RNA-binding protein IGF2BP1 is required for spermatogenesis in an age-dependent manner.

Post-transcriptional regulation mediated by RNA binding proteins is crucial for male germline development. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), an RNA binding protein, is specifically expressed in human and mouse male gonads and is involved in manifold biological processes and tumorigenesis. However, the function of IGF2BP1 in mammalian spermatogenesis remains poorly understood. Herein, we generated an Igf2bp1 conditional knockout mouse model using Nanos3-Cre. Germ cell deficiency of Igf2bp1 in mice caused spermatogenic defects in an age-dependent manner, resulting in decreased numbers of undifferentiated spermatogonia and increased germ cell apoptosis. Immunoprecipitation-mass spectrometry analysis revealed that ELAV-like RNA binding protein 1, a well-recognized mRNA stabilizer, interacted with IGF2BP1. Single cell RNA-sequencing showed distinct mRNA profiles in spermatogonia from conditional knockout versus wide type mice. Further research showed that IGF2BP1 plays a vital role in the modulation of spermatogenesis by regulating Lin28a mRNA, which is essential for clonal expansion of undifferentiated spermatogonia. Thus, our results highlight the crucial effects of IGF2BP1 on spermatogonia for the long-term maintenance of spermatogenesis.

Application of proton density fat fraction imaging in risk stratification of prostate cancer.

Background: Prostate cancer (PCa) as one of the most prevalent malignancies in men. We introduced a non-invasive quantitative measurement of intraprostatic fat content based on magnetic resonance proton density fat fraction (PDFF) imaging. The study aims to determine the fat fraction (FF) of PCa using proton density magnetic resonance imaging (MRI), gather clinical and routine MRI characteristics, and identify risk factors for high-risk PCa through multifactorial logistic regression. Methods: Clinical and imaging data from 191 pathologically confirmed PCa patients were collected. Patients were stratified based on Gleason score (GS), with 63 in the intermediate- and low-risk group (GS =3+3, 3+4) and 128 in the high-risk group (GS ≥4+3). All patients underwent routine prostate MRI and FF imaging. Clinical and imaging data related to PCa were analyzed, including age, body mass index (BMI), prostate volume (PV) measured by MRI, smoking history, alcohol history, diabetes history, serum prostate-specific antigen (PSA) level, apparent diffusion coefficient (ADC) value, T2 signal intensity (T2SI), Prostate Imaging Reporting and Data System 2.1 (PI-RADS 2.1) score, GS, lesion FF, whole gland FF, periprostatic fat thickness (PPFT), and subcutaneous fat thickness (SFT). Independent risk factors for stratifying PCa risk were identified through multivariate logistic regression analysis, and a predictive model was established. Receiver operating characteristic (ROC) curve analysis was conducted for visual analysis. Results: Significant differences were found in BMI, PV, PSA, tumor ADC value, standard T2SI, PI-RADS score, lesion FF, and PPFT between low- and medium-risk and high-risk groups (P<0.05). No significant differences were observed in age, smoking history, drinking history, diabetes history, and SFT between the two groups (P>0.05). GS correlated significantly with FF (ρ=0.6, P<0.001), PSA (ρ=0.432, P<0.001), ADC value (ρ=-0.379, P<0.001), and PI-RADS (ρ=0.366, P<0.001). Multiple logistic regression analysis revealed that an increase in FF, a PI-RADS score increase of 5 points, and a decrease in ADC value and PV were independent predictors of high-risk PCa (P<0.05). The ROC curve showed that the best cut-off value for the model was 0.67, with an area under the curve (AUC) of 0.907, sensitivity of 78.1%, and specificity of 88.9%. Conclusions: The FF of PCa determined by proton density MRI is significantly associated with GS, serving as an independent predictor of high-risk PCa.

Motion and anatomy dual aware lung ventilation imaging by integrating Jacobian map and average CT image using dual path fusion network.

