Eriocalyxin B alleviated ischemic cerebral injury by limiting microglia-mediated excessive neuroinflammation in mice.

Excessive neuroinflammation mediated by microglia has a detrimental effect on the progression of ischemic stroke. Eriocalyxin B (EriB) was found with a neuroprotective effect in mice with Parkinson's disease via the suppression of microglial overactivation. This study aimed to investigate the roles of EriB in permanent middle cerebral artery occlusion (pMCAO) mice. The pMCAO was induced in the internal carotid artery of the mice by the intraluminal filament method, and EriB (10 mg/kg) was administered immediately after surgery by intraperitoneal injection. The behavior score, 2,3,5-triphenyltetrazole chloride staining, Nissl staining, TUNEL, immunohistochemistry, immunofluorescence, PCR, ELISA, and immunoblotting revealed that EriB administration reduced brain infarct and neuron death and ameliorated neuroinflammation and microglia overactivation in pMCAO mice, manifested by alterations of TUNEL-positive cell numbers, ionized calcium binding adaptor molecule 1 (Iba-1)-positive cell numbers, and expression of tumor necrosis factor-α, interleukin 6, IL-1ß, inducible nitric oxide synthase, and arginase 1. In addition, EriB suppressed ischemia-induced activation of nuclear factor kappa B (NF-κB) signaling in the brain penumbra, suggesting the involvement of NF-κB in EriB function. In conclusion, EriB exerted anti-inflammatory effects in ischemia stroke by regulating the NF-κB signaling pathway, and this may provide insights into the neuroprotective effect of EriB in the treatment of ischemic stroke.

Macrophages-derived exo-miR-4449 induced by Cryptococcus affects HUVEC permeability and promotes pyroptosis in BEAS-2B via the HIC1 pathway.

Macrophages have recently been discovered to assume a significant role in the progression of cryptococcosis. However, the potential involvement of macrophage-derived exosomes in the pathogenesis of cryptococcosis remains uncertain. In this study, we investigated the changes of microRNAs in macrophage exosomes (exo-miRNAs) in cryptococcal infections and the role of markedly altered exo-miRNAs in the modulation of Human Umbilical Vein Endothelial Cells (HUVEC) permeability and ROS accumulation and pyroptosis in Human Bronchial Epithelioid Cells (BEAS-2B). Techniques such as microarray analysis and real-time quantitative PCR were used to detect different exo-miRNAs and to screen for the most highly expressed exo-miRNAs. Then its mimics were transfected into HUVEC to study its effect on the monolayer permeability of HUVEC. Finally, the relationship between this exo-miRNAs and the ROS accumulation and pyroptosis was verified by bioinformatics analysis. The results showed that five exo-miRNAs were overexpressed and two exo-miRNAs were reduced, among which, exo-miR-4449 was expressed at the highest level. Exo-miR-4449 could be internalized by HUVEC and enhanced its monolayer permeability. Moreover, exo-miR-4449 was found to promote ROS accumulation and pyroptosis in BEAS-2B through HIC1 pathway. Thus, exo-miR-4449 plays an important role in the pathogenesis of cryptococcosis and holds promise as a significant biomarker for treatment.

Case report: 177Lu DOTA-TATE: a new scheme for the treatment of prostate neuroendocrine cancer.

Background: Most instances of small cell carcinoma originate from the lungs, while the gastrointestinal tract serves as a secondary site. Only a minuscule proportion of cases manifest within the urogenital system. Prostate small cell carcinoma (SCCP) represents an exceedingly uncommon pathological subtype within the realm of prostate cancer, displaying significant rarity in clinical settings. This scarcity has resulted in a paucity of adequate foundational and clinical research for SCCP treatment. While investigations have unveiled a certain therapeutic efficacy of radiotherapy and chemotherapy for SCCP, clinical practice has revealed suboptimal treatment outcomes. We hereby present a case report detailing the utilization of 177Lu-DOTA-TATE in the treatment of SCCP, aiming to investigate the therapeutic efficacy of 177Lu-DOTA-TATE for SCCP. Case presentation: A male patient in his 80s presented with elevated prostate-specific antigen (PSA) levels and underwent a biopsy that revealed prostate adenocarcinoma. The patient received CAB (bicalutamide + goserelin) therapy. One year later, disease progression was detected, and a second biopsy confirmed the presence of prostate small cell carcinoma. Following the diagnosis of prostate small cell carcinoma, the patient underwent two cycles of 177Lu-DOTA-TATE treatment. Subsequent to the treatment, the original lesions showed shrinkage, metastatic lesions disappeared, and there was significant improvement, approaching complete remission. Conclusion: SCCP exhibits a high degree of malignancy and aggressive invasiveness, currently lacking effective therapeutic modalities. The treatment course of this patient serves as compelling evidence for the efficacy of 177Lu-DOTA-TATE in managing SCCP, thereby opening new avenues for future SCCP treatments.

