122 incorporation to the chain termini via click coupling, affording an amphiphilic polycarbonate-DOX-miR122 conjugate, PBis-Mpa30-DOX-miR122 that can self-assemble into stabilized SNA. Besides the desired biodegradability, another notable merit of this nanoplatform is the use of miR122 not only for gene therapy but also for enhanced innate immune response. Together with the ICD-triggering effect of DOX, PBis-Mpa30-DOX-miR122 SNA-mediated DOX and miR122 codelivery leads to synergistic immunogenicity enhancement, resulting in tumor growth inhibition value (TGI) of 98.1 % significantly higher than those of the groups treated with only drug or gene in a Hepa1-6-tumor-bearing mice model. Overall, this study develops a useful strategy toward biodegradable SNA construction, and presents a drug and gene-based self-codelivery SNA with synergistic immunogenicity enhancement for efficient HCC therapy. STATEMENT OF SIGNIFICANCE: Facile construction of a fully biodegradable SNA nanoplatform is useful for in vivo applications but remains relatively unexplored likely due to the synthetic challenge. We report herein construction of a polycarbonate-based SNA nanoplatform for co-delivering a chemotherapeutic drug, DOX, and a human liver-specific miR-122 for synergistic HCC treatment. In addition to the desired biodegradability properties, this SNA nanoplatform integrates DOX-triggered ICD and miR-122-enhanced innate immunity for simultaneously activating adaptive and innate immunities, which leads to potent antitumor efficiency with a TGI value of 98.1 % in a Hepa1-6-tumor-bearing mice model.

Aspirin versus low-molecular-weight heparin for thromboprophylaxis after orthopaedic surgery: a systematic review and meta-analysis.

The article aimed to compare the efficiency and safety of aspirin with low-molecular-weight heparin (LMWH) for thromboprophylaxis in orthopaedic surgery patients. According to the inclusion and exclusion criteria, PubMed, Embase and Cochrane Library database were searched for studies comparing aspirin and LMWH in venous thromboembolism (VTE) prophylaxis until 25 April 2023. The outcome measures included deep venous thrombosis(DVT)/Pulmonary embolism(PE) events, major bleeding events, wound complications, wound infection and death. Six studies met the requirements of our meta-analysis, including 12 470 patients in the aspirin group and 10 857 patients in the LMWH group. The meta-analysis showed that results showed that LMWH was superior to aspirin in preventing VTE events (odds ratio (OR) 1.44, 95% CI 1.24-1.68, P  < 0.00001), whereas there was no significant difference between them in bleeding events (OR 0.95, 95% CI 0.86-1.05, P  = 0.33), wound complication (OR 0.58, 95% CI 0.28-1.17, P  = 0.13), wound infection (OR 1.12, 95% CI 0.86-1.47, P  = 0.39) and mortality (OR 1.04, 95% CI 0.70-1.55, P  = 0.83). In addition, subgroup analysis showed that compared with aspirin, LMWH was more likely to reduce the incidence of DVT events in orthopaedic surgery patients (OR 1.59, 95% CI 1.33-1.91, P  < 0.00001), whereas there was no advantage in reducing the incidence of PE events (OR 1.22, 95% CI 0.62-2.40, P  = 0.56). Despite the similar safety profiles, this meta-analysis showed that LMWH was significantly superior to aspirin in thromboprophylaxis after orthopaedic surgery. LMWH was still the first-line drug for thrombosis prevention in patients who underwent major orthopaedic surgeries.

Arylacryl amides: Design, synthesis and the protection against cisplatin-induced acute kidney injury via TLR4/STING/NF-κB pathway.

Arylpropionic ester scaffold was found as anti-inflammatory agents for the treatment and prevention of acute kidney injury (AKI). To further study the structure-activity relationship (SAR) of this scaffold, a series of acryl amides were designed, synthesized, and evaluated their anti-inflammation. Of these, compound 9d displayed the protective effect on renal tubular epithelial cells to significantly enhance the survival rate through inhibiting NF-κB phosphorylation and promoting cell proliferation in cisplatin-induced HK2 cells. Furthermore, 9d can interact with TLR4 to inhibit TLR4/STING/NF-κB pathway in the RAW264.7 cell. In vivo AKI mice model, 9d significantly downregulated the level of serum creatinine (Scr), blood urea nitrogen (BUN) and the inflammatory factors (IL-1ß, IL-6, TNF-α) to improve kidney function. Morphological and KIM-1 analyses showed that 9d alleviated cisplatin-induced tubular damage. In a word, 9d was a promising lead compound for preventive and therapeutic of AKI.