BACKGROUND: Deep learning-based computed tomography (CT) ventilation imaging (CTVI) is a promising technique for guiding functional lung avoidance radiotherapy (FLART). However, conventional approaches, which rely on anatomical CT data, may overlook important ventilation features due to the lack of motion data integration. PURPOSE: This study aims to develop a novel dual-aware CTVI method that integrates both anatomical information from CT images and motional information from Jacobian maps to generate more accurate ventilation images for FLART. METHODS: A dataset of 66 patients with four-dimensional CT (4DCT) images and reference ventilation images (RefVI) was utilized to develop the dual-path fusion network (DPFN) for synthesizing ventilation images (CTVIDual). The DPFN model was specifically designed to integrate motion data from 4DCT-generated Jacobian maps with anatomical data from average 4DCT images. The DPFN utilized two specialized feature extraction pathways, along with encoders and decoders, designed to handle both 3D average CT images and Jacobian map data. This dual-processing approach enabled the comprehensive extraction of lung ventilation-related features. The performance of DPFN was assessed by comparing CTVIDual to RefVI using various metrics, including Spearman's correlation coefficients (R), Dice similarity coefficients of high-functional region (DSCh), and low-functional region (DSCl). Additionally, CTVIDual was benchmarked against other CTVI methods, including a dual-phase CT-based deep learning method (CTVIDLCT), a radiomics-based method (CTVIFM), a super voxel-based method (CTVISVD), a Unet-based method (CTVIUnet), and two deformable registration-based methods (CTVIJac and CTVIHU). RESULTS: In the test group, the mean R between CTVIDual and RefVI was 0.70, significantly outperforming CTVIDLCT (0.68), CTVIFM (0.58), CTVISVD (0.62), and CTVIUnet (0.66), with p < 0.05. Furthermore, the DSCh and DSCl values of CTVIDual were 0.64 and 0.80, respectively, outperforming CTVISVD (0.63; 0.73) and CTVIUnet (0.62; 0.77). The performance of CTVIDual was also significantly better than that of CTVIJac and CTVIHU. CONCLUSIONS: A novel dual-aware CTVI model that integrates anatomical and motion information was developed to synthesize lung ventilation images. It was shown that the accuracy of lung ventilation estimation could be significantly enhanced by incorporating motional information, particularly in patients with tumor-induced blockages. This approach has the potential to improve the accuracy of CTVI, enabling more effective FLART.

Impact of enhanced recovery after surgery (ERAS) on surgical site infection and postoperative recovery outcomes: a retrospective study of 1276 cases.

This retrospective observational study aimed to evaluate the incidence of surgical site infection (SSI) in the era of enhanced recovery after surgery (ERAS) and the effect of ERAS on postoperative outcomes. Totally 1,276 patients (565 in ERAS group and 711 in non-ERAS group) who underwent operations at the department of general surgery during 2017-2021 were included. Risk factors were identified via logistic regression analysis and meta-analysis of all relevant published studies was performed. Subsequently, propensity score matching was used to match different risk factors. Overall, 40 patients were diagnosed with SSI, and the pooled incidence of SSI was 3.13%. In total, 14 (2.48%) and 26 (3.66%) patients in the ERAS and non-ERAS groups, respectively, were diagnosed with SSI (P = 0.230). Among patients for whom the ERAS protocol was adopted, 7 independent risk factors of SSI were identified. After propensity score matching, in patients without SSI, the number of hospital days was significantly lower in the ERAS group than in the non-ERAS group (2 [2, 5] vs. 3 [2, 7], P = 0.005), whereas in patients with SSI, the number of hospital days was similar between the ERAS and non-ERAS groups. ERAS had no effect on the incidence of SSI but could significantly accelerate the discharge of uninfected patients. In the era of ERAS, SSI incidence was affected by the type of surgery; number of postoperative hospital days; type of incision; serum hemoglobin, total protein, and albumin levels; and antibiotic prophylaxis. Furthermore, these results will significantly affect the implementation of the ERAS protocol and optimal preoperative management.