Study on Matrix Damage and Control Methods of Fracturing Fluid on Tight Sandstone Gas Reservoirs.

Hydraulic fracturing is a highly effective method for stimulating the development of gas reservoirs. However, the process of pumping fracturing fluid (FF) into the reservoir unavoidably causes damage to the surrounding matrix, leading to a decrease in the overall stimulation effect. To assess the extent of matrix permeability damage caused by the intrusion of FF, as well as its impact on the pore throat structure, and to propose appropriate measures to control this damage, we conducted a series of experimental studies on tight gas reservoirs. These studies included mercury intrusion, core flow, nitrogen adsorption, linear expansion, and contact angle measurements. The findings revealed that the damage inflicted on matrix permeability by FF was significantly greater than that caused by its gel-breaking counterpart. Surprisingly, the damage rate of the rejecting fluid to the matrix was found to be comparable to that of its gel-breaking counterpart. The fractal dimension (D2) was observed to have a strong correlation with surface area, pore volume, and mean pore size, making it an effective means of characterizing pore structure characteristics. After the rock samples were displaced by the formation water, the D2 value decreased, leading to a decrease in the complexity of the pore throat structure and an increase in matrix permeability. Conversely, the displacement of the FF increased the D2 value, indicating a gradual complication of the pore throat structure and a more uneven distribution of pore sizes. The inclusion of polyamide in antiexpansion FF, as well as its gel-breaking counterpart, proved to be effective in inhibiting the hydration and expansion of clay minerals, thereby reducing water-sensitive damage. Additionally, the use of surfactants with low surface tension enhanced the flowback rate of FF by increasing the contact angle and reducing the work of adhesion. This, in turn, helped to decrease the apparent water film thickness and expand gas flow channels, ultimately improving gas permeability.

Radiomic features from multiparametric magnetic resonance imaging predict molecular subgroups of pediatric low-grade gliomas.

BACKGROUND: We aimed to develop machine learning models for prediction of molecular subgroups (low-risk group and intermediate/high-risk group) and molecular marker (KIAA1549-BRAF fusion) of pediatric low-grade gliomas (PLGGs) based on radiomic features extracted from multiparametric MRI. METHODS: 61 patients with PLGGs were included in this retrospective study, which were divided into a training set and an internal validation set at a ratio of 2:1 based on the molecular subgroups or the molecular marker. The patients were classified into low-risk and intermediate/high-risk groups, BRAF fusion positive and negative groups, respectively. We extracted 5929 radiomic features from multiparametric MRI. Thereafter, we removed redundant features, trained random forest models on the training set for predicting the molecular subgroups or the molecular marker, and validated their performance on the internal validation set. The performance of the prediction model was verified by 3-fold cross-validation. RESULTS: We constructed the classification model differentiating low-risk PLGGs from intermediate/high-risk PLGGs using 4 relevant features, with an AUC of 0.833 and an accuracy of 76.2% in the internal validation set. In the prediction model for predicting KIAA1549-BRAF fusion using 4 relevant features, an AUC of 0.818 and an accuracy of 81.0% were achieved in the internal validation set. CONCLUSIONS: The current study demonstrates that MRI radiomics is able to predict molecular subgroups of PLGGs and KIAA1549-BRAF fusion with satisfying sensitivity. TRIAL REGISTRATION: This study was retrospectively registered at clinicaltrials.gov (NCT04217018).