Protective effects of pulsed electromagnetic field therapy attenuates autophagy and apoptosis in osteoporotic osteoarthritis model rats by activating PPARγ.

Osteoporotic osteoarthritis (OPOA) is a specific phenotype of OA with high incidence and severe cartilage damage. This study aimed to explore the protective efficacy of PEMF on the progression of OPOA and observed the effects of PEMF on PPARγ, autophagy- and apoptosis-related proteins in OPOA rats. Rats were randomly divided into three groups: control group, OPOA group, and PEMF group (n = 6). One week after surgery, the rats in PEMF group were subjected to PEMF (3.82 mT, 8 Hz, 40 min/day and 5 day/week) for 12 weeks. Results showed that PEMF retarded cartilage degeneration and bone loss, as evidenced by pathological staining image, decreased MMP-13 expression and increased bone mineral density. PEMF inhibited the serum levels of inflammatory cytokines, and the expressions of caspase-3 and caspase-8, while upregulated the expression of PPARγ. Moreover, PEMF significantly improved the autophagy disorders, represented by decrease expressions of Beclin-1, P62, and LC3B. The research demonstrates that PEMF can effectively prevent cartilage and subchondral bone destruction in OPOA rats. The potential mechanism may be related to upregulation of PPARγ, inhibition of chondrocyte apoptosis and inflammation, and improvement of autophagy disorder. PEMF therapy thus shows promising application prospects in the treatment of postmenopausal OA.

Osteoporotic osteoarthritis (OPOA) is a very common combination disease, that characterized by chronic pain, swollen joints and susceptibility to fractures. It is particularly common in postmenopausal women. At present, drug therapy is the main treatment method, but the adverse reactions are serious and can not stop the progression of the disease. PEMF is a safe physical therapy that has been shown to increase bone density, reduce pain, and improve joints mobility. In this study, we aimed to explore the protective effect and potential mechanism of PEMF on OPOA. We found that PEMF significantly inhibited the inflammatory response, ameliorated the damaged cartilage and subchondral bone in OPOA rats, that maybe related to the regulation of chondrocyte autophagy and apoptosis. This study provided a new vision for PEMF' treatment on OPOA and has positive significance for the clinical promotion of PEMF.

Rapid removal of decabromodiphenyl ether by mechanochemically prepared submicron zero-valent iron with FeC2O4·2 H2O layers: Kinetics, mechanisms and pathways.

The utilization of nano zero-valent iron (nZVI) in polybrominated diphenyl ethers remediation has been studied extensively. However, challenges in balancing cost and reactivity have been encountered. A submicron zero-valent iron coated with FeC2O4·2 H2O layers (OX-smZVI) was synthesized via a mechanochemical method, aiming to resolve this contradiction. Characterization via SEM, TEM, and XPS confirmed the structure as FeC2O4·2 H2O coated iron lamellate with a surface area 24-fold higher than ball-milled zero-valent iron (smZVI). XRD highlighted an Fe/C eutectic in OX-smZVI, boosting its electron transfer capacity. Decabromodiphenyl ether degradation by OX-smZVI follows a two-stage process, with initial degradation by FeC2O4·2 H2O and a subsequent phase dominated by electron transfer. OX-smZVI exhibits a 4.52-34.40 times faster BDE209 removal rate than nZVI and scaled-up OX-smZVI displayed superior reactivity with preparation costs only 1/680 of nZVI. Given its enhanced reactivity and cost-efficiency, OX-smZVI emerges as a promising replacement for nZVI.

Self-Assembled nanoparticles of natural bioactive molecules enhance the delivery and efficacy of paclitaxel in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Paclitaxel (PTX) is a well-established and highly effective anti-cancer drug for peripheral solid tumors. However, the application of PTX in GBM is hindered by several limitations, including poor water solubility, restricted entry across the blood-brain barrier (BBB), and enhanced excretion by efflux transporters. P-glycoprotein (P-gp) is a crucial efflux transporter that is abundantly present in cerebral vascular endothelial cells and GBM cells. It plays a significant role in the exocytosis of PTX within tumor tissues. METHODS: Recently, we have developed a novel technique for creating self-assembled nanoparticles utilizing a range of natural bioactive molecules. These nanoparticles can encapsulate insoluble drugs and effectively cross the BBB. In additional, we revealed that certain nanoparticles have the potential to act as P-gp inhibitors, thereby reducing the excretion of PTX. In this study, we conducted a screening of bioactive molecular nanoparticles to identify those that effectively inhibit the function of P-gp transporters. RESULTS: Among the candidates, we identified ursolic acid nanoparticles (UA NPs) as the P-gp inhibitors. Furthermore, we prepared co-assembled UA NPs embedded with paclitaxel, referred to as UA-PTX NPs. Our results demonstrate that UA-PTX NPs can enhance the blood concentration of PTX, facilitate its entry into the BBB, and inhibit the function of P-gp, resulting in a decrease in the excretion of PTX. This discovery effectively addressed the above three issues associated with the use of PTX in glioma treatment. CONCLUSIONS: UA-PTX NPs demonstrate strong anti-tumor effects and show great potential for treating GBM.