Isolation, purification, characterization and stability analysis of melanin pigment from Mesona chinensis.

In this study, the isolation and purification of melanin pigment from Mesona chinensis (MCM) were conducted, and the structural characterization and stability evaluation of MCM were performed. The results indicate that MCM is consistent with the spectral features of catechins and polyphenols, identified the stretching vibrations of functional groups such as OH, CH, CO, and CO. It is inferred that the structure of MCM is consistent with that of theophylline and it is mainly composed of phenolic acids, terpenoids, and organic acids. Stability evaluations indicate that MCM exhibits stability under white light, ultraviolet (UV) light, neutral, and alkaline environments, and it shows low sensitivity to reducing agents.

A case of multiple soft fibromas complicated with pityriasis versicolor during pregnancy: A case report.

Dermatological conditions in pregnancy pose unique challenges due to concerns for maternal and fetal health. We present a case of a 32-year-old primigravida who, at 36 weeks of gestation, exhibited melanotic papules and neoplasms on her neck, chest, and breasts. Seeking evaluation for potential effects on her unborn child and breastfeeding, she presented to our dermatological outpatient facility. Physical examination revealed varied pigmented papules and verrucous proliferations. Laboratory tests and imaging were unremarkable, with histological analysis confirming fibromas and pityriasis versicolor. The patient declined treatment during pregnancy, and postpartum, spontaneous regression of lesions occurred, with complete resolution within 1 year. The child exhibited normal development, with no recurrence observed at the 2-year follow-up. This case underscores the importance of multidisciplinary care and long-term monitoring in managing dermatological manifestations during pregnancy.

Comparative Analysis of Repeatability in CT Radiomics and Dosiomics Features under Image Perturbation: A Study in Cervical Cancer Patients.

This study aims to evaluate the repeatability of radiomics and dosiomics features via image perturbation of patients with cervical cancer. A total of 304 cervical cancer patients with planning CT images and dose maps were retrospectively included. Random translation, rotation, and contour randomization were applied to CT images and dose maps before radiomics feature extraction. The repeatability of radiomics and dosiomics features was assessed using intra-class correlation of coefficient (ICC). Pearson correlation coefficient (r) was adopted to quantify the correlation between the image characteristics and feature repeatability. In general, the repeatability of dosiomics features was lower compared with CT radiomics features, especially after small-sigma Laplacian-of-Gaussian (LoG) and wavelet filtering. More repeatable features (ICC > 0.9) were observed when extracted from the original, Large-sigma LoG filtered, and LLL-/LLH-wavelet filtered images. Positive correlations were found between image entropy and high-repeatable feature number in both CT and dose (r = 0.56, 0.68). Radiomics features showed higher repeatability compared to dosiomics features. These findings highlight the potential of radiomics features for robust quantitative imaging analysis in cervical cancer patients, while suggesting the need for further refinement of dosiomics approaches to enhance their repeatability.

Automatic planning for functional lung avoidance radiotherapy based on function-guided beam angle selection and plan optimization.

Objective.This study aims to develop a fully automatic planning framework for functional lung avoidance radiotherapy (AP-FLART).Approach.The AP-FLART integrates a dosimetric score-based beam angle selection method and a meta-optimization-based plan optimization method, both of which incorporate lung function information to guide dose redirection from high functional lung (HFL) to low functional lung (LFL). It is applicable to both contour-based FLART (cFLART) and voxel-based FLART (vFLART) optimization options. A cohort of 18 lung cancer patient cases underwent planning-CT and SPECT perfusion scans were collected. AP-FLART was applied to generate conventional RT (ConvRT), cFLART, and vFLART plans for all cases. We compared automatic against manual ConvRT plans as well as automatic ConvRT against FLART plans, to evaluate the effectiveness of AP-FLART. Ablation studies were performed to evaluate the contribution of function-guided beam angle selection and plan optimization to dose redirection.Main results.Automatic ConvRT plans generated by AP-FLART exhibited similar quality compared to manual counterparts. Furthermore, compared to automatic ConvRT plans, HFL mean dose,V20, andV5were significantly reduced by 1.13 Gy (p< .001), 2.01% (p< .001), and 6.66% (p< .001) respectively for cFLART plans. Besides, vFLART plans showed a decrease in lung functionally weighted mean dose by 0.64 Gy (p< .01),fV20by 0.90% (p= 0.099), andfV5by 5.07% (p< .01) respectively. Though inferior conformity was observed, all dose constraints were well satisfied. The ablation study results indicated that both function-guided beam angle selection and plan optimization significantly contributed to dose redirection.Significance.AP-FLART can effectively redirect doses from HFL to LFL without severely degrading conventional dose metrics, producing high-quality FLART plans. It has the potential to advance the research and clinical application of FLART by providing labor-free, consistent, and high-quality plans.