Role of N6-methyladenosine RNA modification in gastric cancer.

N6-methyladenosine (m6A) RNA methylation is the most prevalent internal modification of mammalian messenger RNA. The m6A modification affects multiple aspects of RNA metabolism, including processing, splicing, export, stability, and translation through the reversible regulation of methyltransferases (Writers), demethylases (Erasers), and recognition binding proteins (Readers). Accumulating evidence indicates that altered m6A levels are associated with a variety of human cancers. Recently, dysregulation of m6A methylation was shown to be involved in the occurrence and development of gastric cancer (GC) through various pathways. Thus, elucidating the relationship between m6A and the pathogenesis of GC has important clinical implications for the diagnosis, treatment, and prognosis of GC patients. In this review, we evaluate the potential role and clinical significance of m6A-related proteins which function in GC in an m6A-dependent manner. We discuss current issues regarding m6A-targeted inhibition of GC, explore new methods for GC diagnosis and prognosis, consider new targets for GC treatment, and provide a reasonable outlook for the future of GC research.

Exposure to Commonly Used Drugs and the Risk of Gastric Cancer: An Umbrella Review of Meta-Analyses.

Recently, attention has been paid to some medications and gastric cancer (GC) risk. This review aimed to evaluate associations between commonly used drugs and GC risk and to grade evidence from published systematic reviews and meta-analyses. This umbrella review was registered in PROSPERO (CRD42022320276). The systematic reviews and meta-analyses of observational studies were retrieved by searching Embase, PubMed, and Web of Science. The evidence strength of commonly used drugs and GC risk was categorized into four grades: weak, suggestive, highly suggestive, and strong. Of 19 associations between commonly used drugs and GC risk and its subtypes, none was supported by convincing or highly suggestive evidence. The risk of GC related to non-steroidal anti-inflammatory drugs (NSAIDs), non-aspirin NSAIDs, and acid-suppressive drugs, as well as the risk of non-cardia GC related to NSAIDs and aspirin, was supported by suggestive evidence. The results showed that a reduced GC risk was associated with two drug types (NSAIDs and non-aspirin NSAIDs), and an increased GC risk was associated with acid-suppressing drugs at the suggestive evidence level. Moreover, NSAIDs and aspirin reduced non-cardia GC risk as supported by suggestive evidence. However, the evidence supporting statins or metformin in reducing GC risk was weak, and thus future studies are required to clarify these associations.

Chinese botulinum toxin A for the treatment of lower urinary tract dysfunction: It works just as well.

The botulinum neurotoxin type A (BoNT/A) is a neurotoxin produced by Clostridium botulinum. It causes botulism and represents the most powerful natural poison. In urological practice, the indications for BoNT/A therapy include neurogenic detrusor overactivity (NDO), idiopathic overactive bladder (OAB) or idiopathic detrusor overactivity (IDO), detrusor-sphincter dyssynergia (DSD), interstitial cystitis/bladder pain syndrome (IC/BPS), urinary tract infections (UTI), benign prostatic hyperplasia (BPH), and, more recently, chronic prostatic pain (CPP). BoNT/A is not only conducive to the treatment of muscle spasticity but also effectively works on hyperalgesia associated with various disorders of the lower urinary tract, thanks to its anti-nociceptive properties. While Botox® (Allergan Inc., Irvine, CA) is currently being used across the globe, we have been using Chinese BoNT/A for many years for the treatment of DSD, NDO, idiopathic OAB, IC/BPS, BPH and UTI. Our experience showed that Chinese BoNT/A was as good as other BoNT/A products in terms of efficacy, safety, and tolerability. In this study, we explored the current and potential applications of Chinese BoNT/A in urology, and reviewed the background information regarding the toxin.

Exosomal circRNAs: A key factor of tumor angiogenesis and therapeutic intervention.