Treatment of brainstem and fourth ventricle lesions by the full neuroendoscopic telovelar approach.

OBJECTIVE: To explore the surgical techniques, advantages, and disadvantages of neuroendoscopic telovelar approach in the treatment of brainstem and fourth ventricle lesions. METHODS: The clinical data of 5 patients treated by neuroendoscopic telovelar approach from March 2020 to March 2022 were analyzed retrospectively. RESULTS: Among the 5 patients, there were 3 cavernous hemangiomas in pontine arm and 2 tumors in brainstem and fourth ventricle. All patients could successfully complete the operation, and 4 patients recovered well, other 1 patient discharged automatically for serious complications of other systems after the operation. CONCLUSION: The telovelar approach has gained popularity as a safe and effective strategy for lesions in fourth ventricular and brainstem. However, without removing the posterior arch of the atlas, it is difficult to enter the upper part of the fourth ventricle under a microscope. Transcranial neuroendoscopy can effectively compensate for the shortcomings of microscopy, whether used as an auxiliary measure for microsurgery or alone with proficient endoscopic techniques, it will provide greater application in minimally invasive surgery for fourth ventricle and brainstem lesions. By utilizing the excellent degree of freedom of transcranial neuroendoscopy, there is no need to open the posterior arch of the atlas, making the surgery more minimally invasive. However, the sample size of this study is small, and it was completed under the very mature neuroendoscopic technology of our team. Its general safety and practicality still require extensive clinical research validation.

A Systematic Review and Meta-analysis of Atherectomy Plus Balloon Angioplasty Versus Balloon Angioplasty Alone for Infrapopliteal Arterial Disease.

OBJECTIVE: The article aimed to compare the efficiency and safety of atherectomy plus balloon angioplasty (BA) with BA alone for the treatment of infrapopliteal arterial disease. METHODS: According to the inclusion and exclusion criteria, PubMed, Embase, and Cochrane Library database were searched for studies comparing atherectomy plus angioplasty and angioplasty alone in treating infrapopliteal artery lesions until November 2022. The endpoints included technical success, primary patency, clinically-driven target lesion revascularization (CD-TLR), periprocedural complications, distal embolization, target limb major amputation, and all-cause mortality. RESULTS: Ten studies met the requirements of our meta-analysis, including 7723 patients in the atherectomy plus BA group and 2299 patients in the BA alone group. The meta-analysis showed that atherectomy plus BA was associated with reduced CD-TLR (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.34, 0.78, p=0.002) and target limb major amputation (OR: 0.43, 95% CI: 0.19, 1.01, p=0.05) at 12-month follow-up. No statistically significant difference was found in technical success, primary patency, periprocedural complications, distal embolization, or all-cause mortality. Subgroup analysis found a higher rate of primary patency at 6 and 12 months (6 months: OR: 2.26, 95% CI: 1.11, 4.60, p=0.02; 12 months: OR: 2.38, 95% CI: 1.16, 4.86, p=0.02), and lower rates of CD-TLR (OR: 0.45, 95% CI: 0.25, 0.82, p=0.009) and target limb major amputation (OR: 0.43, 95% CI: 0.19, 1.01, p=0.05) at 12 months in patients treated with atherectomy plus drug-coated balloon (DCB) but not in patients treated with atherectomy plus plain old balloon angioplasty (POBA). CONCLUSIONS: This meta-analysis suggests that compared with BA alone, atherectomy plus BA may reduce the need for CD-TLR and the incidence of target limb major amputation at 12-month follow-up in the treatment of infrapopliteal artery occlusive lesions, even though there are no significant advantages in technical success, primary patency, periprocedural complications, distal embolization, or all-cause mortality. To go further, atherectomy plus DCB shows significant benefits in primary patency, CD-TLR, and target limb major amputation rate but atherectomy plus POBA does not'. However, due to the limitations of this article, more randomized controlled trials (RCTs) are needed to confirm these conclusions. CLINICAL IMPACT: According to our research, atherectomy combined with BA has the advantages of higher primary patency rate, lower CD-TLR and target limb significant amputation rate in treating infrapopliteal artery occlusive lesions, which may replace the current mainstream surgical method ---BA alone. For the clinician, although the surgery may take longer, it will significantly improve the prognosis and quality of life of patients and hold considerable significance for the management of patients with infrapopliteal arterial disease. Based on the characteristics of infrapopliteal artery disease, this study explored the feasibility of atherectomy combined with BA for infrapopliteal artery disease. Moreover, we found that atherectomy combined with DCB had better clinical efficacy, which should be the innovation of this study.