Comprehensive investigation in oncogenic functions and immunological roles of NCBP2 and its validation in prostate cancer.

BACKGROUND: Nuclear cap-binding protein 2 (NCBP2), as the component of the cap-binding complex, participates in a number of biological processes, including pre-mRNA splicing, transcript export, translation regulation and other gene expression steps. However, the role of NCBP2 on the tumor cells and immune microenvironment remains unclear. To systematically analyze and validate functions of NCBP2, we performed a pan-cancer analysis using multiple approaches. METHODS: The data in this study were derived from sequencing, mutation, and methylation data in the TCGA cohort, normal sample sequencing data in the GTEx project, and cell line expression profile data in the CCLE database. RESULTS: Survival analyses including the Cox proportional-hazards model and log-rank test revealed the poor prognostic role of NCBP2 in multiple tumors. We further validated the oncogenic ability of NCBP2 in prostate cancer cell lines, organoids and tumor-bearing mice. A negative correlation was observed between NCBP2 expression and immune score by the ESTIMATE algorithm. Simultaneously, the NCBP2-induced immunosuppressive microenvironment might be related to the decline in CD8+T cells and the increase in regulatory T cells and neutrophils, examined by flow cytometry experiments for NCBP2 overexpressed tumor-bearing mice. CONCLUSION: This research offered strong proof supporting NCBP2 as the prognostic marker and the therapeutic target in the future.

Deciphering the role of zinc homeostasis in the tumor microenvironment and prognosis of prostate cancer.

BACKGROUND: Dysregulation of zinc homeostasis is widely recognized as a hallmark feature of prostate cancer (PCa) based on the compelling clinical and experimental evidence. Nevertheless, the implications of zinc dyshomeostasis in PCa remains largely unexplored. METHODS: In this research, the zinc homeostasis pattern subtype (ZHPS) was constructed according to the profile of zinc homeostasis genes. The identified subtypes were assessed for their immune functions, mutational landscapes, biological peculiarities and drug susceptibility. Subsequently, we developed the optimal signature, known as the zinc homeostasis-related risk score (ZHRRS), using the approach won out in multifariously machine learning algorithms. Eventually, clinical specimens, Bayesian network inference and single-cell sequencing were used to excavate the underlying mechanisms of MT1A in PCa. RESULTS: The zinc dyshomeostasis subgroup, ZHPS2, possessed a markedly worse prognosis than ZHPS1. Moreover, ZHPS2 demonstrated a more conspicuous genomic instability and better therapeutic responses to docetaxel and olaparib than ZHPS1. Compared with traditional clinicopathological characteristics and 35 published signatures, ZHRRS displayed a significantly improved accuracy in prognosis prediction. The diagnostic value of MT1A in PCa was substantiated through analysis of clinical samples. Additionally, we inferred and established the regulatory network of MT1A to elucidate its biological mechanisms. CONCLUSIONS: The ZHPS classifier and ZHRRS model hold great potential as clinical applications for improving outcomes of PCa patients.

The safety and efficacy of five surgical treatments in prostate enucleation: a network meta-analysis.