Over the last few decades, our understanding of the molecular mechanisms underlying tumor angiogenesis has advanced at a significant pace and the clinical translation of these mechanisms has benefited millions of patients. However, limited efficacy and the rapid expansion of drug resistance remain unresolved issues. Recent studies in both preclinical and clinical settings have revealed that circRNAs, as a novel identified non-coding RNA can mediate intercellular communication and regulate the microenvironment within tumors after being selectively packaged, secreted, and transmitted via exosomes. This review aims to provide a comprehensive understanding of how exosomal circRNAs orchestrate inducers and inhibitors of angiogenesis, including their functions, molecular mechanisms, and potential roles as diagnostic biomarkers and therapeutic targets. Finally, we discuss the technological advances in exosome functionalization and exosome-mimetic nanovesicles intending to improve the clinical translation of exosomal circRNAs.

Influencing Factors and Application of Spontaneous Imbibition of Fracturing Fluids in Tight Sandstone Gas Reservoir.

This work is based on high-precision fluid spontaneous imbibition experiments to quantitatively study the imbibition rate, imbibition capacity, and imbibition curve characteristics of fracturing fluids in tight sandstone reservoirs. The objective of the work is to explore the influence of tight sandstone physical characteristics, fracturing fluid composition, salinity, viscosity, surface tension on fracturing fluid imbibition, and further analyze its main controlling factors. To evaluate imbibition characteristics more deeply, the pore throat structure and micromorphology of tight sandstone before and after imbibition were described by mercury intrusion test and scanning electron microscope test, respectively. Furthermore, the mineral composition and dilatation characteristics of the tight sandstone samples were identified by XRD and a linear dilatometer, respectively. The results show that the drilled tight sandstone samples from the Shaximiao Formation reservoir have strong heterogeneity, high clay mineral content, more developed micro/nanopores, less developed fractures, and strong hydration expansion. Since the average pore throat radius of tight sandstone samples is between 0.1 and 0.2 µm, the imbibition driving force is strong. The imbibition rate is fast, and the imbibition basically reaches a steady state within 24 h, which makes the imbibition capacity basically greater than 50%. Based on the analysis of the main control factors of imbibition, the surface tension of the fluid properties has the greatest impact on the imbibition recovery factor. The result not only helps to understand the absorption mechanism of fracturing fluid in tight sandstone reservoirs and then evaluates the degree of interaction between fluid and tight sandstone but it is also crucial for the prediction of flowback rate.

Bone flare after initiation of novel hormonal therapy in patients with metastatic hormone-sensitive prostate cancer: A case report.

BACKGROUND: The 2020 European Association of Urology prostate cancer guidelines recommend androgen deprivation therapy (ADT) in combination with apalutamide and enzalutamide, a new generation of androgen receptor antagonists, as first-line therapy. A decrease in prostate-specific antigen (PSA) levels may occur in the early stages of novel hormonal therapy; however, radionuclide bone imaging may suggest disease progression. During follow-up, PSA, radionuclide bone imaging, and prostate-specific membrane antigen (PSMA) positron emission tomography - computed tomography (PET-CT) are needed for systematic evaluation. CASE SUMMARY: We admitted a 56-year-old male patient with metastatic hormone-sensitive prostate cancer. Initial radionuclide bone imaging, magnetic resonance imaging (MRI), and PSMA PET-CT showed prostate cancer with multiple bone metastases. Ultrasound-guided needle biopsy of the prostate revealed a poorly differentiated adenocarcinoma of the prostate with a Gleason score: 5+4 = 9. The final diagnosis was a prostate adenocarcinoma (T4N1M1). ADT with novel hormonal therapy (goseraline sustained-release implant 3.6 mg monthly and apalutamide 240 mg daily) was commenced. Three months later, radionuclide bone imaging and MRI revealed advanced bone metastasis. However, PSMA PET-CT examination showed a significant reduction in PSMA aggregation on the bone, indicating improved bone metastases. Considering that progressive decrease in the presenting lumbar pain, treatment strategies were considered to be effective. CONCLUSION: ADT using novel hormonal therapy is effective for treating patients with prostate adenocarcinoma. Careful evaluation must precede treatment plan changes.

ThhspA1 is involved in lacA transcriptional regulation of Trametes hirsuta AH28-2 exposed to o-toluidine.