Surgical Clipping of Intracranial Aneurysms Using a Transcranial Neuroendoscopic Approach.

OBJECTIVE: This retrospective study was performed to evaluate the feasibility and safety of surgically clipping intracranial aneurysms using a transcranial neuroendoscopic approach. METHODS: A total of 229 patients with cerebral aneurysms were included in our study, all of whom were treated with clamping surgery at Wuhan University People's Hospital. They were divided into neuroendoscopic and microscopic groups, according to whether or not neuroendoscopy was used for the clamping surgery. We statistically analyzed the patients' baseline data, surgical outcomes, and complications, which were then evaluated to assess the treatment effect. RESULTS: The baseline characteristics were not statistically significant, except for gender, for which the proportions of female patients in the two groups were 69 (56.1%) and 46 (43.4%). There were no patients with incomplete aneurysm clamping or parent vessel occlusion in the neuroendoscopic group, and there were 4 (3.8%) and 2 (1.9%) in the microscopic group, respectively; however, there was no statistically significant difference in the comparison of the two groups. The mean operative times of the two groups were 181 min and 154 min, respectively, and were statistically different. However, the mRS scores of the two groups showed no significant difference in patient prognosis. The differences in complications (including limb hemiplegia, hydrocephalus, vision loss, and intracranial infection) were not statistically significant, except for cerebral ischemia, for which the proportions of patients in the two groups were 8 (6.5%) and 16 (15.1%). CONCLUSIONS: Neuroendoscopy can provide clear visualization and multi-angle views during aneurysm clipping, which is helpful for ensuring adequate clipping and preventing complications.

BCL2A1 is associated with tumor-associated macrophages and unfavorable prognosis in human gliomas.

B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family. Previous studies have shown that BCL2A1 is closely related to the tumorigenesis and resistance to chemotherapy of multiple solid tumors, such as breast cancer. However, the expression pattern and potential biological function of BCL2A1 in glioma remain unknown. For the first time, we found that the expression of BCL2A1 was higher in human glioma tissues than in normal brain tissues (NBTs) in both public datasets and an in-house cohort. High BCL2A1 expression was associated with advanced WHO grade, IDH 1/2 wild type and the mesenchymal (ME) subtype, and its overexpression in glioma predicted resistance to temozolomide (TMZ) chemotherapy and unfavorable prognosis. In addition, Gene set enrichment analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that BCL2A1 was significantly correlated with the immune response and immune-related pathways, and BCL2A1 expression was positively correlated with microenvironmental parameters (immune, stromal, and ESTIMATE scores) and macrophage infiltration. Interestingly, bioinformatic prediction and immunohistochemical/immunofluorescence staining analysis revealed that BCL2A1 expression was obviously associated with the tumor-associated macrophages (TAMs) markers CD68 and CCL2. Notably, knockdown of BCL2A1 significantly inhibited cell proliferation of U87 and U251 in vitro, induced smaller tumor size and prolonged survival time of mice in vivo. Co-culture experiments of macrophages and GBM cells showed that BCL2A1 knockdown inhibited macrophage migration. Meanwhile, knockdown of BCL2A1 was associated with low expression of CD68 and CCL2 in intracranial xenograft model. This may suggest that BCL2A1 promotes the progression of glioma and influences the prognosis of patients by participating in TAMs infiltration. In conclusion, these findings suggest that BCL2A1 could serve as a promising prognostic indicator and immunotherapy target in gliomas.

The potential DNA methylation markers of cardiovascular disease in patients with type 2 diabetes.