PURPOSE: The aim of our study was to investigate the comparative outcomes of five different energy types on surgical efficacy and postoperative recovery in patients with benign prostate hyperplasia. METHODS: The literature was systematically reviewed on December 1st, 2023, encompassing studies retrieved from PubMed, Embase, Web of Science, and The Cochrane Library databases that incorporated clinical studies of holmium laser enucleation of the prostate (HoLEP), Thulium:YAG laser enucleation of the prostate (ThuLEP), transurethral plasmakinetic enucleation of prostate (PKEP), diode laser enucleation of the prostate (DiLEP) and thulium fiber laser enucleation of the prostate (ThuFLEP) in the treatment of prostatic hyperplasia. Two independent reviewers extracted study data and conducted quality assessments using the Cochrane Collaboration's Risk of Bias tool and Newcastle-Ottawa Scale (NOS). Network meta-analysis (NMA) was employed to indirectly analyze the outcomes of endoscopic enucleation of the prostate (EEP) techniques. RESULTS: The study included a total of 38 studies, comprising 21 non-randomized controlled trials (nRCTs) and 17 randomized controlled trials (RCTs), incorporating five distinct techniques: holmium laser, Thulium:YAG laser, bipolar plasma, diode laser and thulium fiber laser. In comparing treatment durations, ThuLEP and HoLEP had shorter overall hospital stays than PKEP, while the enucleation time of ThuLEP and HoLEP was shorter than that of ThuFLEP. Moreover, the enucleation tissue weight of both thulium fiber laser and holmium laser was heavier than bipolar plasma. However, the analysis did not reveal any statistically significant variation in complications among the various types of enucleation. In postoperative follow-up, the IPSS at 3 months post-operation was superior in the Thulium:YAG laser group compared to the holmium laser group. The thulium fiber laser technique demonstrated significant advantages over other enucleation methods in terms of QoL and PVR at 12 months after surgery. CONCLUSION: Theoretical properties may vary among different energy sources; however, there are no discernible clinical differences in operation-related parameters, postoperative complications, and postoperative follow-up. Therefore, the choice of laser does not significantly impact the outcome. However, due to the limited number of included studies, future research should focus on larger sample sizes and multicenter investigations to further validate the findings of this study.

Associations of systemic immune-inflammation index with high risk for prostate cancer in middle-aged and older US males: A population-based study.

BACKGROUND: Systemic immune-inflammation index (SII) provides convincing evaluation of systemic immune and inflammatory condition in human body. Its correlation with prostate cancer (PCa) risk remains uncharted. The principal objective of this investigation was to elucidate the association between SII and the risk for PCa in middle-aged and elderly males. MATERIALS AND METHODS: Analysis entailed multivariate linear and logistic regression, generalized additive model, and smoothing curve fitting using resource from 2007 to 2010 National Health and Nutrition Examination Survey (NHANES). To ascertain robustness and consistency of this association across different demographic strata, we conducted rigorous subgroup analyses and interaction tests. RESULTS: Among 3359 participants, those with elevated SII displayed higher total prostate-specific antigen (tPSA) levels, higher risk for PCa, and lower free/total PSA (f/t PSA) ratio. Specifically, each unit increase of log2 (SII) was associated with a 0.22 ng/mL increase in tPSA (ß: 0.22, 95% confidence intervals [CI] 0.05-0.38), a 2.22% decline in f/t PSA ratio (ß: -2.22, 95% CI -3.20 to -1.23), and a 52% increased odds of being at high risk for PCa (odds ratio [OR]: 1.52, 95% CI 1.13-2.04). People in the top quartile of log2 (SII) exhibited 0.55 ng/mL increased tPSA (ß: 0.55, 95% CI 0.19-0.90), 4.39% reduced f/t PSA ratio (ß: -4.39, 95% CI -6.50 to -2.27), and 168% increased odds of being at high risk for PCa (OR: 2.68, 95% CI 1.32-5.46) compared to those in the bottom quartile. CONCLUSION: Systemic immune and inflammatory condition, as represented by SII, is independently and positively associated with tPSA levels and the risk for PCa, as well as independently and negatively associated with f/t PSA ratio among middle-aged and older US males. These findings may enhance the effectiveness of PCa screening in predicting positive biopsy results.