White rot fungi, especially Trametes spp., respond to a wide range of aromatic compounds and dramatically enhance laccase activity, while the activation mechanisms remain to be elucidated. Here, we show that an Hsp70 homolog named ThhspA1 regulates the transcription of laccase LacA in Trametes hirsuta AH28-2 when confronted with o-toluidine. ThhspA1 is pulled down by lacA promoter sequence from the nuclear mixture extracted from T. hirsuta AH28-2 induced by 2 mM o-toluidine. Silencing of ThhspA1 results in a sharp decrease in lacA transcripts and laccase activity in vivo. By comparison, ThhspA1 overexpression does not affect lacA transcription, and laccase activity shows slight enhancement or remains unchanged upon induction with o-toluidine. Electrophoretic mobility shift assays suggest a direct interaction between ThhspA1 and the lacA promoter region. Further investigation shows that the integrity of ThhspA1 is critical since its substrate binding domain (SBD) and nucleotide-binding domain (NBD) are both necessary for DNA binding, with a higher affinity of SBD than NBD based on fluorescence polarization assay. Our results demonstrate that ThhspA1 functions as an aromatic-stress-related DNA binding transcriptional factor required for LacA expression.

Sedimentimonas flavescens gen. nov., sp. nov., isolated from sediment of Clam Island, Liaoning Province.

A novel Gram-stain negative, aerobic and ovoid to short rod shaped bacterium with a single polar flagellum, named strain B57T, was isolated from sediment of Clam Island, Liaoning Province, China. The optimal growth of this strain was found to occur at 37 °C, pH 6-6.5, and in the presence of 2% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain B57T forms a distinct lineage within the family Rhodobacteraceae, sharing high 16S rRNA gene sequence similarity with Sinirhodobacter populi sk2b1T (97.4%). The average amino acid identity of B57T and the closely related species were lower than the threshold level for genus delineation. The dominant respiratory quinone of strain B57T was identified as Q-10. The major fatty acids were found to be Summed Feature 8 (C18:1ω7c and/or C18:1ω6c), Summed Feature 3 (C16:1ω7c and/or C16:1ω6c) and C16: 0. The polar lipids were identified as phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, diphosphatidylglycerol, two unidentified phospholipids, one unidentified glycolipid, and one unidentified lipid. The DNA G + C content of strain B57T was determined to be 64.1 mol%. Based on the biochemical, phylogenetic and chemotaxonomic analysis, strain B57T is concluded to represent a novel species of a novel genus, for which the name Sedimentimonas flavescens gen. nov., sp. nov.is proposed. The type strain is B57T (= CGMCC1.19488T = KCTC 92053T).

Case Report: 18F-FDG PET/CT and Laparoscopic Nephron Sparing Surgery in the Management of Bleeding From Renal Metastases of Choriocarcinoma.

Choriocarcinoma is a cancer that usually occurs in the uterus during pregnancy. Although choriocarcinoma with renal metastasis and spontaneous renal hemorrhage is very rare, it can occur. We describe a rare case of metastatic choriocarcinoma, wherein the patient presented with acute abdominal pain due to a subcapsular hematoma secondary to a bleeding renal metastasis. We performed a laparoscopic nephron sparing surgery to remove the tumor and control the bleeding. A retrospective analysis revealed that metastasis was detected on 18F-fluorodeoxyglucose PET/CT, but not on CT alone. To our knowledge, a case of choriocarcinoma with such symptoms and treatment has not been described in recent literature. Our case illustrates that acute bleeding from a renal metastasis can be effectively managed by laparoscopic nephron sparing surgery. It also demonstrates the advantage 18F-FDG PET/CT may have in the evaluation of metastatic choriocarcinoma.