BACKGROUND: DNA methylation is associated with cardiovascular (CV) disease. However, in type 2 diabetes (T2D) patients, the role of gene methylation in the development of CV disease is under-studied. We aimed to identify the CV disease-related DNA methylation loci in patients with T2D and to explore the potential pathways underlying the development of CV disease using a two-stage design. METHODS: The participants were from the Jinan Diabetes Cohort Study (JNDCS), an ongoing longitudinal study designed to evaluate the development of CV risk in patients with T2D. In the discovery cohort, 10 diabetic patients with CV events at baseline were randomly selected as the case group, and another 10 diabetic patients without CV events were matched for sex, age, smoking status, and body mass index as the control group. In 1438 T2D patients without CV disease at baseline, 210 patients with CV events were identified after a mean 6.5-year follow-up. Of whom, 100 patients who experienced CV events during the follow-up were randomly selected as cases, and 100 patients who did not have CV events were randomly selected as the control group in the validation cohort. Reduced representation bisulfite sequencing and Targeted Bisulfite Sequencing were used to measure the methylation profiles in the discovery and validation cohort, respectively. RESULTS: In the discover cohort, 127 DMRs related to CV disease were identified in T2D patients. Further, we validated 23 DMRs mapped to 25 genes, of them, 4 genes (ARSG, PNPLA6, NEFL, and CRYGEP) for the first time were reported. There was evidence that the addition of DNA methylation data improved the prediction performance of CV disease in T2D patients. Pathway analysis identified some significant signaling pathways involved in CV comorbidities, T2D, and inflammation. CONCLUSIONS: In this study, we identified 23 DMRs mapped to 25 genes associated with CV disease in T2D patients, of them, 4 DMRs for the first time were reported. DNA methylation testing may help identify a high CV-risk population in T2D patients.

Identification of a novel intermittent hypoxia-related prognostic lncRNA signature and the ceRNA of lncRNA GSEC/miR-873-3p/EGLN3 regulatory axis in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is still the most prevalent type of respiratory cancer. Intermittent hypoxia can increase the mortality and morbidity associated with lung cancer. Long non-coding RNAs (lncRNAs) are crucial in lung adenocarcinoma. However, the effects of intermittent hypoxia-related long non-coding RNAs (IHRLs) on lung adenocarcinoma are still unknown. Method: In the current research, eight IHRLs were selected to create a prognostic model. The risk score of the prognostic model was evaluated using multivariate and univariate analyses, and its accuracy and reliability were validated using a nomogram and ROC. Additionally, we investigated the relationships between IHRLs and the immune microenvironment. Result: Our analysis identified GSEC, AC099850.3, and AL391001.1 as risk lncRNAs, while AC010615.2, AC010654.1, AL513550.1, LINC00996, and LINC01150 were categorized as protective lncRNAs. We observed variances in the expression of seven immune cells and 15 immune-correlated pathways between the two risk groups. Furthermore, our results confirmed the ceRNA network associated with the intermittent hypoxia-related lncRNA GSEC/miR-873-3p/EGLN3 regulatory pathway. GSEC showed pronounced expression in lung adenocarcinoma tissues and specific cell lines, and its inhibition resulted in reduced proliferation and migration in A549 and PC9 cells. Intriguingly, GSEC manifested oncogenic properties by sponging miR-873-3p and demonstrated a tendency to modulate EGLN3 expression favorably. Conclusion: GSEC acts as an oncogenic lncRNA by interacting with miR-873-3p, modulating EGLN3 expression. This observation underscores the potential of GSEC as a diagnostic and therapeutic target for LUAD.

Discrimination of ground-glass nodular lung adenocarcinoma pathological subtypes via transfer learning: A multicenter study.

BACKGROUND: The surgical approach and prognosis for invasive adenocarcinoma (IAC) and minimally invasive adenocarcinoma (MIA) of the lung differ. However, they both manifest as identical ground-glass nodules (GGNs) in computed tomography images, and no effective method exists to discriminate them. METHODS: We developed and validated a three-dimensional (3D) deep transfer learning model to discriminate IAC from MIA based on CT images of GGNs. This model uses a 3D medical image pre-training model (MedicalNet) and a fusion model to build a classification network. Transfer learning was utilized for end-to-end predictive modeling of the cohort data of the first center, and the cohort data of the other two centers were used as independent external validation data. This study included 999 lung GGN images of 921 patients pathologically diagnosed with IAC or MIA at three cohort centers. RESULTS: The predictive performance of the model was assessed using the area under the receiver operating characteristic curve (AUC). The model had high diagnostic efficacy for the training and validation groups (accuracy: 89%, sensitivity: 95%, specificity: 84%, and AUC: 95% in the training group; accuracy: 88%, sensitivity: 84%, specificity: 93%, and AUC: 92% in the internal validation group; accuracy: 83%, sensitivity: 83%, specificity: 83%, and AUC: 89% in one external validation group; accuracy: 78%, sensitivity: 80%, specificity: 77%, and AUC: 82% in the other external validation group). CONCLUSIONS: Our 3D deep transfer learning model provides a noninvasive, low-cost, rapid, and reproducible method for preoperative prediction of IAC and MIA in lung cancer patients with GGNs. It can help clinicians to choose the optimal surgical strategy and improve the prognosis of patients.