First-line hepatic arterial infusion chemotherapy plus lenvatinib and PD-(L)1 inhibitors versus systemic chemotherapy alone or with PD-(L)1 inhibitors in unresectable intrahepatic cholangiocarcinoma.

PURPOSE: Limited treatment options exist for unresectable intrahepatic cholangiocarcinoma (ICC), with systemic chemotherapy (SC) serving as the primary approach. This study aimed to assess the effectiveness of first-line hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib and PD-(L)1 inhibitors (HLP) compared to SC combined with PD-(L)1 inhibitors (SCP) or SC alone in treating unresectable ICC. METHODS: Patient with unresectable ICC who underwent first-line treatment with HLP, SCP or SC from January 2016 to December 2022 were retrospectively analyzed. The study evaluated and compared efficacy and safety outcomes across the three treatment groups. RESULTS: The study comprised 42, 49, and 50 patients in the HLP, SCP, and SC groups, respectively. Median progression-free survival (PFS) times were 30.0, 10.2, and 6.5 months for HLP, SCP, and SC groups. While the SC group had a median overall survival (OS) time of 21.8 months, the HLP and SCP groups hadn't reached median OS. The HLP group demonstrated significantly superior PFS (p < 0.001) and OS (p = 0.014) compared to the others. Moreover, the HLP group exhibited the highest objective response rate (ORR) at 50.0% and the highest disease control rate (DCR) at 88.1%, surpassing the SC group (ORR, 6.0%; DCR, 52.0%) and SCP group (ORR, 18.4%; DCR, 73.5%) (p < 0.05). Generally, the HLP group reported fewer grades 3-4 adverse events (AEs) compared with others. CONCLUSION: In contrast to systemic chemotherapy with or without PD-(L)1 inhibitors, the triple combination therapy incorporating HAIC, lenvatinib, and PD-(L)1 inhibitors showcased favorable survival benefits and manageable adverse events for unresectable ICC.

Molecular landscape for risk prediction and personalized therapeutics of castration-resistant prostate cancer: at a glance.

Prostate cancer (PCa) is commonly occurred with high incidence in men worldwide, and many patients will be eventually suffered from the dilemma of castration-resistance with the time of disease progression. Castration-resistant PCa (CRPC) is an advanced subtype of PCa with heterogeneous carcinogenesis, resulting in poor prognosis and difficulties in therapy. Currently, disorders in androgen receptor (AR)-related signaling are widely acknowledged as the leading cause of CRPC development, and some non-AR-based strategies are also proposed for CRPC clinical analyses. The initiation of CRPC is a consequence of abnormal interaction and regulation among molecules and pathways at multi-biological levels. In this study, CRPC-associated genes, RNAs, proteins, and metabolites were manually collected and integrated by a comprehensive literature review, and they were functionally classified and compared based on the role during CRPC evolution, i.e., drivers, suppressors, and biomarkers, etc. Finally, translational perspectives for data-driven and artificial intelligence-powered CRPC systems biology analysis were discussed to highlight the significance of novel molecule-based approaches for CRPC precision medicine and holistic healthcare.

Verbascoside inhibits oral squamous cell carcinoma cell proliferation, migration, and invasion by the methyltransferase 3-mediated microRNA-31-5p/homeodomain interacting protein kinase 2 axis.