AFF3 is a novel prognostic biomarker and a potential target for immunotherapy in gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common cancers worldwide with a poor prognosis. The tumor microenvironment (TME) serves a pivotal role in affecting the prognosis and efficacy of immunotherapy. Given the poor prognosis of GC patients and the limitation of immunotherapy, we urged to identify new prognostic and immunotherapeutic biomarkers. METHODS: The transcriptome data were downloaded from the TCGA, GEO, and GEPIA databases, and performed differential analysis of AFF3 in tumor samples and normal samples. The UALCAN, Kaplan-Meier plotter and GEPIA databases were employed to assess the correlation of AFF3 with clinicopathological characteristics and prognosis. The potential mechanism of AFF3 was explored by the GO and KEGG enrichment. The potential role of AFF3 on tumor-infiltrating immune cells (TIICs) was explored by TIMER2.0 and TISIDB. TIMER2.0 and SangerBox3.0 databases were, respectively, used to determine the correlation of AFF3 with immune checkpoint (ICs), tumor mutational burden (TMB), and microsatellite instability (MSI) in GC. RESULTS: We found significant downregulation of AFF3 in GC tissues as compared with normal tissues. However, GC patients having a higher expression of AFF3 were found to have worse clinicopathological characteristics and prognosis. Moreover, the GO enrichment analysis illustrated that AFF3 might regulate the immune cells in the TME. In addition, the AFF3 was positively correlated with TIICs, ICs, TMB, and MSI. CONCLUSION: Here, we conclude that AFF3 may be a promising potential marker for the diagnosis and prognosis of GC patients, and may influence response to ICIs by affecting TIICs and ICs expression in the TME.

RIP2 Knockdown Attenuates Vascular Smooth Muscle Cells Activation via Negative Regulating Myocardin Expression.

BACKGROUND: RIP2 is an adaptor protein contributing to the activation of nuclear factor-κB induced by TNF receptor-associated factor (TRAF) and nucleotide oligomerization domain (NOD)-dependent signaling implicated in innate and adaptive immune response. Beyond regulation of immunity, we aimed to elucidate the role of RIP2 in vascular smooth muscle cell (VSMC) phenotypic modulation. METHODS AND RESULTS: In the current study, we observed that RIP2 showed an increased expression in VSMCs with PDGF-BB stimulation in a dose-dependent manner. Knockdown of RIP2 expression mediated by adenovirus dramatically accelerated the expression of VSMC-specific differentiation genes induced by PDGF-BB. Silencing of RIP2 inhibited proliferative and migratory ability of VSMCs. Additionally, we demonstrated that RIP2 knockdown can promoted myocardin expression. Furthermore, RIP2 inhibition also can attenuate the formation of intimal hyperplasia. CONCLUSIONS: These findings suggested that RIP2 played an important role in regulation of VSMCs differentiation, migration, and proliferation that may due to affect myocardin expression. Our results indicated that RIP2 may be a novel therapeutic target for intimal hyperplasia.

OVOL2 inhibits macrophage M2 polarization by regulating IL-10 transcription, and thus inhibits the tumor metastasis by modulating the tumor microenvironment.

Invasion and metastasis of breast cancer cells is an important cause of death in breast cancer patients. In the tumor microenvironment, M2 polarization of macrophages can promote the invasion and metastasis of tumor cells. OVOL2 is an evolutionarily conserved transcription regulator, but its effect in macrophages has not been described previously. The aim of this study was to investigate the effects of OVOL2 on macrophage polarity and the role of these effects in the tumor metastasis. We found that overexpression of OVOL2 in macrophages significantly inhibited M2 polarization and thus inhibits breast cancer metastasis. We propose a novel mechanism in which OVOL2 inhibits M2 polarization of macrophages and thus reduces their ability to induce invasion and metastasis of breast cancer. By shedding new light on the regulation of metastasis in cancers, our study provides a new strategy for the targeted therapy of cancer.

Giant Cell Tumors of Bone in Patients Aged 18 Years Old or Younger: Imaging Features and Tumor Characteristics.