Reproductive health factors in relation to risk of hypertension in postmenopausal women: Results from NHANES 2011-2014.

Few studies have systematically assessed the relationship between multiple reproductive factors and hypertension, and these limited studies paid more attention to age at menarche and menopause, abortion, or the number of live births, and yielded controversial results. This study aimed to explore the relationship between reproductive health factors and hypertension from 5 aspects: history of menstruation, pregnancy, delivery, gynecological surgery, and reproductive-related medication use. We analyzed data from the National Health and Nutrition Examination Survey 2011 to 2014. Data on reproductive factors were collected using a questionnaire survey. The associations between multiple reproductive factors and the risk of hypertension were assessed using multivariable logistic regression models. There were significant inverse associations between age at menopause (odds ratio [OR] = 0.984, 95% confidence interval [CI]: 0.971-0.998, P = .0234 per 1-year increase), age at first live birth (OR = 0.970, 95% CI: 0.944-0.998, P = .0346 per 1-year increase), age at last live birth (OR = 0.982, 95% CI: 0.964-0.999, P = .0488 per 1-year increase), and the risk of hypertension. In contrast, a positive association was found between the risk of hypertension and a history of gestational diabetes (OR = 1.693, 95% CI: 1.042-2.751, P = .0333), hysterectomy (OR = 1.398, 95% CI: 1.139-1.717, P = .0014), ovariectomy (OR = 1.374, 95% CI: 1.074-1.758, P = .0115), and birth control pill use (OR = 1.293, 95% CI: 1.035-1.616, P = .0236). Age at menopause but not menarche, is inversely associated with hypertension. A history of gestational diabetes, hysterectomy, ovariectomy, or birth control pills was associated with a higher risk of hypertension.

Post-operative rebleeding in patients with spontaneous supratentorial intracerebral hemorrhage: factors and clinical outcomes.

OBJECTIVE: To explore factors affecting postoperative rebleeding in patients with spontaneous supratentorial intracerebral hemorrhage (SSICH). METHODS: We retrospectively analyzed data from 724 patients with SSICH treated at Renmin Hospital of Wuhan University from December 2018 to October 2021. Finally, 294 people were eligible to be included in this study. Hematoma locations were classified as basal ganglia, thalamus, subcortex, or intraventricular. Surgery was categorized as neuroendoscopic surgery, burr hole (stereotactic drilling and drainage), or open craniotomy. Postoperative rebleeding was recorded. The incidence, risk factors, and prognosis of postoperative rebleeding were evaluated. RESULTS: All procedures were successfully completed. Postoperative rebleeding occurred in 57 patients (19.83%, 57/294). Univariate logistic regression analysis identified these risk factors for rebleeding: admission Glasgow Coma Scale (GCS) score, irregular hematoma morphology by preoperative Computed Tomography (CT), postoperative hypertension, hematoma location, surgical method (P<0.05), and preoperative hematoma volume (P<0.1). Multivariate logistic regression analysis confirmed admission GCS score, irregular hematoma morphology by preoperative CT, postoperative hypertension, hematoma location, and surgical method as significant risk factors (P<0.05). Burr hole surgery and basal ganglia hematomas were associated with increased odds of rebleeding, and the mortality rates in patients with rebleeding versus no rebleeding were 7.02% versus 0.84%. CONCLUSIONS: Neuroendoscopic surgery, craniotomy, and burr hole are all effective for treating SSICH, but burr hole surgery was an important risk factor for rebleeding and an adverse outcome. Admission GCS score, irregular hematoma morphology, blood pressure control, hematoma location, and surgical method are affected the risk of postoperative rebleeding. 3D Slicer-assisted neuroendoscopic surgery may be the most effective treatment for many patients with SSICH.