OBJECTIVE: The study aimed to investigate the effects of verbascoside on oral squamous cell carcinoma (OSCC) cellular behaviors and underlying molecular mechanisms. DESIGN: For this purpose, SCC9 and UM1 cell lines were treated with verbascoside, and their biological behaviors, including proliferation, migration, and invasion, were evaluated using cell counting kit-8, 5-Ethynyl-2'-deoxyuridine, and Transwell assays. The expression of methyltransferase-3 (METTL3), microRNA (miR)- 31-5p, and homeodomain interacting protein kinase-2 (HIPK2) were examined using quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between METTL3 and miR-31-5p was evaluated by RNA immunoprecipitation and methylated RNA immunoprecipitation, while the interaction between miR-31-5p and HIPK2 was evaluated by dual-luciferase reporter analysis. RESULTS: The results indicated inhibition of OSCC cell proliferation, migration, and invasion post verbascoside treatment. Similarly, METTL3 was upregulated in OSCC cells and was inhibited post-verbascoside treatment. Overexpressing METTL3 promoted the cellular processes. Moreover, miR-31-5p was upregulated in OSCC cells, where METTL3 facilitated the processing of miR-31-5p in an N6-methyladenosine (m6A)-dependent manner. The HIPK2 served as miR-31-5p target, where overexpressing miR-31-5p or HIPK2 knockdown reversed the suppression of verbascoside-induced biological behaviors. CONCLUSIONS: Verbascoside inhibited the progression of OSCC by inhibiting the METTL3-regulated miR-31-5p/HIPK2 axis. These findings suggested that verbascoside might be an effective drug for OSCC therapy.

CDDO, an Anti-Inflammatory and Antioxidant Compound, Attenuates Vasospasm and Neuronal Cell Apoptosis in Rats Subjected to Experimental Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a type of stroke caused by bleeding into the subarachnoid space. SAH is a medical emergency and requires prompt treatment to prevent complications such as seizures, stroke, or other brain damage. Treatment options may include surgery, medication, or a combination of both. 2-Cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), a compound with anti-inflammatory and antioxidant properties, is currently being investigated as a potential treatment for various diseases, including chronic kidney disease and pulmonary arterial hypertension. In this study, the effects of CDDO on rats subjected to SAH were evaluated. Male Sprague-Dawley rats were divided into four groups (n = 6/group): (1) control group, (2) SAH group, (3) SAH + low-dose CDDO (10 mg/kg injected into the subarachnoid space at 24 h after SAH) group, and (4) SAH + high-dose CDDO (20 mg/kg) group. CDDO improved SAH-induced poor neurological outcomes and reduced vasospasm in the basal artery following SAH. It also decreased the SAH-induced expression of proinflammatory cytokines such as TNF-α, IL-1ß, and IL-6 in both the cerebrospinal fluid and serum samples as determined by ELISA. A Western blot analysis confirmed an increase in the p-NF-κB protein level after SAH, but it was significantly decreased with CDDO intervention. Immunofluorescence staining highlighted the proliferation of microglia and astrocytes as well as apoptosis of the neuronal cells after SAH, and treatment with CDDO markedly reduced the proliferation of these glial cells and apoptosis of the neuronal cells. The early administration of CDDO after SAH may effectively mitigate neuronal apoptosis and vasospasm by suppressing inflammation.

Infection may play an important role in the pathogenesis of alveolar osteonecrosis following facial herpes zoster: a case report and literature review.

BACKGROUND: Herpes zoster (HZ) is one of the most common skin diseases caused by viruses. Facial HZ develops when the varicella-zoster virus affects the trigeminal nerve, and alveolar osteonecrosis is a rare complication. However, the exact pathogenesis of postherpetic alveolar osteonecrosis remains unclear. CASE DESCRIPTION: We encountered a patient who presented to the dermatology clinic with facial HZ and tooth exfoliation in the upper right jaw, and panoramic radiography revealed decreased bone density and poor alveolar socket healing in his right maxilla. Biopsy of the alveolar process revealed fragments of nonvital lamellar bone, which were devoid of osteoblasts and osteocytes and were surrounded by numerous neutrophils and bacterial aggregates. Thus, the diagnosis of alveolar osteonecrosis following facial HZ was confirmed. He then underwent resection of the osteonecrotic tissue. The pathological findings of postoperative tissue were similar to those of previous biopsies. Varicella-zoster virus and multiple types of bacteria were detected through next-generation sequencing, and the species of bacteria were consistent with the results of bacterial culture. Antibiotics and valaciclovir were administered during the perioperative period. The patient showed good recovery at the 9-month follow-up. CONCLUSIONS: The coexistence of bacterial and viral infection may play an important role in the pathogenesis of alveolar osteonecrosis following HZ. To our knowledge, we are the first to directly explore microbial pathogens in a case of postherpetic alveolar osteonecrosis through next-generation sequencing and bacterial culture. We recommend that oral examinations be carefully conducted for patients who are diagnosed with facial HZ, even if their facial rashes have faded away. We suggest that a prolonged and full-dose antiviral therapy course may be beneficial for the treatment of facial HZ with intraoral lesions. The implementation of dental preventive measures should be considered for patients with facial HZ. The application of antibiotics and excision of necrotic bone may reduce the abundance of bacteria in lesions and improve wound healing.