OBJECTIVE: The majority of giant cell tumors of bone (GCTB) occur in adult patients, especially between the ages of 20 and 40. This study aims to investigate the imaging features of GCTBs in pediatric patients and compare their characteristics with adult cases. METHODS: Fifty-seven cases of patients aged 18 years old or younger were retrospectively analyzed, accounting for 12.8% of GCTBs in the First Affiliated Hospital of Zhengzhou University from 2001 to 2019. One hundred twenty-six adult patients (19 years of age and older) with GCTB occurring in long tubular bones were also included in this study. The following clinical information was identified from the medical records: age, sex, and follow-up data. Imaging features were reviewed by two musculoskeletal radiologists. Patient characteristics and imaging features between the two groups were compared. RESULTS: A total of 57 patients (32 females, 25 males) were included in the study. The patients' ages ranged from 9 to 18 (median = 17 y). The majority of tumors occurred in tubular bones (n = 38, 66.7%) and the pelvis (n = 8, 14.0%). Imaging features were identified in GCTB cases occurring in the long tubular bones. Compared with adult GCTB patients, pediatric GCTB patients had a larger superior-inferior (SI) diameter (P = 0.005) and smaller left-to-right diameter/SI diameter ratio (P = 0.001). Epiphyseal involvement was relatively less common in pediatric patients with GCTBs than in adult patients (P = 0.009). The median age of patients without epiphyseal involvement was lower than the median age of patients with epiphyseal involvement (11 vs 17 y). CONCLUSION: GCTB in the pediatric age group is rare. This study has found that, in pediatric patients with GCTBs, the epiphysis is relatively less involved, and the tumor is more likely to grow longitudinally. These findings are helpful in the diagnosis of GCTBs in the pediatric population.

Effects of Apolipoprotein Ε Îµ4 allele on early postoperative cognitive dysfunction after anesthesia.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is one of the main causes of morbidity after noncardiac surgery; however, the pathogenic mechanisms of POCD have remained unclear until now. In this study, we performed a pilot study to investigate the association between apolipoprotein E (ApoE) ε4 and POCD in older patients undergoing intravenous anesthesia (IVA) and inhalation anesthesia (IAA). METHODS: In total, 180 patients from Shenzhen People's Hospital were recruited and randomly divided into an IVA group and an IAA group. The IVA group and IAA group received propofol and sevoflurane treatment, respectively. Within 7 days after surgery, the mini-mental state examination (MMSE) was used daily to assess the cognitive function of both groups of patients. The genotypes of the ApoE gene were detected using the restriction fragment length polymorphism technique. In addition, the serum levels of (soluble protein-100ß) S­100ß and (Interleukin- 6) L­6 were also analyzed. RESULTS: Compared to the preoperative and IVA groups, the MMSE score in the IAA group significantly decreased at 3 days after surgery. Furthermore, the IAA group had a higher percentage of patients who scored less than 25 points than the IVA group at 3 days after surgery. The decrease in the MMSE score was closely related to the ApoE ε4 allele in the IAA group, but this correlation was not observed in the IVA group. The levels of S­100ß and IL­6 were increased sharply in patients with the ε4/ε4 genotype who received IAA compared with IVA at 1 day after surgery. CONCLUSION: The results of the study indicated that the ApoΕ Îµ4/ε4 genotype was a risk factor for early POCD in older patients undergoing sevoflurane anesthesia.

CYP3A5*3 polymorphism and age affect tacrolimus blood trough concentration in myasthenia gravis patients.

The study aims to identify clinical factors affecting tacrolimus blood trough concentration (C0) in myasthenia gravis (MG) patients and to optimize the initial dose of tacrolimus in MG treatment. A total of 103 MG patients participated in this study, and their clinical factors, medication regimens, C0 values and CYP3A5*3 polymorphisms were collected in detail. We used a linear mixed model to analyze the effect of multiple factors on the dosage-weighted C0 (C0:D) and performed subgroup analyses to investigate the consistency of correlations between influencing factors and the C0:D ratios. Among all factors, CYP3A5*3 polymorphism and age showed a strong positive correlation with C0:D ratios. The C0:D ratios (ng/ml·mg-1) were higher for CYP3A5*3/*3 than for CYP3A5*1 (mean difference: 1.038, 95% confidence interval [CI]: 0.820-1.256, P-value <0.001), and for age in the range of 45-64 and ≥ 65 years than for age < 45 years (mean difference [95% CI] and P-value: 0.531[0.257-0.805] and P-value <0.001, 0.703 [0.377-1.029] and P-value <0.001, respectively). The C0:D ratios were not related to corticosteroid dosage, body weight, sex, hematocrit or the concomitant use of calcium channel blockers. The consistencies of the correlations between C0:D ratios and CYP3A5*3 polymorphism or age were confirmed by subgroup analyses. Thus, CYP3A5*3 polymorphism and age should be considered in optimizing the initial dose of tacrolimus for MG treatment.