Health care-associated infections after surgical treatment of ruptured intracranial aneurysms.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) is catastrophic, and microsurgery for ruptured intracranial aneurysms is one of the preventive modalities for rebleeding. However, patients remain at high risk of medical morbidities after surgery, one of the most important of which is health care-associated infections (HAIs). We analyzed the incidence and risk factors of HAIs, as well as their association with the outcomes after surgical treatment of ruptured aneurysms. METHODS: We retrospectively enrolled 607 patients with SAH who had undergone surgery for intracranial aneurysms. Information was retrieved from the database using codes of the International Classification of Diseases, Ninth Revision, Clinical Modification. RESULTS: Of the 607 patients, 203 were male and 404 were female. HAIs occurred in 113 patients, accounting for 18.6 % of the population. The independent risk factors for HAIs included age ((p = 0.035), hypertension ((p = 0.042), convulsion ((p = 0.023), external ventricular drain ((p = 0.035), ventricular shunt ((p = 0.033), and blood transfusion ((p = 0.001). The mean length of hospital stay was 25.3 ± 18.2 and 18.8 ± 15.3 days for patients with and without HAIs, respectively ((p = 0.001). The in-hospital mortality rates were 11.5 % in the HAIs group, and 14.0 % in the non-HAIs group ((p = 0.490). CONCLUSION: HAIs are a frequent complication in patients with SAH who underwent surgery for ruptured intracranial aneurysms. The length of hospital stay is remarkably longer for patients with HAIs, and to recognize and reduce the modifiable risks should be implemented to improve the quality of patient care.

Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny.

Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.

Clinical risk prediction model and external validation of positive surgical margin in laparoscopic radical prostatectomy based on MRI lesion location.

OBJECTIVE: To clarify the composition of lesions in different magnetic resonance imaging (MRI) partitions of positive surgical margins (PSM) after laparoscopic radical prostatectomy, explore the influence of lesion location on PSM, and construct a clinical prediction model to predict the risk of PSM. MATERIALS AND METHODS: This retrospective cohort study included 309 patients who underwent laparoscopic radical prostatectomy from 2018 to 2021 in our center was performed. 129 patients who met the same criteria from January to September 2022 were external validation cohorts. RESULTS: The incidence of PSM in transition zone (TZ) lesions was higher than that in peripheral zone (PZ) lesions. The incidence of PSM in the middle PZ was lower than that in other regions. Prostate specific antigen (PSA), clinical T-stage, the number of positive cores, international society of urological pathology (ISUP) grade (biopsy), MRI lesion location, extracapsular extension, seminal vesicle invasion (SVI), pseudo-capsule invasion (PCI), long diameter of lesions, lesion volume, lesion volume ratio, PSA density were related to PSM. MRI lesion location and PCI were independent risk factors for PSM. Least absolute shrinkage and selection operator (LASSO) regression was used to construct a clinical prediction model for PSM, including five variables: the number of positive cores, SVI, MRI lesion location, long diameter of lesions, and PSA. CONCLUSION: The positive rate of surgical margin in middle PZ was significantly lower than that in other regions, and MRI lesion location was an independent risk factor for PSM.